Basic Principles of GMP: Quality Management and Pharmaceutical Quality System

Basic Principles of GMP
Quality Management
and
Pharmaceutical Quality
System
Section 1 and 2
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.

Quality Management
Quality relationships
Quality Management and PQS
Quality Assurance
GMP
Production and Quality Control

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.
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.
 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.
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.
 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 life-

cycle stage
 Should facilitate innovation and continual improvement

– link between pharmaceutical development and manufacturing
activities
1.4.
 Resourced and maintained (premises, personnel, equipment, facilities)

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

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
with the marketing authorization and regulations 1.5.
 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.
 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) 1.5.

(effectiveness should be monitored)
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
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 1.5.
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 1.5.

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
– Should be linked to the protection of the patient 1.8. – 1.9.
(ICH Q9)
Advanced training workshop for GMP inspectors
Nairobi , 9-12 May, 2011

 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)
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)

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.
 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
trends 1.10.
 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.
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.
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

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)
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 2.1 a - c
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 2.1 d - j

Group session – I
 How many GMP deficiencies can you find in the

photographs in the handout?
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

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
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

Basic Principles of GMP: Quality Management and Pharmaceutical Quality System

Uploaded by

Copyright:

Available Formats

Basic Principles of GMP: Quality Management and Pharmaceutical Quality System

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Basic Principles of GMP: Quality Management and Pharmaceutical Quality System

Uploaded by

Copyright:

Available Formats

Basic Principles of GMP

To understand key issues in quality management,

To understand specific requirements on quality

To develop actions to resolve your current problems.

Quality Management and PQS

Production and Quality Control

The manufacturer assumes responsibility. Ensures that

Senior management and participation and commitment

 Senior management - leadership and active participation

 Senior management has the ultimate responsibility to

 PQS should be defined and documented

 Quality manual or equivalent documentation describing

 Periodic management review of the PQS

 Continual improvement of PQS, products and processes

 Quality management is a wide-ranging concept

 Totality of arrangements to ensure that products

 It incorporates good manufacturing practices

 PQS: can extend to the pharmaceutical development life-

 Should facilitate innovation and continual improvement

 Resourced and maintained (premises, personnel, equipment, facilities)

 product realization is achieved

 product and process knowledge is managed

 products are designed and developed (GMP, GLP,GCP)

 SOPs for production and control operations

 responsibilities are clearly specified in job descriptions

 correct starting and packaging materials

 controls on starting materials, intermediate products, and

 the finished product is correctly processed and checked

 finished product release - certified that each production

 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

 quality risk management (QRM)

 suspected product defects and other problems are reported,

 corrective actions and/or preventive actions (CAPAs) 1.5.

 Products are designed and developed in accordance

 Production and control operations are clearly specified in

 Managerial responsibilities are clearly specified in job

 Systems ensure that the correct starting and packaging

 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

 Systems ensure that products are appropriately stored and

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

 Quality Risk Management is implemented 1.5.

Quality Risk Management

 An appropriate tool should be used in risk assessment, such as:

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)