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WHO/VSQ/97.

02
:
:

GMP

2.

WHO/VSQ/97.02
:
:

GMP

2.

1999 .
3


,
.

( GMP)
1.
2.
:
1: WHO/VSQ/97.01
2: WHO/VSQ/97.02







1997 .
1999 .
:

http://www.who.int/gpv-documents/
:
World Health Organization
Department of Vaccines and Other Biologicals
Document Centre
CH-1211 Geneva 27, Switzerland
: + 22 791 4193/4192 . : vaccines@who.ch
, 1999 .
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24

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27

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31

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2:

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36

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3:

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39

11.
:
IQ, OQ PQ
11.1 : IQ, OQ PQ ,
(HVAC)
IQ HVAC

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HVAC.

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IQ,
IQ.
QA
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a) :
()
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:

40

IQ HVAC ()
1




(. )


( )
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(%)

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OQ HVAC

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42

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OQ HVAC ()
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QA.

44

PQ HVAC

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45

PQ HVAC ()
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TRS 823, 1, 1992 .

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46

PQ HVAC ()

( , TRS 823 . 39)

3

A
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C
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0.5-5
3500

> 5

3500
350 000
3 500 000

2000
20 000



3
1
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500


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209 (1992 .)
: 100 ( ), 10 000 (
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47

PQ HVAC ()

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B (a)
C (a)
D (a)
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5
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350 000
2000
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B, C D ,
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( USP)
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SI
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(3)
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3530
1000
35 300
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(3)
100
2000**
20 000**
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* 209, 11 1992 .
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USP


3.5
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100
10 000
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20
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USP
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5 (: 10)
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A
B
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100
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_________________
* : Regulatory and Industry News, PDA Letter, January 1996.

48

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(IES) (. 17)

6.1

6.2
6.3
6.4
6.5
6.6
6.7
6.8
6.9
6.10
6.11-6.13
6.14

1,2,3

1,2,3

1,2,3

1,2,3
1,2
1,2,3
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1,2
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/

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1,2,3

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1,2

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1, (2,3) 1, (2,3)

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49

11.2 : IQ, OQ PQ
IQ

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51

OQ ()
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52

PQ

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3 2
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54

11.3 : IQ OQ PH-
IQ pH-

, pH-, __________________ ,
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pH- .

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( pH-).
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pH ,
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pH- , , ,
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pH-
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pH- , Z
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55

IQ pH- ()
:

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pH-
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56

OQ pH-

, pH-, ________ ,
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pH- .

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,
pH 4, 7, 10.
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Z.

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pH- :
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57

11.4 ,
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IQ,
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58


a) IQ :
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6) ;
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59


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60


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61

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13.

: ________________________________________ . __ ___
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(): _________________________________________________
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QA (): __________________________ : ____________

,

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64

: ________ .__ __
: ______________________
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, ,

( ,
, ).
/ :
_________________________________________________________________________
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, (
) ( , ).
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) ( ,
).
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65

: ________ .__ __
: ______________________
: ________________

66



:
.

.
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.
QC.

.

().
.

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).

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.

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QA .

.

: ________ .__ __
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67

________________________________________________________________________________
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68

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69

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70

: ________ .__ __
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: ___________________________________ : ________________

71

: ________ .__ __
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QA (): ______________________________ : ________________

72

14. ,


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GMP ,
).

73


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25-35 C.
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1/1000, 3000 ). 5
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.

74



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)

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75

15.


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76

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50 %.

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(accuracy)
.

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% (
/ 100 %).
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,
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77

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78

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/ (freeze/thaw stability),
,


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79


(. 16, 21)
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.
(%) = .
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a)
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.
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).
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CV .
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).

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80


, LOD ,
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21).
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.
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81

16.

: ________________________________________ . __ ___
: ____________________
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QA (): __________________________ : ____________

,

.
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.

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82

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).

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.

83

: ________ .__ __
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84

: ________ .__ __
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85

: ________ .__ __
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86

: ________ .__ __
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:

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87

17.

17.1
,

.
,

. , ,
. -
.

17.2
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89

1:


, ,
, .
,
.
A.
1. -
2.
3.
4.
5.
B. (IQ/OQ/PQ)
1.
2.
3.
4.
5.
6.
7.
C. (IQ/OQ/PQ)
1.
2. ()
3.
D. (IQ/OQ/PQ)
1. ()
2.
E. (IQ/OQ/PQ)
1.
2.
F. (IQ/OQ/PQ)
1.
a.
b.
c.
d.
e. ( )
2.
a.

