2.up Apt R - D A Who Pediatrics 52

Pharmaceutical Development
Training Workshop on
with focus on
Paediatric Formulations
Tallinn
15-19th October 2007
Training Workshop on Pharmaceutical Development

Slide 1
with a Focus on Paediatric Medicines 15-19 October
2007
Pharmaceutical Development of
Finished Pharmaceutical Products
(FPPs)
Presenter: Susan Walters
Email: susanw@netspeed.com.au

Slide 2
2007
The Australian view of the world
We are
here!
This place
isn’t too
bad either!

Slide 3
2007
What Australia gave to the world (1)

Slide 4
2007
What Australia gave to the world (2)

Slide 5
2007
Pharmaceutical Development of FPPs
Outline of presentation
We will:
 Look at the development process as a whole & consider
its objectives
 Review relevant guidelines
 Review sources of information
 Go through a worked example

Slide 6
2007
Objectives of Pharmaceutical Development :
What is the purpose?
From the perspective of a generic manufacturer,

the objective is to develop a product that is:
 of appropriate quality, and
 interchangeable with the innovator brand
(so we can avoid .....expensive & time-consuming

studies.....of safety & efficacy)

Slide 7
2007
Objectives of Pharmaceutical Development :
What is the purpose?
From the perspective of the manufacturer of a new dosage form

&/or strength (eg a paediatric dosage form),
the objective is to develop a product that is:
 Of appropriate quality, &
 Of appropriate dosage form & strength, &
 Either has been shown to be safe & effective for the claimed
indications & patient population
or has been shown to .....pharmacokinetically interchangeable
with a brand.....that has been shown to be safe & effective for
the claimed indications & patient population
However safety & efficacy is outside the scope of this presentation so I will deal only with
generics that contain the same API in the same dosage form & strength as the innovator.

Slide 8
2007
Slide 9
2007
DEVELOPMENT OF A DOSAGE FORM
Define drug & dosage regime
for the indication
:Consider
Suitable routes of administration- A
Suitable dosage forms-
Consider :Determine
Review pharmacokinetic Relevant- Review
literature :characteristics of API physicochemical literature
data data
Half life, Cmax, AUC- characteristic of API
and/or and/or
conduct BCS classification (if- Stability of API under- conduct
own )oral route stress conditions own
studies Compatibility of API - studies
Determine & prepare for with common excipients
studies likely to be
required relating to
BA/BE
SELECT
A DOSAGE FORM & B
STRENGTH
B A
Source of possible
formulations & manufacturing
:procedures
Innovator excipients- :Consider
Your company’s prior- Suitable formulation &-
experiences manufacturing procedures
Prepare
Commercially available-
draft
&formulations
prescribing
manufacturing procedures Prepare early batches & information
WHO ‘startpoint’ formulation- test relevant
: characteristics including
Dissolution rate-
Stability-
Pilot BE study, if-
necessary
Define
Apply optimization
design space
techniques / validate
formulation & method of
manufacture
D
C
C D
:Conduct
Confirmatory stability studies-
Confirmatory dissolution studies- Finalise
Final BE study, if needed- prescribing
information
Submit application
for qualification
Product & process development
(sorry don’t know the source of this diagram)
CONTINUOUS
IMPROVEMENT

Slide 13
2007
Terminology –
from ICH Q1A(R2) 2003 (stability)
Production batch:
– A batch of a drug substance or drug product manufactured at
production scale by using production equipment in a production
facility as specified
Pilot scale batch:

– A batch of a drug substance or drug product manufactured by a
procedure fully representative of and simulating that to be applied to
a full production scale batch. For solid oral dosage forms, a pilot
scale is generally, at a minimum, one-tenth that of a full production
scale or 100,000 tablets or capsules, whichever is the larger.
Laboratory scale batch [not an ICH definition]

- A batch smaller than pilot scale that is manufactured for
development purposes
Remember that scale-ups must be validated – batch characteristics may
change during scale-up

Slide 14
2007
Relevant non-WHO guidelines
 ICH Q8 Pharmaceutical Development (2005)
 ICH Q9 Quality Risk Management (Nov 2005)
 ICH Q10 Pharmaceutical Quality System (May 2007)
 Note for guidance on Process Validation

