Documentos de Académico
Documentos de Profesional
Documentos de Cultura
FDA 20049
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1
2
3
Chank@2006
1987
GMP
/-
1
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1
2
3
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4
-;-;-
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1
2
3
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Chank@2006
1987
Chank@2006
Quiz-
1
A.
B.
C.
D.
E.
FDAGMP
1987
FDA
2
A.
B.
C.
D.
E.
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1
2
3
Chank@2006
21 CFR 211
211.42(b)
211.42(c)
211.46(b)
211.46(c)
211.63
211.65(a)
211.67(a)
211.113(b)
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-ISO 5
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Chank@2006
ISO
b
6
(0.5m/)
c
(cfu/)
c,d
(90mm, cfu/4)
100
3,520
1e
1e
1000
35,200
10,000
352,000
10
100,000
3,520,000
100
50
a.
b.
/
ISO 14644-1A
c.
d.
e.
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0.5m3520/
1
Chank@2006
X.E
Chank@2006
(Ref. 3).8
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FDA
ISO 7)
ISO 6) ISO 5)
ISO
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10-15Pa9
.
(Ref. 4).
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12.5Pa).
Chank@2006
10
ISO 8
20
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-
.
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FDA
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-HEPA)11
HEPA
HEPA
Chank@2006
-
HEPA
(Dioctylphthalate
DOP) (poly-alpha-olefin, PAO)
12 . HEPA
99.97%0.33mm.
Chank@2006
-
13, 0.3mm
12
Chank@2006
-
0.01%
HEPA
HEPA
6
HEPA
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HEPA
Chank@2006
14
(Ref. 4)
.
Chank@2006
(SIP)
15
Chank@2006
( 1).
Chank@2006
HEPA
,
Chank@2006
211.63)
Chank@2006
Quiz-
1
A.
B.
C.
D.
E.
7cfu/m3
0.3m3520/
2
A.
B.
1
C.
D.
E.
0.45/
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Quiz-
3
A.
FDA
B.
10-15Pa
C.
D.
12.5Pa
E.
20
4
A.
B.
C.
D.
E.
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Quiz-
5
A.
B.
C.
D.
E.
6
A.
0.3m
B. DOPPAOHEPA
C. HEPA99.97%0.3m
D. HEPAHEPA
E.
Chank@2006
1
2
3
Chank@2006
21 CFR 211
211.22(a)
211.22(c)
211.25(a) (b) (c)
211.28(a) (b) (c) (d)
211.42(c)
211.113(b)
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
(Ref. 5)
Chank@2006
Chank@2006
Quiz-
1
A.
B.
C.
D.
E.
2
A.
B.
GMP
C.
D.
E.
Chank@2006
1
2
3
Chank@2006
/
21 CFR 210 211
210.3(b)(3)
211.80(a)
211.80(b)
211.84(d)
211.94(c)(d)
211.113(b)
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Chank@2006
16
IX
USP
()
Chank@2006
/
/-
USP
Chank@2006
/
/-
99.9%(3 LogsVII17.
Chank@2006
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/-
IX C
EtO)EtO
EtO
EtO
EtO
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/
/-
USP
IX.C
Chank@2006
/
/-
CGMP
211.84(d)(3),
COA
Chank@2006
211.192
Chank@2006
Quiz-
1 Ascorbic Acid Injection USP NMT1.2EU/mg,
A.
Ascorbic AcidNMT1.2EU/mg
B.
1.2 EU/mg
C.
Ascorbic acid injection
NMT1.2EU/mg
D.
USP
E.
0.24EU/mg
2
A.
B.
C.
D.
E.
Chank@2006
Quiz-
3
A.
B.
C.
D. 99%
E.
4
A. USP
B. USP
C. USP
D. USP
E.
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1
2
3
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21 CFR 211
211.63
211.65(a)
211.67(b)
211.94(c)
211.167(a)
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GMP
,
67
GMP
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.
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1
2
3
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21 CFR 211 211.111
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1
2
3
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21 CFR 211
211.63
211.65
211.67
211.84(c)
211.100(a)
211.113(b)
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Chank@2006
18 .
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.
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FDA
.
Chank@2006
500010000
5000
Ref. 8
1)
Chank@2006
Chank@2006
HVAC
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,
USPQCUSP
100CFU
19
Chank@2006
20-352.5
14
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QCQC
QC
FDA
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VI.B
Chank@2006
20
10
Chank@2006
-
FDA
21
Chank@2006
-
QC
Chank@2006
(Ref. 8, 9)
<5000
5000-10,000
1
2
1
2
>10,000
Chank@2006
Section 301(a)
21 U.S.C. 331(a)(
. FDA
.
Chank@2006
22
0.2mm23
Chank@2006
107CFU/cm2 ,
Chank@2006
Chank@2006
(1)
(2) pH,
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Chank@2006
(Ref. 12).
