WHO GMP training course about Quality management

1. Module 2 | Slide 1 of 27 2012
Quality Management
Basic Principles of GMP
Section 1 and 2

2. Module 2 | Slide 2 of 27 2012
Quality Management
Objectives
 To understand key issues in quality assurance/good manufacturing
practices/quality control.
 To understand specific requirements on quality management and
quality assurance including:
 Organization
 Procedures, processes and resources.
 To develop actions to resolve your current problems.

3. Module 2 | Slide 3 of 27 2012
Section 1 and 2
Quality Management
Quality relationships
Quality Management
Quality Assurance
GMP
Production and Quality Control

4. Module 2 | Slide 4 of 27 2012
Quality Management
Philosophy and essential elements
 What is Quality Management?
 The aspect of management function that determines and
implements the “quality policy”
 The overall intention and direction regarding quality, as formally
expressed and authorized by top management

5. Module 2 | Slide 5 of 27 2012
Quality Management
Quality Management
 The basic elements are:
 An appropriate infrastructure or “quality system”
encompassing the organization structure, 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”

6. Module 2 | Slide 6 of 27 2012
Quality Management
Quality Management
 Quality assurance is a management tool
 In contractual situations, it also serves to generate confidence in
a supplier
 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

7. Module 2 | Slide 7 of 27 2012
1.1
Quality Management
Principles of Quality Assurance (QA)
 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
also product design and development

8. Module 2 | Slide 8 of 27 2012
1.2
Quality Management
QA System should ensure that:
 Products are designed and developed in accordance with
GLP, GCP, and GMP
 Production and control operations are clearly specified in
SOPs
 Managerial responsibilities are clearly specified in job
descriptions
 Systems ensure that the correct starting and packaging
materials are used

9. Module 2 | Slide 9 of 27 2012
1.2
Quality Management
QA System should ensure:
 Starting materials, intermediate products, bulk products are
controlled
 In-process controls, calibrations, and validations are carried out
 Finished products are correctly processed and checked
 Products are not sold or supplied before release by authorized
persons
 Systems ensure that products are appropriately stored and
distributed

10. Module 2 | Slide 10 of 27 2012
1.2
Quality Management
QA System should ensure:
 Self-inspection and/or quality audits are done regularly
 Deviations are reported, investigated and recorded
 Changes are controlled
 Systems are followed to verify the consistency of processes and
ensuring continuous improvement
 Quality Risk Management is implemented

11. Module 2 | Slide 11 of 27 2012
1.3
Quality Management
Quality Assurance
 Products must:
– safety, quality and efficacy requirements - fit for their intended use
– comply with the requirements of the marketing authorization
 Senior management is responsible - and all staff must be
committed to achieve this.
 Relies on a comprehensively designed, documented, correctly
implemented system of QA incorporating GMP and QC.
 Relies on competent personnel, suitable and sufficient premises,
equipment and facilities.

12. Module 2 | Slide 12 of 27 2012
1.4 – 1.5
Quality Management
Quality Assurance
 Manufacturers should manage quality risks. Quality Risk
Management (QRM) is a systematic process for:
– assessment, control, communication and review of risks to the
quality of the medicinal product.
 QRM:
– can be applied both proactively and retrospectively
– Should be based on scientific knowledge and experience with
the process
– Should be linked to the protection of the patient

13. Module 2 | Slide 13 of 27 2012
Quality Risk Management
(ICH Q9)
Advanced training workshop for GMP inspectors
Nairobi , 9-12 May, 2011

14. Module 2 | Slide 14 of 27 2012
1.3
Quality Management
Quality Assurance
 Quality Risk Management follows a cycle of assessment, control,
communication and review.
 An appropriate tool should be used in risk assessment, such as:
– Fault Tree Analysis (FTA)
– Hazard and Operational Studies (HAZOP)
– Failure Mode and Effect Analysis (FMEA)
– Hazard Analysis and Criticality Analysis (HACCP)
– Failure Mode, Effect, and Criticality Analysis (FMECA)

15. Module 2 | Slide 15 of 27 2012
Quality Management
Failure Mode Effect Analysis
• Breakdown in manageable steps
• Process and product understanding needed
• Evaluate failure mode and effect on outcome
• Eliminate, contain, reduce, control
• (Identify mode, cause, effect)

16. Module 2 | Slide 16 of 27 2012
1.6
Quality Management
Quality Assurance
Product quality review (PQR)
 Regular, periodic or rolling quality reviews of all medicinal
products
 Normally annually
 Objective:
– Verifying the consistency of the existing process
– appropriateness of current specifications for both starting materials and
finished product
– highlight any trends
– identify product and process improvements.

