Documentos de Académico
Documentos de Profesional
Documentos de Cultura
Sr.
No.
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
19
20
Check points
Is the control copy of store
department SOPs available?
Is the personnel having knowledge
of current GMP requirements?
Is the incoming raw materials entry
register available?
Is the housekeeping maintained?
Is the sampling booth area
cleaned?
Is the weighting balance having
proper tag of calibration status?
Is the balance calibration record
available?
Are the calibrated standard weights
available?
Is
the
calibration
certificate
available?
Is the standard weights are
properly stored?
Is the quarantine, approved and
rejected area designated?
Are the UNDER TEST label pasted
on all the incoming raw materials?
Are the SAMPLE label pasted on
all the sampled raw materials?
Are the APPROVED labels pasted
on all the approved raw materials?
Are the raw materials stored at
their respective place?
Check
the
cleaning
and
housekeeping condition record of
quarantine, approved and rejected
area.
Are the packing materials stored
separately?
Is the cleaning and housekeeping
maintained at packing material
store area?
Is the temperature and relative
humidity record maintained for all
respective area?
Is the approved vendor list
Observation
Recommendatio
n
Action
taken by
available?
Is the FIFO system follow?
Check the production requisition
slip record?
23
Check the issuance record.
24
Check the dispatch record.
25
Check the general cleaning and
housekeeping of store.
26
Check the personnel hygiene.
27
Check the safety equipments.
28
Check the drum storage yard for
cleaning, housekeeping and status.
29
Check the proper segregation at
drum storage yard?
30
Check the other records.
31
Is
line
clearance
activity
performed?
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Check points
Is the control copy of QC department SOPs
available?
Are the personnel having knowledge of
current GMP requirements?
Is the housekeeping maintained?
Is the weighting balance having proper tag of
calibration status?
Is the balance calibration record available?
Are the calibrated standard weights
available?
Is the calibration certificates available?
Observation
Recommendation
Action
taken by
08
09
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
35
36
37
38
33
34
39
40
41
42
43
:This document describes the conduct of the Management review of the quality system for G
Conformance Certification, including the conduct of an internal audit to assure the system meets
requirements of ISO Guidelines and is effectively implemented..
2.0 Objective: To Provide Documented Procedure for review of the quality system for GMP Conformance Certificat
including the conduct of an internal audit to assure the system meets the requirements.
Scope : To define role/responsibility of various functions responsible for Internal audit
4.0 Responsibility
o
Board of Internal Audit and Management Review Committee: Arranges for the internal audit
gathers all information for the Management Review.
QA Management Committee: Provides all information as required by the Board of Internal Audit
Management Review Committee and is responsible for follow-up corrective and preventive actions
o
5.0
The QA Management Committee, by consensus, selects three qualified individuals for the Board
Internal Audit and Management Review Committee. Members to the Committee serve until they
replaced.
The Board of Internal Audit and Management Review Committee arranges for the half yearly inte
audit to be conducted.
The date for the audit is established by mutual agreement between the Board of Internal Audit a
Management Review Committee and the General Manager Production and Asst. Manager Produc
(AMP).
The audit is conducted by any member of the board or Internal auditor qualified to participate on
Certification Board so long as the auditor is not a member of the QA Management Committee
qualified and knowledgeable in certification, auditing.
During the audit, personnel responsible for the area audited are immediately notified of the outco
of the audit of their area.
During an audit, it is possible that a difference of opinion can arise as to the severity of
observation. It is important not to spend too much time debating the merits of the observation.
does not appear that the difference of opinion can be resolved, then the auditee should be inform
that the audit report is subject to review by the Board of Internal Audit and Management Rev
Committee and the QA Management
The draft report is issued to the Board of Internal Audit and Management Review Committee wi
14 calendar days. The Committee members review and comment on the report and a final repo
issued.
The final internal audit report is submitted to the QA Management Committee.
The QA Management committee drafts a response to the audit report that is finalized after review:
Findings, nonconformities, trends, and other opportunities for improvement are identif
investigated to determine the causes; and corrective/preventive actions are developed. These acti
are implemented as soon as possible and recorded.
The response to the internal audit report is submitted to the Board of Internal Audit and Managem
Review Committee for their concurrence.
Upon agreement on the response to the internal audit, the Board of Internal Audit and Managem
Review Committee prepares a complete Certification Program Management Review Report
includes, as appropriate,:
Results of internal and external audits
Feedback from clients and interested parties related to the fulfillment of the Certification Process
Feedback concerning impartiality
Follow-up actions from previous Certification Program Management Review Reports
The status of corrective or preventive actions
The fulfillment of objectives
Changes that could effect the management system
Appeals and complaints
The Board of Internal Audit and Management Review Committee submit their Certification Progr
Management Review Report to the QA Management Committee.
The Certification Program Management Review Report with the response to the internal aud
discussed at the next meeting of the full Board. The expected outputs of the review includes decisi
and actions related to:
Improvement of the effectiveness of the management system and its processes.
Resource needs.
Decisions and actions of the Board are documented in the Board Minutes and all o
Corrective/Preventive Actions are reviewed and their status documented at all subsequent quart
Board Meetings.
Effectiveness of completed actions is reviewed at the next Program Management Review.
6.0
Abbreviations :
QA : Quality Assurance
Check points
Is the control copy of production department SOPs
available?
Are the personnel having knowledge of current GMP
requirements?
Are the lots of raw material properly stored?
Are the lots of raw material having proper labels of
status?
Is the housekeeping maintained?
Is the weighting balance having proper tag of calibration
status?
Is the balance calibration record available?
Are the calibrated standard weights available?
Is the calibration certificate available?
Is the standard weights are properly stored?
Is the reactor area cleaned?
Is the status label of reactor available?
Is the BMR requisition slip record available?
Check the calibration status of temperature gauges.
Check the calibration status of pressure gauges.
Check the status of centrifuge.
Observation
Recommendation
Acti
tak
by
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
Is ECR available?
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
1.
2.
GENERAL:
1.1
Building Maintenance
1.2
Reception
1.3
Administrative Block/O
1.4
Utility Block
1.5
Maintenance
1.6
Surroundings
PERSONNEL:
2.1
Or
2.2
Qu
2.3
Pro
Me
Fo
Fo
2.4
Pe
Fo
Fo
2.5
Fa
Fo
Fo
Wa
2.6
Pe
Sh
WC
Lo
Ca
3
.
2.7
Jo
Re
2.8
Tra
2.9
En
2.10
2.11
:
:
Dr
Sy
2.12
Pe
a)
: Raw Material
____________
b)
: Packing Material
____________
c)
: Intermediate
____________
d)
: Finished Goods
____________
e)
: Cleaning / Schedule
____________
f)
g)
3.2
3.3
____________
3.4
3.5
3.6
3.7
3.8
3.9
3.10
3.11
3.12
3.13
3.14
Lighting level
3.15
3.16
3.17
3.18 : EQUIPMENT
a)
b)
c)
d)
e)
f)
g)
h)
k)
l)
m)
n)
4
.
5.
MANUFACTURING CONTROL:
4.1
4.2
4.3
4.4
Means of Communication
4.5
4.6
TSE QUESTIONNAIRE:
5.1
5.2
5.3
: Have you obtained the COS Certificate from EDQM for the
Material you are supplying to us? If yes please attach the copy.
: Is any of the starting material used in the manufacturing from
Animal Origin. If yes, Please ensure to obtain the TSE free Certificate
from your supplier.
: Is the Production Line dedicated?
5.4 : If NO Please Specify:a) Are the equipments shared with any other product, which uses
original starting material?
b) Do you have sufficient Cleaning Procedure?
b) Is cleaning procedure validated?
5.5
: Is your batch COA contains the TSE / BSE free Declaration. If no submit an
undertaking to send the batch wise TSE / BSE free Declaration for all
supplies to us?
6. RECORD KEEPING :
7.
the animal
6.1
6.2
: Equipment Log
________________
6.3
: Process Record
________________
6.4
: In-Process Results
________________
________________
7.1
__________________
7.2
__________________
7.3
__________________
8.
QUALITY CONROL:
8.1: Raw Material Specification / Test Procedure & its control_______
8.2: Calibration Record
______
_______
FILING SYSTEM:
10.1
11.
_______
Retrievable
______________
12.
CORRECTIVE ACTIONS:
13.
PREVENTIVE ACTIONS:
14.
CLOSURE OF AUDIT:
CONCLUSION
SIGN
DATE
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Check points
01
02
03
Observatio
n
Recommendatio
n
Action
taken by
04
Check the
records.
preventive
05
06
Are the
available?
07
Check the
record.
08
09
Check
the
temperature
calibration record.
10
11
12
13
14
15
16
17
18
19
Are
there
any
postponement
of
maintenance?
20
Is
the
department
follow
the
postponement
of
the
schedule
equipment
equipment
maintenance
qualifications
qualification
gauges
documents
for
the
schedule
22
23
24
25
26
27
Check
the
housekeeping
maintenance store area.
28
of
OBJECTIVE: To lay down a procedure for handling of out of specification (OOS) result in
Microbiological analysis and monitoring.
2.0
RESPONSIBILITY
Quality Control Executive/ Microbiologist
3.0
ACCOUNTABILITY
Quality Control Manager
4.0
PROCEDURE
In all the reports the identified reason shall be written on a continuation sheet to the annexure
provided. A copy of the above investigation report shall be maintained with the batch
manufacturing records concerned to increase awareness and for any future reference
4.1
STERILITY TEST
4.1.1
If evidence of microbial growth is found, the product to be examined does not comply with
thetest for sterility, unless it can be clearly demonstrated that the test was invalid for causes
unrelated to the product to be examined .The test may be considered invalid only when one or
more of the following conditions are fulfilled:
4.1.1.1The data of the microbiological monitoring of the sterility testing facility shows fault;
4.1.1.2 A review of the testing procedure used during the test in question reveals a fault;
4.1.1.3 Microbial growth is found in the negative controls;
4.1.1.4 After determination of the identity of the microorganisms isolated from the test, the
growth of this species or these species may be ascribed unequivocally to faults with respect to
the material and / or the technique used in conducting the sterility test procedure.
4.1.2 If the test is declared to be invalid it is repeated with the same number of units as in the original
test.
4.1.3 If no evidence of microbial growth is found in the repeat test the product examined complies with
the test for sterility. If microbial growth is found in the repeat test the product examined does not
comply with the test for sterility.
4.2 ENVIRONMENTAL MONITORING
4.2.1 If the microbial counts are found to be more than or equal to the alert limit then
open a deviation report (annexure I) through Q.C. Head to the concerned Production head.
Production personnel shall check the working discipline, supply of air, safety measures etc.
4.2.2
If the count exceeds or reaches the action limit then the urgent notification to the Production
head and Engineering Head through Q.C. Head shall be followed by an investigation for the
same.
- Supply of air
- Working discipline
-
Review of data from the same place and others from the incubated plates
If any of the plates does not indicate the same then no action is necessary.
If any of the plates indicates more count then perform additional cleaning, disinfection or
fumigation and retraining to the operator shall be given.
All activities shall be recorded as per the annexure attached with this SOP.
More number of samplings (i.e. double the original) shall be preformed at the same location
where the counts observed were beyond or equivalent to the action limit but an additional
relevant parameter of monitoring shall also be performed which shall be incorporated with the
same annexure.
All the batches manufactured during the said period shall be subjected to the microbial
analysis for MLT / Sterility &BET in order to ensure that the batches manufactured are in
accordance with the relevant finished product specifications. The investigation report shall be
submitted to the Q.C. - Head
4.2.3
If the bio-burden is found out of specified limit in the core areas the identification of the
organism shall be performed.
4.2.4
Stop the production immediately and check all the possible parameters, which can affect bioburden of the area.
4.2.5
Check the pressure differential of the area, which must be within the specified limit.
4.2.6
Check the air velocity of LAF /HEPA filters, which must be within the specified limit.
4.3
4.4
cannot be attributed to the analytical error, sampling error, contamination in the container
sampled then the microorganism detected must be identified / differentiated by taking sample
from all other points.
4.4.1
Adequate sanitization of the system shall be ensured to eliminate the source of contamination
with a rigorous check for the same.
4.4.2
All the investigations made shall be recorded in the annexure III provided with this SOP.
4.5
4.5.1
4.5.2
Retest the same material/product but with a sample size of 25 grams by making allowance for
the larger size specimen.
4.5.3
Results for the same shall be intimated to the Q.A. Head for final decision.
5.0
Harmonization of format
6.0
TRAINING:
Trainer --
Trainees-Period -7.0
One day
DISTRIBUTION:
Original Copy
ANNEXURE I
FORMAT FORDEVIATION REPORT TO PRODUCTION DEPARTMENT
: 00
Page No.: 1 of 1
Effective Date:
Date:
Batch no.:
Deviation :
Parameter:
Requirement :
Results :
Signature :
Repair
Comments
..
Name
Signature
Date:
Repeated Sampling :
Parameter:
Result:
Comments
by
Q.C.
Head
for
Approval
of
Production
Signature :
ANNEXURE - II
Format for Corrective Report After Sampling of Environmental Parameters in Production
Revision No.
: 00
Effective Date:
Page No.: 1 of 1
Date :
Deviation :
Checked
By :
Date :
Signature :
Date :
Signature :
Date :
Signature :
ANNEXURE III
INVESTIGATION REPORT FOR FAILURE IN TEST FOR BACTERIAL ENDOTOXIN & M.L.T
Revision No.
: 00
Page No.: 1 of 1
Effective Date:
Sample
Analyzed on
Analysed By
Checked By
Procedure of sampling
GP test of media
Test tubes
Pipette
LAL reagent
Batch No.
Mfg.
Expiry
Reconstituted
on
Expiry
Blank
Validation Status
Calibration Status
Results of other samples with same conditions tested on the same day.
Details of Raw material used in finished product
Result
Test repeated
Date
Result
Microbiologist
ACTION TAKEN :
Production Head
Engineering Head
Quality
Control Head
CONCLUSION
(Results of MLT for Other Samples to be enclosed)
Microbiologist
QC
Manager
Date:
Date:
Sign
Date :
1.1
1.2
Contact Person:
Name:
2.0
Phone No.:
FACILITIES:
3.0
3.1
Mobile No.:
E-mail ID:
PERSONNEL:
Number of Staff:
Q A:
Q C:
R & D Lab:
Microbiology:
Others:
No.
3.2
S.
No.
3.3
3.4
3.5
3.6
4.0
4.1
Questions
Do you have a written training program for analyst?
Does your training program include the following:
GLP
GMP
Job training
ISO principals
By examination
Yes
No
Comment
s
4.2
4.3
4.4
4.5
5.0
QUALITY MANAGEMENT:
5.1
5.2
S.
No.
5.3
GMP
cGMP
USFDA
ISO 9001:2000
By clients
By National authority
By Foreign authority
By FDA
Questions
Does your Laboratory have GMP/ USFDA
/cGMP/ ISO approval? If Yes specify
Name of authority
1.
Date of Certificate
Yes
No
Comment
s
2.
3.
(Attach copy of certificate)
6.0
6.1
6.2
QUALITY ASSURANCE
Is there system for rejection of sample?
Do you have specification approved by QA for
working/reference standards of the product?
For Physical, Chemical requirements
For Microbiological requirements
6.3
6.4
6.5
Name of customer
Sample quantity
Batch No.
Date
6.6
Analytical procedure?
Cleaning procedure?
7.0
7.1
S.
No.
7.2
7.3
Questions
Yes
Temperature
Relative Humidity
8.0
WATER:
8.1
8.2
No
Comment
s
First Aid
Purpose: To provide a documented guideline for the first aid treatment n case of any accident.
2.0 Objective: To provide a first aid treatment.
3.0 Scope:
4.0 Responsibility :
Follow up
5.0 Procedure :
Training
First aid training shall be given to selected employees of each department.
Detail training of the first aid shall be given to some employees of the company.
The list is as follows and shall be available in each department for easy reach out
during emergency.
Serial No.
The first aid box shall be numbered and located at identified and marked
positions as following
Serial No.
Serial No.
Every Monday from Personnel department personnel or General Manager (Adm) shall
Review the contents of first aid box and shall replenish the required item. The
Record of review shall be kept.
Date/day
Contents
Reviewed
Discarded
checked
details
by
Items
replenishment
OK/not OK
submitted
to QA.
urpose : To provide a documented procedure for preventing accident & Recording accident.
2.0 Objective : To maintain safety aspects
3.0 Scope
4.0 Responsibility :
Follow up
Workman shall engage themselves in the duties which have been assigned to them.
The execution of their duties must be in the safe manner laid down in S.O.P. for the
operation, of the machine or duty concerned.
Workmen working beyond the height of 10 feet shall wear the safety belt.
If any employee / work man working beyond the height of 10 feet on ladder shall work
with one additional work man / employee to hold ladder.
Workman shall not keep sharp edge tools into their pocket.
Any employee / workman working with electricity shall wear safety shoes &
Sock proof gloves.
Any workman working with hazardous chemicals / acid shall wear the safety
Wears like goggles, gloves etc.
Speed of vehicle inside the factory premises shall not exceed 20 km / hr.
When welding work is to be carried out in closed area, extra fire extinguisher
Shall be provided.
After working with oil, floor shall be cleaned thoroughly to wipe out the oil.
Solvents shall be stored in tight closed container.
Entry into transformer yard / explosive storage yard shall be restricted to selected
Personnel.
Workman shall enter into water tank, drainage, septic tank only after permission Of
Personal & Administration department.
Workman shall carry out repairing work of high pressure line / high temperature Line /
or any explosive line only after permission of Engineering In charge.
ecording of Accident
The accidents are categorized as critical major and minor depending on the
The First aid, if required, after the accident shall be provided at the earlier marked
Locations and trained persons are available.
The telephone no. of fire station, doctor, ambulance shall be displayed in all the
Departments to call upon in an emergency.
The affected employee shall be immediately rushed to the hospital, if needed and is
provided the required medical help.
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Purpose
: To provide guideline to ensure that different production activities are carried out in compliance with
safety & cGMP requirement, at pre-determined frequency.
Objective : To provide a documented guideline to ensure that different production activities are carried out in
compliance with safety & cGMP requirement, at pre-determined frequency.
Scope
Primary
: Officer Production
Secondary
5.0
Executive Production
Procedure :
ORGANISATION & FUNCTION:
The department must have a team that would perform all the function meeting cGMP
requirements. It must also address to documentation, audits and training aspects pertaining to
production jobs.
Before starting any process in equipment make sure equipment should be cleaned and line
clearance has been given by QA.
The production area should be clean and free from dust and dirt so the intermediate and final
product could not be contaminated.
TRAINING:
All the staff shall be covered for cGMP, Safety and Job-related training as per the training
procedure.
SOP must be prepared for all activities that are quality critical or safety critical or relate to key
business areas. These SOPs must be prepared, reviewed & authorized and controlled in
accordance with Site SOP.
The SOPs must include specific maintenance instructions, lubrication details, Spares
requirements, frequency of maintenance, responsibilities for carrying out the job &
documentation, etc. as appropriate. The department activities must be reviewed to identify
operations which need preparation of SOP and the current SOPs must be updated / reviewed
as scheduled.
AUDITS:
Department audits must be carried out to monitor the production aspects of departmental
activities in regard to its impact on SHE, Energy Conservation and Quality matters.
VALIDATION:
CHANGE CONTROL:
All changes must be fully documented, assessed and authorized prior to the work being carried
out.
In line with good documentation practice, change in process must be controlled as per the
good manufacturing practices. If any Change occurs it should be reported to QA department
with reason.
n documents.
Equipment Cleaning Record: Before conducting next step in process cleaning of equipment
should be required. To follow cGMP ECR should be filled by production department before
starting every process. By checking ECR, QA department give line clearance to production
department.
Duties:
In case of fire, necessary arrangement and provision of fire squad and systems to the
emergency spot and its neighbouring sections.
Organise necessary ambulance and medical treatment for affected persons if required.
Preserve evidence.
Organise investigation.
Before allowing re-entry to the site check if the conditions are safe (Toxicity, fire hazard,
structural stability etc.).
Re-starting of plant operations only after ensuring steps for prevention of re-occurrence.
ADVISORY TEAM
Responsibility of Advisory Team.
Remain with Emergency Leader at the emergency control center and advice him as needed.
In case Emergency Leader has to leave his post for some reasons any of the member of the
Advisory Team will take over as the Emergency Leader.
If needed Factory Manager can deputy Emergency Leader to the site to be of help to the
incident controller.
ACTION TEAM A
Inform emergency control center / security about location and nature of emergency.
Shutting down the operation as per requirement and other areas as guided by the incident
controller.
Ensuring the appropriate use of fire fighting material by fire fighting squad.
Department Head
Take over the responsibilities of the shift in-charge upon arrival and proceed as
listed above.
ACTION TEAM A
1. As shift in charge will be involved in fire fighting operations senior chemist will ensure
that
Operations of affected area will be stopped and reactions will be stopped in safer mode
with consulting shift-in-charge.
2. Chemists and junior chemists will form fire fighting team with guidance of incident
controller start fire fighting with fire extinguishers and then with fire hydrant system if
required.
ACTION TEAM B
Manager Maintenance
Manager Electricals.
On hearing Alarm
When instructed by the Emergency Leader
Take over responsibilities from shift-in-charges and ready to shut down plant if needed.
Manager Maintenance
Manager Electricals.
Ensure that adequate power supply is made available for sensitive plant operation and
emergency lighting.
ACTION TEAM C
Security Officer / Safety Officer
On hearing Alarm
Security Officer
Control traffic.
Safety Officer
Inform with consultation with advisory team to Factory Inspector and other Authorities.
Offer any help expected, advice with First Aid render First Aid to injured person.
ACTION TEAM D
Doctors.
First Aiders
Stores-incharge
Proceed to the site and hospital as per decided by Emergency Leader to render assistance.
Stores-in-charge.
ACTION TEAM E
All staff members not listed in emergency action team.
On hearing Alarm
Get back to work places (if safe) and await instructions from supervisors.
Avoid panic
Goal of ICH
The goal of ICH is to promote international harmonisation by bringing together
representatives from
the three ICH regions (Europe, Japan & USA) to discuss and establish common
guidelines
Stability
Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug
Substances and Products
Analytical Validation
Q2(R1) Validation of Analytical Procedures: Text and Methodology
Impurities
Pharmacopoeias
Q4 Pharmacopoeias
Specifications
Q6A Specifications : Test Procedures and Acceptance Criteria for New Drug
Substances and New Drug Products: Chemical Substances (including
Decision Trees)
Pharmaceutical Development
Q8(R1) Pharmaceutical Development
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Hence, it is of utmost importance that each one, irrespective of his position in the
organization should exhibit a high sense of responsibility to safeguard the safety of
his area of operation, in his own as well as in the interest of the organization.
The hazards could be of various types, arising from chemical, mechanical, electrical
or civil in nature.
1. Chemical Hazards:
Most of the accidents occurring in chemical industries are of this nature. The
causes for the hazards can be attributed to:
i)
Process deficiencies.
ii)
iii)
Equipment failures.
iv)
v)
vi)
vii)
i)
Chemical processes :
ii)
Equipment design:
iii)
Process equipments:
All process equipments which have bearing on the process control, such as
temperature indicators, pressure / vacuum gauges, safety / control valves etc.
should be of reliable quality and tested for performance before being installed.
There should also be a system for periodic inspection and maintenance of these
equipments.
iv)
Training:
Training plays an important role in the skill development process. All the
operational persons should be adequately trained for the job.
v)
1.
All chemicals based on their chemical properties and incompatible nature with
other chemicals must be stored as stipulated in their MSDS.
2.
3.
Proper personnel safety equipments, such as apron, goggles, face shield, nose
mask, safety shoes should be worn while handling corrosive and hazardous
chemicals.
4.
5.
No loose electrical cables or cables with broken joints should be permitted in the
storage premises. Proper earthing has to be done wherever flammable solvents are
loaded or unloaded.
6.
7.
All electrical fittings, such as lighting, switches etc. in the storage area should be of
flame proof category.
8.
it must be ensured that MSDS (Material Safety Data Sheet) for all the hazardous
chemicals being stored must be made available to the stores incharge and it is the
responsibility of the stores incharge to make sure that the storage and handling is
done in compliance to the procedures stipulated in the MSDS.
9.
10. As a safety need, every storage room should be provided with an exit door, which
is to be properly identified and kept un-locked.
11. Good house keeping is an important requirement in storage godowns. There must
be clear passage area for free material movements.
1.
There are chemicals, which remain harmless if stored in isolation, but upon
allowing coming into direct contact, could pose severe fire, explosion hazards.
i)
ii)
iii)
Con H2SO4
vs
Glycerol
KMnO4
vs
KMnO4
Acetone
Methanol
vs
CrO3
Glycerine
iv)
Co. HNO3
vs
v)
Sodium metal
vi)
Sodium hydride
vii)
Hydrogen peroxide
vs
vs
vs
H2O
flammable organic solvents
In all the above cases instant fire will take place, due to the high amount of heat
produced as a result of the vigorous reaction between these compounds.
2.
1.
2.
3.
4.
5.
6.
Dichromates (ammonium)
7.
8.
3.
There are many chemicals which are highly reactive with water / moisture. Upon
contact with water, they react violently resulting in Fire / Chemical splash. These
are to be stored in leak proof water tight containers in a dry place, e.g.
1. Acetyl chloride
4.
2.
Aluminium chloride
3. Acetic anhydride
4.
Thionyl chloride
5. Calcium hydride
6.
Sodium metal
7. Sodium hydride
8.
Few of the chemicals are very corrosive in nature and can cause severe blisters /
deformity / loss of vision etc, if they come into contact with human body. All
personal protective equipments such as hand gloves, apron, goggles, nose mask,
safety shoes should be worn by those handling these chemicals e.g.
1.
2.
3.
4.
Chloro compounds (acetyl chloride, Thionyl chloride, mono and tri-chloro acetic
acid, aluminium chloride etc.)
v.3.
Based upon the degree of flammability (Flash points), flammable solvents are
classified under the following 3 categories:
i)
ii)
iii)
v.3.1
1.
All solvents of category A and B should be stored only in metallic containers, well
closed, in a cool place at the designated area.
2.
No hot jobs such as welding, cutting or bracing is permitted inside the storage
place or in the vicinity.
3.
4.
5.
6.
7.
8.
Basic training for fire-fighting systems should be imparted to all the operating
staff.
9.
11. Flammable solvent storage warehouse should meet the statutory requirements of
Indian Explosive Act.
One of the most hidden hazard, causing fire and explosion in chemical industry is
associated with the unique property of several solvents and organic compounds to
acquire electric charges termed as static electricity, which subsequently get
discharged in the form of electric spark, causing the disaster.
vi)
1.
2.
3.
4.
5.
6.
7.
Prolonged storage.
8.
9.
2. Preventive Measures
11. Allow flammable solvents to flow through metallic pipes only. These pipes should
be earthed to the ground with proper conduits.
12. While charging a solvent into a reactor/container, ensure that the liquid is not
dropped from the top to fall to the bottom. Always ensure that the liquid reaches
the bottom of the vessel, through metal pipes.
13. Avoid storage in non-conductive containers, such as those with moc PVC/PP/HDPE.
Always store only in metal containers.
14. Loading and unloading of bulk flammable solvents should be permitted only in
authorized premises (refer Petroleum Act of India). Proper earthing connections
should be provided to both the storage container and the receiver.
15. Before operating any centrifuge, ensure that it is being properly earthed to the
ground. Also, before scooping out any material from the centrifuge, ensure that the
metallic scoop is also earthed (plastic or nonconductive equipments are not
advisable for scooping material from centrifuges).
16. To avoid dust explosion, which is likely in large powder handling units, provide
adeauzte ventilation so as to prevent dust accumulation which is the cause for this
kind of hfazards.
17. Wherever possible spray water in the surroundings of large solvent storages, as
higher humidity helps to dissipate static charges (water particles are good electric
conductors).
Caution:
Never ever let any live electric cable come in contact with earthing cables, as the
consequences could be disastrous.
vii)
Handling of compressed and liquefied gases, contained in cylinders calls for special
attention, as these are of potentially high hazards, in case of any leakage or
bursting up of the container.
There are about 101 permanent, as well as liquefied gases, which are being
conveyed in specially designed cylinders and these gases are contained under high
pressures (18 kg/cm2 to 250 kg/cm2) and are identified with unique colour codes.
Some of the commonly used gases and the corresponding colour codes of the
cylinders are:
1.
Always store filled gas cylinders in a cool and ventilated and sheltered area, away
from heat and direct sunlight.
2.
No hot jobs, such as welding, bracing, cutting or grinding, is permitted in the gas
storage area.
3.
Always keep the cylinder properly capped. The cylinder valve is the most delicate
and vulnerable part of the cylinder. Never allow the Needle valve of the cylinder to
get damaged, while loading/unloading and shifting operations.
4.
Store the cylinders in vertical position, near a solid support, properly fastened with
a metal chain to avoid their falling.
5.
In case of any leakage of the cylinder, never attempt to repair the valve. Isolate
the cylinder from the main stream and keep it in an open and cool area and seek
help from the cylinder supplier.
6.
The cylinder storage area should be located always, away from the main/process
building and under no circumstances should any gas cylinder be used inside the
processing areas. Gas cylinders should be kept away from corrosive acid fumes,
which could corrode the cylinder body and damage the cylinder valve.
7.
Never try to apply grease on the cylinder valve/nozzle, as certain highly reactive
gases like hydrogen can ignite the organic mass, causing fire.
8.
For shifting gas filled cylinders, always use cylinder trolleys and never let them roll
on their body.
9.
Never try to open any cylinder without having the appropriate type of regulators.
10. As a safe practice, always store the cylinders outside the building in the proper
designated area, and draw the gases into the operational area through metal pipes
with suitable safety valve.
12. It is always preferable to keep minimum possible inventory for better handling,
especially for toxic and flammable gases.
13. Do not store incompatible gases together, as this could lead to explosion in case of
simultaneous leakage from both the cylinders.
e.g.
Hydrogen
Ammonia
viii)
vs
Chlorine
vs
Chlorine
1.
All the process equipments such as reaction kettles, pressure vessel etc. should be
properly maintained and periodically pressure tested to ascertain their capability to
withstand the optimum pressure for which they are designed.
ix)
2.
Never ever subject the equipment to more pressure than the designed capacity.
All equipments where pressure reactions are carried out, should be provided with
safety pressure releasing valves.
3.
The vent line of process reactors (except pressure reactors, designed for specific
services) should be vented outside the process block, preferably through a
scrubber, depending upon the nature of the effluent gases generated in the
chemical processes.
4.
5.