Chank@2006
Chank@2006
(211.67 211.113).
24
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-
SPI
FDA
Chank@2006
Chank@2006
10-6
FDA/-
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FDA
Chank@2006
Chank@2006
COA
D
D
D
Chank@2006
SIP
Chank@2006
Quiz-
1
A.
B.
C.
D.
E.
2
A.
B.
C.
D.
5000
E.
Chank@2006
Quiz-
3
A.
B.
7
C.
USP
D.
QC
E.
100-300CFU
4
A.
0.22m
B.
[Brevundimonas diminuta (ATCC 19146)]
C.
10-7/cm2
D.
pH
E.
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Quiz-
5
A.
B.
C.
D.
E.
/
10-7
6
A.
5000,
B.
500010000
,
C.
10000,
D.
10000,
E.
500010000
,
Chank@2006
1
2
3
Chank@2006
21 CFR 211
211.22(b)(c)
211.42(c)
211.56(b)(c)
211.110(a)
211.113(b)
211.160(b)
211.165(e)
211.192
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Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
-
SOP
(1)
(2)
(3)
(4)
(5)
(6)
(7)
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-
/
/
70%Bacillus spp.)
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A .
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-
B.
,
FDA
25
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-
C.
Chank@2006
ISO 8)
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Chank@2006
3035487220-25
57
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USP
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IV.A
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Quiz-
1
A.
B.
C.
D.
E.
2
A.
B.
C.
D.
E.
Chank@2006
1
2
3
Chank@2006
21 CFR 210211
210.3(b)(21)
211.110(a)
211.160(b)
211.165(a)(e)
211.167(a)
211.180(e)
211.192
Chank@2006
Chank@2006
Chank@2006
CFR211.194211.165
USP <71>
Chank@2006
USP
10% (Ref.
13). 10,000
0.1%20
98%
Chank@2006
CGMP
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
Chank@2006
FDA
Chank@2006
Chank@2006
Chank@2006
Quiz-
1 C
A.
B.
C.
D.
E.
USP <71>
2
A.
B.
C.
D. USP
E.
Chank@2006
1
2
3
Chank@2006
21 CFR 210211
210.3(b)(21)
211.110(a)
211.160(b)
211.165(a)(e)
211.167(a)
211.180(e)
211.192
Chank@2006
211.188
HEPA/HVAC,
Chank@2006
211.100
211.192)
Chank@2006
1
2
3
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Chank@2006
Chank@2006
1
-
Chank@2006
1
-
FDA
Chank@2006
1
-
Chank@2006
1
-
Chank@2006
1
-
17.5Pa50Pa26.
ISO 5)
Chank@2006
1
-
ISO 5)
ISO 8)
Chank@2006
RTPs)
HEPA-
Chank@2006
1
-
Chank@2006
1
-
Ref.13)
27
46
(Ref. 14).
Chank@2006
1
-
Chank@2006
SIP)
Chank@2006
Chank@2006
211.113)
Chank@2006
Quiz-
1
A. 25-50Pa
B. 6
C.
D.
E.
Chank@2006
1
2
3
Chank@2006
2
/
Chank@2006
2
(BFS)
Chank@2006
BFS
()
Chank@2006
(1) , (2)
(3)(
BFS
SIP)
Chank@2006
BFS
BFS
HEPA
BFS
BFS
V
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BFS
Ref 15
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BFS
Chank@2006
2
/
BFS
Chank@2006
2
/
BFS
BFS
Ref.17
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BFS
211.100
211.192
Chank@2006
Quiz-
1 BFS
A. /
B.
C.
D.
E.
Chank@2006
1
2
3
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3
CBERCDER
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26
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IX.A
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1
2
3
Chank@2006
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
ISO 14644-1: Cleanrooms and Associated Controlled Environments, Classification of Air Cleanliness.
NASA Standard for Cleanroom and Work Stations for Microbially Controlled Environment, Publication NHB 5340.2
(August l967).
Technical Order 00-25-203, Contamination Control of Aerospace Facilities, U.S. Air Force, December l, l972.
Ljungqvist, B., and Reinmuller, B., Cleanroom Design: Minimizing Contamination Through Proper Design;
Interpharm Press, 1997.
Lord, A. and J. W. Levchuk, "Personnel Issues in Aseptic Processing," Biopharm, 1989.
Morbidity and Mortality Weekly Report, "Clinical Sepsis and Death in a Newborn Nursery Associated with
Contaminated Medications" Brazil, 1996, Centers for Disease Control and Prevention, July, 1998; 47(29);610-2.
Grandics, Peter, Pyrogens in Parenteral Pharmaceuticals, Pharmaceutical Technology, April 2000.
