topic 1-gmp overiew of concept
TRANSCRIPT
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
SEARO
Good Manufacturing PracticeOverview of concept
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION
FOR VACCINESHYDERABAD, 10-18 NOVEMBER 2003
By: Alireza Khadem
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
SEARO
Objectives of the workshop
• Ensure that NRA will be able to conduct adequate GMP inspections – All GMP inspectors supervising EPI vaccine manufacturers will
improve their skills in conducting competent and efficient GMP inspections
– identify GMP experts that can participate/facilitate in international peer review audits or GMP training/follow up
• Develop a plan to ease enforcement of GMP in all EPI vaccine manufacturers – training of QA managers in self inspection– Follow up and monitoring of GMP audits findings
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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Expected outcome at the end of the workshop
• A workplan to ease enforcement of GMP in by the NRA
• A workplan to implement and improve GMP in all EPI vaccine manufacturers
• A short term and long term training development plan of GMP inspectors and QA managers
• Identify the best resources persons to participate in WHO GMP audits or GMP training
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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Organization & method of work
• 10-18 November, 8.30 am -5.30 including coffee break and lunch
• Evaluation of knowledge before, during and after the workshop
• Lectures based on need assessment• Mock audit in two facilities (15,16 Nov)• Work plan at the end of the workshop• Plenary and working group sessions
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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Why GMPPatients taking medicines have very little
chance of detecting if anything is wrong
If something is wrong it can be very dangerous
The doctor, pharmacist and patient, all trust those who manufactured and packaged the product
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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History of GMP
Thorough investigations following this incident, it become very
probable that batches of the vaccine were contaminated with the so-called Kiel-strain
251 vaccinated72 deaths because of tuberculosis135 developed clinical tuberculosis44 survived
1930 Lubeck – BCG Vaccine
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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History of GMP
The "miracle drug" came into use. It was marketed as a pediatric elixir.
It was a raspberry flavoured solution in a liquid industrial solvent, etheylene glycol. Generally an elixir is designated as an alcohol based product, but this particular formulation was of dietheylene glycol. Upon ingestion, ethylene glycol was metabolized to oxalic acid.
358 poisonings 107 deaths 251 sick but survived
1938 - Sulphanilamide, the elixir of death
FDCA-1938
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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History of GMP1962- Thalidomide1962- Thalidomide
thousands of babies were born without arms or legsthousands of babies were born without arms or legs
Reason
One enantiomer caused sedation which was the desired effect, One enantiomer caused sedation which was the desired effect, while the other enantiomer caused devastating birth defects while the other enantiomer caused devastating birth defects known as Phocomelia. Solution was to remove the undesired known as Phocomelia. Solution was to remove the undesired enantiomer by a validated purification process assured by Assay enantiomer by a validated purification process assured by Assay Validation. Again, GMP deficiency by not having adequate QA Validation. Again, GMP deficiency by not having adequate QA and QC programmes which could have answered assay and QC programmes which could have answered assay validation. This led to guidelines on the development of New validation. This led to guidelines on the development of New Stereoisomeric Drugs (1992) US FDA.Stereoisomeric Drugs (1992) US FDA.
Drugs must be effective & safe
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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1955 - Polio Vaccine (Cutter Labs, USA) (Lambert, E.C., Medical Mistakes, Indiana University Press, 1978)
History of GMP
51 Children paralysed51 Children paralysed10 Deaths10 DeathsSeveral possible reasons:Several possible reasons:
Inconsistent viral inactivation process.Inconsistent viral inactivation process. ·Quick scale-up production without proper validation of inactivation ·Quick scale-up production without proper validation of inactivation step.step. ·Active live virus production process used heat inactivation step. ·Active live virus production process used heat inactivation step. • For virus; scale-up of heat inactivation step may not have been For virus; scale-up of heat inactivation step may not have been sufficient.sufficient.
Batch release
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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History of GMP
WH0-GMP
EC-GMP
FDA-Aseptic Processing
FDA-cGMP
FDA-GMP
PIC-GMP
GMP Enforcement byGerman National Law
1968 1971 1978 1983 1985 1987 1989
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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History of GMP
PIC-Adapts GMPAccording to EC-GMP
WHO-Revised GMP
WHO-GMP forBiological products
WHO-Guide for Inspection
Revision to Annex 1 EC-GMP
WHO-GMP for Sterile pharmaceuticals
1992 1992 1992 1996 1997 2002 2003
WHO-Revised GMP
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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What is GMP?
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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…More Paper…More Work…More Cost…More Headache
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Quality Management• Determines and implements the “quality policy”• The basic elements are:
– an appropriate infrastructure or “quality system” encompassing the Procedures, Processes, and Resources
– the systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for “Quality”
The totality of these actions is termed “Quality Assurance”
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
HYDERABAD, 10-18 NOVEMBER 2003HYDERABAD, 10-18 NOVEMBER 2003WHO
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• Quality management is defined as the aspect of management function that determines and implements the quality policy.