Ensure that all the moving parts of an equipment, such as the shaft of a drying
oven, blades of a fan, coupling of a mechanical pump, the belt of a motor fan are
provided with proper metal guards so that they do not come into contact with
human body.
6.
7.
All utility lines, conveying steam, chilled water, brine, vacuum, nitrogen etc,
should bear clear identification tags and preferably they are to be identified with
distinct colour code system.
8.
As a safety measure it is highly advisable to purge nitrogen gas into the reaction
vessels before start of the process, thereby reducing the oxygen concentration
inside the reactor and thus reducing the fire risk.
Electrical Hazards:
1.
All electric fixtures such as cables, wires, switches, electronics fittings should be of
standard quality and free from any manufacturing deficiency.
2.
Overloading of any supply point by drawing more power than the recommended
norm should be totally avoided:
3.
It must be ensured that all the electric fittings, fixtures, lightings, induction
motors etc, should be of flame proof quality.
4.
All electric equipments and fittings should be safe guarded against moisture,
chemical fumes etc, and periodically inspected by regular maintenance systems.
5.
Electric panel boxes, main control switches etc. should be properly housed in a
proper ventilated block, away from the plant and must be tagged for easy
identification.
6.
7.
Cables and electric wires used should be of single piece and should not have any
joint.
8.
Never let the electric and earthing cables come in touch with each other at any
point.
9.
10.
Keep the electrical panel box surroundings dry and provide rubber mats in front of
the panel door to avoid any electric shock to the operating personnel.
11.
Whenever any equipment is under maintenance / repairs, ensure that the power to
the equipment is switched off from the main panel and proper tagging is done at
the panel switch, as well as on to the equipment.
12.
a)
A fuel [this can be: any organic matter; such as a solvent, oil, wood, paper, etc.].
b)
c)
d) Free radical reaction. The chemistry of combustion indicates that the union of
Oxygen and the fuel is not direct, but through a series of steps wherein the actual
reaction taken place between Oxygen and the free radicals liberated by the heated
fuel at the point of ignition.
2. CLASSIFICATION OF FIRES:
Basically all the type of fires can be classified into the following major categories.
a)
Class A Fires:
These are fires on ordinary combustible materials, such as paper wood, rags etc.
which can be put off by the quenching and cooling effect of water. For
extinguishments of such type of fires, use of water, form or dry chemical fire
extinguishers would be effective.
b)
Class B Fires:
These are fires occurring in flammable liquids such as oils, organic solvents, petro
chemicals etc., where a blanketing or smothering effect is essential to put the fire
out. Fire extinguishers like Foam, CO2, and Dry chemical are recommended for this
type of fires, which provide a blanketing effect around the fire, thus, preventing air
from coming into contact with the burning substance.
Water is effective for oil fires, only when it is used in the form of a spray or mist, but
as such is not advisable to use in fires involving solvents and oils, which are
immiscible with water.
c) Class C Fires :
These fires are associated with Electrical fittings, fixtures, such as electrical panel
boxes, electric cables, electric ad electronic equipments etc. Non conductive
extinguishing agent such as CO2 gas is the most ideal and recommended fire
extinguisher for Electric Fires.
d) Class D Fires:
These are fires in metals, such as Li, Na, K, Zn, Mg etc. and mishandling of this type
of fires can cause explosion and spread to other areas. Special attention and
training is needed to handle metal fires.
Normal fire fighting agents used for extinguishing are dry sand, dry powder,
graphite etc.
It is important to understand the meaning of some of the fire control terms and
definitions of certain critical physical characteristics of solvents which will help to
understand the degree of flammability of a particular Product.
This is the lowest temperature at which the liquid will give off enough flammable
vapours at or near its surface, such that in an intimate mixture with air and a spark
or flame, it ignites.
The flash point of a flammable liquid is usually determined by the standard method
of test for flash point with the Tag Closed Cup Tester (TCC) or with the Tag Open Cup
Tester (TOC). The results recorded with Tag Open Cup Tester (TOC) is always found
to be 5-10oF higher (less flammable) than that being recorded with Closed Cup
Tester.
The closed cup flash point value is usually several degree lower (more flammable)
than the open cup, as the test in the former case is made on a saturated vapour-air
mixture, whereas in the letter case, the vapour has free access to air and thus is
slightly this reason open cup values more nearly simulate actual condition.
This is the lowest temperature at which a mixture of air and vapour continues to
burn in an open container when ignited. It is usually above the flash point.
Wherever the flash point data is not available, fire point figures can be considered
as significant as flash point to understand the degree of flammability of the
material.
This is the temperature at which a material (solid, liquid or gas) will self-ignite and
sustain combustion in the absence of a spark or flame. This value is influenced by
factors such as the size, shape, the material of the hot surface, rate of heating etc.
etc.
4. Vapour Density:
This value expresses the ratio of the density of the vapours to the density of air.
The vapours of most of the flammable solvents are heavier tan air, with the result
that they tend to travel at ground level making them more dangerous, as the risk
will be more in case of a fire, since the vapours do not get diluted with air. Hence,
in operational areas, where such higher V.D. solvents are used, the ventilating
outlets should be at the lower level. Similarly, wherever, the liquids of low V.D. is
handled, the ventilator should be at the higher level.
This is the temperature at which the solid and liquid forms of a substance exist in
equilibrium. This value also gives the indication at what minimum temperature a
flammable solid substance can become flammable solvent.
This is the temperature at which the vapour pressure on the liquid surface becomes
equivalent to the atmospheric pressure and at this temperature a continuous flow of
vapour bubbles occur from throughout the liquid body and it is an indication as to
how much volatile the liquid could be.
This physical characteristic of liquids can be made use of, in preventing many
hazards like Fire, Thermal decomposition of the product etc by subjecting the
distillation process to take place under reduced pressure.
7. Chemical Formula:
In the event of lack of data regarding the flammable nature of a product, the
chemical formulation of the product can give a clue regarding its flammable nature
to a certain extent. For instance, if a product consists only of Carbon and Hydrogen
(Hydro carbon), it can be assumed to be flammable and if it is in liquid form and
having a low boiling point, it can be considered to be more flammable.
8. Flammable liquids:
v.
vi.
vii.
FIRE PROTECTION
Prevention and 2.
Loss
1. Prevention:
The most undisputed aspect of Fire protection is its prevention. Since, for a fire to
occur, all the 3 basic requirements, Fuel, Oxygen and source of Heat are needed to
combine, by avoiding any of the 3 basic requirements, Fire can be prevented. For
instance let us take an example of an industry which uses large volumes of Acetone
in an open atmosphere. Now, for a fire to happen, among the 3 requirements, two
of them i.e. Fuel and Oxygen (from air) are already available in the vicinity. The
third requirement for Fire is heat.
From the flash point data, Acetone has a Flash point of 0oF, which means that at all
temperatures above 0oF Acetone would give out enough vapours which on
combining with Oxygen of air, can form a flammable mixture in case if it comes into
contact with a spark, flame or a hot surface or any other source of ignition. Thus, in
an installation using Acetone, following avenues are available from Fire Protection
point of view:
1. The working temperature (ambient) should be kept less than the Flash point,
0oF of Acetone, so that the vapour pressure of acetone at that temperature is
lowered to considerable extent and consequently it does to give out enough
vapours for the Fire to take place.
2. The supply of atmospheric oxygen must be cut off. This is possible in two
ways.
i)
By applying vacuum in the processes which taken away the air from the liquid
surface.
ii)
By providing a continuous stream of Nitrogen gas flow over the surface of the
liquid (also termed Nitrogen blanketing).
i)
ii)
Hot operations, such as welding, gas cutting, bracing should not be carried out in
and around the operational area.
iii)
All the electrical fittings and fixtures and electric motors used in the process area
should be Flame proof in nature.
4. The area must be ventilated so that even though acetone gives off enough
vapour to form a flammable mixture with air, the vapour will be drawn out of
the area by means of the fume exhaust as rapidly as it is formed, thus
preventing the accumulation of vapour concentration.
Below is a brief account of the 3 essential supporters of fire and the means to
reduce their influence for Fire Protection.
A)
OXYGEN:
Although under certain specific conditions, chemicals can initiate fire even in the
absence of oxygen for short duration (e.g. Fires associated with sulphur /
phosphorous chlorine, hydrogen etc.), for sustained propagation of Fire, oxygen is
very essential. Also the higher the concentration of oxygen in the atmosphere,
more would be the intensity of fire. In industrial atmosphere it is difficult to
manipulate the oxygen concentration in the working area, particularly since a
concentration of oxygen, far below normal to keep fires from starting, would also be
too low to support human life.
When it becomes necessary to work with such products, which by mere contact with
air of atmosphere, can initiate a Fire, following steps are recommended for their
safe handling.
i)
Isolate such products, such as sodium azide, sodium hydride etc. which are
highly reactive with atmospheric oxygen from the main stream of materials and
store them in containers under vacuum, or follow the guidelines for storage as
mentioned in their respective MSDS.
ii)
Keep such products under a blanket of inert gas such as nitrogen, helium or
argon.
B)
HEAT:
In industrial fires the most easily overlooked fact is that all the major Fires that had
occurred, had a modest beginning in the initial stages, which might have gone
unnoticed and hence uncontrolled. Then, since fires are by definition exothermic,
the very small fire started by a tiny heat source, supplies to its surroundings more
heat than it absorbs, thus enabling it to ignite more fuel and oxygen mixture, and so
on until very quickly there is more heat available than is needed to propagate a
large Fire.
The heat for the initial Fire to start might have been provided by various sources of
ignition such as high environmental (ambient) temperatures, hot surfaces,
mechanical friction, spark from a switch, static electric discharge, an open flame or
from a jot job, like welding, gas cutting etc.
It is worthwhile here to look into the various aspects of the ignition source and
find ways to effectively curtail them.
a) Open flames:
b)
Electrical sources:
Some of the common source of electric heating are from non certified lightings,
cables, switches, starters, electric motors, digital electronic indicators, overloading
of supply point, poor earthing systems etc. As a matter of safety, it is advisable to
have all electrical switches and electric panel board properly housed in a separate
block, away from the main plant / operating premises.
c)
Over heating:
Processes which need high pressure steam and involve high temperature reactions,
runaway reactions, special processes, etc. should be identified and these are to be
segregated from the relatively safer processes. HAZOP study should be undertaken
before the implementation of such processes and special attention has to be paid in
training the persons operating such plants.
i.
Hot surfaces:
The most common hot surfaces in a chemical industry are equipment like, drying
oven, boiler, steam line, hot oil system etc. These equipments must be housed in a
quarantined location preferably away from the operating area (boiler / thermo pack
and electrically) heated drying oven in any case should be way from the process
block). All the supply lines conveying steam, hot oil, hot water, hot air etc. should
be properly insulated and maintained. It must be remembered that Flammable
solvents, having the auto ignition temperature, lower than any of these hot
surfaces, can get ignited themselves in case of their contact.
ii.
Spontaneous ignition:
Many fires are caused by the heat of reaction produced when chemicals,
incompatible in their chemical characteristics come into contact with each other,
which are further accelerated by external source of heat and air. Few of such
commonly used chemicals, having incompatibility with each other are:
i)
ii)
iii)
Con. Nitric acid with organic solvents and any organic mass.
iv)
v)
Sodium hydride, elements like sodium, potassium lithium etc. with water.
Many of fire investigations have proved beyond doubt that the cause of fire in most
of the cases was due to neglect, poor house keeping practices, accumulation of
flammable wastes such as cotton rags, residual oil and grease etc.
iii)
Sparks:
Sparks may be produced from various sources, such as from electric motors,
switches, loose electric connections or by static electric discharges. Sparks are also
generated from friction between mechanical parts, by hammering and chiseling
etc. to avoid electric sparking, some of the recommended precautions are:
i)
ii)
iii)
iv)
v)
All the electrical fittings, such as switches, lighting, induction motors etc. should
be flameproof in nature.
Electric panels, main control switches etc must be away from the process block.
i)
All moving parts of the mechanical equipment, such as the shaft of the gear box,
shaft of the fan in a drying oven, clutches of a centrifuge etc must be greased and
maintained in good condition.
ii)
If at all they have to be done, use hammers / chisles made of brass or gun metal,
which does not produce sparks on hammering.
a)
This is a phenomena in which certain products, mostly of organic liquids and nonpolar solvents get electrically charged on their surface, by virtue of factors, such as
high speed discharge, fall from heights, separation at a higher speed, prolonged
storage etc. Causes for fire in many industries especially chemical and paper, are
attributed to this unique phenomena. Most of these occur during the months when
the atmospheric humidity is low and artificial heating is don(droplets of water in a
humid atmosphere acts as a suitable conduit to carry away the acquired electric
charges from the liquid surfaces, thus preventing a spark to generate by static
discharge). Maintaining a humidity of 40 to 50% in rooms where flammable
solvents are being handled, will greatly help to reduce the risk of a spark due to
static discharge. Electrical grounding of storage tanks, process equipments,
discharge pipings etc. are mandatory as per Indian Petroleum Act and it must be
strictly enforced.
In all the equipments as far as possible the use of belts should be avoided and the
use of metallic chains or direct shaft driven systems should be encouraged.
i.
Friction:
One of the major causes for industrial Fire can be attributed to the heat / spark
generated by friction from the moving parts of mechanical equipments, e.g. fan
blades rubbing the sides of outer casting, poorly lubricated bearings of a rotating
body like hydro extractor, uncooled mechanical seal of a reactor etc.
ii.
Fuel
Combustion takes place most easily between oxygen of air and a fuel in its vapour
or finely divided particle state. As solid chemicals need preheating for their
transformation from solid stage to liquid stage they are relatively safe, particularly if
their melting points are high. But in case of liquids, most of them give out sufficient
amount of vapours even at lower temperatures which can form a flammable mixture
with air and ignite themselves.
As a matter of safety and fire prevention, all solvent storage tanks above ground
level should have dikes constructed out of bricks and cement so that in the event of
any leakage or fire, it can be contained within a limited area, thus preventing it from
spreading.
It is also worth probing when a new process is developed that, whether or not it is
possible to substitute Flammable and Hazardous chemicals with non-flammable/less
flammable and non-hazardous chemicals. If cost is the prime factor in favour of a
flammable solvent other indirect benefits, such as savings in installation of high cost
safety devices, training cost, high insurance premium etc. should be assessed by
substituting with a non-flammable solvent. However in any event, usage of
flammable solvents in a chemical process cannot be avoided irrespective of the
quantum.
Dust Explosion:
Like static electric discharge, another lurking industrial hazard is dust explosion.
Practically any flammable material in the form of the particles or dust, mixed with
air at the right proportion, when comes into contact with a spark (mostly generated
by static discharges), flame or heat will burn so rapidly as to cause a severe
explosion which is termed as Dust Explosion. This kind of hazard commonly occurs
in industries handling, plastic, grain, flour, coal dust, metal powders, fertilizers,
wood dust, powdered milk, detergent powder, paper dust and industries handling
sulphur and phosphorous powders. Some of recommended precautions to minimize
dust explosion are:
b)
c)
Do not allow the dust to accumulate to alarming proportions. This can be achieved
by providing effective exhaust system.
d)
All the dust particles generated in the process, should be taken out through metal
ducts, and the vent of such ducts must be outside the block, preferably, taken to a
distant location.
e)
f)
g)
h)
The use of compressed air to blow the dust off the equipments/floors etc, thus
helping the formation of dangerous dust clouds is totally FORBIDDEN.
i)
j)
k)
As in the case of Flammable solvents, any kind of source of ignition, such as open
flame, smoking, welding/cutting, grinding, electric sparks from loose contacts or
from static discharges, should be avoided.
l)
Use of inert gas like nitrogen, in closed vessel operations has been found very
effective and rewarding in preventing Fire and Explosions.
LOSS (CONTROL)
One of the equally important aspects of Fire protection is also to devise various
alternates/methods to minimize the loss, in case of a major fire. There have been
major Fires all around, and loss of precious human lives and properties. Although
investigations help to identify to some extent the cause of Fire, in most events they
are inconclusive or doubtful, as most the live evidences of fire gets destroyed or
distorted in the fire itself and the findings of the investigations normally are based
on assumptions and hypothesizes.
What is more important is how to prevent a Fire totally from happening and how
best maximum salvage could be done in case of any such unfortunate incident.
Caution:
It must be ensured that there should not be any holes or cracks on the fire wall.
Every hole made on the wall to permit utility pipes / electric cable trays etc. to pass
through must be properly sealed with cement, so that no flammable vapour could
pass through such holes.
3. In many Fire incidents, it has been observed that the Fire Exit Doors provided
in the process blocks, to enable the persons trapped to escape safely, in the
event of fire, had caused more damage than any use, because of the reason
that either they were not maintained regularly for proper functioning, or the
path to the Exit Door were blocked with materials, storage drums etc. as a
result of which access to the door became difficult and the very purpose of
the door was defeated.
It is of utmost importance that the Fire Doors should be greased regularly and must
be tried for smooth functioning atleast once in a day and a record should be
maintained. No materials whatsoever should be stored on the pathway to the Exit
Door, and the approach way should be clearly highlighted with painting.
There should also be proper indicators to locate the Exit Doors and the most
importance caution to be observed is that these doors should never ever be bolted
tightly or locked.
4. Ensure that in the process blocks, the inventory of flammable solvents is kept
to the minimum possible level and the bunks, lids etc of all the storage drums
/ tanks are tightly closed. There should be clear space for movement
between the storage drums and in the event of Fire, these are to be moved
out of the building depending upon the situation. In case if it is not
accessible to reach the drums, they should be kept cool, by spraying a jet of
water from the Fire Hydrant system.
In case there are more than one plant/module, it is suggested that the Fire alarm
system from each of the module may be connected to one main Fire Alarm Display
board located at a central location preferably at the Time Office / Security Office.
Similarly, the fire display board should be provided with suitable indicator system to
identify the exact location of fire.
8. One of the most important aspects in Fire Protection is to prevent the Fire
from spreading from floor to floor in a multistoreyed building. Mostly the fire
spreads through open staircases, elevators, cutouts for future installations
etc. not only that the fire spreads through these `ventilators, these also get
choked with fumes, hot air, noxious gases etc. and the stair cases often
become real death traps. One way to prevent this kind of hazard, is to
provide proper enclosures to stair cases and elevators at each floor with self
closing doors. It is important to remember that these doors should have self
closing arrangement, as there is always a tendency among people to keep
the door open. Similarly, all open cut-out on the floors, must be closed with
brick and cement.
10.However, the most effective way to prevent fire damages can be achieved
only through educating and training the operating staff n regular basis and to
inculcate a sense of ownership and alertness.
FIRE FIGHTING
Although cutting the fuel supply is the best option to contain the Fire, in many cases
either it is difficult or not practicable, but in case the Fire is on a large storage tank
or a big reactor, and it has a pumping system connected to a far off storage vessel,
then the solvent can be pumped out from these containers to the safe storage
vessel as the Fire blazes only on the surface of the liquid. It is also important to
keep the burning tank cool with a jet of high pressure water so that the temperature
is brought down below the ignition temperature of the liquid.
1. Water:
The most commonly used fire extinguishing agent is water. It is the cheapest and
most effective media, especially when applied in the form of a fine spray. It has a
blanketing effect on the fire if sprayed, as the fine droplets of water act as a barrier
to prevent the air ingression to the fire point. More importantly it cools down the
fire surroundings below the autoignition temperature of the liquid, which results in
the extinguishing of the fire.
However, water has certain limitations too. It is good, as describedc earlier, for fires
with materials like wood, paper, cellulose, liquids miscribe with it, etc. but not
suitable for items like Oil, Petrol, Organic solvents having lower density than water,
Liquids immiscible with it, fires in metals etc. etc.
Water is not recommended for oil fires, and fires involving immiscible organic
solvents etc as these being lighter than water will float on the water surface and
also due to the impact of the water jet, will scatter all around carrying the fire along
with it. In such cases blanketing will also be difficult as the fire will be floating
around with water. The consequence could be disastrous, if this floating fire goes
down to the Gutter and Sewerage, as this could result in more spread of the fire,
affecting other plants as well.
Explosions have also been reported inside open gutters resulting in massive loss to
property and human lives.
This kind of extinguishers are operated by inverting them and directing the nozzle
of the hose towards the base of the flame. Int his type, a small bottle of con. H 2SO4
is kept around a saturated solution of sodium bicarbonate inside a metal cylinder,
having an outlet connected to a small rubber-hose. When it is overturned, the acid
comes into direct contact with sodium bicarbonate present in the water, generating
CO2 gas, which in turn pressurizes the water to come out of the extinguishers under
pressure. Such extinguishers need to be recharged once in a year, irrespective of
the fact whether they have been used or not. This type of extinguishers are useful
for ordinary type of fires on paper, wood, cotton, waste rags etc.
In this type, there will be a small high pressure CO2 cylinder inside the body of the
extinguisher, surrounded with fine sodium carbonate powder. When the
extinguisher is put into operation, the CO2 cylinder gets punctured and due to the
high gas pressure generated, the soda powder is driven out through the nozzle of
the cylinder. These are equally effective as the soda-acid extinguishers has a good
blanketing effect on the Dire. These also need annual replacement of the sodium
carbonate powder, as it has a great tendency for cake formation on prolonged
storage.
Another important type of Fire Extinguishing agent is Foam, which is very effective
controlling Fires on oil, paints, organic solvents, liquids immiscible with water etc.
Chemically this Form is produced by bubbling CO 2 or an inert gas through a form
forming liquid. While an operation the entrapped CO 2 gas inside the bubbles formed
by emulsification, gets coated on the burning surface, thus creating an effective
barrier between fire and oxygen of the air.
Despite the limitations, for fighting uncontrollable fire, water is the most effective
fire extinguishing agent and in fact there is no substitute for water. One of the most
effective ways of fire protection is to install a suitable fire hydrant system, having
access for high pressure water at all the crucial locations. In this system sufficient
quantity of water is stored in an underground tank exclusively built for Fire fighting
purpose and from this tank water is circulated through 4 to 6 dia metal pipes laid
underground by a powerful mechanical pump. At all the crucial locations tapping is
provided from the main line and these are connected to the Fire hoses. It is
important to ensure that the pump is maintained regularly by a systematic
maintenance schedule and the hose reel is free from defects. As a good safety
practice, it is suggested that the fire hydrant system should be activated at least
once in a week and checked for the performance.
Some other type of Fires which though not common, are equally disastrous and all
preventive steps must be taken to avert their occurrence.
a)
Gas Fires:
This type of fires can be put out with the use of fire extinguishers of CO 2 dry
chemicals and in certain cases with water also, but the most important step should
be to turn off the gas valve from the source. If source of supply is far away, ad
likely to take time to reach there, the best way to fire fight is to keep the
surrounding area cool by spraying water continuously, till the gas valve is closed
and in the meantime utilizing the Fire extinguishers at the fire.
b)
Metal:
Fires on metals is very dangerous and often difficult to extinguish. Ordinary Fire
fighting agents may not be suitable, depending upon the type of the metal and the
volume. Normal metal Fires are associated with metals, such as sodium, potassium,
Lithium, Magensium, Zinc etc. Fire fighting agents such as sodium chloride, sodium
bicarbonate, graphite, magnesium carbonate, magnesium oxide are found effective
for controlling the Fire.
Caution: Water should never be used to extinguish metal fires, as this can result in
explosion which would further spatter burning metal particles to great distances,
thus helping the fire spread.
a) Explosive chemicals:
These are chemicals which under certain conditions of heat, pressure, shock etc.
undergo rapid decomposition, evolving large volumes of gas and heat, which in
turn further heats up the surrounding air to expand so rapidly that the entire
process ends up in what is called explosion.
Storage and handling of this type of materials should be done with extreme caution.
1.
all type of chemicals falling under this category, such as nitrates, chlorates, per
sulphates, per iodates, azides, perioxides etc should be stored in a separate block,
away from the main buildings and human habitation.
2.
be accepted for storage, if the relevant material safety data sheet (MSDS), is not
available. Remember the old and deteriorated explosives may prove more
dangerous than fresh materials.
3.
4.
Avoid storage for prolonged periods. FIFO system should be followed in the
warehouse.
5.
6.
Rough handling, dragging of the containers, stacking at higher levels thus creating
more strain on the bottom containers, etc should be totally avoided.
7.
No attempt should be made to scrap out the material with any metal object nor
should it be pulverized or powdered.
8.
Disposal of explosive chemicals should be done only as per the procedure laid
down in the MSDS or as per the maufacturers instructions.
a)
Flammable chemicals:
Combustible materials can be of all the 3 types viz; solids, liquids, or gases,
although the rate of Fire propagation is different for each type. The propagation is
least in the case of solids, as the vapour pressure being very low at ambient
temperatures, it takes much longer time for the solids to get heated up to produce
sufficient vapours to get ignited. However, the rate of propagation is much faster in
the case of liquids and still faster in case of gases. As a matter of fact in case of
vapour Fires, the rate of propagation is so fast that they normally end up in
explosions aggravating the situations.
1.
All flammable solvents must be stored in a cool place, under shelter with proper
ventilations. The storage store should be away from the main building.
2.
3.
No hot jobs, such as welding, gas cutting, grinding or any other source of ignition
such as naked flame, smoking etc should be allowed in and around the storage
area.
4.
As far as possible electrical equipments and fixtures, such as lighting fans, water
coolers, air conditioners etc must be avoided in the storage block and if at all they
are to be installed, it must be ensured that they should be flameproof in nature.
5.
6.
7.
8.
9.
Movement in solvent farm area and in flammable solvent storage blocks, should
be restricted and only authorised personnel should be allowed to operate in these
areas.
10.
11. Regular training should be imparted to the staff by competent personnel on fire
fighting and salvage techniques.
a)
Oxidising agents:
Since oxidizing agents are capable of generating oxygen, by way of heat, chemical
decomposition or by interaction with other incompatible materials, they help fire to
ravage, even in the absence of atmospheric air or oxygen. Following categories of
chemicals are considered to be most powerful oxidizers and these are to be handled
very cautiously.
As a general rule, all flammable solvents must be stored away from oxidising
chemicals and these should never be allowed to come into contact with each other.
e.g. Instant Fire will take place if Chromic acid comes into contact with organic
solvents such as acetone, alcohols, hydrocarbons etc. Equally dangerous is the
interaction between potassium permanganate and con. Sulphuric acid which would
also result instantaneous fire.
Similarly potassium permanganate or chromic acid can set ablaze poly hydric
alcohols such as glycerol, if they come into contact with each other.
Also it is advisable to store the oxidizing chemicals in a separate store, away from
the operational areas, having adequate ventilation and cooling arrangement, since
most of these chemicals are susceptible to thermal decomposition.
b)
There are many chemicals which undergo decomposition upon contact with water
and the rate of some of the decomposition processes is so fast that it results in
explosion and Fire.
i)
ii)
iii)
These compounds are to be stored in water proof storage rooms, in air tight
containers preferably on dry sand beds, which normally acts as good adsorbant, in
case of any leakage.
As these are very reactive with water, steam etc., a caution board in bold letters
should be displayed outside the storage room, strictly prohibiting the use of water in
that area, in case of any fire.
Only recommended fire fighting agents, such as Drypowder, CO2 should be used in
the affected area.
c)
Toxic chemicals:
These chemicals can be both Organic or Inorganic, as well as in all the 3 forms viz.
solids, liquids or gases.
1.
Store these chemicals, especially if they are in the liquid form, in well closed
containers in a cool place with adequate ventilation. This is more relevant, if the
material is low in its boiling point.
2.
Ensure that as far as possible they are not allowed to come into contact with
atmospheric oxygen, moisture etc. as many of the otherwise harmless chemicals
become toxic due to chemical degradation, with air and moisture. (Chemicals such
as chloroform, carbon tetrachloride etc., can produce the highly toxic gas phosgene,
by their interaction with atmospheric oxygen and moisture, particularly when stored
in mild steel containers).
3.
Ensure that toxic chemicals are not stored along with other chemicals, particularly
with those meant for human consumption such as IP/BP grade products.
4.
There must be proper identification tags on toxic chemicals, clearly indicating the
route through which they enter human body and severity of toxicity.
5.
All safety aids, such as hand gloves, nose masks, fresh air masks, goggles etc
should be available handy and use of these equipments should be strictly enforced,
through proper education and training.
6.
7.
d)
Material safety data sheet should be consulted before going to handle toxic
products.
Corrosive chemicals:
Some of the common corrosive chemicals, being used in chemical industries are:
As corrosive chemicals can cause severe injuries to human body, including loss of
vision or damage to limbs, causing permanent deformity, it is very important that of
safety aids, such as goggles, face shields, nose and fresh air masks, aprons, hand
gloves, safety shoes etc. should be utilized while handling such hazardous products.
e.g. strong alkalis like sodium hydroxide, potassium hydroxide, liquor ammonia
solution can damage the eye permanently, if there is a splash and they come into
contact with eye. No alkaline material should be handled without goggles and
handgloves.
Contact any part of the body by concentrated mineral acids such as Sulphuric and
nitric acids, can cause severe burns and blisters. Always wear protective aids such
as gloves, goggles, aprons and safety shoes while handling these chemicals.
Hydrofluoric acid:
Dimethyl sulphate:
It is colourless and odourless liquid and contact of this chemical on the skin will not
cause any feeling of discomfort or irritation for hours together, but later on there
would be intense pain and irritation on the affected part of the body causing painful
blisters. Make sure that safety aids like goggles, gloves, aprons and safety shoes
are used while handling this product.
e)
Compressed gases:
There are several liquefied and natural gases used in chemical industry for
manufacturing purposes. These are conveyed in specially designed cylinders with
unique colour codes for easy identification.
1. ammonia
2. carbon dioxide
3. air compressed
4. chlorine
5. Fluorine
6. Helium
7. Hydrogen
8. Mono methylamine
9. Nitrous oxide
10.Nitrogen
11.Oxygen
12.Sulphur dioxide etc.
These gases can be flammable, toxic or corrosive in nature and extreme care should
be taken in their storage and handling.
a)
keep the full cylinders always in a vertical position, near a solid support like the
wall of the building, duly fastened to the wall with metal chains, to prevent them
from falling down.
b)
The storage place should be located away from the main building and should be
provided with suitable cover, so as to avoid direct sun rays falling on to these
cylinders.
c)
d)
Keep the cylinders capped and take all precaution to ensure that the needle valve
of the cylinder is not damaged during transportation from one place to another.
e)
f)
Use the recommended gas regulators while using the cylinder and never try to
repair the valve of a leaking cylinder. In case of leakage remove the leaking
cylinder to an isolated area in a cool place and let the gas bleed off slowly and in
case it is toxic or corrosive, inform the authorized dealer immediately,
g)
Always use cylinder trolleys for shifting the cylinders from one place to another
and never drag or roll the cylinders on hard surface.
h)
Do not apply any grease or lubricants on the cylinder nozzles, as gases like
hydrogen oxygen etc. can ignite the organic matter.
