GOOD MANUFACTURING PRACTICE - an update

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GOOD MANUFACTURING PRACTICE - an update

• Tajuddin Akasah
• B.Pharm.Hons.(USM)., M.Phil., Ph.D. (UK)
• Head of Centre for GMP
• National Pharmaceutical Control Bureau

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SCOPE TO COVER

• QUALITY OF MEDICINE
• WHAT IS GMP? a revisit
• VALIDATION
• WATER SYSTEM
• HVAC
• PREMISE SEPARATION

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WHAT POWERS DO WE HAVE?
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• Sale of Drug Act 1952 (Act 368)
• Control of Drugs and Cosmetics Regulation 1984
• Poison Act 1952 (Act 366)
• Registration of Pharmacist Act 1951 (Act 371)
• Medicines (Advertisement and Sale) Act 1956
• Others

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CONTROL OF DRUGS AND COSMETICS REGULATION 1984
Part III - Section 7 Control of manufacture,
sale, supply and importation

• (1) Except as otherwise provided in these
  Regulations, no person shall manufacture, sell,
  supply, import or possess for sale any product
  unless
• (a) the product is a registered product
• (b) the person holds the appropriate licence
  required and issued under these regulationns
• (2) Subregulations (1) (b) does not apply to
  retailer

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• HOW DO WE KNOW THE QUALITY OF A MEDICINE?

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SOME ASSUMPTIONS

• I like the brand!
• I trust the brand!
• I like the box!
• My mother uses it!
• My friend uses it!
• My doctor says so!
• The pharmacist sells it!

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Regulators concern .

• Quality, Safety and Efficacy
• pharmaceuticals
• Quality and Safety
• health supplements and traditionals

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How do we ensure ?

• Quality (meet specs, intended use) and
• Safety (Heavy metals contents, Microbial counts,
  no prohibited ingredients, ADR monitoring)
• Efficacy (proven clinically)

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• Thai labels

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?
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Quality

• QC test is destructive
• Unable to do on every tablet
• Require sampling
• Compliance to GMP is crucial
• Quality being built-in from the start to finish

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WHAT IS GMP?

• Good Manufacturing Practice
• GMP is that part of QA which ensures that
  products are consistently produced and controlled
  to the quality standards appropriate to their
  intended use and as required by the marketing
  authorisation or product specifications

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WHAT IS QA?

• Quality Assurance
• It is the sum total of the organised arrangements
  made with the objective of ensuring that
  medicinal product are of quality required for
  their intended use. QA therefore incorporates GMP
  plus Quality Control (QC).

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GMP IMPLEMENTATION IN MALAYSIA

• GMP for pharmaceuticals in Malaysia since 1984
• WHO and ASEAN Guidelines
• MALAYSIAN Guidelines
• PIC/S since 1st Jan 2002, Malaysia became the
  26th member state

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Background

• A short history of GMP
• First introduced by the Canadian Authorities
  mid 1960s
• Since then GMP acceptance
• as a way of life in the pharmaceutical
  industry

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Background

• It might be assumed that
• 40 years of experience of GMP
• 84 countries
• Would have eliminated many dangers to the
  patients due to quality failure in manufacturing
  but.

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Mistakes

• 109 infants have died in Nigeria due to failure
  to follow GMP
• Supplier mislabelled ethylene glycol (anti
  freeze) as propylene glycol and the manufacturer
  failed to perform adequate QC identification
  and potency test

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More Mistakes

• In Malaysia
• Adulteration
• Failed QC

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• Slimming pills in Singapore 2002
• Slimming pills in Malaysia 2004

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• GMP COMPLIANCE IS CRUCIAL
• WHAT ARE THE ELEMENTS OF GMP?

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PIC/S GUIDELINES

• Quality Management System
• Personnel
• Premises and Equipment
• Documentation
• Production
• Quality Control
• Contract Manufacture and Analysis
• Complaint and Product Recall
• Self Inspection
• Annexes 1-17 (specific)

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Guidelines on GMP for Traditional Medicines in
Malaysia

• Quality Management System
• Personnel
• Premises
• Sanitation and Hygiene
• Equipment
• Production
• Quality Control

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Guidelines on GMP for Traditional Medicines in
Malaysia.

