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.
2.
3.
4.
5.
6.
7.
8.
Organization and management
Quality system
Control of documentation
Records
Data processing equipment
Personnel
Premises
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.
15.
16.
17.
18.
Incoming sample
Analytical worksheet
Testing
Evaluation of test results
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
(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
Artesunate:
Parameter
Description
Identification
(GMP) - QC
Acceptance
criteria
Result
(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