CHMP/QWP/848/96 (EU 2001)
– An elderly guideline but informative & helpful

Slide 15
2007
Relevant WHO guidelines
 Pharmaceutical Development, Section 3.2 of Guideline on

Submission of Documentation for Prequalification of Multi-
source (Generic) Finished Pharmaceutical Products (FPPs)
Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis,
WHO PQP (2005)
 Extension of the WHO List of Stable (not easily degradable
ARV) APIs, Supplement 2 (Rev 1) to Guideline on
Submission of Documentation for Prequalification of Multi-
source (Generic) Finished Pharmaceutical Products (FPPs)
Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis,
WHO PQP (2005)
 Supplementary guidelines on
Good Manufacturing Practices: Validation, Annex 4 to WHO
TRS 937 (2006)
Slide 16
2007
Some relevant journals
 Pharmaceutical Technology  European Journal of

Pharmaceutics and
 Pharmaceutical Technology Europe Biopharmaceutics
 Pharmaceutical Industry  Pharmazie in Unserer Zeit (often
in German)
 Pharmaceutical Development and
Technology  S.T.P. Pharma Pratiques (often in
French)
 Drug Development & Industrial
Pharmacy  Pharmaceutisch Weekblad (often
in German)
 Pharmaceutical Manufacturing
 Dissolution Technologies - A free on-
line journal at It is often possible to obtain access
http://www.dissolutiontech.com/ to journals via university on-line
databases

Slide 17
2007
Some relevant websites
 http://www.who.int/medicines/en/.
– WHO medicines program.
 http://mednet3.who.int/prequal/
– WHO prequalification program.
 http://www.ich.org
– ICH website
 http://www.emea.europa.eu/htms/human/humanguidelines/background.
htm
– European guidelines for human medicines
 http://www.fip.org/www2/sciences/index.php
– international Pharmaceutical Federation: Pharmaceutical Sciences section
 http://www.accessdata.fda.gov/scripts/cder/dissolution/index.cfm
– Dissolution methods for drug products

Slide 18
2007
How can we optimise the possibility of
developing an acceptable product? - 1
 Form a development team
– Include staff with experience in formulation, manufacturing, quality
control, stability testing
 Prepare a development plan, set goals & timelines, and monitor

progress with regular meetings (eg weekly in the first instance)
 Make use of experienced staff within your company, especially in

relation to manufacturing equipment & procedures
 Review the literature for information on:

– Chemical & physicochemical properties of the API(s)
– Information on the innovator product
Slide 19
2007
 Conduct experiments to fill in the gaps in information,

– Especially concerning API properties & compatibilities
 If possible, use the same excipients as the innovator.

– Less likely to encounter problems with compatibility, stability,
bioequivalence
 If possible, use standard manufacturing procedures with which your

company has experience
– More likely to achieve suitable dissolution properties &
reproducible manufacturing

Slide 20
2007
BOTTOM LINE:
– Ensure our product meets WHO criteria for quality, stability &
interchangeability
– Ensure our product has similar dissolution characteristics as the

innovator at various pH
– May need to confirm bioequivalence with the innovator

• See Annex 8 to WHO TRS 937 (2006) Proposal to waive in vivo
bioequivalence requirements for WHO Model List of Essential
Medicines immediate-release, solid oral dosage forms

Slide 21
2007
What are the chemical & physicochemical properties of
API(s) that we need to know, or are at least useful?
 Solubility at various pH
 Acid or base?
 pKa & partition coefficient
 Stability under stress (eg oxygen, moisture, acid etc)
 Compatibility with common excipients

Slide 22
2007
What literature should we look for?
Look for……
 A WHOPAR, if one is available for your product

– See http://mednet3.who.int/prequal/default.htm. Look for WHO
Public Assessment Reports under Quick Links on the RH side of
the page
 Innovator documentation.
– Can often be found on the innovator website.
– The prescribing information is especially useful & often includes a
list of excipients.
 A drug approval package (DAP) via http://www.fda.gov/cder/foi/nda/
 An EPAR (European Public Assessment Report)

Slide 23
2007
What literature should we look for?
Look for……
 An official monograph in the Ph Int
 A monograph in Clarke’s Analysis of Drugs and Poisons, published

by The Pharmaceutical Press (latest edition 2004).
 A monograph in The Merck Index, published by CambridgeSoft
(latest edition 2001).
 Regulatory information
– See for example the WHO information line e-
drug@healthnet.org.

