Module 14Slide 1 of 23 WHO - EDM Basic Principles of GMP Active Pharmaceutical Ingredients Part Three, 18

Module 14 Slide 1 of 23 WHO - EDM

Basic Principles of GMP

Active Pharmaceutical Ingredients

Part Three, 18



Objectives To discuss the GMP guidelines for the manufacture

of Active Pharmaceutical Ingredients (APIs) To examine key problems experienced during

inspections of the manufacturers of APIs and to seek possible solutions

Part Three, 18.1–18.59



Areas to be Covered General considerations Personnel Premises Equipment Sanitation Documentation Retention of records and samples Production Part Three, 18.1–18.59



General Considerations Overall control Consistent uniform batches Compliance with GMP

production quality control

General guidelines Co-operation in production Human and veterinary preparations




Personnel Qualified and competent

production and quality control sufficient number education, knowledge, experience

Organizational chart with responsibilities Written job description or instructions Trained Health

diseases open lesions




Premises General

suitable construction and environment adequately adapted and sufficient size mix-ups or contamination logical work flow

Special purposes antibiotics, hormones, cytostatic substances separate specifically designed enclosed areas separate air handling systems

Part Three, 18.11–18.13



Premises

Hygiene clothes, washing, toilets eating, drinking, smoking

Part Three, 18.11–18.13



Equipment Design, construction, location and maintenance

intended use, cleaning, contamination validated operation

Cleaning sterilised, used, maintained: SOPs, records and

checks

Part Three, 18.14–18.18



Equipment Process monitoring and control

calibrated, checked records

Defective equipment removed or labelled repaired, documented

Part Three, 18.14–18.18



Sanitation Written programmes

validated for premises and equipment quality standard for water hygiene , health and clothing practices waste disposal

Implementation and training Practices not permitted:

eating, smoking unhygienic practices Part Three, 18.19–18.22


Active Pharmaceutical IngredientsDocumentation

Master formulae written instructions master formula contents authorisation outdated documents amendments

Batch documentation batch manufacturing record contents contract production data recording Part Three, 18.23–18.30



Record and reference sample retention Activities are traceable

production and quality control Retention of records and samples

retention period

Part Three, 18.31–18.32



Production Processing procedures

master formula critical steps defined and validated supervision labelling

– vessels, containers, equipment daily activities - information

Part Three, 18.33–18.37



Production (continued) Starting materials

receiving, quarantine, sampling testing release, reject, storage, labelling dispensing SOP exceptions for hazardous materials

Intermediates testing labelling storage Part Three, 18.38–18.40



Production (continued) Active pharmaceutical ingredients

meet specifications limits for residue and reactants sterile APIs

Part Three, 18.41–18.42



Production (continued) Packaging

packaging material selection procedures to prevent error labelling, including:

– Product name– Quality– Batch number– Expiry or retest date– Warnings, if required– Storage conditions– Names of manufacturers and suppliers Part Three, 18.43–18.45


Active Pharmaceutical IngredientsQuality Control

Independent unit Duties: Approve, reject or release

specifications and methods sampling, sanitation and hygiene reprocessing stability complaints

Laboratory access and requirements Contract laboratories Part Three, 18.46–18.51


Active Pharmaceutical IngredientsStability Studies

Written programme stability indicating methods

Samples containers storage conditions

Expiry or retest date

Part Three, 18.46–18.51



Self-Inspection and Quality Audits Regular independent inspection

expert or team of experts production and quality control

RecordsStorage

Suitable conditions based on stability studies Distribution records for each batch

written SOP facilitate recalls Part Three, 18.52–18.55



Complaints and Defects Written instructions Prompt action and investigation

record facts Product review system

Reject materials Written procedures

starting materials, intermediates, packaging materials identified storage pending fate Part Three, 18.56–18.59


Active Pharmaceutical IngredientsGroup Session

Identify major deficiencies experienced in GMP in active pharmaceutical ingredients manufacture.

Are there any deficiencies that should prevent material being released?

Within what timescale should these deficiencies be corrected?

What are the implications for bulk active supply to your country?


Active Pharmaceutical IngredientsPossible Issues

Manufacturers supplying various types of industries Imports through brokers Hazardous processes Commercial secrecy Unsatisfactory final facilities


Active Pharmaceutical IngredientsPossible Issues

The interpretation of the meanings of expiry dates and re-test dates

The use of APIs close to their expiry date Blending of rejected APIs Reprocessing, recovery and/or reworking of APIs Recycling and treatment of solvents Addition of impurities to batches of APIs Trace-ability, repacking and re-labelling

Documents

Module 14Slide 1 of 23 WHO - EDM Basic Principles of GMP Active Pharmaceutical Ingredients Part Three, 18