Risk Phrases
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
Flammable
R11
Highly flammable.
R12
Extremely flammable
R14
R15
R16
R17
R18
R19
R20
Harmful by inhalation
R21
R22
Harmful if swallowed
R23
Toxic by inhalation
R24
R25
Toxic if swallowed.
R26
R27
R28
R29
R30
R31
R32
R33
R34
Causes burns
R35
R36
Irritating to eyes.
R37
R38
Irritating to skin.
R39
R40
R41
R42
R43
R44
R45
R46
R48
R49
R50
R51
R52
R53
R54
Toxic to flora
R55
Toxic to fauna
R56
R57
Toxic to bees
R58
R59
R60
R61
R62
R63
R64
R65
Combination of R-phrases
R20/21/22
R23/24/25
R26/27/28
R36/37/38
R39/23/24
R39/23/25
and if swallowed.
R39/24/25
R39/27/28
CHEMICAL
Acetic acid
Acetylene
Ammonium
Nitrate
Aniline
Bromine
Chromic Acid
Hydrogen
peroxide
Iodine
Mercury
Acetylene, Ammonia
Oxalic acid
Mercury
Perchloric acid
Potassium
permanganate
Sodium
Sulphuric acid
Oxidising
Substances which give rise to highly exothermic reactions in contact with other
substances, particularly flammable substances.
Flammable
Extremely flammable liquids have a flash point less than 0C and a boiling point less
than or equal to 35C.
Explosive
Substances which may explode under the effect of flame or heat or which are more
sensitive to shock of friction than dinitrobenzene.
Toxic
Corrosive
Substance which, were they to enter into a environment, would present or might
present an immediate or delayed danger for one or more components of the
environment.
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INDEX
Sr .
no
Ref
Procedure
Issue
EP1
01
EP2
01
EP3
01
EP4
01
EP5
Communication
01
EP6
Waste management
01
EP7
Effluent monitoring
01
EP8
01
PURPOSE
SCOPE
THIS PROCEDURE COVERS ALL ACTIVITIES, SERVICES AND PRODUCTS OF THE MPPL.
PROCEDURE
0.0 Scope
This procedure describes the responsibilities and methods for determining aspects,
1.0 Purpose
This procedure exists to ensure that MPPL significant environmental aspects and impacts are
identified in order that the EMS may address them.
2.0 Responsibilities
The Director is responsible for ensuring that all managers & supervisors are aware of those
aspects & impacts, which are generated by their work.
3.0 Procedure:
3.1
Aspects Evaluation
energy consumption
resource consumption
The Director determines the aspect and impacts using an input output process model ,
recording the resources used and products developed .
Having determined these, the Director then determines the impacts of these aspects and
impacts under normal conditions.
Having determined an impact, the Director then uses the criteria test to determine whether or
not an aspect of MPPL operations is environmentally significant. The questions are listed in
order of priority.
2.0 Purpose:
This procedure outlines the responsibilities for supervising the implementation of legislation
relating to the environment .
3.0 Responsibility:
The MR is responsible for maintaining the register of legislation and other requirements, and for
implements any changes triggered by new regulations.
4.0 Procedure:
MPPL operates under a number of different consents imposed by the environment authorities.
The Director holds copies of the COMPANY (ies ) are
1.
These are supported by other acts, statutory regulations. This must be adhered to the
requirements.
All relevant legislation is maintained in a register of legislation and other requirements which is
held in Appendix 2, on Form EPF -R1 (appendix 2) Legal register of key processes ,
legislations, Releases and environmental impacts.
Cross reference:
Legal Register (Form EPF -R1)
1.0 Scope:
This procedure is applicable for setting and reviewing the objectives & targets for MPPL
2.0 Purpose:
The aim of this procedure is to define new objectives and targets, and to review and update
objectives and targets . Targets should be quantifiable where possible and relate to the
objectives contains in the environmental policy.
3.0 Responsibility:
4.0 Procedure:
4.1 On an annual basis the operations Director is responsible for co-coordinating the objectives
and targets within the context of:
Emerging legislation
1.1 The MR is responsible for ensuring that objectives and quantified targets are set for reducing
waste, and energy use in all production departments.
1.2
The MR is responsible for ensuring that any relevant technical objectives and target are set e.g.
development of new procedures, improved management of environmental impacts.
1.3
The maintenance Supervisor is responsible for ensuring that relevant objectives and targets
are set for maintenance activities.
1.4 The Director is responsible for setting relevant objectives and targets, e.g. looking for
environmentally friendly alternatives for hazardous materials, and establishing a phase out
schedule.
4.2 In addition to the annual objectives and target setting, objectives and targets may also be
set by managers when necessary , e.g. in case of new legislation or incidents . These must be
communicated to the Director.
4.3 The Director is responsible for consolidating environmental objectives and target provided
by the managers and for ensuring that targets are consistent with the environmental policy and
objectives
4.4 The Director is responsible for presenting the consolidated objectives and targets for
Management review and for communicating approved targets to relevant personnel.
4.5 Director is responsible for rotating an up to date list of objectives and targets together with
any superseded list and corrective actions.
Cross reference:
Environmental Objectives Chart (EPF- F1)
EP : 4 Communication
1.0 Scope :
2.0 Purpose:
Purpose of this procedure is to establish effective communication between internal & external
customer so that effective Environmental Management System can be established in MPPL.
EP 5: Waste management
5.0 Scope :
This procedure applies to all waste management conducted by MPPL.
6.0 Purpose:
All waste management activities are conducted in accordance with the requirements of relevant
legislation , regulations and other statutory codes .
Consistently high standards of waste management are observed at all times and in all places
The management realizes every opportunity for waste minimization.
7.0 Responsibilities
7.1
7.2
8.0
PRODUCTION MANAGER:
SUPERVISOR:
Procedure
Any waste that is produced at MPPL is appropriately stored treated and disposed off some waste ,
such as scrap & other cloths waste( such as copper iron gun cloths powder etc.) several key
steps must be incorporated from waste production through to final disposal viz.
An example of a waste inventory and a blank pro-forma are included in the appendices of this
procedure .
All waste contractors employed to remove waste materials must be in the list of approved
supplier.
Each waste transfer to a waste carrier shall be recorded with the appropriate waste transfer note
Where waste transfers a repetitive and consists of general waste only an annual transfer note shall
be acceptable.
Waste transfer notes shall be retained for month of 2years.
EP 6 Effluent Monitoring
1.
Scope
This procedure defines the responsibilities and actions to ensure that the company complies
with all the requirements of all trade effluent discharge consent.
2. Responsibilities
The Director is responsible for ensuring compliance with trade effluent discharge consents, and
communicating with Waste control ( AMC ) & control of pollution) authority.
Production Manager is responsible for informing the Director of any planned change in process ,
which may result in change to the nature , and composition of a trade effluent.
3. Procedure
3.1 The company must comply with the relevant consent limits at all times .
3.2 Trade effluent must only be discharged from the specified points as detailed on individual
consents.
3.3 Monitoring points at all times without prior notification for the purpose of inspecting ,testing or
sampling effluent.
3.4 Trade effluent must not contain any oily substances .
A process change that may affect any effluent consent held necessitates a review of this
procedure . The Production manager must be notified of any such change.
Cross reference:
Effluent quality monitoring register.( EPF -R4)
1.0 Scope
This procedure describes the responsibilities for, and the action to be taken , for the disposal ,
storage and handling of cloths waste and prevention of pollution.
2.0 Purpose
This procedure exists to ensure the safe and effective handling and storage of cloths waste, in
order to prevent pollution
3.0 Responsibilities
All personnel involved in the disposal , handling and storage of cloths waste, have a responsibility
for following this procedure .
Relevant seniors are responsible for ensuring all personnel under their jurisdiction are fully aware of
this procedure .
The Production Manager is responsible for regular checks and monitoring.
4.0 Procedure
4.2.1 all waste cloths waste should be stored in designated storage area having three ( 3 ) feet
boundary.
4.2..2 Related person should wear long shoes & equipped with long fork for handling the
scrape.
5.0 GENERAL:
LinkWithin
1.0
INTRODUCTION
This Training Manual is prepared at the beginning of calendar year to enhance the
effectiveness of training procedure existing in the company.
Training Manual includes the various Types of training and cGMP training schedules
for each department, which identifies the name of the topic, targeted audience &
trainer to conduct the training in all organized manner.
SOP training is not included in the Manual, since it will be covered in the change
management system, via a separate SOP. Whenever a new SOP is made (or)
existing SOPs is revised, the respective dept. personnel are trained to make them
familiar with the activities mentioned in the SOPs to make them effective.
2.0
OBJECTIVE
To ensure that all the employees working in Pharmaceutical Ltd., are capable to
perform the duties as per the cGMP, SOPs and procedures and each employee of
Pharmaceutical Ltd., shall improve the relevant knowledge, expertise and to
consolidate the same to discharge their duties effectively. cGMP advises that
appropriate training is required to perform the jobs effectively, which in turn helps in
maintaining the quality system.
3.0
SCOPE
This procedure applies for training of all levels of employees and permanent
workers, working in
Pharmaceutical Ltd.
4.0
RESPONSIBILITIES
Departmental heads are responsible to ensure that the training programs are
conducted as per the schedule in respective departments.
Trainer should prepare / refer the (training) course material and a questionnaire will
be prepared for each topic in consultation with the departmental heads / seniors.
After completion of each session, trainer should evaluate feedback. If some body
needs retraining it should be organized in coordination with the personnel and
administrative department.
Each trainee should sign in their departmental training log after attending the
training program.
Each employee is responsible to attend the training / retraining as per the schedule
communicated to him.
QA shall verify whether the Training program is carried out as per the schedule
during their audits.
5.0
PROCEDURE
TYPES OF TRAINING:
5.1
Induction training
5.2
On job training
5.3
5.4
External training
MANUAL PREPARATION:
A training Manual for the next calendar year may be prepared in the month of
March or in advance as appropriate.
Training Manual should be approved by D.G.M Q.A/Q.C and Authorized by Sr. G.M
Mfg. prior to issuance and implementation.
A copy of the training Manual shall be issued to personnel dept and Personnel
Department will circulate a copy of the departmental training schedules to the
respective head of departments.
A master copy of training Manual shall be retained at Q.A and controlled copy
circulated to Executive P & A.
5.1
Induction training
(Chemists, Officer, Executives & Above)
Each new employee from supervisory and above will be given induction training in the
following aspects:
Importance of GMP and its compliance, key elements of GMP and GLP (Good
laboratory practices) as appropriate.
An induction program will be arranged by Executive P & A, where the new person
will be made familiar with the contact people in each dept. and the activities that are
being carried out in those departments.
Each new employee will be given induction training in the following aspects by
Executive P&A.
5.2
The topics will be selected on the basis of training needs related to the job by
department Heads periodically. The training will be conducted on the job at the work
places like manufacturing floor and in the Q.C lab etc (In brief at the work place.)
Trainer shall write the remark that participants were trained, head of department
review shall be carried out and review comments shall be recorded in the same
format.
On job training shall be documented only in the format Department Training Log.
Schedules are prepared by head of department for on job training and the same will
be complied to make the employees pertinent to their relevant jobs that they carried
out.
5.3
GMP Training:
GMP training schedules are prepared as part of training Manual by each dept. Head,
reviewed by Manager personnel, Approved by D.G.M - Q.A / Q.C, and Authorized by
Sr. G.M - Manufacturing.
session, which shall be documented in the training logs and training cards and brief
summary is recorded in the on the job training format.
The understanding about the topic on which participant was trained will be
assessed by the percentage of marks obtained. The trainee should obtain more
than 80% Marks. The trainee who scores less than 80% will be retrained. Suitable
method of departments can adopted for oral assessments.
5.4
External training:
Validations.
Regulatory aspects.
6.0
6.1
TRAINING RECORD:
All the employees training details are recorded in Training Card
maintained at Personnel dept. and in the respective Log Book for
Training. .
6.2
6.3
All the training related formats are specified in the Annexure. Each training
shall be recorded as in the Annexure as Indicated below.
7.0
7.1
7.2
7.3
7.4
Issued By:
(Executive P & A)
Name of the Employee:
Designation:
Dept:
Date of joining:
Conducted By
Sign
Date
1.
2.
ANNEXURE-II
Name Of Trainer:
Date:
Designation
Location:
Duration of Training:
Title Of Training
Topics Covered
S. No.
Name Of
Designatio
Departme
Employee
Employee
nt
Signature
Trainer Sign
ANNEXURE-III
Issued By:
Sign
Date
Dept
Date
Head - Q.A
Topic:
Type of Evaluation
Written / Oral
Trainer Name:
Sign
ANNEXURE IV
EMPLOYEE TRAINING CARD
NAME
:
JOINING:
DATE OF
DEPARTMENT
:
DESIGNATION:
SR
No
.
Date
of
Traini
ng
Topic
Mode
of
training
Mode of
Evaluati
on
Writte
n/
Oral
Writte
n / Oral
Writte
n/
Oral
Writte
n / Oral
Writte
n/
Oral
Writte
n / Oral
Writte
n/
Oral
Writte
n / Oral
Writte
n/
Oral
Writte
n / Oral
Sign of
Employ
ee
Remark
s by
Trainer
Name
& Sign
of
Trainer
Sign
of
Dept
.
Head
Writte
n/
Oral
Writte
n / Oral
Writte
n/
Oral
Writte
n / Oral
Writte
n/
Oral
Writte
n / Oral
8.0
Training course material should be prepared / referred for each training class or
relevant SOP Procedures, Quality Manuals, Quality Policy and instructions ICH
guidelines.
9.0
10.1
Production
10.2
Stores
10.3
Engineering
10.4
Quality Control
10.5
Personnel
10.6
Quality Assurance
Description
Table of Contents
Revision History
Section: QM 0.1
ISO 9001 Clause Ref.
---
Section No.
QM-0.1
QM-0.2
03
04
05
06
07
08
09
10
11
12
----4.0
5.0
6.0
7.0
8.0
--
QM-0.3
QM-1.0
QM-2.0
QM-3.0
QM-4.0
QM-5.0
QM-6.0
QM-7.0
QM-8.0
QM-9.0
Section: QM 0.2
Rev. No.
Page No.
Section: QM 0.3
Manual Holders
TM / MR
Production / Stores / Quality Control /Purchase / Marketing
Certification Agency
Title: Introduction
Copy No.
01 (Master Copy)
02
03
Section: QM 1.0
Section: QM 2.0
Scope of the Quality Management System for ISO 9001: 2000 Standard Implementation is as
Under :
Manufacturer
Intermediates
and
Exporter
of
Bulk
Drugs
and
Pharma
Section: QM 3.0
The Following Clauses of ISO 9001:2000 Standard are not applicable in purview with the Scope
of the Organization:
Clause 7.3 : Design & Development :The organization is manufacturing as per the IP (31431-39-7), USP and B.P. and doesnt have its
own design hence this clause is not applicable.
Section: QM 4.0
DOCUMENTATION
4.2.1 General
The Quality Management System Documentation includes:
Quality Manual
Quality records
Section: QM 5.0
MANAGEMENT COMMITMENT
The company commits itself to the development and implementation of quality management
system and continually improves its effectiveness. Regular meetings wherein the importance of
meeting customer requirements and feedback are communicated to employees whenever
necessity arises will achieve this. The administrative personnel are briefed regularly about the
statutory and regulatory requirements in meeting.
The quality policy is established and the text of the Quality Policy is given in 5.3
The Quality Policy is supported by tangible Quality Objectives as given in 5.3
Management Reviews are conducted regularly to ascertain effectiveness of QMS (refer 5.6)
The company ensures that adequate resources are made available to meet customer requirement,
Quality System requirements as well as statutory and regulatory requirements.
5.2
CUSTOMER FOCUS
The Company has belief in the philosophy that, CUSTOMER is the purpose of its business.
Employees are regularly trained on customer focus. The feedback from customer in terms of
quality, delivery, quality complaints etc. are accorded top priority and their cause and preventive
measures are immediately implemented.
Customer Satisfaction is enhanced through regular meeting with customer/representatives and
fulfilling their targets in terms of quality, delivery lead-time and price expectations. Periodically
customer feedback form is sent to ascertain their needs and expectations.
ACTIVITY REFERENCE:
PROCEDURE MANUAL - MANAGEMENT REPRESENTATIVE AND MARKETING
The responsibilities and authorities of the organization chart are described as below:
a)
b)
c)
d)
TOP MANAGEMENT
Responsibility:
Overall business development of the organization
Financial Management of the organization
Recruit executives in Managerial Cadre
Formulate quality policy with objectives for the organization
Overall responsible for implemented quality management system
Authority:
Make key decisions and can supercede decisions taken by others
Approve purchase of capital goods
Approve the formulated quality management system
Final authority in all policies of the company
a)
b)
c)
d)
e)
f)
g)
h)
i)
j)
k)
l)
m)
HOD OPERATIONS
Responsibility:
Maintain Harmonic cultures in the company
Liaison and handling prospective customers
Recruitment of personnel at works
Handling and resolving customer complaints
Execution of work orders in time
Procurement of all material and services required for the organization
Manage supplier development
Overall responsible for processes of the organization
To implement on-line inspection stage wise
To plan production and manpower
Impart regular training at shop floor
To maintain plant and machinery and general house keeping
Co-ordinate with Materials, QC&I and Design department
a)
b)
c)
d)
e)
Authority:
a) Approve all purchases of material and services
b) Approve recruitment personnel at works
c) Sanction commercial transactions at work
d) Approve the formulated quality management system
a)
b)
c)
d)
SUPERVISOR
Responsibility:
To Inspect, approve, reject all incoming material
To Inspect, approve, reject process activity
For final inspection of the product
Co-ordination with third party for inspection
Review of document & data control, making current version available, precludes use of
obsolete documents, identifying nature of change.
Conducting the internal quality audit as per schedule, recording non-conformities, and
verification of effectiveness of corrective action against non-conformities.
Conducting the Management Review Meeting and reporting the finding of IQA to Top
Management.
Customer Feed Back: Meetings, Letters, Emails, Feedback form & proactive actions
a)
b)
c)
d)
e)
f)
g)
ACTIVITY REFERENCE:
PROCEDURE MANUAL - MANAGEMENT REPRESENTATIVE
Section: QM 6.0
To implement and maintain the quality management system and continually improve its
effectiveness.
The resource needs are identified through activities such as product planning, internal
audit, management reviews and review of quality objectives.
6.3 INFRASTRUCTURE
Infrastructure needs are assessed on the basis of the resource requirement and business plan.
The infrastructure such as building and amenities for the operators are provided.
Tools & Tackles, Testing Instruments, Testing facilities are provided on the basis of quality plan.
Need for supporting services such as logistics, computer support, etc. are provided.
6.4 WORK ENVIRONMENT
The Company ensures that proper layout, adequate ventilation, lighting, house keeping systems
and safety devices maintain the work environment neatly where appropriate.
Section: QM 7.0
7.4 PURCHASING
7.4.1 Purchasing Process
The Quality System Activities ensure that products, Raw material & Packaging Material are
purchased form approved sources only
Any new source of product / make shall approve based of evaluation and/or trial production,
which shall access the ability of the source to meet the companys quality and delivery
requirements.
The extent of control on the source of supply is based on the product criticality. This is defined in
product quality plan.
The results of supplier performance in terms of adherence to quality and delivery requirements
are monitored. The data is reviewed by HOD Purchase and Top Management and the supplier are
evaluated once in a year.
Records of evaluation, re-evaluation and ratings are maintained.
7.4.2 Purchasing information
Purchasing specification describes the following data.
Product configuration, code, makes, size and other unique information.
Requirements of approval of product such as test certificates, need for Quality system
Certificates and as per Raw Material Testing Plan
The Company ensures that adequacy of Purchase requirements are reviewed prior to release.
Where specified by customer or when required by the company, the verification may be
done at suppliers premises by company or by Customer.
The verification method may include product evaluation, Supplier Quality System Audit.
In such case, purchasing information shall specify the method of verification and sub-sequent
product release.
ACTIVITY REFERENCE:
PROCEDURE MANUAL PURCHASE
Section: QM 8.0
8.1 GENERAL
The Company plans and implements the monitoring, measurement, analysis and improvement
process as follows:
The frequency and duration of an audit is determined based on the volume of activity,
importance of the activity.
By taking action to scrap after due care that the scrapped products do not find its way to
the original intended use.
Measurement data
Defect data
Supplier performance
Tools and techniques such as graphs, charts, brainstorming etc. are used in the analysis of
data
8.5 IMPROVEMENT
8.5.1 Continual Improvement
Continuous improvement in the effectiveness of quality management system is achieved through
the use of :
Management review
ACTIVITY REFERENCE:
PROCEDURE MANUAL QUALITY CONTROL & INSPECTION
PROCEDURE MANUAL MANAGEMENT REPRESENTATIVE
OBJECTIVE : To lay down a procedure for sampling and testing of packing materials.
2.0
RESPONSIBILTY
Microbiologist / Q.C Executive
3.0
ACCOUNTABILITY
Quality Control Manager
4.0
PROCEDURE
4.1
Collect the intact packs of Bottles / ROPP caps / Inner caps or any other primary packing
materials (Annexure-1) from the consignment and transfer to Microbiology laboratory. Carry out
sampling under laminar air flow in MLT area. Seal the containers properly and send it back to
warehouse.
4.2
Prepare 3x100ml of 0.9% of NaCl solution and sterilize by autoclaving ,for sample of each
consignment of packaging material (for small items like caps ,rubber stoppers used for oral
packaging material etc) .
4.3
Open the sample under LAF and submerge 20units in the prepared solution and swirl it for 10
min.
4.4
Transfer the solution in sterile filtration unit & filter the solution with 0.45mm filter membrane of
100ml each.
4.5
Then transfer the filter membrane in sterile SCD agar plate and incubate at 35C for 72 hrs
,for bacteria,
SDA agar plate, for fungi, and incubate at 20-25C for 120 hrs and note the observations, for
pathogens submerge the filter membrane in 100ml of sterile SCD Medium and proceed for the
testing of pathogens as per SOP
Formula : No. of cfu in each unit=Number of cfu observed on filter membrane / 6 (unit)
Limit: Bacteria NMT 5 cfu / unit, Fungi NMT 1 cfu / unit and pathogens nil / unit.
4.6
For vials and bottles used for oral packaging material pour 5 ml of sterile solution into
each of the 15 containers with the help of sterile pipette and thoroughly wet the inner walls and
filter the solution in sterile 0.45mm filter membrane.
4.7
Then pour rinsed solution from 5 vials in each three sterile 0.45mm membrane filter assembly
and filter the solution.
4.8
Then transfer the filter membrane in sterile SCD agar plate and incubate at 35C for 72 hrs ,
(for total bacterial count), SDA agar plate, (for total fungal count) , and incubate at 20-25C for
72 hrs and note the observations ,for pathogens submerge the filter membrane in 100ml of
sterile SCD Medium and proceed for the testing of pathogens as per G.P No.Formula : No. of cfu in each unit =Number of cfu observed on filter membrane / 5 (unit)
4.9
For pathogen testing test for S aureus , Pseudomonas , E. coli and Salmonella as per SOP
No. K/QC/059.
4.10
Limit (for oral packing materials: for bottles or vials): For bacteria: 100 cfu / unit , For
fungi: 10 cfu / unit., pathogens: Nil / unit
4.11
Limit (for injectable packing materials, Like vials, rubber-stoppers etc ): For
bacteria.
NMT 10 cfu / unit , For fungi. <1 cfu / unit , pathogens: Nil / unit
4.11
Foils( Aluminum, PVC / PVDC Films)- Cut (three replicates) inner 20 x 20 cm with sterile
tools and use contact plate (RODAC plate) for sampling
Formula :No. of cfu in 100cm2 =Sum of the number of cfu observed on three RODAC
plates/ 3x 19
Limit: 50 cfu / 100cm2 (for bacteria).
5 cfu / 100cm2 (for fungi). And nil pathogen.
4.12
ABBREVIATIONS :
ANNEXURE 1
Rubber plugs, Caps 20 Nos.
Up to 20ml Bottle- 15 Nos.
30 , 50 , 60 & 100 ml Bottle 12 Nos.
125 ml Bottle 9 Nos.
170 , 250 , 375 ml Bottle 6 Nos.
Vials 20 Nos.
Frequency of testing For every export batches OR as per requirement.
ANNEXURE II
CONSIGNMENT No./DATE
SAMPLE TY./AREA
SAMPLED BY
MEDIA PREPERATIONS:
MEDIA NAME
Bacteria:
PREPAR
For Bacteria
Medium used
For Fungi
SCDA
SDA
-ve
control
control
Cfu / plate
+ve
-ve control
Cfu / plate
control
Ist day
2nd day
3rd day
4th day
5th day
Calculation:
(B)
MEDIA BATCH
NO.
PREPARED ON
LOT NO.
MEDIA NAME
MEDIA B. NO.
PREPARED ON
LOT NO.
Cetrimide agar
Brilliant Green Agar
Xylose Lysine Deoxy. agar
Mac koncy Agar
Primary test
Secondary test
Inference
tested
S.aureus
Pseudomonas
E. coli
Salmonella
TBC=
cfu/unit , TFC=
cfu/unit , Pathogens =
INFERENCE: The above sample complies / does not complies the test.
You might also like:
Sampling, testing and release of raw materials
Dispensing of packing materials
Re-testing of raw materials and intermediates
SAMPLING OF PACKAGING MATERIALS
LinkWithin
2.0
RESPONSIBILTY
Microbiologist / Executive
3.0
ACCOUNTABILITY
Head - Quality Control
4.0
PROCEDURE
4.1
4.2
4.3
Ensure that the marker is connected to either right or left side of the instrument.
4.4
4.5
Switch on the power button. The internal light will be flashed ON and the digital screen will
show 0000 figure in red. Again pressing this button will turn the power. OFF.
4.6
4.7
Now, mark each and every colony one after the other by pressing the tip of the marker.
4.8
The number of colonies will automatically get displayed on the screen can be reset to 0000 by
pressing the RESET button.
4.9
4.10
Switch OFF the instrument and put under cover when not required.
5.0
Harmonization of format.
6.0
TRAINING:
Trainer --
Trainees-Period -
One day
7.0
DISTRIBUTION:
Original Copy
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2.0
RESPONSIBILTY
Microbiologist / Executive
3.0
ACCOUNTABILITY
Head Quality Control
4.0
PROCEDURE
4.5 Now place the objective ( high power / oil immersion whichever is required) in position by
moving the resolving nose piece.
4.6
Place the slides on the stage, set the objective at the closest position w.r.t slide then slowly lift
the objective with coarse adjusting screw, while observing through the eye piece, till the field
appears clearly ( if the oil immersion objective is in use, place on drop of immersion oil on the
slide before placing it on the stage and then lower the objective just to touch the oil drop.
4.7
Make the field clearer with the help of fine adjustment and then observe the slide.
4.8
Slide can be moved in left, upper and lower direction to observe the complete smear area with
help of slide stage screw and coarse adjustment.
4.9
After completion of observation, remove the slide, clean the objective lens and condenser with
cotton soaked in xylene. Bring the 10x objective in the active position. Lower down the
condenser and place low power objective in position.
4.10
5.0
Harmonization of format.
6.0
TRAINING:
Trainer --
Trainees-Period -7.0
One day
DISTRIBUTION:
Original Copy
1.0
OBJECTIVE: To lay down a procedure for handling of out of specification (OOS) result in
Microbiological analysis and monitoring.
2.0
RESPONSIBILITY
Quality Control Executive/ Microbiologist
3.0
ACCOUNTABILITY
Quality Control Manager
4.0
PROCEDURE
In all the reports the identified reason shall be written on a continuation sheet to the annexure
provided. A copy of the above investigation report shall be maintained with the batch
manufacturing records concerned to increase awareness and for any future reference
4.1
4.1.1
STERILITY TEST
If evidence of microbial growth is found, the product to be examined does not comply with
thetest for sterility, unless it can be clearly demonstrated that the test was invalid for causes
unrelated to the product to be examined .The test may be considered invalid only when one or
more of the following conditions are fulfilled:
4.1.1.1The data of the microbiological monitoring of the sterility testing facility shows fault;
4.1.1.2 A review of the testing procedure used during the test in question reveals a fault;
4.1.1.3 Microbial growth is found in the negative controls;
4.1.1.4 After determination of the identity of the microorganisms isolated from the test, the
growth of this species or these species may be ascribed unequivocally to faults with respect to
the material and / or the technique used in conducting the sterility test procedure.
4.1.2 If the test is declared to be invalid it is repeated with the same number of units as in the original
test.
4.1.3 If no evidence of microbial growth is found in the repeat test the product examined complies with
the test for sterility. If microbial growth is found in the repeat test the product examined does not
comply with the test for sterility.
4.2 ENVIRONMENTAL MONITORING
4.2.1 If the microbial counts are found to be more than or equal to the alert limit then
open a deviation report (annexure I) through Q.C. Head to the concerned Production head.
Production personnel shall check the working discipline, supply of air, safety measures etc.
4.2.2
If the count exceeds or reaches the action limit then the urgent notification to the Production
head and Engineering Head through Q.C. Head shall be followed by an investigation for the
same.
- Supply of air
- Working discipline
-
Review of data from the same place and others from the incubated plates
If any of the plates does not indicate the same then no action is necessary.
If any of the plates indicates more count then perform additional cleaning, disinfection or
fumigation and retraining to the operator shall be given.
All activities shall be recorded as per the annexure attached with this SOP.
More number of samplings (i.e. double the original) shall be preformed at the same location
where the counts observed were beyond or equivalent to the action limit but an additional
relevant parameter of monitoring shall also be performed which shall be incorporated with the
same annexure.
All the batches manufactured during the said period shall be subjected to the microbial
analysis for MLT / Sterility &BET in order to ensure that the batches manufactured are in
accordance with the relevant finished product specifications. The investigation report shall be
submitted to the Q.C. - Head
4.2.3
If the bio-burden is found out of specified limit in the core areas the identification of the
organism shall be performed.
4.2.4
Stop the production immediately and check all the possible parameters, which can affect bioburden of the area.
4.2.5
Check the pressure differential of the area, which must be within the specified limit.
4.2.6
Check the air velocity of LAF /HEPA filters, which must be within the specified limit.
4.3
4.4
4.4.1
Adequate sanitization of the system shall be ensured to eliminate the source of contamination
with a rigorous check for the same.
4.4.2
All the investigations made shall be recorded in the annexure III provided with this SOP.
4.5
4.5.1
4.5.2
Retest the same material/product but with a sample size of 25 grams by making allowance for
the larger size specimen.
