WHO GMP Certification M. Mitra CDSCO(NZ)

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WHO GMP Certification Scheme
M.
Mitra Former Dy. Drugs Controller (I), CDSCO, HQ,
New Delhi
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WHO GMP CERTIFICATION

• Originally promugulated in 1969 and revised in
  1975. Main objectives were
• Guidelines be developed for official inspections
  of dug manufacturing facilities
• To assess compliance of GMP
• This would facilitate implementation of the
  scheme

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WHO GMP CERTIFICATION

• With 191 countries members in the scheme a
  solution was found for international commerce
  between these countries. The scheme offered a
  solution for those countries which did not have a
  developed regulatory agency yet wanted to import
  drugs.

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WHO GMP CERTIFICATION

• Basic principles of WHO Good Manufacturing
  Practice is similar to any established GMP
  requirement. Allied documents like Schedule M,
  CFRs, ASEAN GMP, etc are all similar in nature.
  Anyone following any established GMP procedure
  will automatically understand the principles in
  the other GMP requirements.

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WHO GMP CERTIFICATION

• WHO GMP requirements have been developed taking
  into account the principles in various GMP texts
  and also considering the requirements of
  developing countries. These requirements are not
  for domestic use but for international trade.

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WHO GMP CERTIFICATION

• There are around 1000 (?) WHO GMP certified
  manufacturing establishments in the country, with
  West Zone leading followed by the South, North
  and the East Zones.
• New Applications are coming in everyday due to
  increase in exports of drugs, India being a major
  exporter of Drugs Pharmaceuticals Globally.
• Other purchasers like the State governments, ESI
  etc. have also started (erroneously) asking for
  the certificates as preconditions.

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WHO GMP CERTIFICATION

• WHO GMP ensures the following
• Avoidance of Cross- Contamination
• Prevention of Mix-ups
• Provide Traceability
• Accountability of actions
• Responsibility
• Product Performance Guarantee

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WHO GMP CERTIFICATION

• Understanding WHO GMP
• Documents and Literature

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WHO GMP CERTIFICATION

• A series of reports known as the WHO
  Technical Report Series (TRS) are available.
• TRS 823 (1992)
• TRS 834 (1993)
• TRS 863 (1996)
• TRS 885 (1999)
• TRS 902 (2002)
• TRS 908 (2003)
• TRS 917 (2004)
• TRS 929 (2005)
• TRS 937 (2006)

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WHO GMP CERTIFICATION

• Other documents
• A WHO Guide to Good Manufacturing Practice
  (GMP) Requirements (WHO/VSQ/97.02) (for
  validation)

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WHO GMP CERTIFICATION

• Various other documents are available with WHO
  which is freely available for users. WHO website
  is the best source for getting information.
  Similarly documents of other established
  Regulatory agencies can expand knowledge and
  understanding

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WHO GMP CERTIFICATION

• Issue of Certificates
• What are the Certificates?
• Three types of Certificates are recommended by
  the WHO.
• These are
• Product Certificate (COPP) (TRS 823, 863)
• Statement of Licensing Status (TRS 823, 863)
• Batch Certificate (TRS
  823, 863)
• There is another Certificate Site Certificate.
  Described later

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WHO GMP CERTIFICATION

• The member state shall attest the following
  conditions of a manufacturer if required to
  attest a product for the certification
• A specific product is authorized to be placed in
  the market of the exporting country, if not why
  not
• The manufacturing plant is subject to regular
  inspections for WHO GMP compliance
• All product information, including labeling is
  currently authorized in the certifying country.

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WHO GMP CERTIFICATION

• Conditions to be satisfied before opting for the
  scheme by any member country
• Effective national licensing system for products,
  manufacturers and distributor
• Effective control of quality of products,
  including independent laboratory
• A technically competent, experienced, resourceful
  National Pharmaceutical inspectorate, as part of
  NDRA having legal powers for investigations
• Administrative capacity to issue Certificates and
  quickly notify WHO and other member countries

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WHO GMP CERTIFICATION

• Understanding the Technical Report Series
• TRS 823 Salient features
• PART I Quality Management in the Drug Industry
  Philosophy Essential Elements
• Quality Assurance
• Good Manufacturing Practice
• Quality Control
• Sanitation Hygiene
• Validation
• Complaints

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WHO GMP CERTIFICATION

• PART I contd.
• Product recalls
• Contract Production Analysis
• Self-inspection and quality audits
• Personnel (including key personnel)
• Equipment
• Premises
• Material
• Documentation

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WHO GMP CERTIFICATION

• PART II Good Practices Production Quality
  Control
• Good Practices in Production
• Includes General requirements, prevention of
  cross contamination and bacterial contamination,
  processing operations, packaging operations
• Good Practices in Quality Control
• Control of starting material and intermediate,
  bulk, and finished products, test requirements,
  production record review, stability studies

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WHO GMP CERTIFICATION

• PART III Supporting and Supplementary Guidelines
• Sterile pharmaceutical Products
• General requirements (air classifications),
  manufacture of sterile preps, personnel,
  premises, equipment, sanitation, processing,
  sterilization, filtration, finishing, quality
  control,
• Good Manufacturing Practice for Active
  Pharmaceutical Ingredients
• Explanation, general considerations, personnel,
  premises, equipment, sanitation, documentation,
  retention of records and ref samples, production,
  
• Form and content of inspectors report
• Validation of analytical procedures
• A Model Certificate Format is also presented

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WHO GMP CERTIFICATION

• TRS 863 Salient features
• Useful guidelines
• Guidelines for Stability Testing
• Guidelines for Validation
• Import Procedure for Drugs
• Guidelines for implementation of the Scheme
  (including model certificate)
• Guidelines on import procedures for
  pharmaceutical products

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WHO GMP CERTIFICATION

• TRS 885 Salient features
• GMP Authorised Persons - Role, Functions
  Training
• Role and position of authorized person,
  implementation of the quality system, education
  and training., routine duties of an authorized
  person,
• GMP Supplementary Guidelines for the
  Manufacture of Pharmaceutical Excepient
• General considerations, self inspection and
  quality audits, use of equipment, cleaning
  programme, starting material, rejected and
  recovered materials, returned excepients, storage
  practices, specifications, BPRs, change control
  and process validation, prevention of cross
  contamination, blending, microbial contamination,
  water systems, packaging, quality control etc.