• Documentation
• Self Inspection
• Distribution, Complaints and Product Recalls
• Complaints on Adverse Drug Reaction
• Returned and Salvaged
• Contract Production and Testing

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ITS A TOUGH JOB
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QUALITY MANAGEMENT SYSTEM

• Developed, established, implemented
• Policies and objectives
• Organisational structure, functions
• Responsibilities, procedures
• QC and specifications

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PERSONNEL

• separate people responsible for production and
  quality control (independent of each other)
• appropriately trained in quality system, GMP
  and regulatory requirements

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PREMISES EQUIPMENT

• Suitably located, designed, constructed and
  maintained
• The need to
• avoid any risks of contamination from environment
• cross-contamination
• product mix-up

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SANITATION AND HYGIENE

• Personnel should be healthy (regular medical
  check-up)
• Toilets should be separated from the production
  area
• SOPs for cleaning

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• Hormone Production
• Ikan kering telor

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GMP FLOW CONCEPT
Black
Grey
White
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DOCUMENTATION

• Complete history of each batch from starting
  material to finished products
• BMR, SOPs, Formulas

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WHEN ATTEMPTING A TASK WE NEED SOME SORT OF
DOCUMENTATION
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If the documentation is wrong!
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PRODUCTION Starting materials

• Specifications must be defined
• Consistency of production may be influenced by
  quality of starting materials
• Quality water

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Production

• Batch Numbering System
• Weighing and Measurement
• Written Procedures and Processing (SOPs)

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Labelling and Packaging

• Line clearance
• SOPs
• Random checks
• Label reconciliation

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QUALITY CONTROL

• Sampling, inspecting and testing of starting
  materials, IPQC and finished products
• Environmental monitoring programs, sample
  retention and stability studies

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CONTRACT MANUFACTURE CONTRACT ANALYSIS

• Written contract
• Must be clearly defined
• Conforming to agreed standards

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COMPLAINTS/ADRs AND PRODUCT RECALLS

• Person responsible
• Sufficient personnel to handle
• Written procedures/investigation
• Securely stored
• Evaluation and decision

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SELF INSPECTION

• Examination and assessment of quality system
• Conducted by a team designated by the management

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GMP Updates

• VALIDATION
• WATER SYSTEM
• AIR HANDLING SYSTEMS
• ENVIRONMENT CONTROLS
• PREMISE SEPARATIONS

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Validation

• The documented act of proving that any procedure,
  process, equipment, material, activity or system
  actually leads to the expected results.

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Qualification or Validation ?

• A system must be qualified to operate in a
  validated process
• Qualify a system and/or equipment
• Validate a process
• Qualify an autoclave, whereas you validate a
  sterilisation process oven drying

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Validation

• The Validation Master Plan (VMP)
• Cleaning validation
• Process validation
• QC-related validation
• Review and summary

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Water system design

• Pipes sloped so water does not pool and can drain
  easily
• Constructed using suitable material (stainless
  steel)
• Circulate the water
• Incorporate non-return valve (NRV)

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Further Water Treatment

• Filtration
• Disinfection
• Reverse Osmosis or Deionised
• Distillation of Ultrafiltration

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AIR HANDLING SYSTEM

• Heating
• Air Conditioning (Central)
• Ventilation
• Producing cream under Clean Air condition. tab
  prod ve corridor

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ENVIRONMENT is also critical (Product Quality)

• Light, temperature, humidity, air movement
• Microbial particulate contamination
• Uncontrolled environment
• May lead to degradation, contamination cross
  contamination

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PREMISE SEPARATION
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• PHARMACEUTICALS
• Pharmaceuticals hormones/penicillins/cephalospori
  ns/sterile
• OTC
• Cosmetics
• Traditional (extract only)

• TRADITIONALS
• Crude and Extract
• Cosmetics (Separate line except for store and
  sec. labelling

• OTC
• OTC (external)
• Cosmetics
• Traditional (extract only)

• COSMETICS
• External
• External herbal extracts

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• LICENSING DATA

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Data as per 26 Jan 2005
No. of Lic. Manufacturers ptc 227 (7413128)
No. of Licensed Importers 456 (180131 145)
No. of Licensed Wholesalers PNP 888 (415473)
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Some useful websites

• http//www.bpfk.gov.my
• http//www.picscheme.org
• http//www.tga.health.gov.au
• http//www.who.org
• http//www.fda.gov

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TERIMA KASIHDont let fathers take care of
children