4.5.3
Results for the same shall be intimated to the Q.A. Head for final decision.
5.0
Harmonization of format
6.0
TRAINING:
Trainer --
Trainees-Period -7.0
One day
DISTRIBUTION:
Original Copy
ANNEXURE I
FORMAT FORDEVIATION REPORT TO PRODUCTION DEPARTMENT
Revision No.
: 00
Effective Date:
Date:
Batch no.:
Deviation :
Parameter:
Requirement :
Results :
Page No.: 1 of 1
Signature :
Repair
Comments
..
Name
Signature
Date:
Repeated Sampling :
Parameter:
Result:
Comments
by
Q.C.
Head
for
Approval
of
Production
Signature :
ANNEXURE - II
Format for Corrective Report After Sampling of Environmental Parameters in Production
Revision No.
: 00
Effective Date:
Page No.: 1 of 1
Date :
Deviation :
Checked
By :
Date :
Signature :
Date :
Signature :
Date :
Signature :
ANNEXURE III
INVESTIGATION REPORT FOR FAILURE IN TEST FOR BACTERIAL ENDOTOXIN & M.L.T
Revision No.
: 00
Effective Date:
Page No.: 1 of 1
Sample
Analyzed on
Analysed By
Checked By
Procedure of sampling
GP test of media
Test tubes
Pipette
LAL reagent
Batch No.
Mfg.
Expiry
Reconstituted
on
Expiry
Blank
Calibration Status
Results of other samples with same conditions tested on the same day.
Details of Raw material used in finished product
Result
Test repeated
Date
Result
Microbiologist
ACTION TAKEN :
Production Head
Control Head
CONCLUSION
(Results of MLT for Other Samples to be enclosed)
Engineering Head
Quality
Microbiologist
QC
Manager
Date:
Date:
Sign
Date :
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OBJECTIVE: To lay down a procedure for Media Fill operation in the sterile dry powder Filling
facility..
2.0
RESPONSIBILTY
Microbiologist, Operator concerned/Production officer/QA Officer
3.0
ACCOUNTABILITY
Quality Control Manager/ Production Manager
4.0
PROCEDURE
PRE-START UP:
4.0
Ensure that all the equipments, HVAC system, water system and other utility services of the
facility are validated.
4.1
Ensure that the Gamma irradiation certification report of the lactose + SCDM (Soyabean
Casein Digest) mixture (3:1) from BARC and sterility test report (done in-house) is available.
4.2
Ensure that solubility test report and growth promotion/inhibition test report of sterile
lactose+SCDM mixture is available. [Solubility should be NLT 1gm/10 ml of WFI].
4.3
Ensure that solubility test report and growth promotion/inhibition test report of sterile
lactose+SCDM mixture is available. [Solubility should be NLT 1gm/10 ml of WFI].
4.4
Ensure that freshly distilled WFI to be used for filling, is autoclaved and the sample given for
sterility test.
4.5
Ensure that all the contact parts of Dry Powder Filling machine are duly cleaned and
sterilized or sanitized.
4.6
Ensure that the last Environmental Control Reports of the area are conforming to the
acceptance standard.
4.7
Ensure that the Liquid Filling machine is done inside the sterile filling area on the previous day
after autoclaving /sanitization.
4.8 Ensure by manometer readings, that the pressure balancing of the sterile area is as per
requirement.
4.9
Ensure that the cleaning, sanitization and fumigation of the area is done on the previous day.
START UP
4.9
Enter the sterile area as per SOP using gowns sterilized 4days back.
4.10
4.11
4.12
Check and confirm the temperature and RH of liquid filling room is as per the requirement.
4.13
Assemble the Liquid Filling machine.Ensure that that filling of liquid and liquid can be done
simultaneously.
4.14
Measure the nonviable particulate count of filling cabinet and filling room.
OPERATION
4.15 Bring the autoclaved WFI container near the liquid filling assembly.
4.16 Transfer sterile SCDM liquid from the container in to liquid hopper.
4.17 Transfer sterile dried rubber stoppers (sterilized 4 days back) in to the hopper of stoppering unit.
Send sample for sterility testing simultaneously.
4.18
Put the inlet suction tube of Liquid Filling Assembly into the WFI container.
4.19
4.21
Ensure that all the left over rubber stoppers are given outside the sterile area for destruction.
4.22
4.24
Follow the cleaning and sanitization SOP for cleaning of sterile area.
4.25
Do the extra cleaning and sanitization of the floor/walls/machine after media fillrun with 10%
Bacillocide and Lysol solution
ACCEPTANCE CRITERIA:
4.26
Initial validation: During initial validation, it should qualify all three consecutive media fill run i.e.
during each run there should not be growth in more than two vials.
4.27
Revalidation: Only one media fill run in which there should not be any growth in more than two
vials.
Persons involved in media fill should be medically examined and declared fit within last one year.
4.29 Persons should be trained on general hygiene and current gowning procedure, and the present
health condition should be O.K.
4.30
4.31
If the isolated organism is other than the house flora, thorough investigation shall be carried out
by Quality Assurance and Production.
4.33
When there is no assignable cause, media fill shall be repeated three times and production
should commence only after all the three runs meet the acceptance criteria.
4.35
When there is assignable cause, after rectification of the cause, repeat the media fill run
once.
4.36
Before and during media fill run no special cleaning shall be carried out.
4.37
Normal production can resume only after minimum one day of environmental monitoring
compliance report.
4.38
Batches filled before the final result of the media fill run shall not be released to the market till the
media fill run passes in case of initial validation.
4.39 The routine environmental monitoring plates shall be kept for 14 days (in case of any growth) to
help in investigation of any positive growth in the media filled vials.
4.40 If for any reason the media fill run is considered invalid vials shall not be incubated.
4.41 Media fill runs can be aborted for the same reason that a product lot would be aborted. All
media filled units filled before an incident that would cause an aborted fill must be incubated.
4.42 During media fill all the Operators, Officers& Maintenance staff who are authorized to do the
sterile filling, supervision and maintenance must be involved in media fill trial.
4.43
The volume of liquid filled must be sufficient to wet all surfaces including the closure and
to facilitate inspection.
4.44
The line must be run at a slower speed than normal production run to give greater
exposure time.
4.45 Total duration of the routine media fill must be the same or more as the longest process
conducted on that line.
4.45
microbial growth at 30-35oC. for 336hrs(stored upright) followed by 20-25oC. for 336 hrs.
(stored upside down).
4.47
Personnel that conduct the inspection of incubated media fills must have training on
basic microbiological concepts ,concepts of media fill and examples of contaminated container
showing various stages of growth.
POST MEDIA FILL RUN :
4.48
4.49
4.5
Temp. range for incubation 1st two week at30 to 35o C. (vials stored upright).
4.51
4.52
2)
3)
4)
5)
Picking unstoppered vials from the outfeed back to conveyor for stoppering.
6)
Adjustment of separator.
7)
8)
9)
10)
11)
12)
13)
14)
15)
16)
17)
18)
19)
20)
21)
22)
Covering the working shift usually 12 hours and shift Change over
23)
ANNEXURE - III
PERCENTAGE
BATCH SIZES
OF FAILURE
ACCEPTABLE
AT 95%
CONFIDENCE
LEVEL
5000
10000
20000
50000
100000
INFINITY
2469
2668
2808
2912
2951
2995
3676
4047
4339
4575
4670
4747
4684
5207
5670
6044
6207
6294*
24698
26686
29944
46093
47047
47047
62911
62911
2.0
RESPONSIBILTY
Microbiologist /Q. C Executive
3.0
ACCOUNTABILITY
Quality Control Manager
4.0
PROCEDURE
4.1
INTRODUCTION:
4.1.1 Bacteriological culture media contains all the nutritive sources which favors rapid growth of
different types of Micro-organisms. Some selective medias are used for cultivating specific type
of Pathogenic
on enriched or selective
medias if not disposed or destroyed in proper way can cause contamination of the
environment which in turns is very hazardous.
4.2
4.2.1
METHOD:
Collect all the used semi solid medias in plastic bag containing about 50 ml of 2.5% Savlon
solution and close the opening tightly with a tag or rubber-band and transfer the it to the
incinerator.
4.2.2
For liquid media add 2.5% disinfectant (savlon), to the liquid media ,mix it well ,hold for half an
hour and then discard them in a stream of running tap water.
4.2.3
The plates & test tubes are then thoroughly washed with soap water and sterilized by
autoclaving.
4.3
4.3.2.1Keep all the glasswares used in microbiology in the cupboard of the tables used by the
Microbiologists to work.
4.3.2.4Dip all the glass wares in 2% v/v solution (prepared in D.M water)of teepol or liquid soap for at
least 4 hours, for depyrogenation dip it into 2.5% NaOH solution.
4.3.2.5Remove the glass wares from the solution.
4.3.2.6Rinse twice with D.M water followed by rinsing once with W.F.I
4.4
ABBREVIATIONS
W.F.I= Water For Injection, NaOH= Sodium hydroxide, %=Percentage, v/v =Volume by volume
D.M water= De mineralized water
5.0
Harmonization of format.
6.0
TRAINING:
Trainer --
Trainees-Period
7.0
--
One day
DISTRIBUTION:
Original Copy
OBJECTIVE: The objective of this SOP is: to lay down a procedure for preparation of plates
that can be used as settling plates and in various microbiological analysis.
2.0
RESPONSIBILITY
The Microbiologist shall be responsible for preparation of settle plates, their pre-incubation and
related documentation.
3.0
ACCOUNTABILITY:
Executive - Quality Control
4.0
4.1
i)
PROCEDURE:
Media with the content of agar can be used for the preparation of settle plates like.
Soyabean Casein Digest Agar (SCDA) - For enumerating Bacteria and Fungi (required for
Environmental monitoring and Microbial limit tests.)
ii)
Sabarauds Dextrose Agar (SDA) For estimation of fungi.( Required for Microbial limit
tests. )
4.2
4.3
Follow the gowning procedure and enter the M.L.T Room by following SOP.
4.4
Clean the LAF with 70% I.P.A and wait till drying.
4.5
4.6
Open the containers containing sterile petri-dishes (That are previously sterilized by
Autoclaving) and place on the working surface table of L.A.F.
4.7
Open the containers containing sterile petri-dishes and place them on the working table of
LAF.
4.8
Take out the cotton plug of conical flask containing agar medium.
4.9
Sterilize the mouth of the conical flask by flaming it and start pouring about 20-25 ml of
medium to each petri-dish quickly .
4.10
Cover the plates and keep under LAF, till they are solidified.
4.11
After getting solidified, preincubate the plates to the incubator at 30-35C for 48 hrs to check
any accidental contamination.
4.12
Check each and every plate under colony counter before exposure to the environment for
monitoring.
4.13
5.0
Period
6.0
-- One day
DISTRIBUTION:
Certified Copy No. 1
: Microbiology Department
Original Copy
This article provides a practical interpretation and summary of the available guidance
and some suggestions for best practices for conducting forced degradation studies.
Overview of regulatory guidance
According to the available guidance, forced degradation studies are carried out for the
following reasons:
Development and validation of stability-indicating methodology
Determination of degradation pathways of drug substances and drug products
Discernment of degradation products in formulations that are related to drug
substances versus those that are related to nondrug substances (e.g., excipients)
Structure elucidation of degradation products
Determination of the intrinsic stability of a drug substance molecule Degradation
studies have several defining characteristics. They are carried out in solution and/or the
solid state
Involve conditions more severe than accelerated testing (e.g., _40 0C; 75% relative
humidity; in excess of ICH light conditions; high and low pH, oxidation, etc.)
Are typically carried out on one batch of material
Include conditions that analyze thermolytic, hydrolytic, oxidative, and photolytic
degradation mechanisms in the drug substance and drug product (as appropriate)
are not part of the formal stability program.
Summary of requirements at the IND phase
Although the reporting of degradation studies is not required in IND applications,
preliminary studies may be carried out to facilitate the development of stability-indicating
methodology. Studies can be conducted on the drug substance and developmental
formulations to test for degradation by thermolysis, hydrolysis, oxidation, and photolysis
or to evaluate the potential chemical behavior of the active ingredient.
A draft guidance document suggests that results of one-time stress studies should be
included in Phase 3 applications for INDs.
Summary of requirements for marketing application
Completed studies of the degradation of the drug substance and drug product are
required at the new drug application (NDA) stage, including isolation and/or
characterization of significant degradation products and a full written account of the
degradation studies performed.
Drug substance-For degradation studies of a drug substance, FDA requests the
following at the time of registration:
stressing the drug substance in solution or suspension at acidic and alkaline pH and
under oxidation conditions
stressing the solid bulk drug substance at temperature and temperaturehumidity
conditions in excess of accelerated conditions
stressing the drug substance photolytically in the solid state and/or in solution in
excess of ICH conditions
demonstration of the specificity of stability-indicating methods with forced-degraded
samples or with the drug substance spiked with appropriate markers
isolation and/or full characterization (by means of NMR, mass spectrometry [MS], UV
analysis, etc.) of all significant degradation products if possible. Procedures for the
preparation and/or isolation (where applicable) and structure determination of the
degradation products should be reported. Unsuccessful attempts to identify significant
degradation products should also be documented
the chemical and physical properties of degradation products, if available
The mechanism and kinetics of formation of each degradation product, if available.
The
guidance
says
to
determine
reaction
kinetics
if
practicable,
thereby
acknowledging the difficulty in cases in which the mechanism may be complex (e.g.,
autoxidation).
Other issues that may be investigated but are not explicitly requested for degradation
studies are the physical and chemical stability of important crystal forms, mass balance,
and the formation of stereoisomers.
Drug product-The guidance specifies the following for degradation studies of the drug
product at the time of registration:
challenge methods intended for monitoring the stability of the drug product with the
degraded samples or with the drug substance spiked with a mixture of known
degradation products
isolation and characterization of significant degradation products, if possible. The
identity and chemical structure, procedure for isolation and purification, mechanism of
formation (including order of reaction), and chemical and physical
properties should be reported, if available. These degradation products include any drug
substancerelated compounds such as drug substance degradation products, drug
substanceexcipient degradation products, drug substance extractive degradation
products, and so forth.
distinction between degradation products that are related to drug substances and
those related to nondrug substances
photolysis of the drug product in excess of ICH light conditions
Information requested in the submission. The available guidance explicitly requests
the following in the NDA documentation:
for degradation products: identity and structure; procedure for isolation (where
applicable) and characterization; mechanism of formation, including order of reaction;
and physical and chemical properties
information about stress testing of the drug substance and drug product (the guidance
does not state specifically what information is required).
At the time of this writing (May 2001), more-specific guidance for the reporting of stress
testing was found in FDA draft guidance documents dealing with stability and method
validation. According to these documents, the applicant should provide
degradation pathways of the drug substance, alone and in the drug product
a discussion of the possible formation of polymorphic and enantiomeric substances;
the possible formation of any stereoisomers is implied
data showing that neither the freshly prepared nor the degraded placebo interferes
with the quantitation of the active ingredient
data from stress studies of the drug substance and drug product demonstrating the
specificity of the assay and analytical procedures for degradation products. These data
may take the form of representative instrument output (e.g., chromatograms) and/or
degradation information obtained from stress studies (e.g., results of peak purity
experiments performed on degraded samples).
Experimental approach
The experimental protocol for degradation studies of new drug substances and drug
products ideally will result in samples that either have been degraded 10% or have been
exposed to an amount of energy that slightly exceeds that supplied under accelerated
storage conditions (e.g., 400C for 6 months).
Forced degradation studies should be conducted whenever a stability-indicating method
is required. Studies may need to be repeated as methods, processes, or formulations
change. Alternatively, methods can be developed with a mixture of the known
degradation products, if available. Forced degradation studies should be performed on
each unique formulation before formal stability studies begin.
Table I shows a general outline for degradation studies of new drug substances and
drug products that was endorsed at the workshop. Sufficient exposure of a drug
substance or drug product is achieved when the drug substance has degraded 10%
from its initial amount or after an exposure in excess of the energy provided by
accelerated storage (e.g., 400C for 6 months), whichever comes first. Application of this
rule of thumb may result in no degradation in some cases. The goal is to generate
degradation in profile that mimics what would be observed in formal stability studies
under ICH conditions.
The duration of storage required at a given temperature can be estimated by making
conservative kinetic assumptions. The energy of activation, Ea, represents the
quantitative relationship between reaction rate and temperature. The range of activation
energies for most drug substances is 1224 kcal/mole with an average of about 1920
kcal/mole.
Assuming activation energy of 12 kcal/ mole affords nearly a doubling of the reaction
rate for every 100C increase in temperature. (Recognize that this is a conservative
estimate and that activation energy of 20 kcal/mole affords about a 2.5- to 3-fold
increase in reaction rate for every 10 0C increase in temperature.) With this relationship,
one can calculate the amount of time a sample should be stored at a specified
temperature to achieve the energy equivalent of exposure at accelerated stability
conditions (e.g., 400C for 6 months). A sample of bulk drug substance stored at 80 0C
would be stored for 12 days. Thus, for a compound that degrades with Ea -12
kcal/mole, storage at 800C for 12 days is kinetically equivalent to storage at 40 _C for 6
months.
Suggested equipment and exposure levels for photo stability stress testing are
described in ICH and FDA guidance. Light storage should be in sufficient excess of ICH
light conditions. The guidance states that solution-phase degradation studies of a drug
substance can be carried out in solution or in suspension. The use of inert organic
cosolvents may be indicated in cases in which drug substances are extremely insoluble
but recognize the potential of any organic co solvent to react with the drug substance
under a given set of stress conditions.
For drug products, nondrug substance related peaks should be distinguished from
drug substance related compounds. This process can be accomplished through
comparative analysis of stressed samples of drug substance alone, of drug substance
plus excipients, and of excipients alone. Stressing drug substance and/or excipient
blends instead of final dosage forms may be adequate for the determination of
degradation pathways of a drug product. However, there may be significant differences
in degradation profiles observed between blends and actual drug products.
Consideration also should be given to the possibility of a reaction between the drug
substance and components of a film-coating or capsule shell. For combination
parenteral or aerosol products, the guidance recommends an investigation of the
chemical compatibility or stability of multiple actives that will be combined before
administration. By extension, any combination product should be stressed to examine
for drugdrug interactions potentially manifested by accelerated degradation and/or new
degradation pathways and products. Early investigation can facilitate development of an
optimum formulation as well as stability-indicating methodology. Consideration may be
given
to
stereochemical
stability,
mass
balance,
and
crystal-form
stability.
Stereoisomers should be treated like any other potential degradation product. Failure to
observe an increase in stereoisomers during forced degradation studies may be
sufficient justification to eliminate testing for stereoisomers during stability studies.
Investigation of the mass balance in degraded samples can reveal the adequacy of the
analytical methods to examine for degradation products. Assessing mass balance is the
process of adding the assay value and levels of degradation products to see how
closely these add to 100% of the initial value, with due consideration of the margin of
analytical error. In cases in which substantial mass loss is observed, efforts to account
for the missing mass should be made such as consideration of response factors or the
formation of highly retained or volatile degradation products. FDA recognizes that mass
balance may not be obtained in all cases and instead emphasizes the thoroughness of
the investigation to determine the specificity of the assay and the pathways of
degradation. The chemical and physical stability of crystal forms, if relevant, should be
investigated. This analysis could include evaluation of stressed solid-state samples for
changes in crystallinity or crystal form.
Method specificity for the active ingredient can be established by peak purity
experiments using hyphenated techniques such as liquid chromatography (LC)MS,
LCUV (photodiode array detection), and LCNMR or orthogonal methods. If needed,
degradation product structure elucidation can be accomplished with hyphenated
techniques (e.g., LCMS, LCUV, and LCNMR) or by synthesis and/or isolation.
Structure elucidation may be postponed until the drug demonstrates safety and efficacy.
Vaidation
VALIDATION OF ANALYST
1.0
OBJECTIVE
To lay down a procedure to establish capability of analyst to perform analysis accurately.
2.0
RESPONSIBILITY
Quality Control Officer / Quality Control Executive
3.0
ACCOUNABILITY :
Quality Control Manager
4.0
PROCEDURE
4.1.1
Samples of known analytical values shall be identified by the Quality Control Manager.
4.1.2
The analytical value(s) of sampler(s) along with acceptable limit(s), AR no., and code no.
shall
be recorded by Quality Control Manager in a register maintained for this purpose.
4.1.3
used within
All the coded samples shall be kept in sealed vials in the refrigerator and shall be
The necessary information required for analysis of coded samples shall be disclosed to the
analyst.
The analyst shall be undergone validation for either one or more of following areas of
analysis.
4.2.1
4.2.2
4.2.3
4.2.4
4.2 The Analyst validation shall involve use of one or more of the following instruments.
4.2.7
4.2.1
4.2.2
4.2.3
4.2.4
4.2.5
HPLC
UV Spectrophotometer
Auto-apparatus ( Titrator , KF Titrator )
Melting point apparatus
IR Spectrophotometer
4.2.6
The results of analyst shall be checked for cGlp compliance and compared with expected
values.
The capability to perform tests by Analyst shall be considered satisfactory if the results reported
by the
Analyst are within the acceptable limits , and documentation as per the
requirement.
4.2.8
4.2.9
The details like calculations, chromatograms, strip charts alongwith comments of Quality
Control Manager shall be filed in training file of analysts.
TEST
Assay (HPLC) (on as is basis)
ACCEPTANCE LIMIT
+ 0.5% of the initial reported value
2.
Assay (by titration) (on as is basis)
Assay (by UV) on as is basis)
Water (by KF)
IR
Melting range
4.3 ABBREVIATIONS
Scope
Harmonization of format
6.0
TRAINING:
-- Manager Quality Control
Trainer
Trainees
-- Chemist / Assistants
Period
7.0
-- One day
DISTRIBUTION:
ANNEXURES:
Nil
Validation of QC Chemist
1.0 Purpose
Primary
: QC Chemist / QC-Officer
5.0 Procedure
Following method used for the validation of QC Chemist to confirmed his / her
analytical skills.
Identified batch sample shall be coded and hand over to QC Chemist with all
QC Chemist performs the analysis and meets the acceptance criteria as per below
mentioned table.
Incase of QC Chemist fails to meet the criteria, the QC Chemist shall be trained and
re-qualified. The training record shall be recorded
Acceptance Criteria for Chemist Validation
Sr.
No.
01
Test
Acceptance Criteria
02
03
IR test
04
05
UV test
GC test
07
08
Specific Optical
than 2 %
% RSD of six replicates reading should not more
09
Rotation test
Assay by chemically
than 2 %
% RSD of six replicate analysis should not be more
test
than 2 %
06
General concept
Three consecutive validations will be performed to prove that the method is validated.
Whenever a new product is introduced, equipment usage and nature of potential contaminant
will be studied to assess whether it poses a challenging study for cleaning validation.
If the new product represents worst case, study/ identify/develop method of cleaning to be
employed. Simultaneously develop Analytical method for cleaning and validate the same.
Revalidation Policy.
Level of cleaning:
Stages of manufacturing
Cleaning Procedure
o
Identification of equipment
Characterization of products
Cleaning Procedure:
Identification of Equipments:
Identify equipments to be cleaned.
Identify difficult to clean areas
Check for ease of dismantling
Characterization of products:
Study activity/toxicity, solubility of the active substance of current batch and dosage and batch
size of next product to be taken on the equipment.
o
Based on above, prepare detailed written cleaning procedures for each equipment.
In order for the analytical testing of the cleaning validation samples to yield meaningful results,
the analytical methods used should be validated.
Analytical method validation for cleaning should include limit of detection, limit of
quantification, acceptance criteria and rationale for setting the specified limits.
Sampling Procedure:
Sampling Locations:
o
Two easy to clean and two hard to clean areas should be clearly defined in Protocol.
Sampling Procedure:
o
Swab samples should be taken separately for chemical and microbiological studies
For each of chemical and microbiological analysis take 2 swabs from easy to clean hard to clean
locations
Swab samples should be numbered numerically and sequentially like 01, 02 etc for
identification.
Based on the data available calculate acceptance criteria for both Pharmacological dose method
and limiting the level of product to 10 ppm which appear in the following product.
Of these two, choose the criterion with stringent limits and detectable by analytical
method.
Validation Protocol
Quality Control Developing analytical method for cleaning, sampling, testing & recording the
results.
Responsible persons from Production, QC and QA should formally approve the cleaning
validation protocol.
Validation Procedure:
After completion of the manufacturing process, workman will clean the equipment.
If the cleaned equipment is listed in the protocol, production person will inform QC Department
to collect samples for testing and QA department for supervision.
QA/QC chemist will first check visually for cleanliness of equipment.
If it observed not clean, instruct for re-cleaning.
If it observed visually cleaned, collect samples separately for both chemical and microbial
analysis (if required) from locations given in the protocol as per sampling procedure.
Samples are carried to QC, where testing of the samples will be done using validated Analytical
method.
Validation Report:
If the results of validation of any of the three studies are non-conforming to set limits of
acceptance criteria, QC should inform immediately to QA.
Re-validation Policy:
Micro-organisms
This is particularly the case where microbial growth may be sustained by the product.
o
Manual cleaning
COP (clean-out-of-place)
Semi automatic
Automatic
Time considerations
OBJECTIVE :
To establish a procedure for swab sampling for validation of test surface to evaluate cleaning efficacy.
2.0
RESPONSIBILITY:
Quality Control Chemist / Quality Assurance Chemist.
3.0
ACCOUNTABILITY:
Quality Control Manager / Quality Assurance Manager
4.0
PROCEDURE
FOR CHEMICAL EVALUATION:
4.1
SWAB
TRANSPORT
CONTAINER
for
SAMPLING
SOLVENT
4.2
4.2.1
4.2.2
Remove a swab from its protective bag using a clean latex hand glove.
4.2.3
4.2.4
Transfer the swab in transport container (test tube)containing 10ml of sampling solvent and allow the
swab to soak completely.
4.2.5
Take out the swab from sampling solvent and squeeze the tip against inner surface of test tube to
remove excess solvent in such a manner that excess sampling solvent drips inside the test tube.
4.2.6
Hold the stem of swab without touching the head of the swab.
4.2.7
Using one side of moistened swab wipe the test surface of 2 x 2 with 10 firm horizontal strokes as
illustrated in Fig. 1.
4.2.8
4.2.9
Turn the swab over to its other side, wipe the test surface of 2 x 2 with 10 firm vertical strokes as
illustrated in figure no.2.
At the end of each stroke, lift the swab carefully.
4.2.10
4.2.11
Hold the steam of the swab without touching the head of the swab and let the swab drop into
the
transport container. Cap the transport container and send for analysis after labeling the
same.
4.3
4.3.2.
Make the swab with (1) sampling point and (2) Date on outer cover.
4.3.3
Put on the clean latex hand gloves and disinfect the same with 70% IPA.
4.3.4
x
Take out the sterile swab carefully from the outer cover and swab the complete selected area (10
10cm).
4.3.5.
Replace the swab immediately inside the cover, close if and send for analysis.
4.4.
ABBREVIATIONS:
5.0
6.0.
TRAINING:
-Head Quality Control
Trainer
Trainees-Period -7.0.
One day
DISTRIBUTION:
Certified Copy No. 1 : Head of Department Quality Control
Original Copy
: Head QUALITY ASSURANCE.
8.0.
9.0.
ANNEXURES:
Nil.
REFERENCES
In-house.
PROCESS VALIDATION
prospective validation
concurrent validation
prospective validation
2)
cleaning validation
3)
change control
4)
Re- validation
Cleaning validation
equipment.
three consecutive successful production batches should be used as a guide, but there may be
situations where additional process runs are warranted to prove consistency of the process
For retrospective validation, generally data from 10 to 30 consecutive batches should be
examined to assess process consistency, but fewer batches can be examined if justified.
Critical process parameters should be controlled and monitored during process validation studies.
Process parameters unrelated to quality, such as variables controlled to minimize energy
consumption or equipment use, need not be included in the process validation.
Process validation should confirm that the impurity profile for each API is within the limits
specified. The impurity profile should be comparable to, or better than, historical data and, where
applicable, the profile determined during process development or for batches used for pivotal
clinical
and
toxicological
studies.
Approaches to validation
5.1.1 There are two basic approaches to validationone based on evidence obtained through
testing (prospective and concurrent validation), and one based on the analysis of accumulated
(historical) data (retrospective validation). Whenever possible, prospective validation is
preferred. Retrospective validation is no longer encouraged and is, in any case, not applicable to
the manufacturing of sterile products.
5.1.2 Both prospective and concurrent validation, may include:
extensive product testing, which may involve extensive sample testing (with the estimation of
confidence limits for individual results) and the demonstration of intra- and inter-batch
homogeneity;
simulation process trials;
challenge/worst case tests, which determine the robustness of the process; and
control of process parameters being monitored during normal production runs to obtain
additional information on the reliability of the process.
5.2 Scope of validation
5.2.1 There should be an appropriate and sufficient system including organizational structure and
documentation infrastructure, sufficient personnel and financial resources to perform validation
tasks in a timely manner. Management and persons responsible for quality assurance should be
involved.
5.2.2 Personnel with appropriate qualifications and experience should be responsible for
performing validation. They should represent different departments depending on the validation
work to be performed.
5.2.3 There should be proper preparation and planning before validation is performed. There
should be a specific programmed for validation activities.
5.2.4 Validation should be performed in a structured way according to the documented
procedures and protocols.
5.2.5 Validation should be performed:
for new premises, equipment, utilities and systems, and processes and procedures;
at periodic intervals; and
when major changes have been made. (Periodic revalidation or periodic requalification may
be substituted, where appropriate, with periodic evaluation of data and information to establish
whether requalification or revalidation is required.)
5.2.6 Validation should be performed in accordance with written protocols. A written report on
the outcome of the validation should be produced.
5.2.7 Validation should be done over a period of time, e.g. at least three consecutive batches (full
production scale) should be validated, to demonstrate consistency. Worst case situations should
be considered.
5.2.8 There should be a clear distinction between in-process controls and validation. In-process
tests are performed during the manufacture of each batch according to specifications and
methods devised during the development phase. Their objective is to monitor the process
continuously.
5.2.9 When a new manufacturing formula or method is adopted, steps should be taken to
demonstrate its suitability for routine processing. The defined process, using the materials and
equipment specified, should be shown to result in the consistent yield of a product of the
required quality.
5.2.10 Manufacturers should identify what validation work is needed to prove that critical
aspects of their operations are appropriately controlled. Significant changes to the facilities or the
equipment, and processes that may affect the quality of the product should be validated. A risk
assessment approach should be used to determine the scope and extent of validation required.