90

b.
3.
a.
b. CO2
G. (IQ/OQ)
1.
2.
3.
H. (IQ/OQ)
1.
2.
I.
1. () (IQ/OQ/PQ)
a.
b.
c.
2. / (IQ/OQ/PQ)
a.
b.
3.
4. (IQ/OQ/PQ)
a. (EtO)
5.
J.
1. (CIP)
a.
b.
2. (SIP)
3.
a.
b.
c.
d.
e.
f. ()
K.
1. (IQ/OQ/PQ)
a.
b. ( )
c. ( )
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c. ( )
3. //
L.
1.
2.
M. ( )
1.

91

a.
b.
2.
3.
a.
b.
c.
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N.
1.
a.
b.
c.
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1.
a.
b.
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2.
a.
b. -
3.

a.
i.
ii.
b.
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a. , 1
b. , 2, 3 ..
c. ,
5.
P. / (, ,
)
1. /
2.
3.
4.
5. //
Q.
1.
2.
3.
4.
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1. ( )
2. /
3.
a.
b. ()

92

2:
,

,
, ,
.

,
. ,
.

- , ,
MPHBL ,




Partlow IV



Finn-Aqua
Finn-Aqua


Finn-Aqua
Foxboro

Chromalox

1995 .



HVAC
1995 .




100
100


Met-One

93





IQ
OQ


PQ , ,

PQ
PQ HVAC




Sorvall ( )


RCS- (Biotest)


,
MPHBL
OQ





NIST

,

, QC
QC


Biomanguinos/FIOCRUZ,
()
,
( )



pH-


94

Gerencia General de Biologicos y Reactivos, ()


: ( )
l
l
l
l
l
l
l
l
l
l
l
l




2 ( )



IQ
OQ
PQ

. :
. cGMP (cyclic guanosine monophosphate ).

95

3:

1) Agalloco, J., "Points to Consider" in the Validation of Equipment Cleaning Procedures,


Volume 46, No. 5, PDA Journal of Pharmaceutical Science and Technology, Sept/Oct
1992, pp. l63-168.
2) Austin P.R., Design and Operation of Pharmaceutical Bio-cleanrooms and Aseptic
Areas. Contamination Control Seminars, Michigan, 1994.
3) Australia. Therapeutic Goods Administration, Australian Code of Good Manufacturing
Practice For Therapeutic Goods-Medicinal Products, August 1990.
4) Canada, Drugs Directorate Guidelines. Acceptable Methods. Health Protection Branch,
Health Canada, 1994.
5) Canada, Drugs Directorate Guidelines. Good Manufacturing Practices (GMP) Guidelines,
Consultation Draft Fourth Edition. Health Protection Branch, Health Canada, 1995.
6) Chapman K.G., Fields T.J., Smith B.C., "Q.C." Pharmaceutical Technology, January
1996, pp. 74-79.
7) Commission of the European Communities. Analytical Validation (July 1989). Guidelines
on the Quality, Safety and Efficacy of Medicinal Products for Human Use, The Rules
Governing Medicinal Products in the European Community, Volume III (addendum July
1990).
8) Commission of the European Communities. Development Pharmaceutics and Process
Validation (April 1988). Guidelines on the Quality, Safety and Efficacy of Medicinal
Products for Human Use, The Rules Governing Medicinal Products in the European
Community, Volume III, 1988.
9) Commission of the European Communities. Guide to Good Manufacturing Practice for
Medicinal Products. The Rules Governing Medicinal Products in the European
Community, Volume IV, Jan 1992.
10) Commission of the European Communities. Stability Tests on Active Ingredients and
Finished Products (July 1988). Guidelines on the Quality, Safety and Efficacy of
Medicinal Products for Human Use, The Rules Governing Medicinal Products in the
European Community, Volume III, 1988.
11) DeSain C., Documentation Basics That Support Good Manufacturing Practices.
Advanstar Communications, OH, 1993 (from Interpharm Press).
12) DeSain C., Master Method Validation Protocols, Documentation Basics, BioPharm,
June 1992.
13) Green C., Cleaning Validation Programs: How to Get Started. Volume 1, Number 1,
Journal of Validation Technology, Oct/Nov 1994, pp. 46-51.
14) Guide to Inspections of Validation of Cleaning Processes, Interpharm, July 1993.
96