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WHO GMP CERTIFICATION

• TRS 902 Salient features
• Good Practices for National Control
  Laboratories
• Basic elements of GMP (definition)
• GMP for Sterile Products revision
• Inspections
• National GMP Inspectorate
• Guidelines on Packaging of Pharmaceutical
  Products
• Storage areas
• Labels

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WHO GMP CERTIFICATION

• TRS 908 Salient features
• GMP for radio pharmaceuticals
• GMP for Pharmaceutical Products
• Main principles
• HACCP
• Guidance on GMP Inspection report
• Guide to good storage practices for
  pharmaceuticals
• Model Certificate of a Pharmaceutical Product
• Site Certificate does not replace the Product
  certificate

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WHO GMP CERTIFICATION

• TRS 917 Salient features
• Active Pharmaceutical Ingredients API
• Herbal

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TRS 929 Salient features

• Concept of sampling of starting materials
• Heating ventilation and air conditioning
• Validation
• Water for pharmaceutical use
• 
  ..\GMP matters\WHO_TRS_929.pdf

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TRS 937 Salient features

• One of the most important TRS
• Supplementary guidelines on GMP for HVAC
• (Supplementary guidelines on GMP for Herbals)
• Supplementary guidelines on GMP Validation
• HVAC Water Systems
• Cleaning
• Analytical Method
• Computerized Systems
• Qualification of systems and equipment
• Non-sterile process validation
• Good Distribution Practices for pharmaceutical
  products

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WHO GMP CERTIFICATION

• How to Certify a Product
• Certification of products are done after
  thorough examination of the product and the
  facilities where these are manufactured

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WHO GMP CERTIFICATION

• How to Certify a Product
• The facilities are Inspected NRA Inspectors with
  good knowledge of GMP
• The inspection may take two or more days
• Certificates are issued by the Issuing Authority
  on the recommendation of the joint report

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WHO GMP CERTIFICATION

• Requirements
• Procedures Main Requirements
• Product
• Procedures
• Facilities

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WHO GMP CERTIFICATION

• Requirements
• Product
• The basic requirements of the product are
• Product design
• Stability Studies
• Process validation

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WHO GMP CERTIFICATION

• Requirements
• Procedures
• All actions taken in the facility which leads
  to the production of the final product as per
  specification.

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WHO GMP CERTIFICATION

• Requirements
• Facilities
• This encompasses the building, machinery,
  services and utilities, manpower etc. These are
  guided towards making a properly designed product.

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WHO GMP CERTIFICATION

• Inspection Points
• 1. Quality Management
• 2. Sanitation and hygiene
• 3. Validation
• 4. Complaints and recalls
• 5. Contract production and analysis
• 6. Self Inspection
• 7. Personnel

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WHO GMP CERTIFICATION

• Discussions
• 8. Premises
• 9. Equipment
• 10. Materials
• 11. Documentation
• 12. Sterile production
• 13. Active pharmaceutical ingredients

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WHO GMP CERTIFICATION

• GMP consists of various activities which an be
  grouped together as follows
• Training - induction, ongoing, refresher
  etc.alonwith such documents like SOP,
  training calendar, assessment
  etc.
• Cleaning sanitation and hygiene - may also
  include workers entry
  procedure, cleaning of the
  premises etc
• Validation and calibration - qualification of
  machinery,
  equipment etc.
• Storage - apart from normal ware-housing
  facilities, this should also
  address quarantine, procedure Etc.

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WHO GMP CERTIFICATION

1. movement of manpower, material - uni-flow
   movement,
   movements control etc.
2. Quality assurance
3. Quality control
4. Documentation - must include MFR, BPR, SOP
   Documents control
   distribution, cleaning, training, and
   document regulating and
   recording other
   activities
5. Change control
6. Self inspections and audits

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WHO GMP CERTIFICATION

• Usual Problems faced by Regulatory Agencies
• Fund problems
• Lack of knowledge on the part of applicants
• Lethargic mindset
• Back to original condition after Certification
• Usual Problems faced by applicants
• Sometimes lack of Knowledge on the part of
  auditors
• Teacher as well as Examiner status
• Lack of time for thorough auditing

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WHO GMP CERTIFICATION

• Useful Web Sites
• http//www.who.int/en/
• http//www.who.int/bookorders/anglais/
• subscription1.jsp?sesslan1
• http//www.who.int/medicines/organization/
• qsm/activities/qualityassurance/gmp/gm
  pcover.html
• http//www.fda.gov/
• http//www.health.gov.au/tga/docs/html/gmphome.htm
  
• http//www.mca.gov.uk/

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WHO GMP CERTIFICATION

• M. Mitra
• Former Dy. Drugs Controller (India),
• CDSCO
• (M) 9716755102
• Email gmpro_at_rediffmail.com

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Thank you