You might also like:
CYCLE
OF
ANALYTICAL
METHODS
The analytical method validation activity is not a one - time study. This is illustrated
and summarized in the life cycle of an analytical procedure in Figure 1 . An analytical
method will be developed and validated for use to analyze samples during the early
development of an active pharmaceutical ingredient (API) or drug product. As drug
development progresses from phase 1 to commercialization, the analytical method
will follow a similar progression. The fi nal method will be validated for its intended
use for the market image drug product and transferred to the quality control laboratory
for the launch of the drug product. However, if there are any changes in the
manufacturing process that have the potential to change the analytical profi le of the
drug substance and drug product, this validated method may need to be revalidated
to ensure that it is still suitable to analyze the API or drug product for its intended
purpose.
General Concepts
The discussion of the validation of analytical procedures is directed to the four most
common types of analytical procedure:
Identification tests
Quantitative tests of the active moiety in samples of drug substance or drug product or
other selected components in the drug product.
Accuracy
Precision
Specificity
Quantitation Limit
Robustness
Linearity: Mebendazole to be analyzed as per proposed method. The results obtain is used to
statistically evaluate for coefficient of determination (r 2), standard error of estimate and y
intercept.
Precision: Precision of the chemical method is ascertained by carrying out the analysis as per the
procedure and as per normal weight taken for analysis. Repeat the analysis five times.
Calculate the % assay, mean assay, % Deviation and % relative standard deviation and
%RSD.
Accuracy: Accuracy of the method is ascertained by standard addition method at 3 levels.
Standard quantity equivalent to 80%, 100% and 120% is to be added in sample.
Specificity: Resolution of the analyte peak from the nearest peak: Solution of each of the analyte
was injected separately and their retention time is noted. The standard working solution
containing a mixture of the component being analyze is also injected and each of
analyte peaks is check for its resolution from the nearest.
Precision:
Repeatability: Six replicate injections of standard solution for system precision should
analyze as per the proposed method and from the chromatograms obtained the
percentage % RSD is calculated.
Intermediate precision: The purpose of this test is to demonstrate the intermediate
precision of the method when method is executed by a different analyst and on different
day. Results obtained will be compared.
3.3
X
SD
Slope
LOQ
10
X SD
Slope
Standard solution quantity equivalent to 50%, 100% and 150% are added in sample.
The amount recover by the method is compared to the amount added. Percent
deviation is calculated at each levels and a grand average across all the levels are also
calculated.
Methanol standard concentration 3000 ppm
Acetic acid standard concentration 5000 ppm
DMF standard concentration
880 ppm
Robustness:
The evaluation of robustness should be considered during the development phase and
depends on the type of procedure under study. It should show the reliability of an
analysis with respect to deliberate variations in method parameters.
If measurements are susceptible to variation in analytical conditions, the analytical
condition should be suitably controlled or a precautionary statement should be included
in the procedure.
One consequence of the robustness should be that a series of system suitability
parameters (e.g. resolution test) is established to ensure that the validity of the
analytical procedure is maintained whenever used.
PROCESS
OF
ANALYTICAL
METHOD
VALIDATION
The typical process that is followed in an analytical method validation is
chronologically listed
below:
1.
Planning
and
deciding
on
the
method
validation
experiments
2.
Writing
and
approval
of
method
validation
protocol
3.
Execution
of
the
method
validation
protocol
4.
Analysis
of
the
method
validation
data
5.
Reporting
the
analytical
method
validation
6.
Finalizing
the
analytical
method
procedure
The method validation experiments should be well planned and laid out to ensure
effi cient use of time and resources during execution of the method validation. The best
way to ensure a well - planned validation study is to write a method validation protocol
that will be reviewed and signed by the appropriate person (e.g.,
laboratory management
and
quality
assurance).
The validation parameters that will be evaluated will depend on the type of
method to be validated. Analytical methods that are commonly validated can be
classifi ed into three main categories: identifi cation, testing for impurities, and
assay. Table 3 lists the ICH recommendations for each of these methods.
Execution of the method validation protocol should be carefully planned
to optimize the resources and time required to complete the full validation
study. For example, in the validation of an assay method, linearity and accuracy may be
validated at the same time as both experiments can use the same standard solutions.
A normal validation protocol should contain the following contents at a
minimum:
(a)
Objective
of
the
protocol
(b)
Validation
parameters
that
will
be
evaluated
(c)
Acceptance
criteria
for
all
the
validation
parameters
evaluated
(d)
Details
of
the
experiments
to
be
performed
(e)
Draft
analytical
procedure
The data from the method validation data should be analyzed as the data are
obtained and processed to ensure a smooth fl ow of information. If an
experimental error is detected, it should be resolved as soon as possible to reduce any
impact it may have on later experiments. Analysis of the data includes visual
examination of the numerical values of the data and chromatograms followed by
statistical treatment of the data if required.
Upon completion of all the experiments, all the data will be compiled into a
detailed validation report that will conclude the success or failure of the validation
exercise. Depending on the company s strategy a summary of the validation data may
also be generated. Successful execution of the validation will lead to a final analytical
procedure that can be used by the laboratory to support future analytical work for the
drug substance or drug product.
METHOD REVALIDATION
There are various circumstances under which a method needs to be revalidated.
Some of the common situations are described below:
1. During the optimization of the drug substance synthetic process, signifi cant
changes were introduced into the process. To ensure that the analytical method
will still be able to analyze the potentially different profi le of the API, revalidation
may be necessary.
2. If a new impurity is found that makes the method defi cient in its specifi city,
this method will need to be modifi ed or redeveloped and revalidated to ensure
that it will be able to perform its intended function.
3. A change in the excipient composition may change the product impurity
profi le. This change may make the method defi cient in its specifi city for the
assay or impurity tests and may require redevelopment and revalidation.
4. Changes in equipment or suppliers of critical supplies of the API or fi nal drug
product will have the potential to change their degradation profi le and may
require the method to be redeveloped and revalidated.
STABILITY STUDY PROTOCOL FOR ANALYTICAL METHOD VALIDATION
TABLE OF CONTENTS
Item No.
Item
Page No.
--
Table of content
1.0
Objective
2.0
Scope
3.0
Responsibility
4.0
4.1
4.1.1
Batches details
4.1.2
1.0
4.1.3
4.1.4
4.1.5
Results of tests
8-9
Conclusion
11
OBJECTIVE:
To perform long term stability study on production batches to evaluate and justify
the recommended shelf life. Storage conditions and desired packing.
2.0
SCOPE:
Long term stability studies: A minimum of one batch per year for long term
stability study and any batch where a process change is made which will affect the
stability and quality of the product.
3.0
RESPONSIBILITY:
Sr.
No.
Team
Member
Department
Designati
on
Responsibility
1.
2.
3.
4.0
Quality
Assurance
Manager
Quality
Control
Manager
Quality
Control
QC Officer
(QA)
(QC)
The recommended shelf life, storage conditions, and desired packaging should be
accompanied by the results of the testing.
Batches details:
Batch No.
Mfg. Date
Exp. Date
Batch Size
Sr. No.
Test
DESCRIPTION:
IDENTIFICATION (IR)
ASSAY
MELTING POINT
LOSS ON DRYING
CLARITY
RESIDUE ON IGNITION
Limits
All of the analytical methods used for carrying out the above mentioned tests are
the same as those described in European Pharmacopoeia Annexure-I.
Temperature:
25C 2 C
Relative
humidity:
60% 5%
Time interval:
0 Month (initial
month)
3 Months
6 Months
9 Months
12 Months
18 Months
24 Months
36 Months
48 Months
60 Months
The following Test methods were applied to verify product integrity during the
time period tested as per Specification.
DESCRIPTION
DENTIFICATION (IR)
LOSS ON DRYING
MELTING POINT :
CLARITY :
RESIDUE ON
ASSAY :
IGNITION:
Results of tests
All test results shall be recorded in attached Annexure-II:
Conclusion:
Annexure-II
Results of Long term testing at Temperature 25C 2 C & Relative
Humidity 60% 5%
Product name
Batch No
Manufacturing date
Pack
Batch size
Sr.
No.
Test
DESCRIPTION:
IDENTIFICATION (IR)
CHROMATOGRA-PHIC
PURITY
MELTING POINT
LOSS ON DRYING
CLARITY
RESIDUE ON IGNITION
Limit
s
12
Mont
h
Mont
h
Mont
h
Mont
h
Mont
h
Sr. No.
8.
Test
ASSAY
Limits
12
Month
Month
Month
Month
Month
Product name
Batch No
Manufacturing date
Pack
Batch size
Sr.
No.
Test
Limi
ts
18
24
36
48
60
DESCRIPTION:
IDENTIFICATION (IR)
CHROMATOGRA-PHIC
PURITY
MELTING POINT
LOSS ON DRYING
CLARITY
RESIDUE ON IGNITION
Test
Limits
Sr.
No.
8.
12
Month
Month
Month
Month
Month
ASSAY
Conclusion:
Download
LinkWithin
CYCLE
OF
ANALYTICAL
METHODS
The analytical method validation activity is not a one - time study. This is illustrated
and summarized in the life cycle of an analytical procedure in Figure 1 . An analytical
method will be developed and validated for use to analyze samples during the early
development of an active pharmaceutical ingredient (API) or drug product. As drug
development progresses from phase 1 to commercialization, the analytical method
will follow a similar progression. The fi nal method will be validated for its intended
use for the market image drug product and transferred to the quality control laboratory
for the launch of the drug product. However, if there are any changes in the
manufacturing process that have the potential to change the analytical profi le of the
drug substance and drug product, this validated method may need to be revalidated
to ensure that it is still suitable to analyze the API or drug product for its intended
purpose.
General Concepts
Validation is the act of demonstrating and documenting a procedure that operates effectively.
The discussion of the validation of analytical procedures is directed to the four most common
types of analytical procedure:
Identification tests
Quantitative tests of the active moiety in samples of drug substance or drug product or other
selected components in the drug product.
Accuracy
Precision
Specificity
Quantitation Limit
Robustness
Linearity: Mebendazole to be analyzed as per proposed method. The results obtain is used to statistically
evaluate for coefficient of determination (r2), standard error of estimate and y intercept.
Precision: Precision of the chemical method is ascertained by carrying out the analysis as per the
procedure and as per normal weight taken for analysis. Repeat the analysis five times.
Calculate the % assay, mean assay, % Deviation and % relative standard deviation and %RSD.
Accuracy: Accuracy of the method is ascertained by standard addition method at 3 levels. Standard
quantity equivalent to 80%, 100% and 120% is to be added in sample.
Specificity: Resolution of the analyte peak from the nearest peak: Solution of each of the analyte was
injected separately and their retention time is noted. The standard working solution containing a
mixture of the component being analyze is also injected and each of analyte peaks is check for
its resolution from the nearest.
Precision:
Repeatability: Six replicate injections of standard solution for system precision should analyze
as per the proposed method and from the chromatograms obtained the percentage % RSD is
calculated.
Intermediate precision: The purpose of this test is to demonstrate the intermediate precision
of the method when method is executed by a different analyst and on different day. Results
obtained will be compared.
Linearity and Range: Solution of analyte solvent, having different concentration should make
separate from L.O.Q. concentration, which is 50% to 150%. The result obtained is statistically
evaluated for coefficient of determination (r2), standard error of estimate and y intercept.
LOD
3.3
SD
Slope
LOQ
10
SD
Slope
Accuracy / % Recovery (By Standard Addition Method): Accuracy of the method was
ascertained by standard addition method at 3 levels.
Standard solution quantity equivalent to 50%, 100% and 150% are added in sample.
The solutions amount is analyzed by the proposed method and chromatogram obtained.
The amount recover by the method is compared to the amount added. Percent deviation is
calculated at each levels and a grand average across all the levels are also calculated.
Methanol standard concentration 3000 ppm
Acetic acid standard concentration 5000 ppm
DMF standard concentration
880 ppm
Robustness:
The evaluation of robustness should be considered during the development phase and
depends on the type of procedure under study. It should show the reliability of an analysis with
respect to deliberate variations in method parameters.
One consequence of the robustness should be that a series of system suitability parameters
(e.g. resolution test) is established to ensure that the validity of the analytical procedure is
maintained whenever used.
PROCESS
OF
ANALYTICAL
METHOD
VALIDATION
The typical process that is followed in an analytical method validation is chronologically listed
below:
1.
Planning
and
deciding
on
the
method
validation
experiments
2.
Writing
and
approval
of
method
validation
protocol
3.
Execution
of
the
method
validation
protocol
4.
Analysis
of
the
method
validation
data
5.
Reporting
the
analytical
method
validation
6.
Finalizing
the
analytical
method
procedure
The method validation experiments should be well planned and laid out to ensure
effi cient use of time and resources during execution of the method validation. The best way to
ensure a well - planned validation study is to write a method validation protocol that will be
reviewed and signed by the appropriate person (e.g., laboratory management and quality
assurance).
The validation parameters that will be evaluated will depend on the type of
method to be validated. Analytical methods that are commonly validated can be
classifi ed into three main categories: identifi cation, testing for impurities, and assay. Table 3
lists
the
ICH
recommendations
for
each
of
these
methods.
Execution of
the method validation protocol should be carefully planned
to optimize the resources and time required to complete the full validation
study. For example, in the validation of an assay method, linearity and accuracy may be
validated at the same time as both experiments can use the same standard solutions.
A normal validation protocol should contain the following contents at a
minimum:
(a)
Objective
of
the
protocol
(b)
Validation
parameters
that
will
be
evaluated
(c)
Acceptance
criteria
for
all
the
validation
parameters
evaluated
(d)
Details
of
the
experiments
to
be
performed
(e)
Draft
analytical
procedure
The data from the method validation data should be analyzed as the data are
obtained and processed to ensure a smooth fl ow of information. If an experimental error is
detected, it should be resolved as soon as possible to reduce any impact it may have on later
experiments. Analysis of the data includes visual examination of the numerical values of the
data and chromatograms followed by statistical treatment of the data if required.
Upon completion of all the experiments, all the data will be compiled into a
detailed validation report that will conclude the success or failure of the validation
exercise. Depending on the company s strategy a summary of the validation data may also be
generated. Successful execution of the validation will lead to a final analytical procedure that
can be used by the laboratory to support future analytical work for the drug substance or drug
product.
METHOD REVALIDATION
There are various circumstances under which a method needs to be revalidated.
Some of the common situations are described below:
1. During the optimization of the drug substance synthetic process, signifi cant
changes were introduced into the process. To ensure that the analytical method
will still be able to analyze the potentially different profi le of the API, revalidation
may be necessary.
2. If a new impurity is found that makes the method defi cient in its specifi city,
this method will need to be modifi ed or redeveloped and revalidated to ensure
PROCESS VALIDATION
prospective validation
concurrent validation
prospective validation
2)
cleaning validation
3)
change control
4)
Re- validation
Cleaning validation
Documented evidence to establish that cleaning procedures are removing residues to
predetermined levels of acceptability, taking into consideration factors such as batch size, dosing,
and toxicology and equipment size.
Validation
Action of proving and documenting that any process, procedure or method actually and
consistently leads to the expected results.
Process validation
Documented evidence which provides a high degree of assurance that a specific process will
consistently result in a product that meets its predetermined specifications and quality
characteristics
Concurrent validation
Validation carried out during routine production of products intended for sale.
Prospective validation
Validation carried out during the development stage on the basis of a risk analysis of the
production process, which is broken down into individual steps; these are then evaluated on the
basis of past experience to determine whether they may lead to critical situations.
Retrospective validation
Involves the evaluation of past experience of production on the condition that composition,
procedures, and equipment remain unchanged.
- The sources of data for this validation may include batch documents, process control chart,
maintaince logbook, records of personnel change process capability studies, fp data and stability
results.
Validation report (VR)
A document in which the records, results and evaluation of a completed validation programme
are assembled and summarized. It may also contain proposals for the improvement of processes
and/or
equipment.
and
toxicological
studies.
Approaches to validation
5.1.1 There are two basic approaches to validationone based on evidence obtained through
testing (prospective and concurrent validation), and one based on the analysis of accumulated
(historical) data (retrospective validation). Whenever possible, prospective validation is
preferred. Retrospective validation is no longer encouraged and is, in any case, not applicable to
the manufacturing of sterile products.
5.1.2 Both prospective and concurrent validation, may include:
extensive product testing, which may involve extensive sample testing (with the estimation of
confidence limits for individual results) and the demonstration of intra- and inter-batch
homogeneity;
simulation process trials;
challenge/worst case tests, which determine the robustness of the process; and
control of process parameters being monitored during normal production runs to obtain
additional information on the reliability of the process.
5.2 Scope of validation
5.2.1 There should be an appropriate and sufficient system including organizational structure and
documentation infrastructure, sufficient personnel and financial resources to perform validation
tasks in a timely manner. Management and persons responsible for quality assurance should be
involved.
5.2.2 Personnel with appropriate qualifications and experience should be responsible for
performing validation. They should represent different departments depending on the validation
work to be performed.
5.2.3 There should be proper preparation and planning before validation is performed. There
should be a specific programmed for validation activities.
5.2.4 Validation should be performed in a structured way according to the documented
procedures and protocols.
5.2.5 Validation should be performed:
for new premises, equipment, utilities and systems, and processes and procedures;
at periodic intervals; and
when major changes have been made. (Periodic revalidation or periodic requalification may
be substituted, where appropriate, with periodic evaluation of data and information to establish
whether requalification or revalidation is required.)
5.2.6 Validation should be performed in accordance with written protocols. A written report on
the outcome of the validation should be produced.
5.2.7 Validation should be done over a period of time, e.g. at least three consecutive batches (full
production scale) should be validated, to demonstrate consistency. Worst case situations should
be considered.
5.2.8 There should be a clear distinction between in-process controls and validation. In-process
tests are performed during the manufacture of each batch according to specifications and
methods devised during the development phase. Their objective is to monitor the process
continuously.
5.2.9 When a new manufacturing formula or method is adopted, steps should be taken to
demonstrate its suitability for routine processing. The defined process, using the materials and
equipment specified, should be shown to result in the consistent yield of a product of the
required quality.
5.2.10 Manufacturers should identify what validation work is needed to prove that critical
aspects of their operations are appropriately controlled. Significant changes to the facilities or the
equipment, and processes that may affect the quality of the product should be validated. A risk
assessment approach should be used to determine the scope and extent of validation required.
You might also like:
Validation of QC Chemist
VALIDATION OF INCUBATORS
General concept
Three consecutive validations will be performed to prove that the method is validated.
Whenever a new product is introduced, equipment usage and nature of potential contaminant
will be studied to assess whether it poses a challenging study for cleaning validation.
If the new product represents worst case, study/ identify/develop method of cleaning to be
employed. Simultaneously develop Analytical method for cleaning and validate the same.
Revalidation Policy.
Level of cleaning:
Stages of manufacturing
Cleaning Procedure
o
Identification of equipment
Characterization of products
Cleaning Procedure:
Identification of Equipments:
Identify equipments to be cleaned.
Identify difficult to clean areas
Check for ease of dismantling
Characterization of products:
Study activity/toxicity, solubility of the active substance of current batch and dosage and batch
size of next product to be taken on the equipment.
o
Based on above, prepare detailed written cleaning procedures for each equipment.
In order for the analytical testing of the cleaning validation samples to yield meaningful results,
the analytical methods used should be validated.
Analytical method validation for cleaning should include limit of detection, limit of
quantification, acceptance criteria and rationale for setting the specified limits.
Sampling Procedure:
Sampling Locations:
o
Two easy to clean and two hard to clean areas should be clearly defined in Protocol.
Sampling Procedure:
o
Swab samples should be taken separately for chemical and microbiological studies
For each of chemical and microbiological analysis take 2 swabs from easy to clean hard to clean
locations
How the samples are to be taken
Sample Numbering:
o
Swab samples should be numbered numerically and sequentially like 01, 02 etc for
identification.
Based on the data available calculate acceptance criteria for both Pharmacological dose method
and limiting the level of product to 10 ppm which appear in the following product.
Of these two, choose the criterion with stringent limits and detectable by analytical
method.
Validation Protocol
Quality Control Developing analytical method for cleaning, sampling, testing & recording the
results.
Responsible persons from Production, QC and QA should formally approve the cleaning
validation protocol.
Validation Procedure:
After completion of the manufacturing process, workman will clean the equipment.
If the cleaned equipment is listed in the protocol, production person will inform QC Department
to collect samples for testing and QA department for supervision.
QA/QC chemist will first check visually for cleanliness of equipment.
If it observed not clean, instruct for re-cleaning.
If it observed visually cleaned, collect samples separately for both chemical and microbial
analysis (if required) from locations given in the protocol as per sampling procedure.
Samples are carried to QC, where testing of the samples will be done using validated Analytical
method.
Validation Report:
If the results of validation of any of the three studies are non-conforming to set limits of
acceptance criteria, QC should inform immediately to QA.
Re-validation Policy:
Micro-organisms
This is particularly the case where microbial growth may be sustained by the product.
o
Manual cleaning
COP (clean-out-of-place)
Semi automatic
Automatic
Time considerations
Validation of QC Chemist
VALIDATION OF INCUBATORS
LinkWithin
GENERAL:
1.1
Building Maintenance
2.
1.2
Reception
1.3
Administrative Block/O
1.4
Utility Block
1.5
Maintenance
1.6
Surroundings
PERSONNEL:
2.1
Or
2.2
Qu
2.3
Pro
Me
Fo
Fo
2.4
Pe
Fo
Fo
2.5
Fa
Fo
Fo
Wa
2.6
Pe
Sh
WC
Lo
Ca
3
.
2.7
Jo
Re
2.8
Tra
2.9
En
2.10
2.11
:
:
Dr
Sy
2.12
Pe
a)
: Raw Material
____________
b)
: Packing Material
____________
c)
: Intermediate
____________
d)
: Finished Goods
____________
e)
: Cleaning / Schedule
____________
f)
g)
3.2
3.3
3.4
____________
3.5
3.6
3.7
3.8
3.9
3.10
3.11
3.12
3.13
3.14
Lighting level
3.15
3.16
3.17
3.18 : EQUIPMENT
a)
b)
c)
d)
e)
f)
g)
h)
k)
l)
m)
n)
4
.
MANUFACTURING CONTROL:
4.1
5.
4.2
4.3
4.4
Means of Communication
4.5
4.6
TSE QUESTIONNAIRE:
5.1
5.2
5.3
: Have you obtained the COS Certificate from EDQM for the
Material you are supplying to us? If yes please attach the copy.
: Is any of the starting material used in the manufacturing from
Animal Origin. If yes, Please ensure to obtain the TSE free Certificate
from your supplier.
: Is the Production Line dedicated?
5.4 : If NO Please Specify:a) Are the equipments shared with any other product, which uses
original starting material?
b) Do you have sufficient Cleaning Procedure?
b) Is cleaning procedure validated?
5.5
the animal
: Is your batch COA contains the TSE / BSE free Declaration. If no submit an
undertaking to send the batch wise TSE / BSE free Declaration for all
supplies to us?
6. RECORD KEEPING :
7.
6.1
________________
6.2
: Equipment Log
________________
6.3
: Process Record
________________
6.4
: In-Process Results
________________
7.1
__________________
7.2
__________________
7.3
8.
__________________
QUALITY CONROL:
8.1: Raw Material Specification / Test Procedure & its control_______
8.2: Calibration Record
______
_______
_______
FILING SYSTEM:
10.1
11.
Retrievable
______________
12.
CORRECTIVE ACTIONS:
13.
PREVENTIVE ACTIONS:
14.
CLOSURE OF AUDIT:
CONCLUSION
VALIDATION OF INCUBATORS
1.0
OBJECTIVE
To lay down a procedure for validation of incubator in microbiology
laboratory.
2.0
RESPONSIILTY
Microbiologist / Executive.
3.0
ACCOUNTABILITY
Quality Assurance Control
4.0
PROCEDURE
4.1
4.1.2
Type
4.1.3
The incubator is set for desired temperature with the knob on control panel of
incubator
e.g 32.5 0C, 35 0C & 22.5 0C.
`
4.1.4
Wait till the temperature reaches at set point & note down the temp. displayed on
the small screen of incubator and compare this temp. with standard thermometer
kept near the RTD probe.Likewise check the temperature after every 15 minutes up
to one hour and note down the readings on the format.
4.1.5
Record any difference between the displayed temp. & temp. showed by standard
thermometer and set the incubator accordingly
4.1.6
Keep all the apparatus wrapped thrice with aluminum foil inside DHS
as locations shown
in the diagram.
4.2.2
Keep the Spore loaded strips (having spore of B subilis) & Endotoxin
indicator indicators
having 10,000EU/vial in DHS(hot air oven) kept in 30ml vial wrapped thrice with
aluminum foil at locations shown in the diagram keep one vial unbaked as PPC.
Set the hot air oven at 250C ,wait till the temperature reaches upto the set
temperature.
4.2.3
After reaching the set temperature, note the time & temperature, hold for one hour
4.2.4
Take out the baked endotoxin loaded vial from the DHS.
4.3.2
sample to the
depyrogenated reaction tube kept in heating block at 37 0 C and add 100l of
LAL in the
same tube in duplicate.
4.4.
4.3.3
4.3.4
subtilis):
4.4.1
Transfer (spore loaded) strip from backed vials and are inoculated in100ml
sterile SCD
media and incubate at 30 350C for 7 days to observe for any turbidity, if any,
report to Manager QC..
5.0
Harmonization of format.
6.0
TRAINING:
Trainer -
Trainees-Period -7.0
One day
DISTRIBUTION:
ANNEXURES:
REFERENCES:
ANNEXURE-1
INSTRUMENT VALIDATION
.
Microbiology
NAME OF
Incubat
LOCATION
laboratory
INSTRUMENT
or
MANUFACTURED BY
MODEL No.
IDENTIFICATION No.
INSTALLED ON
SET TEMPERATURE =
TIME
TEMP. RECORDED
DISPLAYED
MINIMU
MAXIMU
DEVIATI
TEMP.
ON
CHAMBER
1
6
C
INITIAL
TEMP
C
C
AFTER 15
MIN
C
C
C
C
C
C
LIMIT:-
AFTER 60
MIN
AFTER 45
MIN
AFTER 30
MIN
2% of Set Temperature
CHECKED BY:
DATE:
MANAGER /QC
Item No.
Item
Page No.
--
Table of content
1.0
Objective
2.0
Scope
3.0
Responsibility
4.0
4.1
4.1.1
Batches details
4.1.2
4.1.3
4.1.4
4.1.5
Results of tests
8-9
Conclusion
1.0
11
OBJECTIVE:
To perform long term stability study on production batches to evaluate and justify
the recommended shelf life. Storage conditions and desired packing.
2.0
SCOPE:
Long term stability studies: A minimum of one batch per year for long term
stability study and any batch where a process change is made which will affect the
stability and quality of the product.
3.0
RESPONSIBILITY:
Sr.
No.
1.
2.
Team
Member
Department
Designati
on
Quality
Assurance
Manager
Quality
Control
Manager
(QA)
(QC)
Responsibility
Issue and review of Stability
protocol
Implementation and supervision
of Stability protocol
3.
4.0
Quality
Control
QC Officer
The recommended shelf life, storage conditions, and desired packaging should be
accompanied by the results of the testing.
Batches details:
Batch No.
Mfg. Date
Exp. Date
Batch Size
Sr. No.
Test
DESCRIPTION:
IDENTIFICATION (IR)
ASSAY
MELTING POINT
LOSS ON DRYING
CLARITY
RESIDUE ON IGNITION
All of the analytical methods used for carrying out the above mentioned tests are
the same as those described in European Pharmacopoeia Annexure-I.
Limits
Temperature:
25C 2 C
Relative
humidity:
60% 5%
Time interval:
0 Month (initial
month)
3 Months
6 Months
9 Months
12 Months
18 Months
24 Months
36 Months
48 Months
60 Months
The following Test methods were applied to verify product integrity during the
time period tested as per Specification.
DESCRIPTION
DENTIFICATION (IR)
LOSS ON DRYING
MELTING POINT :
CLARITY :
RESIDUE ON
ASSAY :
IGNITION:
Results of tests
All test results shall be recorded in attached Annexure-II:
Conclusion:
Annexure-II
Results of Long term testing at Temperature 25C 2 C & Relative
Humidity 60% 5%
Sr.
No.
Product name
Batch No
Manufacturing date
Pack
Batch size
Test
DESCRIPTION:
Limit
s
12
Mont
h
Mont
h
Mont
h
Mont
h
Mont
h
IDENTIFICATION (IR)
CHROMATOGRA-PHIC
PURITY
MELTING POINT
LOSS ON DRYING
CLARITY
RESIDUE ON IGNITION
Sr. No.
8.
Test
ASSAY
Limits
12
Month
Month
Month
Month
Month
Product name
Batch No
Manufacturing date
Pack
Batch size
Sr.
No.
Test
Limi
ts
18
24
36
48
60
DESCRIPTION:
IDENTIFICATION (IR)
CHROMATOGRA-PHIC
PURITY
MELTING POINT
LOSS ON DRYING
CLARITY
RESIDUE ON IGNITION
Test
Limits
Sr.
No.
8.
12
Month
Month
Month
Month
Month
ASSAY
Conclusion:
Scope
3.0
Scope
department.
4.0 Responsibility :
Secondary :
5.0 Procedure
Overall: QC Incharge
Opening Procedure.
Check the lock of main door of the department. It should be locked, if the door is not
locked inform to Security department.
Open the lock of Main door.
Check for obnoxious smell or odour and ensure the absence of odour or smell.
Switch ON the departmental lights.
Before switching ON the precise testing equipment ensure that the voltage stabilizer
through which power supply is made to such equipment is under operation.
Closing Procedure.
All the instruments except automatic instrument on which program is going on are
switched OFF.
Purpose
2.0
Objective
4.0
Responsibility
5.0
Primary
Procedure
:
: QC Chemist / QC Officer
After sampling of raw materials / finished products, keep used tools in poly bag.
If required use suitable solvent for the cleaning of tools, then thoroughly wash with water.
s:
Standardization and storage of Reference and Working standards
Purpose : To provide instructions for selection, standardization and storage of reference and working
standards.
Objective: To provide documented procedures for selection, standardization and storage of reference and
cope :
working standard
This procedure is applicable for selection, standardization and storage of reference and working
standards in QC Department.
4.0
Responsibility :
Primary
: QC Chemist
Procedure
Store them in suitable container (e.g. desiccators) moisture free atmosphere under
temperature-controlled condition.
Working standards are selected from amongst the raw materials received and approved by the
QC.
The selected raw materials working standards having high purity or negligible impurities and
low moisture content.
For solvent working standard shall be used from any reputed external manufacturer, pure
grade materials with certificate of analysis.
Selected raw material working standard shall be re-tested and note down the observations in
respective worksheet.
These working standard having high purity or negligible impurities and low moisture / loss on
drying content.