15) Guideline for Good Manufacturing Practice in Egypt, Faculty of Pharmacy, Cairo
University, Central Administration of Pharmacy, WHO, 1994.
16) Institute for Applied Pharmaceutical Sciences. Division of Center of Professional
Advancement. Quality Assurance and Control for Biotechnology, Feb. 1994.
17) Institute of Environmental Sciences. Testing Cleanrooms, Contamination Control
Recommended Practice 006.2, IES-RP-CC006.2.
18) International Organization for Standardization. Accuracy (trueness and precision) of
measurement methods and results: ISO 5725-1, ISO 5725-2, ISO 5725-3, ISO 5725-4,
ISO 5725-6, Geneva, 1994.
19) Lanese J., A Model Standard Operating Procedure for Validation, The Documentation
Department. Vol. 1, Number 4, Journal of Validation Technology, August 1995, pp. 6077.
20) Levchuk J.W, Good Validation Practices: FDA Issues. Volume 48, No. 5, PDA Journal of
Pharmaceutical Science and Technology, Sept-Oct 1994, pp. 221-223.
21) Little Laureen E., Validation of Immunological and Biological Assays.
BioPharm, November 1995 pp. 36 42.
22) Naglak T.J., Keith M.G., Omstead D.R., Validation of Fermentation Processes. BioPharm,
July-August 1994, pp. 28-36.
23) PDA Commentary: EU Guide to Good Manufacturing Practice, Annex on the
manufacture of Sterile Medicinal Products (Draft 4, III/5805/94, 19 June 1995), PDA
Letter, Jan 1996, p. 16.
24) Pedersen H.L., Validation of Manufacturing Processes for Drug Substances: An PDA
Perspective. Volume 1, Number 4, Journal of Validation Technology, August 1995, pp. 7ll.
25) Reeks B.D., The Validation of Steam Sterilisers. Tutorial No. 2, The Parenteral Society,
1990.
26) The Gold Sheet, FDA's Inspection Concern for Bulk Pharmaceutical Chemical Firms,
Quality Control Reports, The Gold Sheet, FDC Reports Inc., 1995.
27) The Use of Process Simulation Tests in the Evaluation of Processes for the Manufacture
of Sterile Products, Technical Monograph No. 4, The Parenteral Society, June 1993.
28) U.S. Code of Federal Regulations, Current Good Manufacturing Practice for Finished
Pharmaceuticals (Part 211), Food and Drug Administration, DHHS, 21 CFR CH. l, 4-1-95
Edition.
29) U.S. Code of Federal Regulations, Current Good Manufacturing Practice in
Manufacturing, Processing, Packing or Holding of Drugs; General (Part 210), Food and
Drug Administration, DHHS, 21 CFR CH. l, 4-1-95 Edition.
30) US-FDA. Guide to Inspections of High Purity Water Systems. July 1993.
31) US-FDA. Guideline on General Principles of Process Validation, Center for Drugs and
Biologies and Center for Devices and Radiological Health, PDA Cat. No-FDAGL-4, May
1987.
32) US-FDA. Guideline on Sterile Drug Products Produced by Aseptic Processing. Center for
Drugs and Biologies and Office of Regulatory Affairs, June, 1987.
97

33) US-FDA. International Conference on Harmonisation; Guideline on Validation of


Analytical Procedures: Definitions and Terminology; Availability. DHHS, Federal
Register Vol. 60, March 1, 1995, p. 11260.
34) US-FDA. Validation of Analytical Procedures: Methodology. Extension of: Text on
Validation of Analytical Procedures, Department of Health and Human Services, FDA,
Vol. 61, No. 46, Docket No. 96D-0030, 1996.
35) USP. Microbiological Evaluation of Clean Rooms and Other Controlled Environments
<1116>, In-Process Revision, Pharmacopeial Forum, The United States Pharmacopeial
Convention, Inc., Volume 21, Number 2, March-April 1995.
36) USP. Validation of Compendial Methods <1225>, General Information, The United States
Pharmacopeia 23, 1995.
37) WHO Expert Committee on Biological Standardization, Good Manufacturing Practices
for Biological Products. Technical Report Series No. 822 Annex 1, WHO Geneva, 1992.
38) WHO Expert Committee on Specifications for Pharmaceutical Preparations, Validation of
Analytical Procedures used in the Examination of Pharmaceutical Materials. Technical
Report Series No. 823 Annex 5, WHO Geneva, 1992.
39) WHO Expert Committee on Specifications for Pharmaceutical Preparations. Good
Manufacturing Practices for Pharmaceutical Products. Technical Report Series No. 823
Annex 1, WHO Geneva, 1992.
:
40) Sharp J., Validation - How Much is Required?. PDA Journal of Pharmaceutical Science
and Technology, May-June, 1995, pp. 11-118.