Slide 24
2007
Case study:
A new brand of Nevirapine 50mg/5 ml
oral suspension - 1
Why do we need to know the chemical structure?

 To determine whether the active is an acid, base or neutral
 To assist in devising assay procedures
 To determine likely compatibilities/incompatibilities
– Based on a knowledge of organic chemistry
 To inform other decisions & predictions that are based on chemistry

Slide 25
2007
Case study:
A new brand of Nevirapine 50mg/5 ml
oral suspension - 2
 We plan to develop a paediatric product that contains the same active in the
same dose & dosage form as an existing paediatric product.
 The innovator is Boehringer Ingelheim. The innovator brand name is

Viramune® 50 mg/5 mL oral suspension.
 The product under development is a multisource (generic) product.
 The quality, safety & efficacy of the existing product have been established.
 The product will be an oral suspension containing 50 mg of nevirapine in

each 5 mL. The drug is present as an equivalent quantity of the hemihydrate
API.
– Note that the API is often a salt or solvate of the active ingredient. In
this case the API is the hemihydrate of nevirapine.

Slide 26
2007
What useful sources of information
did we find?
 An EPAR at
http://www.emea.europa.eu/humandocs/PDFs/EPAR/Viramune/109697en6.pd
f
 A drug approval package (DAP) at http://www.fda.gov/cder/foi/nda/98/20-

933_20-636S009_Viramune.htm
 A letter of approval at http://www.fda.gov/cder/ogd/rld/20933s3.pdf
 An official monograph in the Ph Int.
 A monograph in Clarke’s Analysis of Drugs and Poisons, published by The

Pharmaceutical Press 2004.
 A monograph in The Merck Index, published by CambridgeSoft 2001.
 Regulatory information concerning a possible impurity in the API. See

http://www.medicalnewstoday.com/articles/82050.php
Slide 27
2007
What useful information did we find?
(1)
 Nevirapine is lipophilic (partition coefficient

83) & is essentially nonionized at
physiological pH
 As a weak base (pKa 2.8), nevirapine
shows increased solubility at acidic pH
 The aqueous solubility (of the anhydrate)
is 90 μg/ml at 25°C
 Nevirapine is generally stable when

stressed

Slide 28
2007
(2)
 There are two crystal forms of the API
 No polymorphic changes were observed under stressed conditions
 The API (hemihydrate) is non-hygroscopic
 The synthesis of the two crystal forms is similar until the final drying step
 The impurity profile is well characterised
 Impurities arising from the synthesis have been toxicologically qualified
 No degradation products were detected during stability testing of the API
 The API is milled in order to obtain an acceptable particle size distribution for the
suspension
 Nevirapine is official in the Ph Int
 Batch analysis data confirmed that nevirapine hemihydrate complies with the
specifications

Slide 29
2007
(3)
 The innovator markets an oral suspension (Viramune ® 50 mg/5 ml)

containing nevirapine (present as the hemihydrate at 10.35 mg/ml).
– That is….the active is nevirapine & the API is nevirapine hemihydrate
 Excipients in the innovator formulation are:
– Carbomer 934P (synthetic high molecular weight crosslinked
polymers of acrylic acid), methyl & propyl hydroxybenzoates, sorbitol,
sucrose, polysorbate 80, NaOH, purified water.
 The shelf life of the innovator is 3 years.
– The product should be used within 2 months of opening (‘in-use’
stability).
 The innovator has no special precautions for storage

Slide 30
2007
(4)
 The innovator’s container is a white HDPE bottle with two piece child-
resistant closure (outer shell white HDPE, inner shell natural
polypropylene) with LDPE foam liner. Each bottle contains 240 ml of oral
suspension.
 Included with the innovator product is a clear polypropylene 5-ml
dispensing syringe (0.2 ml graduations) with silicone rubber piston seal,
and a clear low density polyethylene bottle-syringe adapter.
See
http://www.emea.europa.eu/humandocs/PDFs/EPAR/Viramune/109697en
6.pdf
http://www.fda.gov/cder/ogd/rld/20933s3.pdf
 A monograph (Ph Int) is being developed for the FPP, nevirapine oral
suspension
– NB check the WHO website for the latest information
Slide 31
2007
(5)
 The HDPE bottle is inert & has been shown to be compatible with the active
substance & other ingredients of the innovator’s formulation.
 % content of antimicrobial preservatives has been correlated with

