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14 Pi 021-3-2 Inspection of Quality Control Laboratories
14 Pi 021-3-2 Inspection of Quality Control Laboratories
14 Pi 021-3-2 Inspection of Quality Control Laboratories
PI 0232
25 September 2007
AIDE-MEMOIRE
INSPECTION OF PHARMACEUTICAL
QUALITY CONTROL LABORATORIES
Editor:
PIC/S Secretariat
e-mail:
web site:
info@picscheme.org
http://www.picscheme.org
PI 023-2
25 September 2007
TABLE OF CONTENTS
Page
1.
Document History...........................................................................................1
2.
Introduction ....................................................................................................1
3.
Purpose .........................................................................................................1
4.
Scope.............................................................................................................2
5.
Aide-Memoire ................................................................................................2
6.
1.
DOCUMENT HISTORY
13 September 2005
1 January 2006
2.
INTRODUCTION
Inspections of sites involved in testing of medicinal products should be more
and more specific, thorough and conducted under normal working environment.
These inspections may include a complete assessment of laboratorys
conformance with the code of GMP or they may be limited to specific
methodology or aspects of the laboratory. Inspection process of a laboratory
involves the assessment of laboratory functions in full operation. Consequently,
PIC/S has developed the Aide Memoires, which can be considered a good tool
for enhancing the understanding and performance of inspectors.
3.
PURPOSE
3.1.
3.2.
The Aide-Memoire was drafted with the aim of facilitating effective planning and
conducting of GMP inspections of laboratories. The Aide-Memoire should
enhance the efficiency of the GMP inspection and evaluation process.
PI 023-2
Page 1 of 2
25 September 2007
4.
SCOPE
4.1.
4.2.
At the time of issue, this document reflected the current state of the art. It is not
intended to be a barrier to technical innovations or the pursuit of excellence.
5.
AIDE-MEMOIRE
The AIDE MEMOIRE in Annex consists of 9 tables containing general subjects
and items to be investigated during the GMP inspection of laboratories. Some
important questions and relevant references to the PIC/S documentation are
included as well.
Some more and specific aspects to be investigated by inspectors, respecting
the special type of laboratory and nature of testing, are included in two
supplements of Annex.
6.
REVISION HISTORY
Date
25 September 2007
PI 023-2
Version
Number
PI 023-2
Page 2 of 2
25 September 2007
AIDE-MEMOIRE
FOR INSPECTIONS OF PHARMACEUTICAL QUALITY CONTROL LABORATORIES
TABLE OF CONTENTS
Page
1.
General information.................................................................................................. 1
2.
2.1.
General....................................................................................................................... 1
2.2.
2.3.
2.4.
Change Control........................................................................................................... 1
2.5.
Trending...................................................................................................................... 1
2.6.
Risk Management....................................................................................................... 1
3.
3.1.
3.2.
Laboratory Documentation.......................................................................................... 2
3.3.
Data Traceability......................................................................................................... 2
3.4.
4.
Personnel .................................................................................................................. 3
4.1.
General ...................................................................................................................... 3
4.2.
Training....................................................................................................................... 3
5.
5.1.
Premises..................................................................................................................... 3
5.2.
Equipment................................................................................................................... 3
5.3.
Equipment Validation.................................................................................................. 4
5.4.
Cleaning/Sanitation..................................................................................................... 4
5.5.
Maintenance ............................................................................................................... 4
6.
6.1.
Materials ..................................................................................................................... 4
6.2.
7.
7.1.
Sampling .................................................................................................................... 5
7.2.
Samples...................................................................................................................... 5
7.3.
8.
Testing....................................................................................................................... 6
8.1.
8.2.
8.3.
8.4.
8.5.
8.6.
8.7.
PI 023-2
Page i of ii
25 September 2007
Page
9.
9.1.
9.2.
9.3.
9.4.
PI 023-2
Page ii of ii
25 September 2007
Annex to PI 023-1
Explanation to all tables below:
PIC/S G. = PIC/S Guide to GMP; It.= item ; SMF = Site Master File; IPCs= in process controls; EuPharm= 4thed. 2002;
VMP = Validation Master Plan;
1.
GENERAL
Area of
operation /
items
1.
General
information
Notes
show me..
1.1.
1.2.
Test activities
Activities
contracted out
Name(s)/ address/addresses) of
the company / companies
(Contract
testing)
2.
2.1.
Crucial questions
General
Document available?
2.3.
PIC/S G. 1;
PIC/S G.
7.1; 7.15;
7.13
2.2.
Supporting
documents
Functionality of QA
Suppliers
quality
ensuring
Self inspection
PIC/S G.
1.2.; 1.4.
PIC/S G.1;
2.6; 2.7; 6.1
and Annex
16
PIC/S G.
1.2.; 4.14;
5.25 and
Annex 2; It.
25; Annex 8
It.3
PIC/S G .
1.2.; 9.1
9.2.; 9.3.
2.4.