98

, :
Australia: Therapeutic Goods Administration: GMP Audit and Licensing Section, PO Box
100, Woden, ACT 2606.
BioPharm: Advanstar Communications, Marketing Services, 7500 Old Oak Blvd,
Cleveland, OH, 44130, USA.
Canada: Publishing Division of Canada Communications Group, Ottawa, Canada,
K1AOS9.
Commission of the European Communities: Office of Publications of the European
Communities, 2 rue Mercier, L-2985, Luxembourg.
Institute for Applied Pharmaceutical Sciences: 144 Tices Lane, East Brunswick New Jersey,
08816, USA.
Institute of Environmental Sciences: 940 East Northway Highway, Mount Prospect, Illinois,
60056, USA.
International Standards Organization: Geneva, Switzerland.
Interpharm Group of Companies: 1358 Busch Parkway, Buffalo Grove,Illinois, 60089,
USA.
Parenteral Drug Association (PDA) 7500 Old Georgetoen Road, Suite 620Bethesda
Maryland. 20814, USA.
Parenteral Society, The: 6 Frankton Gardens, Stratton St Margaret,Swindon,
Wiltshire.
U.S. Code of Federal Regulations (CFR): Superintendant of Documents,US Government
Printing Office, Washington DC 20402, USA.
United States Pharmacopoeia (USP): US Pharmacopeial Conventions Inc., Order
Processing Dept, PO Box 2248, Rockville, Maryland, 20852, USA.
U.S. Food and Drug Administration: Office of Regulatory Affairs, 5600 Fishers Lane,
Rockville Maryland, 20857, USA.
World Health Organization: Office of Publications, WHO, Geneva, Switzerland.

100

4:

(
3. ).
(acceptance criteria)

.
, ,

. (19)
(accuracy) ,
,
( ),
( , ),
( ),
.
. (7)
(analytical procedure)
.
.
( ):
, /
, ,
, ..
(33)
(bias)
() .
(
) (
). , -

. (4)
(calibration) ,

( ),
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,
.
,
. (39)

101

(change control) ,
, ,
, ,

.

, ,
.

,
. (19)
(coefficient of determination (R2))
,
.
, .
,
. (4)
/ (coefficient of variation (CV))
,
. CV
(relative standard deviation (RSD)). (4)
(control) -,
,
,
.
.
. (4)
(correlation coefficient (r))
.
.
1, . (4)
(critical areas) ,
/
. (32)
(critical parameter) ,
,
,
. (19)
(critical process) ,
. (39)
(critical surfaces) ,
/
. (32)

102

D- (D value) ( ) ,
90 %. (32)
/ (freeze/thaw stability)

.

. /
() . ,
/
0 5 . ,

. (21)
(front-to-back)
, ,
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. , ,

. (21)
(installation qualification (IQ))
,
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) -,
,
/
. (19)
() (intermediate precision)
,
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-, .. (33)
(intra-assay precision)
.
(33)
(limit of detection (LOD))
, ,
. LOD
. (7)
(limit of quantitation (LOQ))

,

.

103

, ,
/ . (33)
(linearity)
( )
, ()
. (7) (33)
(lot-to-lot precision)
,

, , ,
. (21)
(operating range) ,

. (19)
() (operational qualification (OQ))
,

- ,
, GMP (,
, , ..).
(19)
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, 12-

D- 1 . (32)
(performance qualification (PQ))
, ,

, ,
,
, ,
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. (19)
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.
,
(q. v.).

. , ,

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,
104

. (33)
. (7)
(process system)
,
(, HVAC, ,
..),
.
GMP (,
, , ),
,
. (19)
(prospective validation)

,
,
.
.
,
100 . ,
. (19)
(protocol) ,
,
,
.

. (19)
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,
,
. PAR

.
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PAR
,
. (19)
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,
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).
(range)

105


( ),
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. (7)
(reference standard)
.
,
, , USP .



.
(
)
. (4)
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, : -, ,
, . (7)
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,
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,

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106

, -.
. (4)
(selectivity) . (specificity).
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(

).
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, ),
-
,
. (4)
-
= 100
- +
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.
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) ,

. (33)
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,
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107

( ) . (4)
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Pseudomonas diminuta
107 2 ,
. (32)
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, , :
,
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108

,
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5:
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109

-
1)
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-

: /
: 1
: 11GN018

: B. Rost & D.Povey
: 5 1995 .
: 20/01/94
:
:
:
QA:
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. 1 9
:

I.


,
,
.

, .

II.


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, ,
, ,
.

III.

-
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, (IQ)
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(PQ)
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. QA

, .

110

, QA,

,
(
IPQA-007).
: 11GN018
: 1
. 2 9
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IV.

V.



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, 11GN011 11GN012
,
.
A. :
, (HVAC).
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.
( Crown),
SMMA 15990.

2. (OQ): HVAC
, .
:
a.
b.
c.
d.
e.
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.


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,
.
.
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.

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.
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, .

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.
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11EN022).
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.
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6. 11GN009 MPHBL
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8. 11GN011
9. 11GN012
10. 18EN001 -

11. 18EN003 (E-048) -
Ingersoll-Rand
12. 18EN004 (E-049) -
Sullair
13. 18EN005 (E-050) -
Van-Air
14. 18EN007 -
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15. QC D2a
16. QC D22

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M.A. Strege, J.J. Dougherty, W.R. Green, and A.L. Lagu (1994) Total Protein Analysis of
Swab Samples for the Cleaning Validation of Bioprocess Equipment. BioPharm. Non. 1994
pp. 40-42.