Recommendations of PQRI Aseptic Processing Working Group, Product Quality Research Institute; March, 2003.
Technical Report No. 36, Current Practices in the Validation of Aseptic Processing," Parenteral Drug Association,
Inc., 2002.
Leahy, T. J. and M. J. Sullivan, Validation of Bacterial - Retention Capabilities of Membrane Filters,"
Pharmaceutical Technology, Nov., l978.
Pall, D. B. and E. A. Kirnbauer, et al., "Particulate Retention by Bacteria Retentive Membrane Filters," Pall
Corporation Colloids and Surfaces, l (l980) 235-256, Elsevier Scientific Publishing Company, Amsterdam.
Technical Report No. 26, "Sterilizing Filtration of Liquids," Parenteral Drug Association, Inc., 1998.
Sigwarth, V. and A. Stark, Effect of Carrier Materials on the Resistance of Spores of Bacillus stearothermophilus to
Gaseous Hydrogen Peroxide, PDA Journal of Pharmaceutical Science and Technology, Vol. 57, No. 1,
January/February 2003.
Isolators used for Aseptic Processing and Sterility Testing, Pharmaceutical Inspection Convention Cooperation
Scheme (PIC/S); June, 2002.
Price, J., Blow-Fill-Seal Technology: Part I, A Design for Particulate Control, Pharmaceutical Technology, February,
1998.
United States Pharmacopoeia
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Some relevant FDA guidance documents include:
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Air lock- A small room with interlocked doors, constructed to maintain air pressure control
between adjoining rooms (generally with different air cleanliness standards). The intent of an aseptic
processing airlock is to preclude ingress of particulate matter and microorganism contamination from a lesser
controlled area.
Alert Level- An established microbial or airborne particle level giving early warning of potential
drift from normal operating conditions and triggers appropriate scrutiny and follow-up to address the
potential problem. Alert levels are always lower than action levels.
Action Level- An established microbial or airborne particle level that, when exceeded, should
trigger appropriate investigation and corrective action based on the inverstigation.
Aseptic Manufacturing Area- The classified part of a facility that includes the aseptic
processing room and ancillary cleanrooms. For purposes of this document, this term is synonymous with
aseptic processing facility as used in the segregated segment context.
Aseptic Processing Room- A room in which one or more aseptic activities or processes is
performed.
Asepsis- A state of control attained by using an aseptic work area and performing activities in a
manner that precludes microbiological contamination of the exposed sterile product.
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Critical Area - An area designed to maintain sterility of sterile materials. Sterilized product,
containers, closures, and equipment may be exposed in critical areas.
Critical surfaces- Surfaces that may come into contact with or directly affect a sterilized product or its
containers or closures. Critical surfaces are rendered sterile prior to the start of the manufacturing operation, and
sterility is maintained throughout processing.
Decontamination- A process that eliminates viable bioburden via use of sporicidal chemical agents.
Disinfection- Process by which surface bioburden is reduced to a safe level or eliminated. Some
disinfection agents are effective only against vegetative microbes, while others possess additional capability to
effectively kill bacterial and fungal spores.
DD value- The time (in minutes) of exposure at a given temperature that causes a one-log or 90 percent
reduction in the population of a specific microorganism.
Dynamic- Conditions relating to clean area classification under conditions of normal production.
Endotoxin- A pyrogenic product (e.g., lipopolysaccharide) present in the bacterial cell wall. Endotoxin
can lead to reactions in patients receiving injections ranging from fever to death.
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HEPA filter- High efficiency particulate air filter with minimum 0.3 mm particle
retaining efficiency of 99.97 percent.
Isolator- A decontaminated unit, supplied with Class 100 (ISO 5) or higher air quality,
that provides uncompromised, continuous isolation of its interior from the external environment (e.g.,
surrounding cleanroom air and personnel). There are two major types of isolators:
Closed isolator systems exclude external contamination from the isolators interior by accomplishing material
transfer via aseptic connection to auxiliary equipment, rather than use of openings to the surrounding
environment. Closed systems remain sealed throughout operations.
Open isolator systems are designed to allow for the continuous or semi-continuous ingress and/or egress of
materials during operations through one or more openings. Openings are engineered (e.g., using continuous
overpressure) to exclude the entry of external contamination into the isolator.
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Laminar flow- An airflow moving in a single direction and in parallel layers at constant
velocity from the beginning to the end of a straight line vector.
Operator- Any individual participating in the aseptic processing operation, including line
set-up, filler, maintenance, or other personnel associated with aseptic line activities.
Sterile Product- For purposes of this guidance, sterile product refers to one or more of
the elements exposed to aseptic conditions and ultimately making up the sterile finished drug
product. These elements include the containers, closures, and components of the finished drug
product.
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http://www.fda.gov/cder/guidance/5882fnl.pdf
Chank:
chank@etang.com
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