Trending
Results/OOS-results
PIC/S G .
6.9.
2.5.
Change control
PIC/S G.
1.3. ; Annex
15. It.43.
2.6.
Risk
management
Risk management
method/approach
Annex to PI 023-2
Page 1 of 8
PIC/S
G.Annex 15.
It..44
25 September 2007
3.
DOCUMENTATION
Area of
operation /
items
3.1.
3.2.
General
information
Laboratory
documentation
Notes
show me..
3.4.
PIC/S G.
4.1.-4.11
Specifications (SPECs)
PIC/S G. 1;
4.1.-4.3
SOPs
PIC/S G .
Annex 18
It.6.7. - 6.10.
4.4.
4.19.-4.29
PIC/S G .
4.15.-4.18.
Log books
Data
traceability
Supporting
documents
3.3.
Crucial questions
Sample tracking
PIC/S G .
4.28.-4.29
PIC/S G .
4.8.; 6.17-
Electronic
documentation/ No difference in requirements on documentation whether in paper form or electronic form. Aide Memoire related
computerised to control of computerised systems (e.g. access control, audit trail, back up) is covered by PIC/S document PI 011-1
systems
Annex to PI 023-2
Page 2 of 8
25 September 2007
4.
PERSONNEL
Area of
operation /
items
4.1.
4.2.
General
Training
Notes
5.2.
show me..
Supporting
documents
PIC/S G 2.8;
2.9; 6.6.;
PIC/S.G.
2.6 viii; 2.8;
2.9.
2.10.; 2.20
What specific training is given e.g. maintenance, PI 012-1,
cleaning staff etc.)?
7.1.-7.3.
Documentation on training
5.
5.1.
Crucial questions
Premises
Equipment
Labelling
Instrumentation
Assembly (DQ,IQ,OQ,PQ)
Calibration
Labelling
Log books
Cleaning
Note see also item 5.4. below
Annex to PI 023-2
Page 3 of 8
PIC/S G
3. 26.- 3.29.;
6.5.; 6.6
PIC/S G.
3.1.
PIC/S G.
3.3.
PIC/S G.
4.8.; 4.9.;
3.44.
PIC/S G.
3.34 - 3.44
2.6.vii
2.6.vi
25 September 2007
Equipment
validation
Notes
Crucial questions
show me..
Qualification
Installation qualifications(IQ)
5.4.
5.5.
Cleaning
sanitation
Maintenance
System
Preventive maintenance
Documentation
6.
6.1.
Cleaning/sanitation system
Supporting
documents
PIC/S G.
2.6.vii;
and
Annex 15
PIC/S G.
3.2.
Materials
Annex to PI 023-2
Page 4 of 8
PIC/S G.
6.19.-6.21.
25 September 2007
Water and
water systems
Notes
show me..
Water system/quality
Water sampling
Water testing
7.
7.1.
Crucial questions
Annex 1 to
PIC/S G.
It.35;44
Sampling
General policy
Sampling
7.2.
Supporting
documents
Samples
Starting/packaging materials
sampling
Procedures/records
Retained samples
Re-sampling
Note: for re-sampling see item
9.3.below
Handling of samples
Annex to PI 023-2
Retained samples
Samples tracking
Note: For samples tracking see
Item 3.2. above
PIC/S G.
1.4; 6.116,14 and
Annex 8
It.1.9.
PI 012-1;
11.1
Annex 8 to
PIC/S G.1.
It.2- 5
PIC/S G.
6.7.-6.11
PIC/S G. It.
6.4.; and
Annex 8
PIC/S G. 64;
6.14.
Page 5 of 8
It. 6 - 9
25 September 2007
Personnel for
sampling
Notes
show me..
Staff
8.
8.1.
8.2.
8.3.
8.4.
8.5.
Crucial questions
Specifically trained?
Supporting
documents
Annex 8 to
PIC/S G. It.
2; PI 007 1,
8.1.-8.9.
TESTING
Testing general
Testing of raw
materials
Testing in
process,
controls (IPC)
Testing of
intermediates
Testing of final
products
Annex to PI 023-2
QC system
Flow sheets
Methods
(see also item 8.2. below)
Contract testing
Re-testing
Note:
for re-testing see Item 9.3.below
System
Methods
Testing methods/equipment
System
Sampling
System
Sampling
Samples handling
Page 6 of 8
PIC/S
G.6.15-6.21
PI 012-1,
11.2.
PIC/S G.
4.10; 5.31
and Annex
8, It.3-4
PIC/S G.1.
It.1.4. vi;
1.4 vii; 6.14;
6.17;
25 September 2007
TESTING continued
Area of
operation /
items
8.6.
8.7.
Stability testing
Validation of
test methods
Notes
Crucial questions
show me..
System
Approach/policy described?
Matrixing/bracketing applied? Performed in
place or contracted? Full testing made? Critical
parameters defined?