VIII.


3.03.95

,
, 1.0 %
SDS 50 Na3PO4.
,
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121

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CIP/COP
: ____________________

: _______________________

1. : ________________________________________
2. CIP/COP (): _____________________________________________
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3. .

//

QC
( /100 2)

QC: _________________________________________ : ______________________


QC (): ___________________________ : _______________________

: 3/95
:

122

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: -26
QA:

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__________________________________________________________________________________

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:
:
(): ___/___/___ Val-G3 ____
(): ___/___/___ Val-G ____ /
A.
B.
C.
D.
E.
F.
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I.


1.
2.
3.
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1. /

2.

III.


1. /
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123

H.
1.

2.
: 4/93
:

: 1/93
:
3.08.93

: 17
QA:

IPQC-097
:
5.08.93

-



:

(): ___/___/___ Val-G ____


(): ___/___/___ Val-G ____ /
/

A.

B.

C.

D.

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F.

I.


1.
2.
3.

/
/
/

II.
III.

/
VAL-G

1. /
Val-G , G.

124

VAL-G

2.
14

: 4/93
:

: 1/93
:
3.08.93

: 17
QA:

IPQC-096
:
5.08.93

-

: __________________________

: __________________ : _____________
: _____________________ : _________________
.
.
/
: _____________________ : ___________________

( )
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/

( )
: ______________________________

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/: _________

: VALG- ________

: ______________ Val G- _______________


: ______________ Val G- _______________
:
: ________________ : _____________________ (VAL G- ________________) /
(): _______________________
: _____________________ (VAL G- ________________)
:
: ________________ : _____________________ (VAL G- ________________) /
(): _______________________
: _____________________ (VAL G- ________________)
, / :
____________________________ (VAL G- ________________)
, / :
____________________________ (VAL G- ________________)

125

QC B11
: 12/91

. 2 3

-

: _________ VALG- _______________ VALG- _______________

.
.
.
/
: _____________________________ : _______________

( )

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: ______________________ (VAL G- __________________ )
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(.. I II, ):
__________________________________________________________________________________
: __________________________________________________________________

__________________________________________________________________________________

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( )

14 :
/

QC

126

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/ /
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:
/
: __________________________________________________________________
_______________________________________________________________ /
/. _____________________ : _____________
QC B11
: 12/91

VAL-G 4.11.94
. 1 2




: ( ) , ,
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:

_______________________________________________________________________________
:

116-N006

18.11.94

VAL G 110494

TSB-153

BG-34

1 :

1.25

17 100

3 47

127

1-5
RODAC -
:
:
100:-----G.McN/fc

128

VAL-G 4.11.94
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24
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0.5 1
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6
7
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9 10 11 12 13 14 15 16 17 18 19
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0

21
1

22
1

23
1

: .
(): ___________________________
(): ___________________
:

30.11.94

QA (): 30.11.94

129



. 1 2

I.

VAL-G
VAL-G

153

VAL-G

110494

__110494__
__________
__

- ,


____16 965____
______________

______________

/
____________

____16 695_____

( 1 2)

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/ (
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VAL-G 110494
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III.

A
B
C
D
G
H

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( 100)

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-

3
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* D.M.Welch
1.12.94

(): ______________________ :

12.12.94

( )

(): _______________________ :

12.12.94

(/. )

1 VAL-G ________________________

QC-33-AS-19/06/91 (): _________________1.12.94

131

-

()

:
()
_____ 153_______

______

______

(): _________________________ : 07.10.94


(): _____________ : 11.10.94
(): ______________ : 01.11.94
( QA

File #PRBLKCS1.FRP

132

/ . )

,



FR-027



9/02/89

___________

05FX001

Emflon

16/06/94

___________

19FX002

16/09/94

___________

FR-028

11/92

___________

FR-052

7/91

FR-053

8/91

FR-056

4/91

___________

19/2/89

___________

FR-137

5/93

1FX002

23/06/94

___________

11FX001

0.2

16/09/94

___________

FR-041

11/87

FR-109

11/87

___________

______________
______________
______________
______________
______________
______________

___________
___________
___________
___________
___________
___________

________
________
________
________
________
________

_________
_________
_________
_________
_________
_________

_____________________________
_____________________________
_____________________________
_____________________________
_____________________________
_____________________________

():
: 30/11/94
()
133

HDWP WELCH/fc Frac.SOP


G110494 (-153)


.