R&D and QA should authorize procedures for the preparation of intermediate and finished
products working standard.
Working standards should be standardized at regular intervals against the reference standards
or previous working standards.
Loss On Drying / Moisture content and Assay tests parameters taken for standardization.
Note down the observations in respective worksheet. And maintained relevant graphs in
respective working standard file.
Bottle of working standards should be stored in a desiccators having activated silica gel, and
kept at controlled temperature.
Information on status label includes name of material, working standard batch number, purity,
LOD / moisture content, date of preparation, valid up to etc.
(Approx 2 to 10 gm each) and filled appropriate vials / bottles (minimum 2 to 4). Vials should
be cleaned and dried.
Each vial/bottle is to be used for three months from the date of opening and then discarded.
Open on date shall be mentioned on the label.
The other information of the label includes name of material, open on date, purity, LOD/Water
value, and use before date and valid up to.
The bottles are then sealed and kept in desiccators at the prescribed storage condition for the
future use.
The last bottle is kept for use as a reference std. during next standardization. Reference
standard to be re-validated every year.
You might also like:
Reaction
s:
Preparation, Standardization and Shelf-life of Volumetric solutions, Standard reagent
solution and Indicators
Purpose
: To provide instructions for the Preparation, Standardization and Shelf-life of Volumetric solutions,
Standard reagent solution and Indicators.
Objective : To provide documented procedures for Preparation, Standardization and Shelf life of Volumetric
solutions, Standard reagent solution and Indicators
cope
volumetric
Responsibility :
Primary
: QC Chemist
Procedure
Volumetric Solutions
Volumetric solutions shall be prepared by accurately weighing a specified quantity & dissolving
it to produce a specific volume.
Volumetric solutions shall be standardized before use; shelf life of this solution is one month
from the date of preparation. Discard the solution after one month or if observed hazy.
Note: Strength of the volumetric solutions should not deviate more than 10% of the prescribed
strength.
All volumetric solutions should be standardized in triplicate set & % RSD should not be more
than 0.20 %. Average value shall be reported.
All the bottles should be labeled indicating the name, strength of the solution, date of
preparation, signature of the person who prepared it, use before date, standardization due on,
date of standardization.
Records shall be maintained for each solution starting with the value determined when the
solution was prepared & continuing with the values determined throughout the shelf life of the
solutions in respective register.
This record shall be retained for at least 1 year after the solution has expired.
Solutions of limited stability should be prepared on the day of use & discarded on completion
of analysis.
Standard Reagent solutions shall be prepared by accurately weighing a specified quantity &
dissolving to produce a specific volume.
All the bottles should be labeled indicating the name, strength of the standard reagent solution,
date of preparation, signature of the person who prepared it, use before date.
Shelf life of these standard reagent solutions is Three months from the date of preparation.
Discard the solution after three months or if observed hazy.
This record shall be retained for at least 1 year after the solution has expired.
Indicators:
Objective: To provide a documented procedure for raw material sample quantity for testing.
3.0 Scope : This procedure for raw material sample method for testing in QC Department.
4.0 Responsibility :
Primary
: QC Chemist
5.0 Procedure
On receiving the requisition of the raw material from the store. The QC Chemist will draw the
sample from store with proper safety. If sample is in tanker from outside factory gate.
SS sample tube.
If the sample is in liquid form then sample will be taken by glass sample tube.
If the sample is in tanker the chemist will take the sample from the each compartment of the
tanker of the bottom. And top of the each compartment with the help of glass sample tube.
If the sample is in solid form (like crystal or powder) then 50.0 Gms of the sample to be
withdraw.
If the sample is in liquid form then 250.0ml of the sample to be withdraw.
Sample to be taken from each batch or lot as per the package label. If the package are less
than 10. The sample should be drawn from each & every package is more than 10. Then
sample should be taken as per this rule n + 1.
We after drawing the sample chemist will put the label of UNDER TESTING on the package or
drums from where sample has been taken.
Chemist will bring the sample to QC lab and test the sample as per SOP of testing method.
If the sample is approved as per SOP then sample will be approved QC Manager and test
report will be sent to store incharge and production incharge and chemist will put the approved
label on the package of the new material and remove the under test label.
If the sample is not passed as per SOP testing method. The QC Manager will reject the raw
material and sent the report to the store incharge and plant in- charge, after that QC Chemist
will put the REJECT label on the package or drum and remove the UNDERTESITNG label.
This document describes the conduct of the Management review of the quality system for GMP Conforma
Certification, including the conduct of an internal audit to assure the system meets the requirements of
Guidelines and is effectively implemented..
To Provide Documented Procedure for review of the quality system for GMP Conformance Certification, inclu
the conduct of an internal audit to assure the system meets the requirements.
To define role/responsibility of various functions responsible for Internal audit
4.0
o
Responsibility
Board of Internal Audit and Management Review Committee: Arranges for the internal audit and gather
information for the Management Review.
QA Management Committee: Provides all information as required by the Board of Internal Audit
Management Review Committee and is responsible for follow-up corrective and preventive actions.
o
5.0
The QA Management Committee, by consensus, selects three qualified individuals for the Board of Inte
Audit and Management Review Committee. Members to the Committee serve until they are replaced.
The Board of Internal Audit and Management Review Committee arranges for the half yearly internal aud
be conducted.
The date for the audit is established by mutual agreement between the Board of Internal Audit
Management Review Committee and the General Manager Production and Asst. Manager Production (AMP
The audit is conducted by any member of the board or Internal auditor qualified to participate on
Certification Board so long as the auditor is not a member of the QA Management Committee, is qualified
knowledgeable in certification, auditing.
During the audit, personnel responsible for the area audited are immediately notified of the outcome of
audit of their area.
During an audit, it is possible that a difference of opinion can arise as to the severity of an observation.
important not to spend too much time debating the merits of the observation. If it does not appear that
difference of opinion can be resolved, then the auditee should be informed that the audit report is subjec
review by the Board of Internal Audit and Management Review Committee and the QA Management
The draft report is issued to the Board of Internal Audit and Management Review Committee within
calendar days. The Committee members review and comment on the report and a final report is issued.
The QA Management committee drafts a response to the audit report that is finalized after review:
Findings, nonconformities, trends, and other opportunities for improvement are identified; investigate
determine the causes; and corrective/preventive actions are developed. These actions are implemented
soon as possible and recorded.
The response to the internal audit report is submitted to the Board of Internal Audit and Management Rev
Committee for their concurrence.
Upon agreement on the response to the internal audit, the Board of Internal Audit and Management Rev
Committee prepares a complete Certification Program Management Review Report that includes,
appropriate,:
Feedback from clients and interested parties related to the fulfillment of the Certification Process
The Board of Internal Audit and Management Review Committee submit their Certification Prog
Management Review Report to the QA Management Committee.
The Certification Program Management Review Report with the response to the internal audit is discusse
the next meeting of the full Board. The expected outputs of the review includes decisions and actions rela
to:
Resource needs.
Decisions and actions of the Board are documented in the Board Minutes and all open Corrective/Preven
Actions are reviewed and their status documented at all subsequent quarterly Board Meetings.
6.0
Abbreviations :
QA : Quality Assurance
Maintenance Department
Production Department
Quality Control Department
Store Department
Quality control should be carried out during all stages of manufacturing operation which is the primary
requirement of good manufacturing practices.
Emptyhard capsules
According to Japanese Pharmacopoeia, the test called purity uses five capsules which are tested
individually. Each is placed in a 100 ml conical flask and shaken vigorously after adding 50 ml of water
37C throughout the test. The capsule passes the test if it completely dissolves within 10 mins giving
odorless, neutral (or slightly acidic).
Weight variation
For hard capsules: Accurately weigh 10 capsules. By suitable means the contents of each capsule should
be removed. The weights of emptied shells should be recorded individually. The difference of both the
weights will yield the net weight of the contents. Then calculate acceptance value.
For soft capsules: pre weigh 10 capsules. Cut the capsules by suitable means (either scissors or any
open blade) remove the contents by washing with a suitable solvent and let the solvent evaporate by
placing them at room temperature for about 30 mins. Weigh the individual shells. Calculate the
acceptance value.
Content uniformity
Hard capsules containing 25 mg or more of the drug contents should meet content uniformity
requirements.
Assay 10 capsules individually and calculate the acceptance value.
The requirement is met if the acceptance value of 10 capsules is less than or equal to 15%. If acceptance
value is greater than 15% or is about 25 % then, test the next 20 units and calculate the acceptance
value. The 30 capsules if less than or equal to 15% and no individual unit is 1-25*0.01 nor more than
1+25*0.01.
Calculation of acceptance value:
(Reference value-mean of individual contents ) + acceptability constant * sample standard deviation
Disintegration:
The disintegration of capsules is different from those of tablets because the determination of end point is
difficult owing to the adhesive nature of shell. The shell pieces after disintegration may agglomerate
forming large mass of gelatin taking more time to dissolve and may adhere to the mesh thus, blocking the
holes.
According to USP, place one dosage unit in each of the tubes of the basket with water or any other
specified medium (depends on individual monograph) maintained at 37 + 2C. Attach a removable wire
cloth with a plain square weave of 1.8-2.2 mm of mesh aperture and a wire diameter of 0.60-0.655 mm to
the surface of upper rack of the basket assembly. Observe the capsules for a time limit (specified in
individual monograph), at the end of prescribed time, all of the capsules must have been disintegrated
excluding the fragments from the capsule shell. If 1 or 2 capsules fail, the test should be repeated on
additional of 12 capsules. Then, not fewer than 16 of the total 18 capsules tested should disintegrate
completely.
Dissolution
Place each of the capsules in the apparatus 1, excluding air bubbles from the surface of the capsule.
Operate immediately at specified rate within specified dissolution medium at 37 + 0.5C. Aliquots should
be withdrawn at specified time points mentioned in individual monograph.
The requirements are met if the quantity of active ingredients dissolved conforms the following:
1) At stage 1 (S1): When 6 capsules are tested, amount of each of the dissolved content should not be
less than +/- 5% of the mentioned in monograph.
2) At stage 2 (S2): when 6 capsules are tested, the average of 12 (both from step 1and 2) should be
equal to or greater than 15% and no capsule should be than 15%.
3) At stage 3 (S3): when 12 capsules are tested, the average of 24 capsules (all 1,2 and 3 steps) should
be equal to or greater than the amount mentioned in the monograph, not more than two units are less
than 15% and no unit s less than 25%.
NOTE: 15%, 25% represent Q1 and Q2 unless and otherwise mentioned in the monograph.
Quality is not the step that can be incorporated at last, it is mandatory and should be inbuilt into the
products to, make this happen, apart from all these mandatory tests certain other tests can be performed
like
Raw materials1
The gelatin of the capsule shells should be assayed for various physical properties like bloom strength 3,
viscosity and its loss (by atomic force microscopy).4 Chemical tests like purity, microbial properties, and
limits for heavy metals like arsenic, ash content should be determined.
The colorants should also be checked for purity, limits for heavy metals, color properties, dye content,
subsidiary dye content and color value.5
Machine output
The manufacturing machines output should be monitored continuously via the dimensional correctness
during each lot production.
The color of the capsules should be checked against a standard strip; in case of any changes the gelatin
solution should be adjusted by adding standardized dye solutions which can be ensured via thin layer
chromatography.
Moisture content
Moisture content can be monitored with the aid of data the drying kilns can be adjusted.
Loss on drying
Determination of loss on drying via the oven method consumes more time. To prevent this advanced
methods like infrared balances, humidity meter etc.
Sorting of defects
After electronic or manual inspection, they are sampled by quality control inspectors. The results should
meet the inspection plan, if not the capsules should be resorted or rejected depending upon frequency of
faults.
Printing inspection
Quality inspectors sample the lot and are inspected for quality of print. The results will again be compared
with the inspection plan and in case if it does not match then, either capsules should be resorted or
rejected depending upon number of faults present.
Final inspection
After the capsules are placed in final containers, samples are checked for various parameters like
dimensions, physical defects and color. These samples are also subjected to various microbial tests also.
OBJECTIVE : To lay down the procedure for operation and calibration of Disintegration test
apparatus
2.0
RESPONSIBILITY
Quality Control Chemist / Quality Assurance Officer.
3.0
ACCOUNTABILITY
Quality Control Manager
4.0
PROCEDURE
4.1
Clean the equipment with a clean dry cloth per day. Occasionally wet cloth dipped in dilute
soap solution may be used. Precaution has to be taken to clean the equipment immediately
with dry cloth to remove the moisture.
4.1.2
OPERATING INSTRUCTIONS
4.2.1 Ensure the apparatus is properly connected to the power supply.
4.2.2 When the power is switched ON the TIMER and TEMP. shows digital value.
4.2.3 Set the temperature 37C by using SET, TEMP. , D , , DISP.SEL and ENTER
keys.
4.2.4 Set the timer 15.00 by using SET, TIME. , D , , DISP.SEL and ENTER keys.
4.2.5 Start the temperature by push the ENTER key.
4.2.6 Fill the beaker of DT apparatus with Purified water and adjust the temperature
between 37 1 OC
4.2.7 Fix the beaker in its position and adjust the level of water so that when the basket
is in upper most position, wire mesh of the basket is 25 mm below the water level, and when it is
at lower most position the wire mesh is at least 25 mm above the bottom of the beaker.
4.2.8 Once the set temperature is attain 37 1 OC.
4.2.9 In case of dispersible tablets, water temperature should be maintained within 15
to 25 OC.
4.2.10 Place on tablet / capsule in each of the tube and insert a disc in each of the tube.
4.2.11 Start the apparatus and Note the time taken by the last tablet / capsule for
complete disintegration.
4.2.12 Switch OFF the apparatus and power supply after the test is over, clean the
basket, discs and beaker.
4.3
CALIBRATION PROCEDURE
4.3.1 Follow steps 4.2.1 to 4.2.7
Note the temperature of water in the beaker and Oscillation per minute of the basket-rack
assembly.
4.3.5
Switch OFF the apparatus and record the observations in the calibration record as per
annexure 1.
4.3.6 Report and discrepancy observed during calibration or operation of the instrument to Quality
Assurance Manager and notify the defect to Service Engineer to rectify the defect. Affix Under
Maintenance label on the instrument.
4.4
ACCEPTANCE CRITERIA
FREQUENCY OF CALIBRATION
ABBREVIATIONS :
QA = Quality Assurance
DT = Disintegration test
5.0
Harmonization of format.
6.0
TRAINING:
Trainer --
Trainees-Period
7.0
One day
DISTRIBUTION:
Original Copy
ANNEXURE I
Effective from:
Name of Instrument
Instrument Ser.
Page No. : 1 of 1
No.
Make & Model
Calibration date
Calibration due on
Sr.No.
PARAMETER
OBSERVATIONS
LIMIT
29- 32 cycles /
min.
Basket 1
5
37 1 OC
Basket 2
7
53-57 mm
LinkWithin
OBJECTIVE : To lay down the procedure for operation and calibration of friability test
apparatus
2.0
RESPONSIBILITY
Quality Control Chemist / QA Chemist
3.0
ACCOUNTABILITY
Quality Control Manager / QA Manager.
4.0
PROCEDURE
4.1
GENERAL CLEANING
4.1.1 Clean the apparatus free of dust with dry cloth from out side every day.
4.1.2 Clean the rotating disc and unloading pan from inside with dry cloth at the start and end of every
operation. Wet cloth may be used occasionally if cleaning is not proper with dry cloth but this
should follow drying of the inner surface by first wiping with dry cloth and exposure to
atmosphere air.
4.2
OPERATING INSTRUCTIONS
After the completion of set rotations, the apparatus will automatically unload the tablets into the
tray. Observe the tablets.
4.2.9 Dedust the tablets, weigh and record the weight {W2}.
Calculate the percentage Friability by the following formula;
Initial Wt. of Tablets (W1) Wt. of tablets After 100 rotation (W2)
X 100
CALIBRATION PROCEDURE
4.3.1
4.3.2
Set the RPM to 25 and start the machine simultaneously with the stop watch. Count the actual
rotations and not the time required for the same.
4.3.3
Similarly set the RPM to 100 and note the time required and actual rotations.
4.3.4
4.3.7
4.3.5
4.3.6
In case of any discrepancy, report the observations to QC manager / QA Manager and notify
the defect to Engg. Department. Affix an UNDER MAINTENANCE label on the instrument.
4.4.
FREQUENCY
Once in a month and after each maintenance job.
.0
Harmonization of format.
6.0
TRAINING:
Trainer --
Trainees-Period
7.0
One day
DISTRIBUTION:
Original Copy
ANNEXURE 1
Revision No.: 00
Effective from:
Page No. : 1 of 1
Name of Instrument
Instrument Ser. No.
: Electrolab.
Calibration date
Calibration due on
:
:
SET
ROTATION
Sr.
ROTATION
ROTATIONS
DISPLAYED
No.
OBSERVED
MA
NUALLY
TIM
E
ACCEPTANCE
CRITERIA
25
1 min 05
sec
1.
100
2
4 min
20 sec
Reaction
s:
Calibration of serological water bath
BJECTIVE: To lay down the procedure for operation and calibration of serological water bath.
2.0
RESPONSIBILITY:
Q.C. Chemist
3.0
ACCOUNTABILITY:
Head - Q.C.
4.0
PROCEDURE:
4.1.
PRECAUTIONS
4.1.1 Ensure that the Water Bath is cleaned every week .
4.1.2 Ensure that water bath is never operated without DM water, otherwise heater will
be damaged.
4.1.3 Check that water does not fall on the thermostat knob ( bellow the tray ).
4.1.4 Ensure that the mercury bulb of the thermometer is always dipped in water.
4.2
WORKING PROCEDURE
4.2.1 Maintain the DM water level in the water bath & switch 'ON' the main switch of the
Water Bath.
4.2.2 Set the thermostat knob to the desired temperature setting on the knob ( 0 100
settings ).
4.2.3
If desired temperature is not achieved, then fine tune the thermostat knob as per
requirement.
4.2.4
CLEANING OPERATION
4.3.2 Scrap the side and bottom of Water Bath with help of Nylon gauze.
4.3.3. Wash with soap solution and rinse thoroughly it with DM water.
4.3.4
CALIBRATION
4.4.1
Once in a week
Set the temperature of serological water bath at 45C and switch on the
instrument.
4.4.2 Wait till temperature gets stabilized .
4.4.3
temperature.
4.4.4 After one hour again note the temperature.
4.4.5 Follow the similar procedure by setting the temperature to 100C.
4.4.6 Record the observations in the calibration format as mentioned in annexure I
Acceptance Criteria: The temperature should be within 2 C of the set
4.4.7
temperature.
4.4.8 Affix calibration tag , if calibration is satisfactory & under maintenance if found
unsatisfactory.
4.5
ABBREVIATION
C
5.0
- Degree centigrade
Harmonization of format.
6.0
TRAINING:
Trainer --
Trainees-Period -7.0
One day
DISTRIBUTION:
Original Copy
Revision No.: 00
Page No. : 1 of 1
Effective from:
Manufactured By
Medica Instrument/
Identification No.
Date Of Calibration
Name Of Instrument
Set
Initial
Temperature
Temperature
Temperature
after 1 Hr. ( C )
( C )
Limits
Remarks
( C )
45
43 47 C
100
98 102 C
1.0
OBJECTIVE:
To lay down a procedure for sampling of packing materials so as to get the representative sample
of the whole lot.
2.0
RESPONSIBILITY
2.1
2.1.1. Responsible for receiving the GRN and entering the details in Packaging Material
register.
2.1.2. Responsible for the ensuring appropriate cleanliness of sampling area and
integrity of consignment.
2.1.3. Responsible for ensuring proper documentation for sampling and assembling of
adequate number of samples for analysis purpose.
2.1.4. Responsible for proper sampling of PM as per Military Standard 105 D from the
pack (s) and its appropriate identification on each sampled container (s).
2.1.5. Responsible for carrying out analysis of material (s) accurately & precisely.
2.1.6. Responsible for maintaining the Reserve Sample and its Record.
2.1.7. Responsible for ensuring proper labelling on packs.
2.1.8. Responsible for recording the data in the samplers remarks and test data sheet.
2.1.9. Responsible for intimating to Executive QC, in case of any non-conformance.
2.2
2.2.1
Responsible for verifying the recorded data of sampled consignment by Quality Control
Officers and review of the same.
2.2.2
Responsible for updating the document as per regulatory requirement
2.2.3
Responsible for imparting training to sub-ordinates.
2.2.4
Responsible for taking decisions on non-conformance in co-ordination with Head
Quality Assurance / Quality Control
3.0
ACCOUNTABILITY
4.0
PROCEDURE:
4.1
Receive Goods Receipt Note (GRN) from Warehouse and record relevant
informations in packaging material register (Refer Annexure-1).
4.2
Take out Photocopy of Samplers Check List - PM (Refer Annexure 2).
4.3
The separate samplers remark shall be used for each lot of Batches.
4.4
Prepare the UNDER TEST label from the computer system to affix on the
consignment.
4.5
Check the delivered items to ensure that the quantity received corresponds with
the GRN Quantity
4.6
Fill the necessary details in Samplers Check List by taking the reference of
Goods Receipt Note (GRN). If discrepancy found in GRN inform to warehouse for
corrective action.
4.7
Go to the Quarantine area and identify the material to be sampled from
Quarantined label which is affixed by Warehouse on the packs.
4.8
In case of Aluminium and PVC foils carry out the sampling under Laminar Air
Flow (LAF).
4.9
Cleaning of LAF shall be carried out on every alternate day or early if required.
The LAF shall be cleaned with wet mop followed by dry mop.
4.10
The cleaning shall be recorded in the cleaning record for LAF as given in
Annexure - 3.
4.11
Ensure that the surrounding area is clean, if not get it clean, prior to start of the
sampling.
4.12
Check the packing condition of the material and details mentioned on the Under
Test labels.
4.13
Verify that the Quarantine Labels are affixed by Warehouse Personnel.
4.14
In case of any discrepancies intimate to Executive / Head - Quality Assurance or
Head - Quality Control for necessary action.
4.15
Ensure that packs are cleaned externally and open the packages only after
ensuring the proper cleaning. Observe the material for any abnormalities and record it on
the Samplers Check List.
4.16
Check the following points during sampling of the material: 4.16.1
Mode of packing,
4.16.2
Indication of packing,
4.16.3
Details available on pack (Containers),
4.16.4
No. of packs (containers) received,
4.16.5
Total quantity received,
4.16.6
No. of packs (containers) sampled,
4.16.7
Quantity to be sampled.
4.16.8
Name of the person who sampled along with date of sampling.
4.17
Boxes as per n +1 and take out sampling quantity for visual inspection as per sampling
plan MIL STD 105D Acceptable Quality Level (AQL) (Refer Annexure 5).
4.18
Note down the sampled quantity in Samplers checklist based on the number of
packages to be sampled.
4.19
Examine the sampled material as per AQL against the approved standard for
general appearance, deviation from normal visual quality, colour, text etc. wherever
applicable.
4.20
Record the results in approved Visual Inspection Report for Aluminium foil and
PVC Foil.
4.21
After completion of sampling the material pack shall be resealed with BOPP
Tape or tied with the help of cable tie.
4.22
Affix the UNDER TEST refer Annexure 4. to all the rolls of sticker labels,
foils and every container of rubber plugs. For all other packaging materials at least one
UNDER TEST Label shall be affixed on bottom container/ pack of each pallet.
4.23
Affix the SAMPLED BY QC (Refer Annexure 4) sticker label duly signed and
mentioning the container number according to sampling plan, on outer container of the
material from which sample is taken.
4.24
Check that the number of packs is correct as mentioned in under test label.
4.25
Take out composite sample for analysis as per respective Packing Material
Specifications. Put the sampled quantity in self-sealing polybag bearing the label of
SAMPLE FOR ANALYSIS Refer annexure 4.
4.26
Carry out testing of the packaging material as per the laid down specifications of
respective material.
4.27
The sampling procedure described above will not be applicable for Tertiary
Packaging material like Shipper, pad, partition and corrugated trays. For these materials
only one unit shall be collected and carry out the analysis as per laid down specification.
5.0
REASON FOR REVISION
Harmonization of format
6.0
TRAINING:
Trainer
Trainee
Period
---
-Manager QC
Chemist / Associate QC Packaging
One day
7.0
DISTRIBUTION:
8.0
ANNEXURES:
Annexure - 1
Annexure - 2
Annexure - 3
Annexure 4 : Format for labels of UNDER TEST, SAMPLE FOR ANALYSIS and
SAMPLED
Annexure 5 : 105 D Military Standard Acceptable Quality Level Chart
9.0
REFERENCE:
APPROVAL AND REJECTION OF PACKAGING MATERIALS
1.0.
OBJECTIVE:
The objective of this SOP is to describe the procedure for Approval and
Rejection of Packaging
Material.
2.0.
RESPONSIBILITY:
2.1
2.1.1. Responsible for ensuring proper documentation of sampling and adequate number
of quantity sampled.
2.1.2. Responsible for carrying out analysis of packing material (s) accurately & precisely
by following specification and standard testing procedure.
2.1.3. Responsible for maintaining the Packaging Material Register.
2.1.4. Responsible for preserving the reserve sample along with Analytical Test Report.
2.1.5. Responsible for recording the correct results in the Analytical Test Report for every
PM in a stipulated time.
2.2
2.1.1
2.1.2
2.1.3
2.1.4
2.1.5
3.0.
ACCOUNTABILITY:
4.0.
4.1.
PROCEDURE:
The sampling of the packaging material shall be carried out as per the SOP
4.2.
Before starting the analysis take out Standards and Results Sheet from
Respective Product File and take out photocopy and get it issued from Sectional
Head by signing the space provided.
4.3.
The sampled items shall be analysed as per respective laid down specifications
and general test procedure. The results shall be recorded in the Analytical Test
Report and compare for its limits.
4.4.
4.5.
Then compile the results along with Samplers Remark and keep one Reserve
Sample for printed packaging material by affixing Reserve Sample Label on nonprinted part (Refer Annexure 2 for Reserve Sample Label).
4.6.
The Goods Receipt Note (GRN) along with complete analytical report shall be
checked thoroughly by another person.
4.7.
4.8.
The results are not within the specified limits and standards, the material shall be
rejected
4.9.
If the material is rejected, the Material Rejection Note (Refer Annexure 3) shall
be prepared and get it approved from Head Plant Operation, Head QA / QC.
4.10.
If all parameters found within the prescribed range Executive or Head QA shall
approve the Analytical Test Reports and GRN.
4.11.
The report with regards to the disposition of the said consignment is then made &
the status label as whether it is APPROVED or REJECTED (Refer Annexure 2) shall
be generated by using the computer System.
4.12.
4.13.
Each approved pack of packing material shall be identified by affixing the small
green label (Refer Annexure 2) having the A.R. No. for identity of the Consignment.
4.14.
Forward the approved / rejected copies of GRN to Warehouse for further actions.
4.15.
4.16.
File the entire report along with Quality Control GRN Copy.
Then Warehouse personnel shall shift the Approved / Rejected material in the
designated areas.
4.17.
The rejected consignment shall be shifted to the designated Rejected
Areas under lock and
Key.
4.18.
4.19.
5.0
Harmonization of format.
6.0
TRAINING:
Trainer
Trainees
Period
-- One day
7.0
DISTRIBUTION:
9.0
ANNEXURES:
Annexure 1
Annexure 2
Annexure 3
9.0
REFERENCES:
In house
ANNEXURE 1
FORMAT FOR CERTIFICATE OF ANALYSIS
CERTIFICATE OF ANALYSIS
ALKEM
LABORATORIES LIMITED
PACKAGING MATERIAL
(NAME)
DAMAN
Material name:
Item code:
Batch No.:
Mfr. Name:
Supplier Name:
Challan no.:
Challan Date:
GRN No. :
Date Received:
Quantity received:
Containers Received:
Containers sampled:
Date Of Sampling:
Sampled by:
A. R. No.:
TESTS
RESULTS
SPECIFICATIONS
APPROVED / REJECTED
Remarks: Sample COMPLIES / DOES NOT COMPLIES as per above Specification
ANALYST
CHECKED BY
APPROVED BY
(SIGNATURE / DATE)
(SIGNATURE / DATE)
(SIGNATURE / DATE)
K/QC/002/F-1/00
ANNEXURE 2
FORMAT FOR APPROVED, REJECTED, RESERVE SAMPLE AND A.R. NO.
LABEL
REF. SOP NO.: K/QC/002
Revision No.: 00
Page No.: 1
of 1
Effective from:
NAME
ITEM CODE
A.R. No.
B. No.
G.R. No
QTY.
POTENCY
NO. OF CONTAINERS
RETEST DATE
SIGN.
Date
APPROVED
DOC/QC/001
ITEM CODE & NAME
A.R.NO
B. NO.
G.R. NO.
QTY.
POTENCY
NO. OF
CONTAINERS
SIGN.
Date
REJECTED
DOC/QC/002
RESERVE SAMPLE
A.R. No.
G.R.N. No.
Signature
Date
(149P 2A/01)
ANNEXURE 3
FORMAT FOR MATERIAL REJECTION NOTE
To
Head Warehouse
Name Of Item:
Item Code No.:
Name Of Manufacturer/Supplier:
GRN. No./Date:
A.R. No.
Qty. Received:
Batch No.
Qty. Rejected:
Date Of Analysis:
Reason For Rejection:
Remarks:
Checked By/Date
Rejection Approved By/ Date
(Executive QA)
Head QA / QC
2.
Head Purchase.
K/QC/002/F-2/00
Purpose
Objective : To provide a documented procedure for role of quality assurance in the handling of
rejection
Scope
4.0
Primary: QA-Officer
Overall: QA-Manager
5.0
Responsibility :
Procedure:
Rejection of Raw Material:
Supply Rejected by QC
o
If QA find that supply needs to be rejected, QA In-charge will approve the Out of
Specification (OOS).
On receipt of Online rejection note from production department, inspect the rejection.
If any corrective measures are required from the supplier, Inform to purchase
department for corrective actions.
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0 Purpose: To provide instructions for numbering system for Standard Operating Procedures and
Index of Standard Operating Procedure. (SOPs).
3.0 Scope
: This procedure is applicable for numbering system for Standard Operating Procedures
and Index of Standard Operating Procedure. (SOPs).
4.0 Responsibility:
Primary: OfficerQA
Secondary: Manager-QA
5.0 Procedure:
SOP is prepared after studying total activities and interacting with all the concerned
Departments.
Sr. No.
1
2
Department
Code
PA
PR
SOP No.
ABC/XX/SOP/YYY
ABC/XX/SOP/YYY
3
4
5
6
Engineering Services
Quality Control Department
Quality Assurance
Store Department
MT
QC
QA
ST
ABC/XX/SOP/YYY
ABC/XX/SOP/YYY
ABC/XX/SOP/YYY
ABC/XX/SOP/YYY
Where,
o
1.0
Purpose : To provide an instruction for analytical report numbering procedure (AR No.)
