module 2 | slide 1 of 31 2013 quality management and pharmaceutical quality system basic principles...

Module 2 | Slide 1 of 31 2013

Quality Management

and

Pharmaceutical Quality System

Basic Principles of GMP

Section 1 and 2


Quality ManagementQuality 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 Management

Quality relationships

Quality Management and PQS

Quality Assurance

GMP

Production and Quality Control


PQS and Quality ManagementPQS 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.




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.




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

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

1.4.



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

responsibilities are clearly specified in job descriptions1.5.



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 improvement1.5.




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) (effectiveness should be monitored)

1.5.



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

1.5.



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.


Quality Risk ManagementQuality Risk Management

(ICH Q9)Advanced training workshop for GMP inspectors

Nairobi , 9-12 May, 2011


Quality Risk Management 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)


Quality Risk Management 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)


Product Quality ReviewProduct 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 accuracy1.10.



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


2.1


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 Contamination and cross-contamination Mix-ups (confusion)


2.1 a - c


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, transportLaboratories and in-process control


2.1 d - j


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



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


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