1 3 gmp-purpose-principles-guidelines

Good Manufacturing PracticesPurpose and Principles of GMP

Tony Gould

2 | PQ Workshop, Abu Dhabi | October 2010

Why GMP?

Provides a high level assurance that medicines are manufactured in a way that ensures their safety, efficacy and quality

Medicines are manufactured to comply with their marketing authorization

Quality is built in– Testing is part of GMP, but alone does not provide a

good level of quality assurance


Why inspect?

Verify compliance with GMP

Verify compliance with marketing authorization– Dossier: "Dedicated equipment is used"

Inspection: Observation that this means "dedicated while used for the product or not being used for another product"

– Dossier: "The vials are removed from the lyophilliser and crimped in a grade A environment"

Inspection: Correct, but before crimping they are stored in an uncontrolled corridor


WHO GMP

Quality assurance of pharmaceuticals

A compendium of guidelines and related materials

Volume 2, 2nd updated edition

Good manufacturing practicesand inspection


Guidelines and references

GMP applies to both Active Pharmaceutical Ingredients (APIs) and Finished Pharmaceutical Products (FPPs)

– FPP:WHO Good Manufacturing Practices for pharmaceutical products: main principles. WHO Technical Report Series, No. 908, 2003, Annex 4.

– API:WHO good manufacturing practices for active pharmaceutical ingredients - Annex 2, WHO Technical Report Series 957, 2010 (Based on ICH Q7) 5


Other WHO GMP Guidelines

Pharmaceutical excipients Sterile pharmaceutical products Biological products Pharmaceutical products containing hazardous

substances Investigational pharmaceutical products for clinical trials iHerbal medicinal products Radiopharmaceutical products Water for pharmaceutical use HVAC for non-sterile pharmaceutical dosage forms Validation


Good Manufacturing Practices (FPP):

1. Quality assurance2. Good manufacturing practices for pharmaceutical

products 3. Sanitation and hygiene4. Qualification and validation5. Complaints6. Product recalls7. Contract production and analysis

– General– The contract giver– The contract accepter– The contract


Good Manufacturing Practices (cont'd)

8. Self-inspection and quality audits– Items for self-inspection– Self-inspection team– Frequency of self-inspection– Self-inspection report– Follow-up action– Quality audit– Suppliers’ audits and approval

9. Personnel– General– Key personnel

10. Training



11. Personal hygiene

12. Premises– General

– Ancillary areas

– Storage areas

– Weighing areas– Production areas– Quality control area

13. Equipment



14. Materials– General– Starting materials– Packaging materials– Intermediate and bulk products– Finished products– Rejected, recovered, reprocessed and reworked materials– Recalled products– Returned goods– Reagents and culture media– Reference standards– Waste materials– Miscellaneous



15. Documentation– General– Documents required:

• Labels

• Testing procedures• Specifications for starting and packaging materials, for

intermediate and bulk products and for finished products• Master formulae and Batch Processing Records• Packaging instructions and Batch Packaging Records

• Standard Operating procedures (SOP's) and records

• Logbooks



16. Good practices in production– General– Prevention of cross-contamination and bacterial

contamination during production– Processing operations– Packaging operations

17. Good practices in quality control– Control of starting materials and intermediate, bulk and

finished products– Test requirements– Batch record review– Stability studies


GMP is actually Good Common Sense

Quality Management

Quality Assurance

GMP

Production and Quality Control

Section 1 and 2


Quality management in the drug industry

Philosophy and essential elements:

"The concepts of quality assurance, GMP, quality control and quality risk management are interrelated aspects of quality management, and should be the responsibility of all personnel. ……their relationship and their fundamental importance to the production and control of pharmaceutical products."

Glossary


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 referred to as “Quality Assurance”


The five P's

Premises

Primary materials

People

Procedures

Processes defined and recorded


Quality Assurance

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 1.1


Quality Assurance

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 continuously of the right

quality for the intended use

Quality Assurance incorporates GMP– and also includes product design and

development, with special focus on process design 1.1


The position of QA

DirectorDirector

QAQA

ProductionProduction QC labQC lab Other DeptsOther Depts


Quality Assurance means to assure:

Products are designed and developed correctly– Complying with, e.g. GMP, GCP, GLP

Production and control operations are defined

Managerial responsibilities are defined– In job descriptions

The manufacture, supply and use of correct starting and packaging materials 1.1 a- d


Quality Assurance means to assure: (cont'd)

Controls are performed, including intermediates, bulk, calibration and validation