134

211.28a.001

2/94

211.28a.002

3/94

211.28d.001

10/87

211.67b.002

7/91

211.67b.003

6/92

211.67b.004

6/92

211.67b.001
211.67b.006

5/90
6/91

211.67b.007

6/92

211.67b.008

11/92

211.94d.002

5/91

211.94d.004

5/91

211.94d.005

5/93

211.94d.006

4/93

19FL002

10/94

211.100b.004

8/89


Chase-Logeman
West
(. -4)

,
( BG-34)


Dus

Chase (-3)
(BG34)
BG-34


13 20


13 20


DUS-50

211.100b.006

6/92

211.100b.007

5/90

211.100b.008

10/93

211.100b.010

6/92

11GN006

6/9/94

211.100b.013

6/92

211.100b.014

6/92

211.100b.015

1/91

211.100b.019

4/92

211.100b.020

8/92

211.110a.001

4/94

211.110b.001
211.113b.001

8/93
5/91

211.113b.002

4/89

211.113b.003

12/92

211.188.001

6/93









HIAC/ROYCO,
5250
Getinge (.
4)





Chase



BG-34

():

: 18/11/94

135


(-153)

VAL-G110494

/ (
)

(): _______________________ :

18.10.94

(): __________________________ :

14.11.94

: 14/1092 hg FILL&PACK

136


BG-34

: ___________________________________________________________

: __________________________ : __________________________________

STA

STA

1) Rodac 30-35C _____


: __________ : _________

A
B
C
D
E





,

,

(
)


( )

10 /

()

1 /

3
3


/ ( IPQC-025)
QA.

137

: 3/93

: 11/90

: D4

IPQC-020

. 1 2


BG-34

: ___________________________________________________________
: __________________________ : __________________________________

30-35C _____
STA : _______________ : ________________________

: ____________________________________________________________

-
( )

. . 1
STA

0.03 /3


0.1 /3 3

- /
/3 =
()
_________ / = ____________ /3
( ): / /


/ (
IPQC-025) QA.
: ____________ : _______ (): ____________ : ________
. (): ______________ : ________

: 3/93

: 11/90

: D4

IPQC-020

: 16.4. 93

QA:

: 16.4. 93

138

. 2 2


BG-34

: ___________________________________________________________

: __________________________ : __________________________________

STA
STA

Rodac 30-35C _____


Rodac : __________________ : __________________


(. .)

-
(
)


( )

1
2
3
4
5
6

12 /

3

/ 3

()

2 /

3 / 3

/ 3


/ ( IPQC-025)
QA.
: _____________ : _______ (): _____________ : _________
. (): ________________ : _________
: 3/93

: 11/90

: D4

IPQC-022

139

: 16.4. 93

QA:

: 16.4. 93


BG-34

: ___________________________________________________________

: __________________________ : __________________________________

STA

STA

Rodac 30-35C _____


Rodac : __________________ : __________________


(. .)

-
(
)


( )

1
2
3
4
5
6

12 /

3

/ 3

()

2 /

3 / 3

/ 3


/ ( IPQC-025)
QA.
: _____________ : _______ (): _____________ : _________
. (): ________________ : _________
: 3/93

140

: 11/90

: D4

IPQC-023

: 16.4. 93

QA:

: 16.4. 93

II
-

_____________ : ____________ (): ______________


_____________ : ___________ (): _____________
_____________ : _________ (): ____________
:

___________________________________

_____________________________

(%) ( () () :
Rodac ________________ _____________________ ____________________
: _____________

__________________

_____________________

: _______________________________________________________________
: ____________________

1 ___________________________________ : _____________________________
2 ___________________________________ : _____________________________
():_________________________________ : ____________________________

: 9/93

: 3/93

: D4, F1a

IPQC-24

: 12.10. 93

QA:

: 12.10. 93

141

QC/QA


/
: _______________________________ : ___________________
: _______________________
: __________________________

STA-

Rodac ()
Rodac ()
Rodac - ()

Rodac - ()


( )
/

-
( )
1-
2-
3-

1-

2-

3-

1-

2-

3-

1-

2-

3-

1-

2-

3-

:
l

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______ _________ C .