CPMP/ICH
2736/99;
CPMP/ICH
420/02;
On going
Premises/equipment
Policy
Validation process
Supporting
documents
CPMP/ICH
4104/00;
PIC/S G.
4.10;
ICH Guide
Annex to PI 023-2
Validation data
Accuracy,
Specificity
Reproduceability
- linearity (range),
- limit of detection,
- limit of quantitation,
- robustness (including solution stability
and filter compatibility)
Method transfer
Page 7 of 8
25 September 2007
9.
9.1.
9.2.
9.3.
9.4.
Notes
show me..
Handling of test
results
Failures - Out
of Specification
(OOS) test
results
Release of test
results/
analytical
reports/
certification
Crucial questions
Trending
Note: For questions see item 2.4.
above.
System/OOS
Corrective action
Companys procedure
(re-testing programme,
criteria for re-sampling)
SOP available?
Supporting
documents
Annex 11 to
PIC/S G.
PI 012-1
It.13
PIC/S G.
1.2.Vii; 1,4,;
2.6.i; 5.595.60
Note:
Some more details and specific items related to testing in chemical, physical-chemical and microbiological laboratories to be
investigated in addition to above described subjects, are involved in Supplements 1 and 2
Annex to PI 023-2
Page 8 of 8
25 September 2007
Area of
operation /
items
1.1.
Chemical
testing
show me..
Procedures in place
Reagents preparation
Volumetric glassware
Volumetric solutions
1.2.
Physical and
physicalchemical
testing
Crucial questions
Notes
Supporting
documents
PIC/S
G.6.15.-6.21
Eupharm.
4.2.1.; 4.2.2.
PIC/S G.
3.41. 6.5;
6.19;
Eupharm.
Eupharm.
2.2.4.
Water bath
Titrations
Eupharm.
2.2.3.
Conductometric and pH
measurements
Eupharm.
2.2.38.
Temperature controlled/adjusted?
EuPharm.
2.2.7.
Temperature controlled/adjusted?
EuPharm.
2.2.8.;2.2.9.
Refractometry
Polarimetry
Viscosity testing
Supplement 1 to PI 023-2
Page 1 of 2
Eupharm.
2.2.6.
25 September 2007
Area of
operation /
items
1.3.
Qualification
for some
laboratory
apparatuses
Crucial questions
Notes
show me..
Balances
pH meters
Conductometer
Reference thermometers
Disintegration
Supporting
documents
PIC/S G.
It.3.41
Eupharm.
2.2.3.
Eupharm.
2.2.38.
EuPharm
2.2.14-16;
2.2.6.; 2.2.7.
Dissolution
Is instrument calibrated?
EuPharm
EuPharm
UV VIS spectrophotometers
Eupharm.
2.2..25.
IR spectrophotometers
Eupharm.
2.2..24.
Eupharm.
2.2.23.
HPLC/GC
EuPharm.
2.2.28.
Supplement 1 to PI 023-2
Page 2 of 2
25 September 2007
Crucial questions
Notes
1.
1.1
1.2.
Supporting
documents
show me..
Equipment
PI 012-1
It.8.1.; 8.3.
Area of preparation
Washing room
Incubators
Autoclave
Sterilisation by autoclave
HEPA Filters
(validation/maintenance)
PI 012-1
It.11.6
PI 012-1
It.8.1.2.
Annex to
PIC/S G. It.
7-9;
PI 014-1
Supplement 2 to PI 023-2
Page 1 of 3
Annex 1 to
PIC/S G.
It.36;
Annex 1 to
PIC/S G.
It.29;
PI 012-1
It.8.1.2.
25 September 2007
Area of
operation /
items
Crucial questions
Notes
Supporting
documents
show me..
PREMISES AND EQUIPMENT - continued
1.2.
Equipment
continued
Particle counter
Microscope
2.
2.1
2.2.
MATERIALS
Testing
materials
Protective
garments
Settle plates
Preparation
Use in performance
3.
3.1.
PI 012-1
It.11.3.
TESTING
Microbiological
testing
(product)
Incubation
Growth promotion
Positive controls
Bioburden
Micro-organism identification
Negative controls
Supplement 2 to PI 023-2
Page 2 of 3
EuPharm.2.
6.1. and
Suppl.4.7.
It.2.6.1.13.
PI 012-1,
11.3.-11.6.
PI 007-1,
5.2.-5.5.;
9.9.1.-9.9.2
PI 012-1,
It.11.5.
25 September 2007
Area of
operation /
items
3.2.
Microbiological
testing
Environmental
Notes
Crucial questions
Supporting
show me..
documents
System of performance
Sampling location
Swabs
Settle plates
PIC/S G.
1.3. ; Annex
15. It.43.
PI 012-1,
It.10.3
PI 012-1,
It.10.4-10.5.
Which media used? What is the method, time
exposure, surface area/limits and recovery rate?
The recovery plate for the surfaces validated:
How?
Contact plates
Supplement 2 to PI 023-2
Page 3 of 3
25 September 2007