Good Manufacturing

Practices
Guilin, PRC
Dr AJ van Zyl
for
Quality Assurance and Safety: Medicines
Medicines Policy and Standards
Health Technology and Pharmaceuticals Cluster
World Health Organization

Program
Good Manufacturing Practices
Presentation on GMP (Production
focus)

Presentation on GMP (QC focus)
Product specific focus
Group session
Guidelines and references
GMP: World Health Organization

WHO Technical Report Series, No. 908,
2003, Annex 4. Good Manufacturing
Practices for pharmaceutical products:
main principles

WHO Technical Report Series, No. Annex
3.

WHO Technical Report Series, No. Annex
3.
Good Manufacturing
Practices (GMP)
Introduction
General considerations
Glossary


1. Quality assurance
2. Good manufacturing practices for
pharmaceutical products (GMP)
3. Sanitation and hygiene
4. Qualification and validation
5. Complaints
6. Product recalls
7. Contract production and analysis
Good Manufacturing
Practices (GMP)
8. Self-inspection and quality audits
9. Personnel
10. Training
11. Personal hygiene
12. Premises
Quality control areas
13. Equipment
14. Materials
Reagents and culture media
Reference standards
15. Documentation
Good Manufacturing
Practices (GMP)

16. Good practices in production

17. Good practices in quality control
Control of starting materials and
intermediate, bulk and finished
products
Test requirements
Batch record review
Stability studies
Good Practices for Quality
Control Laboratories
(GPQCL)
Part One. Management and infrastructure

1. Organization and management
2. Quality system
3. Control of documentation
4. Records
5. Data processing equipment
6. Personnel
7. Premises
8. Equipment, instruments and other
devices
Good Practices for Quality
Control Laboratories
(GPQCL)
Part Two. Materials and set-up of
equipment, instruments and other
devices

9. Specifications archive
10. Reagents
11. Reference materials
12. Calibration, validation and verification
of equipment, instruments and other
devices
13. Traceability
GPQCL
Part Three. Working procedures

14. Incoming sample
15. Analytical worksheet
16. Testing
17. Evaluation of test results
18. Retained samples

Part Four. Safety in pharmaceutical
control laboratories
19. General rules
Good Manufacturing
Practices (GMP)
Where to start the inspection?
Laboratory layout overview of the QC
laboratory, activities, personnel
Chemical analysis, instrumentation,
micro
Product to be inspected
API, excipients, bulk, FP
Specification, test methods,
parameters and acceptance criteria
Utilities (HVAC, water, etc)
Good Manufacturing
Practices (GMP)
Where to start the inspection? (2)

Packaging material control
Data verification (e.g. stability)

Other documents:
SOPs
Reports and records
Validation and qualification
OOS
Trend analysis
(GMP) - QC
"On site" inspection
Sample inward register
Artesunate and selected
excipients
Date of entry
Date received and cross
references
Purchase order and delivery note
Approved supplier and
manufacturer
Number of containers and batch
number(s)
Damaged containers
Samples taken
Control number (AR) allocated
(GMP) - QC
Documents requested:
Select specific batches for verification
Artesunate specification and
excipients specifications
Standard Test Methods
Analytical reports for the batches
selected
Pharmacopoeia
SOPs (e.g. sampling, pooling of
samples and sampling plan),
reagents and volumetric solution
preparation, reference standard
control . . .
(GMP) - QC
General information:

How are the samples taken?
Size of the sample?
Pooling for composite samples?
Sample containers?
Sampling tools?

Sample storage
Work allocation
Current specifications
(GMP) - QC
Data verification:
Analytical reports against the
specifications
COAs (suppliers, own) and raw data

1. Number of samples verified
(cross check)
2. Tests as per specification with
acceptance criteria
3. Individual tests/parameters
4. Source or raw data in analyst
work books or data sheets
5. Issuing of the sheets/books
(GMP) - QC
Artesunate:

Parameter Acceptance
criteria
Result
Description
Identification
(GMP) - QC
Artesunate: Identification (and assay?)

Each sample, from each container
Method used "in-house" or
pharmacopoeia
Validated method
Reference standard (RS) used
Official RS or Working standard
Preparation
Control
Records
Storage, container etc
Chromatograms or spectra
Date, traceability (batch numbers,
time, analyst, equipment)
(GMP) - QC
Artesunate (cont):
Chromatograms or spectra (cont)
Manual integration, Peak symmetry,
system suitability
Equipment logbook
date used, analyst, calibrated (records),
maintenance (record), qualification
reports, computer system validated,
access control, changes, column used,
column performance, column log, column
washing and storage, analyst
information, qualification, training,
signature
(GMP) - QC
Artesunate:
Follow the same procedure for
each test or selected tests

Excipients:
Follow the same procedure for the
excipients

Also micro tests as applicable

Finished product:
Follow the same procedure

Release and rejection procedure
(GMP) - QC
Other checks may include:

Environment of the laboratory
Glassware calibration and use
Equipment and instruments
Other products and materials
tested
Impact
Glass ware
Cleaning, condition, storage
SOPs
Specifications archive
Analytical method validation
Analyst performance
(GMP) - QC
Documentation review may include:

OOS
SOP, reports, investigations
CAPA
Water system
Water system qualification
Water sampling and testing
Cleaning validation
Environmental control
Particulate matter
Micro
Air samples, settle plates, contact
plates, personnel
(GMP) - QC
Primary packaging material, e.g.

Aluminium foil and PVC, PVDC
HDPE containers
Cotton wool
Dessicant

Procedure for receiving, sampling,
testing
Where? Who? How? How many?
Supplier? Batch control? AR
numbers? Traceability?

Specifications, test methods,
release reports
(GMP) - QC
Printed packaging material e.g.

Labels and cartons
Leaflets

Procedure for receiving, sampling,
testing
Where? Who? How? How many?
Supplier? Batch control? AR
numbers? Traceability?

Specifications, test methods,
release reports
(GMP) - QC
Retention samples

APIs
Excipients
Packaging materials
Finished Products

Area
Environmental conditions
Period kept
Packaging
Quantity
(GMP) - QC
Stability testing

Conditions e.g. Zone II, Zone IV
(now a and b)
Periods
Accelerated
Real time
Procedure and plan with intervals
Compliance with program
Verify source data
Incubators or chambers
Qualification (DQ, IQ, OQ, PQ)
Packaging
(GMP) - QC
Stability

P
(GMP) - QC
Micro lab

Personnel
Organization structure, job
descriptions and responsibilities
Qualifications and experience
Activities
Excipients
Environmental monitoring
Water monitoring
Instruments and equipment
Status (qualification,
calibration, SOPs and records)
(GMP) - QC
Micro lab

Media
Storage
Preparation procedure and
records
Positive and negative
control
Microbiologist training
Waste materials
Cleaning
(GMP) - QC
Micro lab

P