antimicrobial effectiveness when tested according to Ph Eur methodology
 Acceptable data are available to demonstrate the precision & accuracy of the
innovator’s dosing syringe
 None of the synthesis impurities are degradants
 The method of preparation of the oral suspension is standard for this dosage
form & has been well described. Validation data presented for three (3)
production batches manufactured using three (3) different lots of nevirapine
demonstrated that the process is under control & ensures both batch-to-
batch reproducibility & compliance with standard specifications. Tests at
release are typical & ensure reproducible performance of the product.

Slide 32
2007
(6)
 Stability data are available for up to 18 months for the innovator.

Long-term stability data have been promised on an ongoing basis.
 An in-use stability study has been performed that mimics delivery of

a 2 mL dose, representing one of the lowest projected doses using
the delivery device intended for marketing
 An additional study has been conducted on the stability of the

product exposed to freeze-thaw conditions
 On the basis of results from these studies, an in-use shelf life of 60

days with no special storage precautions is claimed

Slide 33
2007
(7)
In vivo data provided by the innovator included the following :
 Nevirapine is readily absorbed (> 90 %) after oral administration in healthy
volunteers & in adults with HIV-1 infection.
 A 3-way crossover study comparing the bioavailability of three (3)
production/commercial scale batches that had varying dissolution profiles
showed that all three (3) batches were bioequivalent with respect to systemic
exposure (AUC). The statistically significantly different values for Cmax and
tmax were considered not to be clinically relevant.
 In studies in which the suspension was administered directly using a syringe, it
was demonstrated that the suspension & tablet formulations were comparably
bioavailable with respect to extent of absorption.
 In a study in which the suspension was administered in a dosing cup without
rinsing, the suspension intended for marketing was bioequivalent to the
suspension used during clinical trials but was not bioequivalent to the
marketed tablets. This was attributed to incomplete dosing of the two
suspensions since there was about 13 % of the dose remaining in the cup.
Slide 34
2007
(8)
 Based on adult experience, a comparable lead-in period of two

weeks was suggested for paediatric population. A 4 mg/kg dose is
proposed for all children regardless of age. Although no particular
study has been performed to find the optimal lead-in dose, this
dose was considered acceptable considering the enzyme induction
to achieve initial antiretroviral activity.
 The following doses were approved:

– Patients from 2 months to 8 years, 4mg/kg once daily for 2
weeks followed by 7mg/kg twice daily
– Patients from 8 years to 16 years, 4 mg/kg once daily followed
by 4mg/kg twice daily

Slide 35
2007
Benchmarking the innovator
(these slides were taken from a presentation by János Pogány )
(1)
 Obtain a sample for confirmation of characteristics
– Batch numbers
– Shelf life: 3 years and within 2 months of opening.
– Storage instructions: No special precautions for storage
– Container and closure system: as per EPAR
 QC analysis (hypothetical figures)

– Assay: 99.9% of labelled amount (LA)
– Methylhydroxy benzoate (HPLC): 0.18% w/v
– Propylhydroxy benzoate (HPLC): 0.02% w/v
– Total related substances: 0.03%
– Specific gravity (at 25oC): 1.150
– Viscosity (at 25oC): 1,150 cPs
– pH: 5.80

Slide 36
2007
(2)
The qualitative composition
suggests that:
 Sucrose and sorbitol are used

to adjust the density of the
medium
 Carbomer 934P is used to

adjust viscosity
 Polysorbate is a wetting agent
 Sodium hydroxide is used to

adjust the pH to 5.8

Slide 37
2007
Our tests show…..
(3)
Time (minutes) % API dissolved  Dissolution profile (% labeled
(hypothetical figures) strength)
5 27
 Apparatus: USP II (paddle, 25 rpm)
10 42
 Medium: 0.1N HCl
15 55
 Volume: 900ml
20 65
See
30 76 http://www.accessdata.fda.gov/scrip
ts/cder/dissolution/dsp_SearchResu
45 88 lts_Dissolutions.cfm downloaded
on 13 March 2007
60 92

