Basic Principles of GMP

1
Good Manufacturing Practices (GMP) and
Inspections
Training Workshop on Pharmaceutical Development
with a focus on Paediatric Formulations 15
October 2007 Tallinn, Estonia
Dr A J van Zyl Technical Officer HTP/PSM/QSM World
Health Organization (WHO) Geneva,
Switzerland vanzyla_at_who.int
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2
Good Manufacturing Practices (GMP) and
Inspections

• Outline and Objectives of presentation
• Introduce WHO GMP texts
• Main principles
• Supplements
• Others
• In the context of Prequalification
• Current and future approaches
• Inspections in prequalification

3
Good Manufacturing Practices (GMP) and
Inspections

• WHO GMP text Main principles
• WHO Technical Report Series, No. 908, 2003
• Annex 4
• Regularly reviewed and updated
• Divided into "chapters" or "quality systems"
• Quality assurance,

4
Good Manufacturing Practices (GMP) and
Inspections

• 1. Quality assurance
• 2. Good manufacturing practices for
  pharmaceutical products (GMP)
• 3. Sanitation and hygiene
• 4. Qualification and validation
• 5. Complaints
• 6. Product recalls
• 7. Contract production and analysis
• 8. Self-inspection and quality audits

5
Good Manufacturing Practices (GMP) and
Inspections

• 9. Personnel
• 10. Training
• 11. Personal hygiene
• 12. Premises
• 13. Equipment
• 14. Materials
• 15. Documentation
• 16. Good practices in production
• 17. Good practices in quality control

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Good Manufacturing Practices (GMP) and
Inspections

• Other texts
• Sterile products
• Herbal medicines
• Radiopharmaceuticals
• HVAC
• Water systems
• Sampling etc

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Good Manufacturing Practices (GMP) and
Inspections

• Also to consider when necessary
• PIC/S guidelines
• ISO guidelines
• Sampling
• Risk management
• Clean rooms
• ICH guidelines
• ICH Q9
• USA FDA
• Guidelines and guidance

8
Good Manufacturing Practices (GMP) and
Inspections

• Context in Prequalification
• Product specific (dosage form) inspections
• SOPs followed
• Planning, preparation, conduct, report
• Inspection team
• Appropriate guidelines used
• Report with references to text, and rating
• Critical, major, minor

9
Good Manufacturing Practices (GMP) and
Inspections

• A critical deficiency was defined as a deficiency
  which had produced, or led to a significant risk
  of producing, either a product which was harmful
  to the human patient or a product which could
  result in a harmful residue in a food producing
  animal.
• A major deficiency was defined as a non-critical
  deficiency, which had produced or might produce a
  product which did not comply with its marketing
  authorisation.
• A minor deficiency was defined as a deficiency
  where an observation made could improve the
  quality system and quality assurance approach of
  the manufacturer, but which did not have a major
  impact on the quality of the product.

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Good Manufacturing Practices (GMP) and
Inspections

• Inspection approach
• Normally a "routine type" of GMP inspection
• Opening meeting, follow the flow, closing meeting
• On site inspection (production and quality
  control) and documentation review
• Quality systems approach
• Modern challenges including risk assessment

11
Good Manufacturing Practices (GMP) and
Inspections

• Guiding principles
• Risk based orientation
• Science based policies and standards
• Integrated quality systems
• International standards
• Public interest

12
Good Manufacturing Practices (GMP) and
Inspections

• Product quality and performance ensured through
• design (manufacturing processes)
• Product and process specifications
• Understanding of affect of formulation and
  process factors on product quality and
  performance
• Quality by design (build quality into the
  product)
• Interaction between review, compliance and
  inspection

13
Good Manufacturing Practices (GMP) and
Inspections

• Where to start?

14
Premises

• Principle
• Important aspects to be kept in mind to ensure
  the suitability of
• the operations to be carried out for different
  dosage forms and
• product range
• Location
• Design
• Construction
• Adaptation
• Maintenance

12.1
15
Premises

• Principle
• Premises must be located to minimize risks of
  cross-contamination, e.g. not located next to a
  malting factory with high airborne levels of yeast

12.4
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Premises

• General
• The layout and design should aim to
• Minimize risks of errors
• Permit effective cleaning
• Permit effective maintenance
• Avoid cross-contamination, build-up of dirt
  and dust
• Avoid any adverse effect on the quality of
  products

12.2
17
Premises

• Design Principles
• Keep in mind
• Material flow
• People flow
• Process flow
• Ensure logical flow

12.10
18
Premises

• Example of Materials and People Flow
• Arrival of goods Entrance for visitors
  Entrance for Workers Shipment of goods
• 
  
  
• 
  
  
  Material Flow
• 
  
  
  People Flow
• 
  
  
  Zone Clean
• 
  
  
  Zone Packaging
• 
  
  
  Zone Controlled
• 
  
  
• 
  

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Premises

• Construction
• Suitable materials
• Electrical supply
• Suitable lighting (especially for visual on-line
  checks)
• Temperature and relative humidity control
• Appropriate and effective ventilation
• These may affect products during manufacture or
  storage as well as functioning of equipment

12.8, 12.32
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Premises

• The temperature and relative humidity should be
  controlled, monitored in accordance with an SOP,
  and the results recorded. The limits should be
  appropriate according to the materials stored and
  product processed

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Premises
22
Premises

• Specific areas
• Review some recommendations for specific areas in
  the following slides (Part 2)
• Ancillary areas
• Storage areas
• Weighing areas
• Production areas
• Quality control areas

12.11