active pharmaceutical
TRANSCRIPT
Module 15 | Slide 1 of 23 January 2006
Basic Principles of GMP
Active Pharmaceutical Ingredients
Part Three, 18
Module 15 | Slide 2 of 23 January 2006
Active Pharmaceutical Ingredients
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
Module 15 | Slide 3 of 23 January 2006
Active Pharmaceutical Ingredients
Areas to be Covered
General considerationsPersonnelPremisesEquipmentSanitationDocumentationRetention of records and samplesProduction Part Three, 18.1–18.59
Module 15 | Slide 4 of 23 January 2006
Active Pharmaceutical Ingredients
General ConsiderationsOverall controlConsistent uniform batchesCompliance with GMP
production quality control
General guidelinesCooperation in productionHuman and veterinary preparations
Part Three, 18.1–18.6
Module 15 | Slide 5 of 23 January 2006
Active Pharmaceutical Ingredients
Personnel
Qualified and competent production and quality control sufficient number education, knowledge, experience
Organizational chart with responsibilitiesWritten job description or instructionsTrainedHealth
diseases open lesions
Part Three, 18.7–18.10
Module 15 | Slide 6 of 23 January 2006
Active Pharmaceutical Ingredients
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
Module 15 | Slide 7 of 23 January 2006
Active Pharmaceutical Ingredients
Premises (continued)
Hygiene clothes, washing, toilets eating, drinking, smoking
Part Three, 18.11–18.13
Module 15 | Slide 8 of 23 January 2006
Active Pharmaceutical Ingredients
EquipmentDesign, construction, location and maintenance
intended use, cleaning, contamination validated operation
Cleaning sterilized, used, maintained: SOPs, records and checks
Part Three, 18.14–18.18
Module 15 | Slide 9 of 23 January 2006
Active Pharmaceutical Ingredients
Equipment (continued)
Process monitoring and control calibrated, checked records
Defective equipment removed or labelled repaired, documented
Part Three, 18.14–18.18
Module 15 | Slide 10 of 23 January 2006
Active Pharmaceutical Ingredients
SanitationWritten programmes
validated for premises and equipment quality standard for water hygiene, health and clothing practices waste disposal
Implementation and trainingPractices not permitted:
eating, smoking unhygienic practices
Part Three, 18.19–18.22
Module 15 | Slide 11 of 23 January 2006
Active Pharmaceutical Ingredients
DocumentationMaster formulae
written instructions master formula contents authorization outdated documents amendments
Batch documentation batch manufacturing record contents contract production data recording Part Three, 18.23–18.30
Module 15 | Slide 12 of 23 January 2006
Active Pharmaceutical Ingredients
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
Module 15 | Slide 13 of 23 January 2006
Active Pharmaceutical Ingredients
ProductionProcessing procedures
master formula critical steps defined and validated supervision labelling
– vessels, containers, equipment daily activities - information
Part Three, 18.33–18.37
Module 15 | Slide 14 of 23 January 2006
Active Pharmaceutical Ingredients
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
Module 15 | Slide 15 of 23 January 2006
Active Pharmaceutical Ingredients
Production (continued)
Active pharmaceutical ingredients meet specifications limits for residue and reactants sterile APIs
Part Three, 18.41–18.42
Module 15 | Slide 16 of 23 January 2006
Active Pharmaceutical Ingredients
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
Module 15 | Slide 17 of 23 January 2006
Active Pharmaceutical Ingredients
Quality 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
Module 15 | Slide 18 of 23 January 2006
Active Pharmaceutical Ingredients
Stability Studies Written programme
stability indicating methods
Samples containers storage conditions
Expiry or retest date
Part Three, 18.46–18.51
Module 15 | Slide 19 of 23 January 2006
Active Pharmaceutical Ingredients
Self-Inspection and Quality Audits Regular independent inspection
expert or team of experts production and quality control
Records
Storage Suitable conditions based on stability studies Distribution records for each batch
written SOP facilitate recalls Part Three, 18.52–18.55
Module 15 | Slide 20 of 23 January 2006
Active Pharmaceutical Ingredients
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
Module 15 | Slide 21 of 23 January 2006
Active Pharmaceutical Ingredients
Group 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?
Module 15 | Slide 22 of 23 January 2006
Active Pharmaceutical Ingredients
Possible Issues
Manufacturers supplying various types of industries
Imports through brokers
Hazardous processes
Commercial secrecy
Unsatisfactory final facilities
Module 15 | Slide 23 of 23 January 2006
Active Pharmaceutical Ingredients
Possible Issues (continued)
The interpretation of the meanings of expiry dates and retest 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 Traceability, repacking and relabelling