Slide 38
2007
Our tests show…..
(4)
% API dissolved % API dissolved % API dissolved
(hypothetical (hypothetical (hypothetical
figures) figures) figures)
Time (minutes) pH 1.2 buffer pH 4.5 buffer pH 6.8 buffer
5 27 15 22
10 42 25 27
15 55 36 35
20 65 42 42
30 76 48 49
45 88 49 57
60 92 49 65
90 100 50 76
Dissolution profile (% LA), Apparatus: USP II (paddle, 25rpm), Volume: 900ml – Different
speeds to be investigated
Slide 39
2007
Pharmaceutical development protocol
 API experiments
– Particle size distribution
 Formulation experiments
– Screening laboratory batches with different proportions of
excipients to match innovator dissolution
– Stress testing of the selected composition
– Compatibility with excipients
– Antimicrobial effectiveness test according to Ph Eur
 Packing materials
– Dimensions and tolerances of packing components
– Precision & accuracy of the dosing syringe

Slide 40
2007
Product-specific API properties
 Ph Int specifications + limits on residual solvents from API manufacture
 Product-specific physical properties depend on crystallization and

subsequent physical processing.
 Density and particle size distribution of nevirapine hemihydrate are

critical quality attributes.
 Acceptance criteria are established by measurement of particle size of

innovator’s API in suspension & through the similarity of dissolution
profiles of innovator and generic products.

Slide 41
2007
Undertake stress testing of the API
if not already available in existing documentation
Stress type Conditions Assay (%)
Control 25o C 99.8
36% HCl 80o C, 40 min. 72.0
5N NaOH 80o C, 2h 20’ 98.6
30% w/w H2O2 80o C, 2h 20’ 98.6
Heat 130o C, 49h 101.5
Light 500 W/m2, 68h 101.7
Water 25o C, 92% RH, 91h 101.2

Slide 42
2007
Solubility of nevirapine hemihydrate at 37oC
If not already available in existing documentation
Note:
 Nevirapine hemihydrate belongs to BCS2 (low solubility, high
permeability)
– See Annex 8 to WHO TRS 937 (2006)
 Solubility data are also important for cleaning validation
Slide 43
2007
Dissolution profiles of
innovator & generic FPPs
Hypothetical data
M
e
a
n
% innovator ▀
A generic ▀
P
I
d
Similarity
i factor
s
s f2=73
o
l
v
e
d
Time (minutes)

Slide 44
2007
Selected generic composition
Hypothetical numbers
Ingredients mg/5 ml
 Active
– Nevirapine hemihydrate 51.7
 Excipients
– Carbomer 934P 7.0
– Methyl parahydroxybenzoate 9.0
– Propyl parahydroxybenzoate 0.9
– Sorbitol 900.0
– Sucrose (!) 500.0
– Polysorbate 80 4.0
– Sodium hydroxide q.s.
– Purified water to make 5.0 ml

Slide 45
2007
Proposed FPP specifications
A hypothetical set of limits
 Description: including at least colour, texture, odour

 Identification (HPLC)
 Dissolution (UV): Q = 70% in 45 minutes
 pH = 5.0 – 6.1
 Deliverable volume
– Average fill volume: NLT 240 ml
– Fill volume variation: Meets Ph Int requirements
 Related substances: NMT 0.1% of any one imp & NMT 0.3% total imps
 Preservative content (HPLC)
– Methylparaben: 98 to 102% of labeled strength
– Propylparaben: 98 to 102% of labeled strength
 Assay: 95.0 to 105.0% of labeled strength

Slide 46
2007
Compatibility with excipients
May not need to do this if use only
the same excipients as the innovator
Nevirapine hemihydrate in solid state – illustrative example: heat

Slide 47
2007
Development of
manufacturing process
 Select a standard process for oral aqueous suspensions, if possible using our
existing method
 Manufacture a lab scale batch
– If necessary make adjustments & manufacture another lab scale batch
 When satisfied with the formulation, manufacture a pilot scale batch
– If necessary make adjustments & manufacture another pilot scale batch
– Recollect that a pilot batch is manufactured by a procedure fully representative
of and simulating that to be applied to a full production scale batch
 Manufacture primary* batches in the proposed container & closure systems for:
– Bioequivalence & dissolution studies
– Regulatory stability studies (including an in-use stability study & a stress study
under freeze-thaw conditions)
– Validation of bioequivalence, dissolution & stability batches
* Primary as defined in WHO/ICH guidelines