: _________________________

. : __________________________________

. : /

MPHBL:

, , :

________________________________________________________________________
_______________________________________________
(): ____________________ : _______________________
: _________________________

: 3/93

142

: D4

IPQC-025

. 1 2

,

-154

B2



,

Steritest

,





,







( , , )

(BG9A)



QC
Rodac,
,
()



:
,

B2a
B5a

B5b
B11
B12
B13
B17
B33
D7
D14
D17
E6
F1a
F2
F7
F10

3/92

_____________

14/3/95

_____________

7/91

_____________

7/91

_____________

4/91

_____________

7/95

_____________

12/10/93

_____________

2/11/94
13/01/95

_____________
_____________

5/12/94

_____________

21/04/95

_____________

21/07/94
19/05/93

_____________
_____________

31/07/95

_____________

13/01/95
21/07/94

_____________
_____________

13/04/94

_____________


(): __________________________________ :

17.11.95

143

TSB.VAL
17/11/95

I
-


()

()

________________

: _____________________________________ .
:
HAB-

MVZIG-

MVICMV-

ISG-

BPIG-

TSB-

LIVCMV-

LIVRSV-

: ___________________________________________________
-

()

()

IV

: _________________________________ : __________________________
(): ___________________________ : __________________________
, ,
________________ () ___________ () ____________________
()
( QC)

: 7/94

: 9/93

: 10

IPQC-050

: 1.08.94

QA:

: 1.08.94

144

II
-



___________________________________________________________________________
: ______________ : ______________ : _____________
: ___________________ : _______________________________________

: _______________
: ________________

: ________________
: ________________

: _________________
:_________________

: _________________

: 14 30-35 C

: _________________

/ : _______________
50 / 100 /
:

_______________________
_______________________
_______________________
_______________________

: ___________

30-35 C
_____ _____
______________________
______________________
______________________
______________________


():
______________________
______________________
______________________
______________________

: _____________________________
(): _________________________
:
14 , .
: _________________ /
.
:

(): ___________________________ : ________________________


2
10/91

145

III
-



__________________________________________________________________________________
: ______________ : ______________ : _____________
: ___________________ : _______________________________________

: _______________
: ________________

: ________ : __________
:

: _________________
:_________________

: _________________

30-35 C 14
20-25 C 14
/ : _______________

: _________________

50 /
100 /

50 /
100 /

: ________________________

/ -
: _______________________

__________
__________
__________

___________
___________
___________
___________

30-35 C
____
_____________
_____________
_____________
_____________

()
________
________
________
________

20-25 C
__
___________
___________
___________
___________

()
________
________
________
________

: ___________________________ : _____________________________
(): ______________________

(): _________________________

:
14 , .
: _________________ /
.
:

146

(): ___________________________ : ________________________


2
10/91

147

-

: __________________ -: ______________________ : _________________
: _________ : ___________ : _____________ -: ___________

Bacillus
subtilis
Clostridium
sporogenes

- 3, 4, 7

/*

5
Bacillus subtilis
20-25 C
30-35 C
Clostridium
20-25 C
sporogenes
30-35 C
*
/
:
, : - 7 ,
100 ;
- ;
- / 100.
(): _________
(): ______
: __________________ ___ ___ .
GPQ4: ____________
: __________________ : ______________ (): _________________ : ________________
: 4/96
:
4

: 7/91
:

: 5, 5
QA:

. :
GPQ (growth promotion qualification) .

148

IPQC 387
:

-

: __________________ -: ______________________ : _________________
: _________ : ___________ : _____________ -: ___________

Bacillus subtilis
Candida albicans

Bacillus Subtilis
Candida albicans
*

20-25 C
20-25 C

3, 4,
5


/*

- /
:
, : - 7 ,
100 ;
- ;
- / 100.
(): _________

(): ______
: __________________ ___ ___ .
GPQ: ____________
: __________________ : ______________ (): _________________ : ________________
: 4/96
:

: 7/91
:

: 5, 5
QA:

IPQC 388
:

149

-
,

: Bacillus subtilis / Clostridium sporogenes /
Candida albicans
:

, /

: _______________________ : __________________________
:

__________________________________

- /0.1 :

__________________________________


API5 20E / API 50 CHB / API 20 C / /

: ____________________ : _________________________
:
Bacillus subtilis
(. )

Candida albicans
(. )

Clostridium sporogenes
:

___________
: ______________ : ________ (): ______________ : __________

: 4/96

: 7/91

: 5, 5

IPQC-389

QA:

. :
API (analytical politest identification of microorganisms) [,
] .

150

-


:_________________________________________________________________
: _______________________________
: __________________________
: ___________________________________
( + 9 )

:
_________
_________
_________
________

() ______________ ________

: 11/95

: 11/94

: D7

IPQC-059

:
21.11.95

QA:

:
21.11.95

151

-


:

( / / /)
_____

QC ______________ ________


MPHBL ():

: 11/95

: 11/94

: D7

IPQC-064

:
21.11.95

QA:

152

21.11.95

-



I
__________________________________________________________________________________
:

: ___________

: _____________________________

- : ___________

: ________

_________

- , : ___________
:
__________________________________________________________________________________
( ): _________________________
:

30-35 /20-25 C

( 7- ) : _______ (): __/__/____


( 14- ) : ____ (): __/__/__
1: _________________________
2: ____________________
__________________________________________________________________________________

: _________________ : ______________ %

1.
2.
3.
4.
5.
6.
7.

a) /
b)
c) [
]
d) [
]
8.