5.0
Responsibility :
Primary
: QC Chemist / QC-Officer
Procedure:
= Intermediate
WWW or WW
R-
XXX/ZZ/R1.
For re-test Raw material: R-XXX/ZZ/R1 (e.g. R-001/09/R1)
Where,
= raw material
XXX
ZZ
I- WWW/XXX /ZZ/I1
For Intermediate: I- WWW/XXX/ZZ/I1 (e.g. I-001/001/09/I1)
Where,
= intermediate
ZZ
department.
2.0 Objective : To provide a documented procedure for record maintained by
control department.
4.0 Responsibility :
Primary
: QC Chemist / QC Officer
Secondary :
Overall : QC In Charge
5.0 Procedure :
Following are control documents.
List of Instruments.
Following are records.
Indicator logbook.
3.0
Scope
4.0
Responsibility :
5.0 Procedure :
Testing and release or rejection of all incoming raw materials, packing materials, inprocess / intermediates and finished products as per specified specifications.
Maintaining testing records as per standard procedures for raw materials, packing
materials, in-process / intermediates and finished products.
Follow safety norms at all the stage during handling of chemicals and using
instruments.
columns.
3.0 Scope
QC Department.
4.0 Responsibility :
Primary : QC Chemist / QC-Officer
Secondary : Overall QC In charge
5.0 Procedure :
After completion of analysis stop the pump, keep the reservoir in the distilled
remove air bubbles. Close the purging valve by decreasing the flow rate up to
zero.
Wash the HPLC column initial with HPLC grade water for about 15-20
minutes.
Then wash the HPLC column with respective solvent mixtures (e.g. 50:50
1.0
Purpose :
intermediates.
2.0
intermediates in QC department.
4.0 Responsibility :
Primary : QC Chemist / QC Officer
Secondary : Overall: QC Incharge
Procedure:
After the receipt of re-testing intimation note from store department, QC
Chemist takes its entry in the respective Re-testing logbook and gives AR No. to
Procedure.
Raw material may also be approved on the basis of physical appearance.
containers.
Re-testing of any raw materials should be four times only.
Frequency of re-testing for raw material is every year, and for intermediate is
material should carry out, whose due date for re-test is earlier.
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Scope
Department.
4.0 Responsibility :
Follow up
5.0 Procedure
: Officer Stores
Stores Officer
Receive the raw material issue requisition and record the serial number, material code
and date of receipt. Check for the entries in all the columns viz. Dept, Batch Size., Batch
No. and signatures for requisite by and authorizes by. If any of these columns is
missing, return the requisition to production.
From the raw material stock register, check the quantities of material available and
quantities requested for. If any of the material in stock is less than the requisitioned
Quantity, inform to Stores Incharge.
Stores Incharge.
Stores Assistant
Batch No.
Batch size.
A.R.No.
Quantity
No. of container.
Tare Wt
Gross Wt.
Net Wt.
Date
Signature
Check the tare weight of the empty container and note down on the dispensed label.
Select the bulk raw material container of appropriate AR No as per FIFO system.
Check the retest date on the label. If the retest date falls in the month of issue, inform
QC regarding the retesting.
Transfer the material to the dispensing area. Carefully transfer the material into the
container till the quantity required is transferred.
Note down the final weight of the container and record on the dispensing label for
gross weight.
Calculate the net weight and record on dispensing label and sign for issued by.
Close the bulk raw material container and transfer back the bulk raw material container
to the original space.
Repeat the steps for remaining materials of the raw l issue requisition one after the
other.
Never keep more than one material in the dispensing area. Transfer the second
material only after the first has been dispensed and transferred back to its original
space.
Always use clean dispensing devices and do not contaminate one with other material.
Enter the details of issue into the raw material stock register for the material.
Verify the quantities dispensed against the raw material issue requisition and sign for
Store officer.
Inform the Asst. Manager Production / Manager Production regarding the checking
of the material.
Material requisition will be made two copies. One copy will be kept in store department
and duplicate copy attach with B.M.R.
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Purpose : To provide the procedure for receiving liquid raw materials in road
tankers.
bjective
: To provide documented procedure for receiving liquid raw materials in road tankers.
Scope
: This procedure defines instructions for receiving liquid raw materials in road tankers in
the stores department.
4.0 Responsibility :
Receive and verify the delivery documents (DC, Performa Invoice, Central Excise
Invoice, COA) and check for the Purchase Order copy for the material. The documents
shall essentially consist of the following information.
Manufacturing date
Contact the Purchase department, if PO copy for the material received is not available.
Check for the security inward stamp on the delivery documents and the signature of the
security personnel along with the Security inward number.
Inform QC Dept in writing about the arrival of tanker for tanking sample giving the
following details:
Date
Time of Reporting
Quantity
If the sample from the tanker does not conform to the specification, inform the purchase
department regarding the REJECTION. Return back the tanker.
On receipt of approval of the tanker from the QC, assign a Stores Asst. to the tanker
and send it to approved public weighing bridge for taking the gross weight.
Instruct the tanker driver to position his vehicle near to the unloading point.
Inform the engineering personnel to make arrangements for connecting the delivery
lines to the tanker, connect the earthing cable from the tanker outlet to the earthing point
to ensure the discharge of static electricity.
Ensure all the safety precautions for unloading the material from the road tanker have
been taken.
After the unloading is completed verify the compartments of the tanker by checking the
individual compartments and opening the outlet valves completely.
Assign a store asst. and send the tanker for weighing to the weight bridge.
On receipt of the weight of the empty tanker compute the net weight of the material
transferred. Check against the delivery documents and compute the difference if any.
Enter in the raw material inward register including the actual content of the material
transferred.
Sign for received on the delivery documents and retain the original copy.
Return the duplicate copy to the driver and mention deviations observed for suppliers
reference.
Prepare the GRN and forward the same to the QC Dept for analysis of composite from
the storage tank.
On receipt of report from QC, forward copy of the GRN to Accounts and
Purchase
department.
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Purpose : To provide store management instructions for Engineering department as per safety and
cGMP requirements.
Objective
Scope
After getting the intimation, receive the material at the gate house.
Check the material at gate house, as per delivery challan and quality of material i.e.
damage, scratches, finishing etc.
Take the required quantity and use for it was indented.
After getting the Receiving Report (RR) from store department, check with the original
purchase order (PO).
If okay, release the intermediate payment as per terms and condition mentioned in the
PO.
If party has already completed all the terms and condition under his scope and supply,
then fill the certificate for Final Payment.
Release the final payment as per PO.
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2.0 Objective : To provide a guide line how and when to clean the sampling area.
3.0 Scope
4.0 Responsibility :
Cleaning
: Work man
Follow up
: Officer Stores
:
Floor
Clean the floor using detergent solution after using disinfectant solution use. And
Using lint free cloth.
If the sampling area is not in use then clean the floor once in a day using
detergent after using with lint free cloth.
Walls -If the dispensing area is not in use then clean the walls once in a day
using Detergent after using disinfectant solutions and with lint free cloth.
Door
Clean the door using detergent after using disinfectant solution and mop with
Using lint free cloth. If the Sampling area is not in use then clean the door once
In a day using same procedure.
Weighing balance
Clean the surface of balance with slightly wet lint free cloth.
Labeling
Brand
Teepol
Dettol
Savlon
Quantity
0.6 % Detergent solution
0.5 % Disinfectant solution
0.5 % Disinfectant solution
1.0 Purpose :To provide a documented guideline for Storage & Handling of Inflammables.
2.0 Objective : To use for Storage & Handling of Inflammables.
3.0 Scope
: Stores
4.0 Responsibility :
Follow up : Officer Stores
Over all responsibility : Q.A. Incharge, Store Incharge
5.0 Procedure
:
Storage area of such inflammable solvents should be away from main building
of Plant &Warehouse with lock & Key arrangement. There should be restricted
entry in this area.
proper and each & every drum and pump is covered by earthing connection.
Unload the material by Deduction of drums & checking for weight take the
damage in drums.
While unloading or during storage, if leakage of damage observed, shift the
solvent in other empty drum with help of pneunimetric pressure pump. Empty
drum must have been used previously for the same solvent. Ensure that
facemask etc.
While opening the lid, unscrew it slowly so as to let the air / vapors pass out.
Ensure earthing connection to the pump. Put SS Pneumetric pump inside of
the
drum. Switch on air pressure. Start pneumatric pump. Dispense the required
identification.
Switch off lights. Lock the Inflammable solvent storage room.
Put the filled 25 liter drums in a carrier trolley & carry to air lock of coating area
To
provide
documented
procedure
Extinguisher.
2.0 Objective : Operation of Fire Extinguisher
for
Operation
of
Fire
5.0 Procedure :
It should be used for fires involving solvents, oils, greases, fats, charcoals etc.
As these articles being lighter than water, will float on water and are likely to splash
burning liquids on all sides.
This type of extinguisher can also be used for fires involving inflammable liquids such
as solvents, oils, greases etc.
The only difference between foam type and CO2 type fire extinguishers must always be
used in the event of an electrical fire.
Compressor.
2.0 Objective : Operation of Air Compressor.
3.0 Scope : This SOP is applicable for Operation of Air Compressor.
4.0 Responsibility :
Primary: Technician Engineering
Secondary: Manager Engineering
5.0 Procedure :
Before starting the compressor, check the water level of cooling tower tank, if
starter.
Remove the air bubble from the vent.
Push the green color Push Button on panel to start the air compressor.
Air compressor will start in UNLOAD condition and after 30 second it will
pressure is achieved, compressor will cut off automatically and run in UNLOAD
condition.
Open the plant air supply valve of the receiver. Air pressure in receiver will
start to reduce and when air pressure is reduced to 6 kg/cm 2 the compressor will
UNLOAD condition.
Switch OFF the main switch on panel of air compressor.
Drain the pressure in receiver from drain valve and close the drain valve
button on starter.
Close the cooling water inlet valve of cooler and cylinder jacket.
Drain the water in cylinder head jacket.
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1.0
plant.
4.0 Responsibility :
Primary : Officer Safety and Environment
Secondary : Manager Safety and Environment
Overall responsibility: General Manager (PA)
5.0 Procedure :
Effluent/sewage generated should be drained into the drainage system.
pump.
Neutralization Tank:
The effluent pump from Equalization Tank is collected in Neutralization Tank.
In Neutralization Tank effluent is adjusted to proper pH .
Flocculation Tank:
Neutral effluent is send to the flocculation Tank from Neutralization Tank.
Tank.
Secondary Settling Tank:
In Secondary Settling Tank Biomass is being settled down.
It is being recycled to aeration tank for maintaining MLSS & MLVSS of the
Aeration Tank.
Excess sludge is being transferred to the Sludge Drying Beds.
The treated effluent is being collected in Treated Water Sump.
Carbon Filter:
Finally, effluent is being given Tertiary Treatment in Carbon Filter.
The filter reduces the color of the treated effluent having almost colorless and
less COD.
Discharge into GIDC drain.
Flocculating agent are added here which emphasis fast settling in the
urpose : To provide a documented procedure for preventing accident & Recording accident.
2.0 Objective : To maintain safety aspects
3.0 Scope
4.0 Responsibility :
Follow up
5.0 Procedure :
Accident Prevention
Workman shall engage themselves in the duties which have been assigned to them.
The execution of their duties must be in the safe manner laid down in S.O.P. for the
operation, of the machine or duty concerned.
Workmen working beyond the height of 10 feet shall wear the safety belt.
If any employee / work man working beyond the height of 10 feet on ladder shall work
with one additional work man / employee to hold ladder.
Workman shall not keep sharp edge tools into their pocket.
Any employee / workman working with electricity shall wear safety shoes &
Sock proof gloves.
Any workman working with hazardous chemicals / acid shall wear the safety
Wears like goggles, gloves etc.
Speed of vehicle inside the factory premises shall not exceed 20 km / hr.
When welding work is to be carried out in closed area, extra fire extinguisher
Shall be provided.
After working with oil, floor shall be cleaned thoroughly to wipe out the oil.
Solvents shall be stored in tight closed container.
Entry into transformer yard / explosive storage yard shall be restricted to selected
Personnel.
Workman shall enter into water tank, drainage, septic tank only after permission Of
Personal & Administration department.
Workman shall carry out repairing work of high pressure line / high temperature Line /
or any explosive line only after permission of Engineering In charge.
ecording of Accident
The accidents are categorized as critical major and minor depending on the
The First aid, if required, after the accident shall be provided at the earlier marked
Locations and trained persons are available.
The telephone no. of fire station, doctor, ambulance shall be displayed in all the
Departments to call upon in an emergency.
The affected employee shall be immediately rushed to the hospital, if needed and is
provided the required medical help.
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Personnel Hygiene
First Aid
Security Personnel
Uniform of Employees
LinkWithin
Appraisal of Employee
1.0 Purpose
: Employees
4.0 Responsibility
Follow up
:
: Personnel & Administration In charge
Poor
Normal
Good
Very Good
Out Standing
Appraisal panel
Department head
Personnel & Administration In charge
General Manager
Appraisal Form
Name of employee
Department
Designation
Job carried out
Best performance by employee
Best output
Sign
Commitment
By Department Head opinion
Sign
Commitment
Personnel Hygiene
Uniform of Employees
Security Personnel
Appraisal of Employee
1.0 Purpose
: Employees
4.0 Responsibility
Follow up
:
: Personnel & Administration In charge
Poor
Normal
Good
Very Good
Out Standing
Appraisal panel
Department head
Personnel & Administration In charge
General Manager
Appraisal Form
Name of employee
Department
Designation
Job carried out
Best performance by employee
Best output
Sign
Commitment
By Department Head opinion
Commitment
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Personnel Hygiene
Sign
Uniform of Employees
Medical check up of Employees
Security Personnel
1.0
2.0
practices.
3.0
Scope
follow.
4.0 Responsibility :
Premises :
Equipments :
Control lab should be fully equipped with appropriate instruments for the
testing procedures.
calibration date.
Defective equipment should be withdrawn from use until the fault has been
rectified.
should be available.
being performed.
Sampling:
Cleanliness :
Control lab should be kept clean in accordance with the written procedure.
A written procedure for cleaning the glass apparatus of chemical assay
Method of sampling.
Equipment to be used.
Raw materials are to be collected as per the lot numbers or batch numbers
Documentation:
analytical reports.
received, date of removal indicating the reason and the product details with the
Manufacturing
Nature of complaint.
known buffers.
Controls :
The transfer of entries from the note books to the final records is to be
Specifications:
Starting material
Finished products
Packing material
Intermediates.
Facilities:
Vacuum line.
Fire extinguishers.
Training :
Checking all the manufacturing and in-process data along with the
2.0
3.0
Scope
4.0
Responsibility :
5.0 Procedure:
All information related to activities should be recorded clearly and easy to read.
All documents should be made in black ball pen / ink pen only.
If any error is found immediately after recording the data, cross out incorrect information
with a single line and not by using erasable pens or Corrective fluids. Enter correct data,
sign and date near correction.
Numbering system for Standard Operating Procedures and Index of Standard Operating
Procedure
1.0
Breakdown.
3.0 Scope : This SOP is applicable for. Restart The Activities After Power
Failure / Breakdown.
4.0 Responsibility :
Primary: Technician Engineering
Secondary: Manager Engineering
5.0 Procedure :
Power failure:
Check the main power circuit panel for voltage and break down.
Start the D.G. Set and check the voltage and frequency, it should be 430 V
Purpose
and 50 HZ.
operation.
After resuming the power supply from G.E.B. check the voltage and
frequency.
Before changing over power supply from D.G. Set power supply inform the
critical
Processing areas personnel and switch. the power supply for normal
working.
BREAKDOWN :
In case of breakdown of power supply, confirm the nature of breakdown.
Start the D.G. Set
Check the voltage and frequency; it should be 430 V & 50 HZ.
Change over the power supply from G.E.B. to D.G. Set for normal working.
After attending the breakdown of power supply, restore the power supply and
Then changeover the power supply from G.E.B. to D.G. Set for normal
1.0
reconciliation.
2.0 Objective : To provide a documented procedure for Issuance of labels
and reconciliation.
3.0
Scope
: This procedure is applicable for Issuance of labels and
Purpose
Code, Product Stage, Batch Number, Manufacturing Date, Expiry Date, and
1.0
2.0
analysis.
3.0 Scope
department.
4.0 Responsibility :
Primary: Officer QA / Officer-Store
Secondary: Officer QA Manager.
5.0 Procedure:
Spot-check once a week all registers, reagents and volumetric standard
solutions.
Frequently observe the actual testing done by the chemist.
Review analytical reports and before signing check and confirm for:
Complete entries in to the logbooks, test data sheets etc.
Reagents should be stored in bottles.
Reference / working standards stored in desiccators should be checked for
be taken.
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If any mistake occur during filling the data on label, issue another new label
OBJECTIVE
To lay down a procedure for Handling of Samples for Analysis of Raw Materials./ Formulations.
2.0
RESPONSIBILITY
ACCOUNTABILITY
PROCEDURE
4.1
RAW MATERIALS
4.1.1
samplers
The Quality Control Officer shall receive the samples along with the GRN and
check list.
4.1.2
The samples shall be kept in the tray labeled Under Test Raw Material, till those are
allocated for analysis.
4.1.3
4.1.4
The samples shall be allocated for analysis by Quality Control Manager and relevant
details
shall be mentioned in the register.
4.1.5
4.1.6
destruction
4.1.8
4.19.
The container shall be destroyed by breaking (in case of glass), by cutting (in case of
plastic).
4.1.10 Collected material shall be destroyed by putting the material in water , but the cephalosporin
materials shall be destroyed by putting the material in 2% w/v solution of sodium
hydroxide.
Then all the collected material closed properly and send to the burning pit.
4.2
FORMULATIONS
4.2.1
form and he
The Quality Control Officer shall receive the samples along with the sample request
shall ensure intactness of the samples by visual checking.
4.2.2
The entries of the samples shall be made in the respective register by the Quality Control Officer.
4.2.3
Sample shall be kept in the tray labeled as Under Test formulation till those are allocated for analysis.
4.2.4
4.2.5
4.2.6
4.2.7
4.2.8
The samples shall be allocated for the analysis by the Quality Control Manager. The relevant details of
allocation and green sheet number shall be mentioned in the respective registers.
The excess samples shall be destroyed after completion of analysis .
The samples for destruction shall be kept in a container labeled as Samples for destruction and shall be
destroyed as mentioned below.
Tablets, capsules, dry syrups and powder of vials shall be removed from their respective pack.
4.2.8
4.3
Packaging material shall be destroyed by burning at burning pit and product shall be
destroyed by burning at burning pit after breaking.
All Formulations / Raw Material Samples of Cephalosporin group of products shall be disposed off after
treating with 2% w/v Sodium Hydroxide solution.
4.4
No samples shall Under Test for more than 60 days. Any sample found pending for analysis
for more than 60 days shall be investigated for delay in analysis & documented.
4.5 ABBREVIATIONS
SOP = Standard Operating Procedure
GRN = Goods Receipt Note
W/v = Weight by Volume
5.0
Harmonization of format.
6.0
TRAINING:
Trainer
--
Trainees-Period -7.0
One day
DISTRIBUTION:
Nil
ANNEXURES:
9.0
REFERENCES:
In house.
1.0
OBJECTIVE :
The objective of this SOP is to lay down the procedure for giving Analytical Reference Number
(A.R. No.) for Raw Material, Packaging Material, Finished Product, Blend and Validation
samples.
2.0
RESPONSIBILITY
3.0
ACCOUNTABILITY
4.0
PROCEDURE
4.1
RAW MATERIAL
4.2
PACKING MATERIAL
4.3
FINISHED PRODUCT:
The A.R. No. is a unique code having 12 digits.
For example
: 02C-5A/30156
First two digits stands for the month of manufacturing.
Third digit stands for the dosage forms i.e. C for Capsules, S for Dry Syrups, T for Tablets, I for
Injection,
The fourth digit is -
Fifth digit 5 stands for Year 2005.
Sixth digit A stands for ALKEM LAB LTD,
G stands for GALPHA LAB LTD,
I stands for INDICHEMI HEALTH SPECILIETIES .
Seventh digit is /.
Then the advice sheet No.(Who is having five digits) shall be followed.
4.4
BLEND /INPROCESS:
The A.R. No. is a unique code having 12 digits.
For example
: 2BC-5A/30156 / 2IC-5A/30156
First digits stands for months for manufacture.
Second digit stand for Blend /Inprocess.
Third digit stands for the dosage forms i.e. C for Capsules, S for Dry Syrups, T for
Tablets, I for
Injection
The fourth digit is -
Fifth digit 5 stands for Year 2005.
Sixth digit A stands for ALKEM LAB LTD.
G stands for GALPHA LAB LTD ,
I stands for INDICHEMI HEALTH SPECILIETIES
Seventh digit is /.
Then the advice sheet No.(Who is having five digits) shall be followed.
4.5
VALIDATION SAMPLES:
After location code there is / followed by V, which stands for validation sample followed by
4.6
LOCATION CODE :-
INJ- Injection
TAB- Tablet
BET- Betalactum
CAP- Capsules
6.0
TRAINING:
Trainer -Head Quality Control
Trainees--
ANNEXURES:
Nil
9.0
REFERENCES:
In house.
OBJECTIVE
2.0.
RESPONSIBILITY
Micobiologist .
3.0.
ACCOUNTABILITY
4.0
4.1
PROCEDURE
4.2
Check and reconcile number of containers and the total quantity as
shown in Under Test.
Compare the details like manufacturing date, expiry date and
pharmacopoeial status
mentioned on Samplers checklist-RM with that mentioned on
manufacturers label. Ensure
that each container is affixed with UNDER TEST label. In case of
any discrepancies
inform to Quality Control Manager / Ware-House Manager.
4.3
Check the packing condition of the containers for any damages.
Physically damaged
containers shall not be considered for sampling and the same shall
be Rejected..
4.4
In case of material received in triple laminated bags, the sample
container received alongwith
the material shall be used for microbiological and chemical testing.
4.5
In case of sterile material received in aluminium containers, follow
the procedure given
below,
4.5.1.
Select the containers to be sampled and inform Ware-House Officer to
transfer these containers to the raw material storage area of production block.
4.5.2
4.5.3
Prepare label for individual container sample, with details of name of the
material, Batch no., and container number.
4.5.4.
4.5.5.
Prepare labels (annexure-II ) for Sample for Analysis, microbiology test and
control sample.
4.5.6.
Transfer the containers to the buffer zone. Follow the SOP on Raw material
receipt, storage, and transfer to sterile area.
4.5.7.
Enter into the sterile area following gowning and degowning procedure for sterile
area.
4.5.8.
4.5.9.
Ensure that temperature inside the room is less than 25 deg.C. & RH is less than
40% or as specified on Manufacturers label.
4.5.10. Place one container under LAF. Peel off the outer tape/seal from the mouth of the
container and open the lid of the container aseptically.
4.5.12. Observe carefully the physical appearance of the material for any abnormalities
like discolouration, lumps, foreign matter and physical heterogenicity.
4.5.13. If any abnormalities are observed, collect the sample in two separate vial, for
separate evaluation.
4.5.15. Close the lid of the container tightly, wrap the mouth with adhesive tape and
remove the container from LAF booth.
4.5.16. Mark the sample containers using glass marker with batch number and container
number in case of individual sample and only batch number in case of pool, control
sample & micro sample.
4.5.17. Mark containers / packs which are selected for sampling with marker as N/1/n,
N/2/n.N/S/n (N stands for total number of packs / containers, S for serial number
of container selected for sampling and n for total number of containers taken for
sampling).
4.5.18. Similarly sample the rest of the containers aseptically. Refer annexure-II for total
quantity to be sampled.
4.5.19. Seal all the vials with aluminium tear off seals.
4.5.21. Transfer all the samples & sampling aids in the Air lock-1.
4.5.22. Clean the LAF bench and room and leave the sterile area alongwith the samples.
4.5.24. Affix SAMPLED labels (Annexure III) duly signed with date of sampling on the
container.
4.5.26. Give the samples along with the Samplers checklist-RM, Suppliers COA (if
available) to Quality Control Laboratory for Chemical Analysis.
4.5.27. Inform the Ware-House Officer to shift all the containers back to Stores UNDER
TEST STORAGE area after performing decontamination of external surfaces.
4.6
4.6.1.
4.6.2.
4.6.3.
Spoons : Wash the spoon dry and wrap in 3 layers of aluminium foil,
depyrogenate in Dry Heat Sterilizer at 250 degree Celsius for one hour.
4.6.4.
4.7
ABBREVIATIONS :
SOP = Standard Operating Procedure
COA = Certificate of Analysis.
5.0
Harmonization of format
6.0
TRAINING:
Trainer
Trainees
-- Chemist / Assistants
Period
-- One day
7.0
DISTRIBUTION
Original Copy
8.0
REFERENCES
USP 25 Page no.:- 1878 , E.P: - Page no. 125 , 2.6.1
9.0
ANNEXURES:
Annexurer-1
Attached
ANNEXURE I
SAMPLING PLAN
Revision No.: 00
Effective from: 10.01.2005
Page No. : 1
of 1
10 containers
ANNEXURE II
QUANTITY TO BE SAMPLED
Tests
Chemical
20g
Control sample
20g
Total quantity
80g
ANNEXURE- III
SAMPLED
SING. /DATE
2.0 RESPONSIBILITY
3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 Cleaning of General Glassware
4.1.1 Dip the used glassware in a basin of water containing detergent.
4.1.2 Brush each item thoroughly, to remove stains and or grease.
4.2.3 Glass ware used for Sterility / Endotoxin purposes must be sterilized /
depyroginated for 30 minutes at 250 C .
4.2.4Glass ware used for microbiological analysis etc. must be sterilized by heating
for 30 minutes at 120 C .
4.3.1 After routine cleaning treat for 24 hours with 5 % solution of sodium carbonate
followed by soaking in hydrochloric acid for 24 hours. Wash thoroughly with R.O
water & final rinsing is given with purified water.
4.5 CAUTION
4.5.1 While preparation of chromic acid solution ensure that must wear
gloves and goggles.
4.7CAUTION
4.7.1
when using.
4.8 ABBREVIATIONS
Harmonization of format
6.0
TRAINING:
Trainer
Trainees
-- Chemist / Assistants
Period
-- One day
7.0 DISTRIBUTION:
Original Copy
8.0. ANNEXURES:
Nil
9.0. REFERENCES:
IP/BP/USP
CLEANING OF QUALITY CONTROL LABORATORY
1.0
OBJECTIVE
2.0
RESPONSIBILITY
Hygiene supervisor
3.0
ACCOUNTABILITY
4.0
PROCEDURE
4.1
Broom the floor of all the sections including the staircase, daily and then
mope with wet mope.
4.2
Clean all the tables and reagent racks with dry mopping.
4.3
Empty the dust bins, clean them and keep them at place.
4.4
4.5
4.6
4.7
4.8
After cleaning the area by workmen, check the cleanliness of the area and
put the Yes in
the cleaning record as per the ANNEXURE I
4.1.
Frequency :
S.No
.
Activity
Frequency
Mopping
Dustbin Cleaning
Instrument cleaning
Once a day
Once a week.
Once a week
5.0.
Harmonization of format
6.0
TRAINING:
Trainer
Trainees
-- Chemist / Assistants
Period
-- One day
7.0
DISTRIBUTION:
8.0
ANNEXURES:
REFERENCES:
In house
ANNEXURE I
Q.C. CLEANING RECORD
Revision No.: 00
Effective from:
Page No. : 1
of 1
CLEANING RECORD
QC Lab : Wet chemistry lab / Instrument rooms / chemical stores / Control sample room.
Frequency
Date
Brooming
and
general
cleaning
Mopping
Dustbin
Cleaning
Instrument
cleaning
Walls
and
Ceiling
Reagent
racks in
chemical
stores
Two times
a day
Two
times a
day
Two
times a
day
Once a day
Once a
week.
Once a
week.
Checked
by.
1.0.
2.0.
RESPONSIBILITY:
2.1
2.1.1.
2.1.2.
3.0.
ACCOUNTABILITY:
Head - Quality Control
4.0.
PROCEDURE:
4.1
4.1.1
Ensure that the power supply to the instrument is switched off and main cord is
removed from supply.
4.1.2
Clean the instrument with a clean dry cloth everyday. A wet cloth dipped in dilute
soap solution may be used occasionally.
4.1.3
4.2
Precaution must be taken to clean the instrument immediately with dry cloth.
OPERATING INSTRUCTIONS:
4.2.1
4.2.2
4.3
4.3.1
Use HPLC grade solvent / water & AR/Excel/ HPLC grade reagent only.
4.3.2
Filter the mobile phase through 0.45 membrane filter after mixing it in required
proportion and de-gas on ultrasonic bath for about 5 minutes.
4.4
4.4.1
4.4.2
Turn the drain valve knob to 180 in anti- clockwise to open the drain valve to run
the purge system.
4.4.3
4.4.4
4.4.5
Press pump key. The pump will run and indicator will glow.
4.4.6
Purge the auto injector by pressing purge key on auto sampler display.
4.4.7
4.5
4.5.1
4.5.2
4.5.3
It will show Confrigration, Real Time, and Sample Shedule & Post Run Analysis.
4.5.4
4.5.5
From the file menu create a new method or load the existing method.
4.5.6
Create a new sample shedule and feel sample name, batch number,,sample
volume , method name and file name ,after then save the shedule .
4.5.7
4.5.8
For system suitability test, inject six continuous injections of same standard and
RSD should not be more than 2.0 %, otherwise it is specified in standard test
procedure.
4.5.9
After every ten injection of sample (5 samples in duplicate), the standard solution
shall be injected 3 times and the RSD shall be calculated and ensure that it is within
the limit.
4.6
4.6.1
4.6.2
4.6.3
4.6.4
Switch-off CBM.
4.6.5
4.6.6
Stop pump by pressing, Pump key and switch off the pump module.
4.7
CALIBRATION PROCEDURE.
4.7.1
FOR PUMP:
4.7.1.1 Disconnect the column and connect the inlet and outlet tubings with a union.
4.7.1.2 Prime all the lines at 5 ml/min flow rate with water and ensure that flow line is
free from air bubbles.
4.7.1.3
Set the flow rate at 1ml / min and collect the mobile phase (water) in a dry
preweighed beaker and collect the mobile phase for 10 min. weigh the beaker to get
the weight of mobile phase.
4.7.1.4 Calculate the flow rate by dividing the weight obtained with weight per ml and 10
(run time).
4.7.1.5
Calculate the corresponding flow rate. Carry out the experiment in duplicate.