Slide 48
2007
Development of
manufacturing process
Note that the progress from pre-formulation to

formulation to pilot manufacture to production
scale manufacture
 should be described in the PQP dossier, shown to be
logical,
reasoned and
continuous

Slide 49
2007
Scale up activities
 Test a large number of samples from pilot scale batches to establish
provisional acceptance limits for the control of critical process parameters
(prospective validation, in-process control limits) in order to
 define the design space* & a control strategy that encompasses batch
scale, equipment, packaging, as well as final product stability. The
process will be well understood when:
– all critical sources of variability have been identified & explained
– variability is managed by the process
– product quality attributes can be accurately & reliably predicted
 A validation protocol is written
* See ICH Q8, Q9 & draft Q10 for further explanation

Slide 50
2007
Dissolution & bioequivalence testing
Innovator FPP Generic FPP

Conduct a dissolution test Select a production batch, or
on at least 3 batches one NLT 1/10th of final size
Select a batch showing
intermediate dissolution
Reference product Test product
Dissolution profile
Bioequivalence study

Slide 51
2007
Summary and conclusion
The probability of producing a product that is:

- Of high quality
- Stable
- Consistent from batch to batch, &
- Bioequivalent to the innovator
can be significantly improved by employing:

 a planned & systematic approach to product
development, &
 using all the information that has been published

Slide 52
2007

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Pharmaceutical Development

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

From the perspective of a generic manufacturer,

 of appropriate quality, and

 interchangeable with the innovator brand

(so we can avoid .....expensive & time-consuming

Training Workshop on Pharmaceutical Development

From the perspective of the manufacturer of a new dosage form

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

Pilot scale batch:

Laboratory scale batch [not an ICH definition]

Training Workshop on Pharmaceutical Development

 ICH Q8 Pharmaceutical Development (2005)

 ICH Q9 Quality Risk Management (Nov 2005)

 ICH Q10 Pharmaceutical Quality System (May 2007)

 Note for guidance on Process Validation

Training Workshop on Pharmaceutical Development

 Pharmaceutical Development, Section 3.2 of Guideline on

 Pharmaceutical Technology  European Journal of

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

 Prepare a development plan, set goals & timelines, and monitor

 Make use of experienced staff within your company, especially in

 Review the literature for information on:

 Conduct experiments to fill in the gaps in information,

 If possible, use the same excipients as the innovator.

 If possible, use standard manufacturing procedures with which your

Training Workshop on Pharmaceutical Development

– Ensure our product has similar dissolution characteristics as the

– May need to confirm bioequivalence with the innovator

Training Workshop on Pharmaceutical Development

 pKa & partition coefficient

 Stability under stress (eg oxygen, moisture, acid etc)

 Compatibility with common excipients

Training Workshop on Pharmaceutical Development

 A WHOPAR, if one is available for your product

Training Workshop on Pharmaceutical Development

 An official monograph in the Ph Int

 A monograph in Clarke’s Analysis of Drugs and Poisons, published

Training Workshop on Pharmaceutical Development

Why do we need to know the chemical structure?

Training Workshop on Pharmaceutical Development

 The innovator is Boehringer Ingelheim. The innovator brand name is

 The product under development is a multisource (generic) product.

 The product will be an oral suspension containing 50 mg of nevirapine in

Training Workshop on Pharmaceutical Development

 A drug approval package (DAP) at http://www.fda.gov/cder/foi/nda/98/20-

 A letter of approval at http://www.fda.gov/cder/ogd/rld/20933s3.pdf

 An official monograph in the Ph Int.

 A monograph in Clarke’s Analysis of Drugs and Poisons, published by The

 A monograph in The Merck Index, published by CambridgeSoft 2001.

 Regulatory information concerning a possible impurity in the API. See

 Nevirapine is lipophilic (partition coefficient

 Nevirapine is generally stable when

Training Workshop on Pharmaceutical Development

Training Workshop on Pharmaceutical Development

 The innovator markets an oral suspension (Viramune ® 50 mg/5 ml)