________________
________________
________________
________________
________________
________________
________________
________________
________________
________________
________________
________________
(): ________________________

: 3/93

: 6/92

: -6

IPQC-034

:
19.05.93

QA:

:
19.05.93

153

-



II

(): 1. _________________________
: ________________
2. _________________________
: ________________
5 20-25 C
QC GPQ
/
5 30-35 C
QC GPQ
/

(): _________________________________
: 3/93
:

154

: 6/92
:
19.05.93

: ________________

: -6
QA:

IPQC-035
:
19.05.93

-


III A
: ______________________

- : _________

:
/

:
a: /
b:
c:
d:
e:
f:

: 3/93
:

: _________________________
: _________________________
(): __________________

: 6/92
:
19.05.93

: -6
QA:

IPQC-036
:
19.05.93

155

-


III B
: ______________________

- : _________

:
a: /
b:
c:
d:
e:
f:

:
/

- : ___

_________________ ______________
_________________ ______________
_________________ ______________
_________________ ______________
_________________ ______________
. - QC: ______________ /
. ________
QC __________________________
_______________________________________________

: _________________ : ___________
: _________________ : ___________
(): __________ : ___________
: 3/93
:

156

: 6/92
:
19.05.93

- : _____

: -6
QA:

IPQC-037
:
19.05.93

-



IV
: _________________________

: ________________________

- : ___________

- : ______________________

20-25 C _________ / 30-35 C _________


: __________________________

:
?

( , _________ , _________ ,
________________ )
- 100
(%) = = %
-

(): _______________________________

: ________________

(): ___________________________

: ________________

: 3/93
:

: 6/92
:
19.05.93

: -6
QA:

IPQC-038
:
19.05.93

157

-

/

V
: ______________________

:
/

:
a: /
b:
c:
d:
e:
f:

: 3/93
:

158

: 6/92
:
19.05.93

: -6
QA:

IPQC-039
:
19.05.93

II
-

,

___________________________________________________________________________
: Bacillus subtilis / Clostridium sporogenes /
Candida albicans
:

, /

: _______________________ : __________________________
:

__________________________________

- /0.1 :

__________________________________


API 20E / API 50 CHB / API /
/
: ____________________ : _________________________
:
Bacillus subtilis
(. )

Candida albicans
(. )

Clostridium sporogenes
:

___________
: _______________________________ : ____________________________
(): _________________________ : ____________________________

5
: 7/91

159

III

-


: ________________ -: ______________________ : _________
: __________________

Bacillus subtilis
Clostridium
sporogenes

3, 4,
5



/*

Bacillus subtilis

20-25 C
30-35 C
Clostridium
20-25 C
sporogenes
30-35 C
*
/
:
, : - 7 ,
10 - 100 ;
- .
: ________________ ___ / ___ .
: _______________________

(): ____________________________

: ____________

160

: ___________________

IV

-


: ________________ -: ______________________ : _________
: __________________

Bacillus subtilis
Candida albicans

Bacillus subtilis

20-25 C

Candida albicans

20-25 C

3, 4,
5



/*

:
, : - 7 ,
10 - 100 ;
- .
: ________________ ___/ ___ .
: _______________________
: ____________

(): ____________________________
: ___________________

161

162

4) ,
___________________________________________________________________________
-

:
:
: 21
: Roger Anderson
: 2/94
: /
:
: 15.3.94
. 1 3
QA:
: 15.3.94
: 15.3.94
: ,
.
I.


.
.

II.

,
, .
,
QC.
,
QC.

III.

- QC
, QC
,
.

IV.



,
, . , U.S.P.
.
A. : ( )
, ?
1. (CV) (/
(S.D.) 100) ,
?
2. , CV 5 %?
B. :
?
1.
, ?

163

21
:
. 2 3
: ,
.
2.
,
?
3. ,
, ?
4.
, ?
C. :
,
?
D. :
,

?
E. :
?
1.
,
?
2.
?
3.
?
4.

?
F. :

?
1.
( 6)
, ?
, 0.98?
2.
,

?
3.
?
G. :
?
,
?

164

21
:
. 3 3
: ,
.
1. ,
50 150 %
?
2.
?
H. ( ) (
):
1. ,
,
?
2. ?
3.
( 6) (..
)?
I.

:
1. ?
?
2.

?


. QC
.
V.



QC .
QA.
,
,
. QC
.

VI.


Czajkowski, T. (1993) Methods Validation Guidelines. In: Chromconnection. Scientific
Products. June pp. 12-13.

165

.
166

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