Transcript GMP Updated Training Modules

Basic Principles of GMP
Quality Management
and
Pharmaceutical Quality
System
Section 1 and 2
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Slide 1 of 31
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Quality Management
Objectives
To understand key issues in quality management,
quality assurance, good manufacturing practices and
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.
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Slide 2 of 31
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Quality Management
Quality relationships
Quality Management and PQS
Quality Assurance
GMP
Production and Quality Control
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Slide 3 of 31
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PQS and Quality Management
Comprehensive Pharmaceutical Quality System,
GMP and Quality Risk management:
The manufacturer assumes responsibility. Ensures that
products:
–fit for their intended use
–comply with marketing authorization
–do not place patients at risk due to inadequate safety, quality
or efficacy
Senior management and participation and commitment
of staff, suppliers and the distributors
1.1. – 1.2.
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Slide 4 of 31
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PQS and Quality Management
Pharmaceutical Quality System
 Senior management - leadership and active participation
in the PQS is essential. Ensure the support and
commitment of all staff to the PQS.
 Senior management has the ultimate responsibility to
ensure:
– effective PQS is in place
– adequately resourced and that roles, responsibilities, and
authorities are defined, communicated and implemented
throughout the organization
1.1. – 1.2.
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Slide 5 of 31
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PQS and Quality Management
 PQS should be defined and documented
 Quality manual or equivalent documentation describing
the quality management system including management
responsibilities.
 Periodic management review of the PQS
 Continual improvement of PQS, products and processes
1.6. – 1.7.
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Slide 6 of 31
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PQS and Quality Management
Pharmaceutical Quality System
 Quality management is a wide-ranging concept
 Totality of arrangements to ensure that products
are of desired quality
 It incorporates good manufacturing practices
(GMP) and other factors such as product design
and development
1.3.
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Slide 7 of 31
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PQS and Quality Management
 GMP applies to the life-cycle stages
– from the manufacture of investigational medicinal products,
technology transfer, commercial manufacturing through to
product discontinuation
 PQS: can extend to the pharmaceutical development lifecycle stage
 Should facilitate innovation and continual improvement
– link between pharmaceutical development and manufacturing
activities
1.4.
 Resourced and maintained (premises, personnel, equipment, facilities)
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Slide 8 of 31
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PQS and Quality Management
The PQS should ensure that:
 product realization is achieved
– designing, qualifying, planning, implementing, maintaining and
continuously improving a system
 product and process knowledge is managed
 products are designed and developed (GMP, GLP,GCP)
 SOPs for production and control operations
1.5.
 responsibilities are clearly specified in job descriptions
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Slide 9 of 31
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PQS and Quality Management
PQS should ensure that (2)
 correct starting and packaging materials
 controls on starting materials, intermediate products, and
bulk products and other in-process controls, calibrations
and validations are carried out
 the finished product is correctly processed and checked
 finished product release - certified that each production
batch has been produced and controlled in accordance
1.5.
with the marketing authorization and regulations
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Slide 10 of 31
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PQS and Quality Management
PQS should ensure that (3)
 management of outsourced activities
 storage, distribution and subsequently handling
 self-inspection and/or quality audit
 investigation of deviations and preventive action
 changes and their approval
 regular reviews of the products (PQR) - need for improvement
1.5.
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Slide 11 of 31
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PQS and Quality Management
PQS should ensure that (4)
 monitoring and control systems for process performance and
product quality
 continual improvement
 quality risk management (QRM)
 suspected product defects and other problems are reported,
investigated and recorded
 corrective actions and/or preventive actions (CAPAs)
(effectiveness should be monitored)
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Slide 12 of 31
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1.5.
PQS and 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
1.5.
 Systems ensure that the correct starting and packaging
materials are used
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Slide 13 of 31
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PQS and 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
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Slide 14 of 31
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1.5.
PQS and 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
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Slide 15 of 31
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1.5.
PQS and Quality Management
Quality Risk Management
 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
1.8. – 1.9.
– Should be linked to the protection of the patient
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Slide 16 of 31
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Quality Risk Management
(ICH Q9)
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training
Slide 17 of 31Advanced 2013
workshop for GMP inspectors
Nairobi , 9-12 May, 2011
Quality Risk Management
Quality Risk Management
 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)
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Slide 18 of 31
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Quality Risk 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)
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Slide 19 of 31
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Product Quality Review
Product quality review (PQR)
 Regular, periodic or rolling quality reviews of all medicinal
products
 Normally annually – can also be more frequently
 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.
1.10.
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Slide 20 of 31
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Product Quality Review
 PQR should include at least a review of:
– starting materials and packaging materials (especially from
new sources and review of supply chain)
– 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
1.10.
trends
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Slide 21 of 31
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Product Quality Review
 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
1.10.
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Slide 22 of 31
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Product Quality Review
Product quality review (PQR)
 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
1.10.
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Slide 23 of 31
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Product Quality Review
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
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Slide 24 of 31
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PQS and Quality Management
Good Manufacturing Practices (GMP)
 That part of QA that ensures that products are consistently
produced and controlled
 Quality standards
 Marketing authorization, clinical trial authorization and/or
product specification
 Aim: Diminishing risks that cannot be controlled by testing of
product
2.1
 Contamination and cross-contamination
 Mix-ups (confusion)
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Slide 25 of 31
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PQS and Quality Management
Basic Requirements for GMP – I
 Manufacturing processes are clearly defined and systematically
reviewed for risks – scientific knowledge and experience
 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
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Slide 26 of 31
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2.1 a - c
PQS and 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
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Slide 27 of 31
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2.1 d - j
PQS and Quality Management
Group session – I
 How many GMP deficiencies can you find in the
photographs in the handout?
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Slide 28 of 31
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PQS and 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
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Slide 29 of 31
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PQS and Quality Management
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
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Slide 30 of 31
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PQS and Quality Management
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
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Slide 31 of 31
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