Correct processing and checking of the finished product

Products are sold/supplied only after review by the authorized person– Complying with marketing authorization,

production and QC requirements

Proper storage, distribution and handling

1.1 e - h


Quality Assurance means to assure: (cont'd)

Procedures for self-inspection and quality audits are applied

Deviations are reported, investigated and recorded

System for change control is applied

Regular evaluation of product quality to verify consistency and continued improvement

1.1 i - l


Quality Assurance includes:

Responsibility of the Manufacturer for the quality of the product

– Fit for intended use– Comply with marketing authorization– Safety, efficacy and quality

Commitment of senior management and involvement of all staff

Comprehensively designed and well implemented quality system

Full documentation and monitoring of effectiveness

Competent personnel, sufficient premises, equipment and facilities 1.3


Good Manufacturing Practices

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) 2.1


Basic requirements for GMP:

Clearly defined and systematically reviewed processes

Qualification and validation is performedAppropriate 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: (cont'd)

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


GMP = continuous urge for improvement

Involvement of the management

Annual Product Quality Review

Quality risk management

Complaints handling

Self-inspection


Involvement of the management

The senior management is responsible to attain the company's quality objectives

All different departments and all levels within departments should be involved; and it's the senior management who should facilitate this

Also suppliers and distributors should be involved

The senior management should make available the required resources

The basis of the quality system is the quality statement and quality policy, by the senior management


Product Quality Review

Objectives of Product Quality Review:

To review and verify the consistency and appropriateness of the existing process

To identify and highlight any trends in the process, e.g. in analytical results, yields etc.

To identify any possible product or process improvements


Product Quality Review (cont'd)

Review of starting materials/ packaging materials, especially from new sources

Review of in-process control results and finished product analytical control results

Amount of batches and packaging units produced and their yields

Reviews of:– Out-of-spec situations, rejections, deviations, changes– Plus investigations and analysis of causes


Annual Product Quality Review (cont'd)

Review of Marketing Authorization variations submitted, granted or refused (incl. third countries)

Review of stability programme and trendsReview of adequacy of previous decisions on

changes or improvements or corrective actionsFor new Marketing Authorizations (plus new

variations) a review of post marketing commitmentThe qualification status of all relevant equipment

and utilities (like water, HVAC, gases, etc.)Review of Technical Agreements (if applicable)


5.1

Complaints handling

Complaints: Principle

“All complaints and other information concerning potentially defective products must be carefully reviewed according to written procedures and corrective action should be taken.”


5.2 – 5.3

Complaints Procedure

Designated responsible person:– To handle complaint– Decide on measure to be taken– May be authorized person - if not, must advise

authorized person of results– Sufficient support staff– Access to records

Written procedure (SOP):– Describes action to be taken– Includes need to consider a recall (e.g. possible

product defect)


5.4 – 5.6

Complaints Procedure – cont'd

Thorough investigation:– QC involved– With special attention to establish whether

"counterfeiting" may have been the cause– Fully recorded investigation – reflect all the details

Due to product defect (discovered or suspected):– Consider checking other batches– Batches containing reprocessed product


5.7 – 5.9

Complaints Procedure – cont'd

Investigation and evaluation should result in appropriate follow-up actions– May include a "recall"

All decisions and measures taken should be recorded

Referenced in batch records

Records reviewed - trends and recurring problems


5.10

Complaints - other actions

Inform competent authorities in case of serious quality problems such as:– Faulty manufacture– Product deterioration– Counterfeiting

� Have a thorough recall procedure that is consistent with the complaints handling procedure

� Trend complaints, their investigations and results


Self-Inspection

Purpose is to evaluate whether a company’s operations remain compliant with GMP

The programme should – cover all aspects of production and quality control– be designed to detect shortcomings in the implementation of

GMP – recommend corrective actions– set a timetable for corrective action to be completed

Should be performed routinelyAlso on special occasions such as

– Recalls– Repeated rejections 8.1


8.3, 8.4

Self-Inspection (cont'd)

Performed by team appointed by management, with:– authority– sufficient experience, expertise in their own field.

knowledge of GMP– may be from inside or outside the company

Frequency should normally be at least once a year– May depend on company requirements– Size of the company and activities


8.5, 8.6

Self-Inspection (cont'd)

Report prepared at completion of inspection, including:

– results

– evaluation

– conclusions– recommended corrective measures

Follow-up action– Effective follow-up programme

– Company management to evaluate both the report and corrective actions


Summary and conclusions:

GMP compliance is not an option Quality should be built into the productGMP's are very similar and are really

Good Common SenseGood Practices cover all aspects of

manufacturing activities prior to supplyThe role and involvement of senior

management is crucial


http://www.who.int/prequal

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