• The quality policy is a statement by the top management of the company of its overall intentions and direction relating to quality, formally expressed as a corporate policy.
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Quality Management• Terminology may differ
– “Quality System” is said to be rarely used in drug manufacturing
• The concepts of QA, GMP and Quality Control are interrelated aspects of Quality Management. – They are described on the following slides in
order to emphasize their relationship and their fundamental importance to the production and control of pharmaceutical products
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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There are two basic elements of this aspect of the management function of a pharmaceutical company:
• A working infrastructure = quality system. This includes:– Organizational structure– Procedures– Processes– Resources
• Systematic actions to bring the quality policy to life. The totality of these actions is termed quality assurance (QA).
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Quality Relationships
Quality Management
Quality Control
GMP
Quality Assurance
Management AspectQuality systemQuality Policy…
PersonnelTrainingValidationSelf inspection
Quality ObjectiveQuality Manual
SamplingSpecificationsTesting
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Principles of Quality Assurance
• Wide-ranging concept – covers all matters that individually or
collectively influence the quality of a product • Totality of the arrangements
– to ensure that the drug is of the right quality for the intended use
• Quality Assurance incorporates GMP– and also product design and development
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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• Inside an organization, QA is a management tool. In contractual situations, it provides confidence in the supplier.
• QA is not the duty of one organizational unit in the company alone, but is the responsibility of all staff members who in any way can influence product quality.
Principles of Quality Assurance
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Requirements for QA Systems – I
1. Ensure products are developed correctly2. Identify managerial responsibilities3. Provide SOPs for production and control4. Organize supply and use of correct
starting materials5. Define controls for all stages of
manufacture and packaging
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Requirements for QA Systems – II
6. Ensure finished product correctly processed and checked before release
7. Ensure products are released after review by authorized person
8. Provide storage and distribution 9. Organize self-inspection
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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GMP
• Ensure that products are consistently produced and controlled
• Diminishes risks that cannot be controlled by testing of productCross-contaminationMix-ups
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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What is Good Manufacturing Practices (GMP)?
World Health Organization defines GMP as: ”that part of quality assurance which
ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization”
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Quality Standards
WHO GMP
National GMPPharmacopeias
Inspection
Marketing Authorization
NRA NCLDRA
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Basic Requirements for GMP – I
1. Clearly defined and systematically reviewed processes
2. Critical steps validated3. Appropriate resources: personnel,
buildings, equipment, materials4. Clearly written procedures 5. Trained operators
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Basic Requirements for GMP – II
6. Complete records, failure investigations
7. Proper storage and distribution 8. Recall system9. Complaint handling
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Defined Processes Premises Validated
Processes
Complaints andRecalls
WrittenProcedures and
Records
TrainedPersonnel and
Hygiene
Laboratories and Validated Tests
Contract production
and analysis
Materials andStorage
Equipments
What aspects of manufacturing does GMP cover?What aspects of manufacturing does GMP cover?
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Quality Control (QC) Department
• Each holder of a manufacturing authorization should have a QC Department
• Independence from production and other departments is considered to be fundamental
• Under the authority of an appropriately qualified and experienced person with one or several control laboratories at his or her disposal.
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Basic Requirements for Quality Control
Resources
• Adequate facilities• Trained personnel• Approved procedures
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Basic Requirements for Quality Control
Tasks• Sampling• Inspecting• Testing• Monitoring• Releasing/rejecting
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Basic Requirements for Quality Control - I
Objects• Starting materials• Packaging materials• Intermediates• Bulk products• Finished products• Environmental conditions
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Basic Requirements forQuality Control – II
1. Sampling approved by QC department2. Validated test methods3. Records4. Review and evaluation of production
documentation5. Failure investigations for all deviations 6. Ingredients comply with the marketing
authorization
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Basic Requirements for Quality Control – III
7. Ingredients are of the required purity8. Proper containers9. Correct labelling10. Release of batches by the authorized
person11. Retained samples of starting materials
and products
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Other Duties of the Quality Control Department
1. Establish QC procedures2. Reference standards3. Correct labelling 4. Stability testing 5. Complaint investigations6. Environmental monitoring
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Assessment of Finished Products
Should embrace all relevant factors. For example:
• production conditions• in-process test results• manufacturing documentation• compliance with finished product specification• examination of the finished pack
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Other Issues
• GLP• GEP• GCP• GSP• GDP
WORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINESWORKSHOP ON GOOD MANUFACTURING PRACTICES (GMPs) INSPECTION FOR VACCINES
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Case study
• List the most important barriers or Inhibitors against to Implement GMP