17. Module 2 | Slide 17 of 27 2012
1.6
Quality Management
Quality Assurance
 PQR should include at least a review of:
– starting materials and packaging materials (especially from
new sources)
– critical in-process controls and finished product results
– all batch failures and their investigation
– deviations or non-conformances (and investigations and
CAPAs)
– all changes made to the processes or analytical methods
– dossier variations submitted, granted or refused
– results of the stability monitoring programme and any adverse
trends

18. Module 2 | Slide 18 of 27 2012
1.6
Quality Management
Quality Assurance
 PQR should include (cont).:
– quality-related returns, complaints and recalls and the
investigations
– adequacy of previous corrective actions on product process or
equipment
– Post marketing commitments
– qualification status of relevant equipment and utilities
– technical agreements

19. Module 2 | Slide 19 of 27 2012
1.6
Quality Management
Quality Assurance
 Results should be reviewed- assessment should be made
whether CAPA or revalidation should be undertaken
 CAPA completed in a timely and effective manner – verified
 Product types can be grouped
 Agreements in case of contracted parties
 PQR in a timely manner and verified for accuracy

20. Module 2 | Slide 20 of 27 2012
Quality Management
Quality Assurance
When inspecting PQR, also verify:
 Correctness of data transferred
 Trending of results
 Calculations such as process capability index (CpK) - where
appropriate
 Accuracy in terms of APIs reflected, approved suppliers used,
number of batches, variations, changes, complaints etc.
 CAPAs and conclusion

21. Module 2 | Slide 21 of 27 2012
2.1
Quality Management
Good Manufacturing Practices (GMP)
 That part of QA that ensures that products are consistently
produced and controlled
 Quality standards
 Marketing authorization
 Aim: Diminishing risks that cannot be controlled by testing of
product
 Contamination and cross-contamination
 Mix-ups (confusion)

22. Module 2 | Slide 22 of 27 2012
2.1 a - c
Quality Management
Basic Requirements for GMP – I
 Clearly defined and systematically reviewed processes
 Qualification and validation is performed
 Appropriate resources are provided:
 Qualified and trained personnel
 Premises, space, equipment and services
 Materials, containers, labels
 Procedures, storage, transport
Laboratories and in-process control

23. Module 2 | Slide 23 of 27 2012
2.1 d - j
Quality Management
Basic Requirements for GMP – I
 Clear, written instructions and procedures
 Trained operators
 Records of actions, deviations and investigations
 Records for manufacture and distribution
 Proper storage and distribution
 Systems for complaints and recalls

24. Module 2 | Slide 24 of 27 2012
Quality Management
Group session – I
 How many GMP deficiencies can you find in the
photographs in the handout?

25. Module 2 | Slide 25 of 27 2012
Quality Management
Group session II
 Imagine you are inspecting a pharmaceutical company for
compliance with GMP
 Consider the situations in the next slides which may have impact
on a company’s quality management programme
 Describe the action to be taken in each case

26. Module 2 | Slide 26 of 27 2012
Issues – I
 Quality Management manual not established in writing
 Limited human resources
 Lack of qualified people
 Processes not properly validated
 Poor SOPs or standard batch documentation
 More consideration to cost than quality
 Family members in key positions of authority
Quality Management

27. Module 2 | Slide 27 of 27 2012
Issues – II
 Substandard materials deliberately purchased
 Technical staff not involved in purchasing
 Inability to re-export substandard materials
 Owner insists on selling rejects
 Corruption
 No commitment to training
Quality Management