4.7.2.1 Install union in place of column & flush solvent lines (A&B) at flow rate of 2ml/min
with water.
4.7.2.2 Prepare the mobile phase.
4.7.2.3 Prepare 0.3% acetone with HPLC grade water.
4.7.2.4 Fill reservoir A with 100% HPLC grade water & reservoir B with 0.3% acetone in
HPLC grade water as mobile phase.
4.7.3
4.7.3.1
FUNCTION
VALUE
0.01
B CONC
10
10.00
B CONC
10
10.01
B CONC
50
20.00
B CONC
50
20.01
B CONC
90
30.00
B CONC
90
30.01
B CONC
100
40.00
B CONC
100
40.01
B CONC
50.00
B CONC
4.7.3.2
4.7.3.3
4.7.3.4
The gradient valve test shall be accepted if actual concentration with 1% of set
concentration.
4.7.4
CALIBRATION OF INJECTOR:
CHECK FOR PRECISION: Purge the injector system with 100% water to ensure the
complete washing of injector.
4.7.5
4.7.5.1
STANDARD PREPARATION:
Transfer about 50 mg of Uracil to a 250ml volumetric flask. Add 100ml of
Methanol, sonicate to dissolve and make up the volume with Methanol to obtain a
solution containing about 0.02 mg/ml of Uracil.
4.7.5.2
4.7.5.3
4.7.5.4
Instrumental Set Up
Column
4.7.5.5
Flow rate
: 1.0 ml/min
Injector Volume
: 20m litre
Detector
: 254 nm
Inject the standard preparation six times in the system. The peak areas observed
shall be consistent.
4.7.5.6
The relative standard deviation for area counts calculated shall not be more than
1.0%.
4.7.5.7
4.7.6
4.7.6.1 Inject 10, 20, 30, 40 & 50m litre of standard preparation in duplicate. Calculate
the average area counts corresponding to each set of injection.
4.7.6.2 Tabulate the average area against each injection. Plot a graph for area counts vs
mlitre the resulting graph shall be linear.
4.7.6.3 The correlation co- efficient calculated shall be not less than 0.99.
4.7.6.4 Record the observation as per the Annexure - 3.
4.7.7
4.7.7.1
CALIBRATION OF DETECTOR:
Standard preparation. Mobile phase, Instrument set- up same as mentioned in
calibration of Injector.
4.7.7.2
4.7.7.3
4.7.7.4
Record the results in the detection calibration record as per the Annexure - 4.
4.7.7.5
4.7.7.6
SINCE
:
SIGNATURE:
4.7.8.1
Detector :
4.7.8.2
Pump
4.7.8.3
Injector :
4.7.8.4
Gradient :
Once in six months and after each maintenance job in the pump.
6.0
TRAINING:
Trainer
-Trainees
Period
7.0
--
One day
DISTRIBUTION:
Certified Copy No. 1 : Head of Department Quality Control
Certified Copy No. 2 : File copy in HPLC Calibration Data
Reference Copy No. 3 : Display copy Near HPLC System
Original Copy
8.0
ANNEXURES:
Annexure 1
9.0
Annexure 2
Annexure 3
Annexure 4
REFERENCES:
In house.
ANNEXURE 1
FORMAT FOR CALIBRATION RECORD OF HPLC
Revision No.: 00
Calibration Record
Instrument No.
Page No.: 1 of 1
Effective from:
Calibration Date
Calibration Due On
:
Calibration Of Pump (Flow Rate):
1 2
Mean wt. /
Mean
min
Vol. / min
Limit in ml
/ min.
Pump-A
Weight of beaker + water after 10
min. (W2)
Weight of beaker (W1)
0.99 to
1.01
(W2 W1) / 10
Pump-B
Weight of beaker + water after 10
min. (W2)
Weight of beaker (W1)
(W2 W1) / 10
0.99 to
1.01
________ gm.
Calibrated By:
Checked By:
Date
Date :
ANNEXURE 2
FORMAT FOR CALIBRATION RECORD OF HPLC
Revision No.: 00
Page No.: 1 of 1
Effective from:
Calibration Record
Instrument No.
Calibration Date
Calibration Due On
Wavelength
: 254 nm.
Flow rate
: 2 ml / min.
Tine
Range
Value
Obtained
The Program
0.01 To
(Lt: 9.9 To
10.0
10.1)
10.01 To
(Lt: 49.5 To
20.0
50.5)
20.01 To
(Lt: 89.1 To
30.0
90.9)
Value :
Height of B Concentration
-------------------------------------Height of a 100 % Concentration
Remarks:
Calibrated By:
Checked By:
Date
Date :
ANNEXURE 3
FORMAT FOR CALIBRATION RECORD OF HPLC
Revision No.: 00
Effective from:
Calibration Record
Instrument No.
:
:
Page No.: 1 of 1
Calibration Due On
micron)
Wavelength : 254 nm.
Injection volume : 20 l.
Inject six replicate injection of standard solution and calculate RSD for area of main
peak.
Injection no.
Area
% of RSD
Limit
1
2
3
4
5
6
Sr.
Injection
No.
volume
10 l.
Correlation coefficient
Area Mean
Observed
Limit
results
i)
ii)
i)
20 l.
ii)
i)
30 l.
ii)
i)
40 l.
ii)
i)
50 l.
ii)
Remarks: Satisfactory / Not satisfactory.
Calibrated By:
Checked By:
Date
Date :
ANNEXURE 4
FORMAT FOR CALIBRATION RECORD OF HPLC
Revision No.: 00
Effective from:
Calibration Record
Calibration Date
Calibration Due On
Page No.: 1 of 1
Calibration Of Detector
Standard Preparation:
Take _____ mg of Uracil ( about 50 mg.) 250 ml. 5ml 50ml with Methanol.
Parameters:
Mobile Phase: Methanol HPLC grade
micron)
Wavelength: 252- 264 nm with 2 nm increment.
Injection Volume: 20 l.
Sr.No.
Wavelength (nm)
Area
1)
252
2)
1)
254
2)
1)
256
2)
1)
258
2)
1)
260
2)
1)
262
2)
Mean
1)
7
264
2)
Checked By:
Date
Date :
OPERATION
OPERATION
OPERATION
OPERATION
AND
AND
AND
AND
CALIBRATION
CALIBRATION
CALIBRATION
CALIBRATION
OF
OF
OF
OF
REFRACTOMETR
POLARIMETER
MICROPIPETTE
ANALYTICAL BALANCE
LinkWithin
OBJECTIVE:
The objective of this SOP is to describe a procedure for the destruction of balance
analytical samples after analysis and control samples.
2.0.
RESPONSIBILITY:
2.1
2.2
3.0.
ACCOUNTABILITY:
Head Quality Control
4.0.
PROCEDURE:
NOTE: 2% w/v solution of sodium hydroxide shall be used to inactivate
samples before Disposal.
4.1
4.2
Bulk Analysis
After analysis, discard each and every capsule or tablet into the wet bin containing
2 % w/v solution of sodium hydroxide. Deface the label of poly bag and discard the
bag into waste bin.after treating it with 2 % w/v solution of sodium hydroxide.
4.3
4.4
4.5
Raw Materials
After analysis, discard balanced sample of raw material into the wet bin containing
2 % solution of sodium hydroxide. Deface the label of polybag and discard into the
waste bin.
4.6
Packaging Materials
4.6.1
After analysis, cut the material into pieces and it to scrap yard.
4.6.2
At the end of the day remove the wet bin from the laboratory premises and send
it to the ETP to discard the waste.
5.0.
TRAINING:
6.0.
Trainer
--
Trainee
--
Period
--
One day
DISTRIBUTION:
7.0.
Excutive Micro
Original Copy
ANNEXURE:
Nil.
8.0.
REFERENCE:
In-House
You might also like:
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Create a Link
OPERATION AND CALIBRATION OF MICROPIPETTE
1.0
OBJECTIVE
RESPONSIBILTY
Microbiologist / Q.C Executive
3.0
ACCOUNTABILITY
Head - Quality Control
4.0
PROCEDURE
4.1 For 0-200l micropipetter. (carry out all the activities at Temperature 25C )
4.1.1
4.1.3
Pipette out in previously tared beaker on weighing balance and note the reading.
4.1.4
Carry out the procedure twice and note the weight displayed on the balance,
calculate the mean and standard deviation of three readings and record it in the
format as given in annexure-I.
4.1.5
The weight per ml of water at 25C when weight in air is 0.99602 g .Divide the
mean with weight per ml to get the volume dispensed.
4.1.6
4.2.1
Repeat the same procedure as above by setting 200, 500 & 1000l
quantity.
4.2.2
4.3
ACCEPTANCE CRITERIA :
4.3.1 Standard deviation between three readings should not be more than
1%.
4.3.2
The volume dispensed should not vary by more than 1% of the set
volume.
4.4
FREQUENCY OF CALIBRATION
Quarterly
5.0
Harmonization of format.
6.0
TRAINING:
Trainer -
Trainees-Period -7.0
One day
DISTRIBUTION:
ANNEXURES:
REFERENCES:
In house.
ANNEXURE I
FORMAT FOR CALIBRATION OF MICROPIPETTER
Revision No.
: 00
Effective Date:
Page No.: 1 of 1
DISPENSED
WEIGHT RECORDED
Temperature of water =
STANDARd
OBSERVE
DEVIATION
MEAN
( NMT- 1% )
(l )
VOLUME
LIMITS
(l )
(l )
II
III
0 200 l
50
49.550.5
100
99.0-101
200
198-202
200 1000 l
200
198-202
500
495-505
1000
990-1010
Done by:
Checked
by:
Sign.& Date
Sign.& DatE
You might also like:
OBJECTIVE
To lay down a procedure for preparing of media for microbiological tests.
2.0
RESPONSIBILTY
ACCOUNTABILITY
Head - Quality Control
4.1.1
4.0
PROCEDURE
4.1
INTRODUCTION
Before employing any dehydrated media for analysis ensure that the growth
promotion test has been performed for that particular batch or lot or any new media
procured.
4.1.2
requirements.
4.1.3
For preparing any culture media (Solid or Liquid) take properly cleaned glass
container of different volumes as per requirement.
4.1.5
Select the glass container such that the medium volume be prepared, is half of its
capacity.
4.1.6
Follow the instructions given by the manufacturer for preparing the culture media
(Name of the Mfr.).
4.1.7
Weigh the media powder as mentioned on the label of the container and Annexure
II . Reconstitute with distilled water and mix the powder stirring with glass rod.
4.1.8
powder
Completely & check the pH of the solution with the help of pH
indicator strips.
4.1.9
Plug the mouth of the container by non-absorbent cotton and wrap butter paper
/Alue. Foil to prevent any Contamination and label.
4.1.10
instruction and
check the pH after aterilization.
4.1.11
After completion of all the above procedures label each media containers with
media name, media lot no. date of preparation, and Use before date on the
container . Pre-incubation must be done at 30-35C
for at least 48 hrs before taken for use. In case if the medium is
required to be use
immediately, keep appropriate negative and positive control to
ensure the proper
sterilization and fertility of the medium.
4.1.12
preparation record
as mentioned in Annexure I.
4.1.13 Prepared media can be used within 1month period if properly sealed and stored at
temperature < 25C.
4.1.14
Whenever new bottle is opened write the date of opening , Date of growth
promotion test and signature on the bottle.
5.0
Harmonization of format.
6.0
TRAINING:
Trainer --
Trainees-Period -7.0
One day
DISTRIBUTION:
ANNEXURES:
Annexure I
9.0
REFERENCES:
Himedia Manual
ANNEXURE I
LIST OF MEDIA
Sl.n
Revision No.
: 00
Effective Date
Media
Gms. /L
Page No.: 1 of 1
pH
o.
1.
Soyabean
Caesin
Digest 30.00
Fluid
Thioglycollate
Media 29.75
40.00
58.00
5.
52.33
for 20 min
7.7 Boiling
0.2
6.
Deoxycollate
Citrate
Agar 70.52
at
1210C
at
1210C
at
1210C
for 20 min
6.9 Sterilization
0.2
1210C
for 20 min
7.3 Sterilization
0.2
at
for 20 min
7.1 Sterilization
0.2
(SCDA)
4.
7.3 Sterilization
0.2
(FTGM),
3.
for
preparation
Media (SCDM),
2.
Procedure
7.5 Boiling
(DCA)
7.
0.2
23.00
7.0 Boiling
0.2
8.
77.4
/ --
Boiling
980ml
9.
Mac
Conkey
Broth
Purple 35.0
(MB),
10.
Xylose
0.2
Lysine
Deoxycholate 56.68
Agar (XLDA),
11.
7.3 Sterilization
48.5
12.
Sabaurud
Dexterose
Agar 65.0
(SDA),
13.
34.7
14.
61.0
15.
16.
17.
6.8 Sterilization
ml DW
0.2
111.0
7.4 Sterilization
63.0
19.
13.0
20.
45.3
21.
17.5
22.
51.5
at
1210C
at
1210C
at
1210C
at
1210C
at
1210C
at
1210C
at
1210C
at
1210C
for 20 min
for 20 min
7.0 Sterilization
0.2
1210C
for 20 min
7.2 Sterilization
0.2
at
for 20 min
7.4 Sterilization
0.2
1210C
for 20 min
7.0 Sterilization
0.2
at
for 20 min
18.7/50
0.2
1210C
for 20 min
7.2 Sterilization
0.2
at
for 20 min
7.2 Sterilization
0.2
1210C
for 20 min
5.6 Sterilization
0.2
at
for 20 min
7.1 Sterilization
0.2
1210C
for 20 min
7.4 Sterilization
0.2
at
for 20 min
7.2 Sterilization
0.2
23.
37.85
7.0 Sterilization
0.2
24.
65.0
for 20 min
for 20 min
OBJECTIVE
2.0
RESPONSIBILITY
3.0
ACCOUNTABILITY
Manager Q.C.
4.0
4.1.
PROCEDURE
OPERATION
1210C
at
1210C
for 20 min
7.4 Sterilization
0.2
at
4.1.1.
MAIN
STRT
SET
4.1.2.
4.1.3.
4.1.4.
NXT
CHK
4.1.5.
4.1.6.
4.1.7.
4.1.8.
screen.
4.1.9.
After the completion of the specified stroke .The apparatus will go OFF
automatically with a buzzer.
4.1.12 Calculate the bulk density of the sample by measuring the volume of the
sample on
measuring cylinder , occupied after setting it specified strokes.
Wt. of sample
B.D =
---------------- X gm / c.c
Volume
4.2.
CALIBRATION PROCDURE
4.2.1.
4.2.2.
4.2.3.
4.2.4.
4.2.5.
check actual strokes.
50
75
100
4.2.6.
49-51
:
:
73-77
98-102
4.3.
FREQUENCY
Monthly.
5.0
Harmonization of format.
6.0
TRAINING:
Trainer
Trainees-Period -7.0
One day
DISTRIBUTION:
8.0
ANNEXURES:
9.0
REFERENCES:
In house.
ANNEXURE I
Name of
Instrument
Revision No.: 00
Effective from:
Make
Calibration
date
SET STROKE
Page No. : 1
of 1
Instrument Id
Model
OBSERVED STROKES
LIMITS ( STROKES )
50
50 1
75
75 2
100
100 2
CALIBRATED BY
CHECKED BY
OBJECTIVE
To lay down a procedure for operation & calibration of polarimeter.
2.0
RESPONSIBILITY
Q.C. Chemist / Q.C Executive.
3.0
ACCOUNTABILITY
Manager Q.C.
4.0
PROCEDURE
4.1
OPERATION
4.1.1.Following are the keys present on the instrument:
STOP
4.1.2.
FILE
HELP
Zero
START
Switch on the instrument power supply, and wait for few minutes.
4.1.3.
As soon as the power is switched on ,the monitor shows the companys name and go on
initializing For 5.13 minutes.
4.1.4
After that the Instrument is in the "READY" mode for automatic operation indicated by
READY. Display :
4.1.5.
Lift the door of the sample compartment and place the sample cell filled with media in which
sample is prepared (ensure that no air bubbles are there ). Push ZERO keys for zero clearing.
4.1.6.
4.1.7.
ANGLE OF ROTATION
13.33
26.61
39.86
53.06
66.23
Harmonization of format.
STERILITY TESTING
1.0
OBJECTIVE
RESPONSIBILTY
Microbiologist/ Q.C Executive
3.0
ACCOUNTABILITY
Quality Control Manager
4.0
PROCEDURE
4.1
4.1.2
4.1.3
Disinfect LAF station wth 70% filtered IPA solution & check the
ABBREVIATIONS :
REFERENCES
USP 25 Page no.:- 1878 , E.P: - Page no. 125 , 2.6.1
7.0
ANNEXURE- I
QUANTITIES OF THE PRODUCT TO BE EXAMINED IN THE TEST OF STERILITY (AS PER
E.P)
Type of
Quantity per
preparation
container
Parenteral
preparations
Liquids
Less than 1 ml
1 ml or more
Solids
Less than 50
mg
50 mg or more
150 mg
more
MINIMUM NUMBER OF ITEMS RECOMMENDED TO BE TESTED(AS PER E.P)
Number of items in the batch
10 containers
containers
More than 500 containers
ANNEXURE -II
STERILITY TEST REPORT
(MEMBRANE FILTRATION METHOD)
Page 01 of 02
SAMPLE QTY.
BATCH NO.
MFG. DATE
EXP. DATE
QTY./BATCH SIZE
DATE OF
SAMPLED BY
SAMPLE
SAMPLING
DATE OF TEST
DATE OF REPORT
ANALYZED BY
MEDIA PREPARATIONS
.DATE OF PREPARATION
.DATE OF PREPARATION
MEDIA BATCH NO
TEST RESULT
NAME OF
MEDIA
NO. OF DAYS
10
11
12
13
14
GROWTH
OBSERVED
NAME OF
MEDIA
NO. OF DAYS
10
11
12
13
14
10
11
12
13
14
10
11
12
13
14
GROWTH
OBSERVED
NEGATIVE CONTROLS
NAME OF
MEDIA
NO. OF DAYS
GROWTH
OBSERVED
NAME OF
MEDIA
NO. OF DAYS
GROWTH
OBSERVED
POSITIVE CONTROLS
MEDIA
FLUID THIOGLYCOLLATE
MEDIUM
MEDIUM
DAYS
S. aureus
NA
C albicans/A
+v
+v
+v
+v
+v
niger
ve
ve
C. sporogenes
NA
INFERENCE:
+v
+v
+v
+v
+v
+v
ve
+v
+v
+v
+v
+v
+v
ve
NA
-ve : - No growth
and
+ve : - Growth
MICROBIOLOGIST
SIGN / DATE
MANAGER QA/QC
SIGN / DATE
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s:
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OBJECTIVE
To lay down the procedure for checking correctness of the computerized formulation order issue
system.
2.0
RESPONSIBILITY
Production Planning Supervisor / Quality Control Chemist
3.0
ACCOUNTABILITY
Production Planning Manager / Quality Assurance Manager
4.0
PROCEDURE
4.1.
4.2.
Manufacturing Date
4.3.1.
The formulation order printed in the month of Jun2005 shall have the manufacturing
date
as Jun 2005.
4.3.2.
Expiry Date
Check the expiry date of active Ingredient(s), against Analytical Report Number (AR. No.)
Mentioned in the formulation order. Check the correctness by comparing with expiry date
mentioned in COA. Following guideline shall be followed while assigning Expiry for the
product.
4.4.
Domestic Products
The expiry date of the Finished Product shall be as per the expiry date of the product or expiry
date of its active Ingredient (s), whichever is earlier. Products having multiple active
ingredient(s) shall have expiry of Raw Material having the least expiry.
4.5.
Export Products
The expiry date of the Finished Product shall be as per the Shelf life assigned in Master
Formula.
4.6.
4.6.1.
MASTER FORMULA
Check the Formulation Order against the master formula issued by Product Development
Laboratory for following.
4.6.1.1. Code No.
4.6.1.2.Ingredient(s)
4.6.1.3.Batch Quantity
4.6.2.1. Collect potency and moisture data of the active ingredients issued in the formulation order by
referring to the Certificate of Analysis from Quality Control and check the same with the
formulation order.
4.6.2.2. Calculate the actual quantity of active ingredients to be issued by referring to the
formula
specified in the Master Formula given by Product Development Laboratory and
the quantity of
the Filler.
4.6.2.3. Check the correctness of the quantity by comparing with quantity mentioned in Formulation
order.
4.7.
4.7.1. Check the First in First out System for any two ingredients issued in Formulation
order.
4.7.2. In case of active ingredients, Check for the material in stock having less expiry
than that of the
issued material. If there is no stock of material having less
expiry, the First out system shall be
followed.
4.7.3.
After taking out the Formulation Order, check Analytical Report Number wise stock on
computer screen. In case of other ingredients, If there is no stock of previous Analytical Report
Number in the system, the First in-First out principle shall be considered to be followed.
4.8.
4.8.1.
4.8.2.
4.8.3.
4.8.4.
FREQUENCY OF VALIDATION
Five Formulation Orders of different products shall be checked during each Calendar Month
4.10. ABBREVIATIONS:
AR No. = Analytical Reference Number
COA = Certificate of analysis
5.0.
6.0.
TRAINING:
Trainer
Period -7.0.
One day
DISTRIBUTION:
Certified Copy No. 1 : Head of Department Quality Control
Original Copy
: Head QUALITY ASSURANCE.
8.0.
ANNEXURES :
Annexure I Investigation report.
Annexure II General Check List.
9.0.
REFERANCE
In-house
ANNEXURE-1
Investigation report
Revision No.: 00
Effective from:
Page No. : 1 of 1
Date
Product
Batch Number
Market
Batch Size
Date
Sl.
No.
Ingredients
AR.
No
Data
from
Potency
Manual
Calculation
Moisture
Expiry
Date
As per
formulation
Actual
Quantity
Sign
Remarks
Quantity
ITEM
A. Manufacturing Date
Revision No.: 00
Effective from:
Page No. : 1 of 1
CHECKED
SIGN
B. Expiry Date
C. Master Formula
DONE BY
CHECKED BY
Numbering system for Standard Operating Procedures and Index of Standard Operating
Procedure
1.0
OBJECTIVE :
To lay down a procedure for operating of pH meter.
2.0
RESPONSIBILITY
Chemist / Executive.
3.0
ACCOUNTABILITY
Manager Q.C
4.0
PROCEDURE
4.1. OPERATION
4.1.1.
4.1.2.
Clean the electrodes with purified water and wipe with tissue paper.
4.1.3.
4.1.4.
To check the pH of the sample by dipp electrode in the sample solution taken in a suitable
container.
4.1.5. .Push READ bottom ,it beep .When reading be stable by showing [A]
record the results.
4.1.6.
Remove the electrode from the sample solution, wash with purified water and place in a
beaker of fresh purified water.
NOTE : ENSURE THAT THE TEMPERATURE OF THE SOLUTION IS
WITHIN 23C - 27
4.2.
In three, dry separate beakers take 1 buffer tablet of pH 4.0, 7.0 and 9.2
respectively.
4.2.2. Add 70 ml of Distilled Water to dissolve the tablets.
4.2.3. Transfer the preparation from beakers to clean 100 ml volumetric flasks
separately.
4.2.3. Rinse the beakers with distilled water and transfer to the volumetric
flasks.
4.2.4. Make the volume accurately to 100 ml with Distilled Water in each case.
4.2.5. Transfer the prepared buffer solutions of pH 4.0, pH 7.0, pH 9.2, in three
different
bottles, appropriately labeled.
4.2.6. Affix the labels on the bottles indicating the USE BEFORE---- Date of solution.
4.2.7.
4.3.
Clean the electrode with purified water and wipe excess water with tissue
paper.
4.3.2.
Deep electrode in pH 4.0 buffer and push CAL bottom, after stabule ,record the result
.Repeat the process with pH 7.0 and pH 9.2 buffers .
4.3.3.
4.4.4.
4.4.6.
4.5.
While checking the pH of buffer 4.0, 7.0 and 9.2 clean the electrode with purified water
every time.
After use keep the electrode dipped in the purified water .
4.4.5. Record the results in the format attached Annexure-1.
If the results of calibration are not conforming to the specified limits report to eh department
head for an appropriate action.
FREQUENCY
Daily
4.6.
ACCEPTANCE CRITERIA
0.05 pH
5.0
Harmonization of format.
6.0
TRAINING:
Trainer
Period -7.0
One day
DISTRIBUTION:
Certified Copy No. 1 :
Certified Copy No. 2:
Original Copy
8.0
ANNEXURES:
Annexure I. Format for calibration of pH meter.
9.0
REFERENCES:
ANNEXURE I
FORMAT FOR pH METER CALIBRATION
Revision No.
MAKE
: 00
Effective Date:
SERIAL No :
MODEL :
DATE
Page No.: 1 of 1
Ref. SOP :
CLEANLINESS
Limits
STANDARD BUFFERS
DONE BY
4.0
7.0
9.2
4.0
0.05
7.0
0.05
9.2
0.05
CHECK
BY
pH Meter
OPERATION AND CALIBRATION OF POLARIMETER
OPERATION AND CALIBRATION OF REFRACTOMETR
OPERATION AND CALIBRATION OF ANALYTICAL BALANCE
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OBJECTIVE
2.0
RESPONSIBILITY
3.0
ACCOUNTABILITY
4.0
PROCEDURE
4.1.0
4.1.1
Check that the air bubble is in the center of the level & if necessary adjust the
level by turning the leveling screws.
4.1.2
4.2.1
4.2
Calibration Procedure :
4.2.0
Internal calibration
Ensure that the balance pan is not loaded & the doors of the weighing chamber is
closed properly.
4.2.2
4.2.3
Press Enter button the balance will displays CAL TYPE '
4.2.4
Then press Enter button the balance will display CAL TYPE ' InCAL
4.2.5
Then again press Enter button the balance will display INCAL
After a few seconds the balance will display CAL SET & then return to WEIGH
mode & displays as WEIGH 00000.
4.3
4.3.1
4.4
4.4.1
4.4.2
4.4.3
Remove the weight & again place the weight on the pan & record the
display once again.
4.4.4
Repeat the above operation to get ten readings Calculate the standard
deviation of ten readings.
4.4.5
4.4.6
4.4.7
Report any discrepancy noted at the time of calibration to Q.C Manager &
notify the defect to rectify the instrument. & affix an UNDER MAINTENANCE label
on the instrument.
4.5
FREQUENCY OF CALIBRATION:
Daily
5.0.
Harmonization of format
6.0
TRAINING:
Trainer
Trainees
-- Chemist / Assistants
Period
-- One day
7.0
DISTRIBUTION:
9.0
ANNEXURES:
ANNEXURE -I Attached.
ANNEXURE -II Attached.
9.0
REFERENCES:
In house/Manufacturer Manual
ANNEXURE -I
FORMAT FOR BALANCE CHECKING
Revision No.
MAKE
MODEL
SERIAL No
DAT
E
CLEANLIN
ESS
: 00
Effective Date:
STANDARD WEIGHTS
50 mg
100 mg
1 gm
Page No.: 1 of 1
DONE
BY
10 gm
50 gm
CHECKE
D BY
Limits
50mg
0.1
100mg
0.1
1g
1mg
10g
10 mg
50g
50 mg
ANNEXURE -II
FORMAT FOR CALIBRATION FOR MEASUREMENT UNCERTAINTY
Revision No.
Effective Date:
Name of
Instrument
Instrument Ser.
No.
: Analytical Balance
Calibration date
Calibration due on
MEASURED UNCERTAINTY :
S.No.
1
2
3
Displayed weight
(X)
: 00
Page No.: 1 of 1
4
5
6
7
8
9
10
Standard deviation ( ) =
3 x
CALIBRATED BY
APPROVED BY
Analytical balance-Libror
OPERATION AND CALIBRATION OF REFRACTOMETR
OPERATION AND CALIBRATION OF POLARIMETER
Analytical balance- Mettler Toledo
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OPERATION AND CALIBRATION OF BURSTING STRENGTH TESTER
1.0.
OBJECTIVE:
1.2
2.0.
RESPONSIBILITY:
2.1
2.1.1.
2.1.2.
2.1.3.
2.1.4.
3.0.
ACCOUNTABILITY:
4.0.
PROCEDURE:
4.1.
CLEANING PROCEDURE:
4.1.1.
Switch OFF Power Supply of the equipment before cleaning. Clean the
equipment with a dry cloth every day.
4.1.2.
If necessary wet cloth shall be used for effective cleaning it shall be dried
immediately using a dry cloth.
4.2.
OPERATING INSTRUCTIONS
4.2.1.
Switch On the mains. This will bring the plunger to its starting positions. If the
plunger is already at its starting position, motor will not start on switching ON main.
4.2.2.
4.2.3.
4.2.4.
The tripod plate shall tightened to apply sufficient clamping pressure in such a
way that sample does not slip.
4.2.5.
Select the gauge [II] for 3 ply shippers and partitions and gauge [I] for 5 ply and
7 ply shippers.
4.2.6.
Set the maximum hand of the gauge at zero or a point on the scale below the
point at which bursting will occur.
4.2.7.
Push the RED push button and keep it pressed so that plunger will start rotating
in clockwise direction till sample bursts. The push button is released as soon as the
sample bursts. Note down the gauge reading in Analytical Test Reports.
4.2.8.
Release the pressure on the test piece by rotating the clamp wheel in anti-cock
wise direction and remove the sample specimen.
4.3.
4.3.1.
4.3.2.
CALIBRATION PROCEDURE
4.3.3.
Take the standard Aluminium foil of 5.4 Kg / cm 2 for Gauge II and 9.5 kg / cm 2
for Gauge I provided by the manufacturer.
4.3.4.
4.3.5.
4.3.6.
4.3.7.
Acceptance Criteria
4.4.
Frequency of calibration:
4.4.1.
Quarterly.
5.0
6.0.
TRAINING:
Trainer
Trainee
--
Period
--
One day
7.0.DISTRIBUTION:
Original Copy
8.0.ANNEXURE:
Annexure 1
Tester
9.0.REFERENCE:
Manufacturers Manual.
ANNEXURE 1
FORMAT FOR CALIBRATION RECORD OF BURSTING STRENGTH TESTER
Revision No.: 00
Effective from:
Instrument no.
Name of instrument
Frequency
Page No.: 1
of 1
:
:
Quarterly
Gauge I
(Lt. 9.0 to 10.0
kg /cm2)
Gauge II
(Lt. 5.2 to 5.6
kg /cm2)
Calibrate
d by
Checke
d by
Rema
rks
OPERATION
OPERATION
OPERATION
OPERATION
AND
AND
AND
AND
CALIBRATION
CALIBRATION
CALIBRATION
CALIBRATION
OF
OF
OF
OF