Good Manufacturing Practices

Guilin, PRCDr AJ van Zyl

for Quality Assurance and Safety: Medicines

Medicines Policy and StandardsHealth Technology and Pharmaceuticals Cluster

World Health Organization

ProgramProgramGood Manufacturing Practices

• Presentation on GMP (Production

focus)

• Presentation on GMP (QC focus)• Product specific focus• Group session

Guidelines and referencesGuidelines 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 Good Manufacturing Practices (GMP)Practices (GMP)

IntroductionGeneral considerationsGlossary

1. Quality assurance2. Good manufacturing practices for

pharmaceutical products (GMP)3. Sanitation and hygiene4. Qualification and validation5. Complaints6. Product recalls7. Contract production and analysis

Good Manufacturing Good Manufacturing Practices (GMP)Practices (GMP)

8. Self-inspection and quality audits9. Personnel10. Training11. Personal hygiene12. Premises

Quality control areas13. Equipment14. Materials

Reagents and culture mediaReference standards

15. Documentation

Good Manufacturing Good Manufacturing Practices (GMP)Practices (GMP)

16. Good practices in production

17. Good practices in quality controlControl of starting materials and intermediate, bulk and finished productsTest requirementsBatch record reviewStability studies

Good Practices for Quality Good Practices for Quality Control Laboratories Control Laboratories

(GPQCL)(GPQCL)

Part One. Management and infrastructure

1. Organization and management2. Quality system3. Control of documentation4. Records5. Data processing equipment6. Personnel7. Premises8. Equipment, instruments and other

devices

Good Practices for Quality Good Practices for Quality Control Laboratories Control Laboratories

(GPQCL)(GPQCL)

Part Two. Materials and set-up of equipment, instruments and other devices

9. Specifications archive10. Reagents11. Reference materials12. Calibration, validation and verification

of equipment, instruments and other devices

13. Traceability

GPQCLGPQCL

Part Three. Working procedures

14. Incoming sample15. Analytical worksheet16. Testing17. Evaluation of test results18. Retained samples

Part Four. Safety in pharmaceutical control laboratories

19. General rules

Good Manufacturing Good Manufacturing Practices (GMP)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 Good Manufacturing Practices (GMP)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(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(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(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(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 criteria3. Individual tests/parameters4. Source or raw data in analyst work books or data sheets5. Issuing of the sheets/books

(GMP) - QC(GMP) - QCArtesunate:

ParameterParameter Acceptance Acceptance criteriacriteria

ResultResult

DescriptionDescription

IdentificationIdentification

(GMP) - QC(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

PreparationControlRecordsStorage, container

etc•Chromatograms or spectra

Date, traceability (batch numbers, time, analyst, equipment)

(GMP) - QC(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(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(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(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(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(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(GMP) - QC

Retention samples

•APIs•Excipients•Packaging materials•Finished Products

•Area•Environmental conditions•Period kept•Packaging•Quantity

(GMP) - QC(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(GMP) - QC

Stability

•P

(GMP) - QC(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(GMP) - QC

Micro lab

•Media•Storage•Preparation procedure and records•Positive and negative control

•Microbiologist training•Waste materials•Cleaning

(GMP) - QC(GMP) - QC

Micro lab

•P