Good Practices in Production and Good Practices in Production and Quality Control.

JOHN STARTUPRelated Guidelines Quality Control Related Guidelines

John Startup

Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and .assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda 1 | February 23-27, 2009, Kampala, Uganda

Artemisinin based combined medicines

Basic Principles of GMP

Good Practices in Production and Quality Control. Related Guidelines

Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

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Basic Principles of GMP

The Ten Commandments of GMP

Section 16 and 17

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

The Ten Commandments of GMP
1 Build Adequate Premises 2 Equip Your Premises with plant and services fit for purpose. 3 Maintain your premises and equipment 4 Write procedures 5 Validate your work/procedures
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Section 16 and 17

Basic Principles of GMP

The Ten Commandments of GMP
6 Train your workforce 7 Record your work 8 Be clean in all things 9 Test for Quality 10 Audit for compliance.

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

The WHO Guidelines EEC Guidelines(ORANGE GUIDE Eudralex Guidelines FDA Guidelines(CFR) MHRA Specific Topics
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

Well documented and respected guidelines. Most available on the internet (OG is the exception)

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

Do not forget EP, BP,USP Setting standards as opposed to guidelines

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

PREMISES
EEC 1.3 Specifically Annexe 1 Sterile Manufacture WHO Chapter 1 .12 HVAC Chapter 3 Sterile Manufacture. Eudralex Monograph

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

EQUIPMENT
EEC 3 and 5 (production) Specifically Annexe 1 Sterile Manufacture WHO Chapter 1 (includes HVAC) Chapter 3 Sterile Manufacture. Eudralex Guideline. Also Sterile Manufacture.

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

CARE and MAINTENANCE
EEC 3.34 to 3.44 Cleaning and maintenance. WHO 1.13 Company SOP for service schedule and pre programmed Maintenance (PPM)

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

WRITE PROCEDURES
Addressed in the Documentation chapters of the guidelines
EEC 4.19 to 4.29 Include but not limited to Inventory control Sampling Testing and status control Manufacture and packaging Hygiene /environmental monitoring & control

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

WRITE PROCEDURES
Addressed in the Documentation chapters of the guidelines WHO 1.15 Eudralex PIC Annexe 13

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

VALIDATION
Validation protocols usually have a generic format # See WHO 1 appendix 6 Validation Master Plan PIC guideline 10063

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

VALIDATION
A recorded protocol which demonstrates with a high degree of probability that any activity will repeatedly produce a result within a pre determined specification/requirement. All aspects of pharmaceutical manufacture require validation. Sufficiently important to be referred to throughout the guidelines. eg. WHO 1 appendix 6 Normally states the requirement (not negotiable) but rarely how to
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

TRAINING
WHO 1.10 and EEC 2.8 to 2.12
Detail training requirements General company culture On the job Outside courses Tests for proficiency Authorisation Training records
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

RECORDS
Found in the documentation chapters of the guidelines. Examples Analytical test records Batch manufacturing documents (BMR) Cleaning records

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

CLEANLINESS AND HYGIENE
Fleeting reference in EEC and WHO Guidelines

PIC gives better information #

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

QUALITY
Quality Assurance Both OG and WHO describe in detail the elements of a robust quality system. Emphasises its all embracing function

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

QUALITY
Quality Control Quality control of raw materials Components Intermediates and finished products. Microbiology
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

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Basic Principles of GMP

QUALITY
Quality Control WHO 1.17 EEC 12.6 Quality control of raw materials Components Intermediates and finished products. Microbiology $#
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

AUDITING FOR COMPLIANCE
WHO 1.8 EEC2.9 Describes the procedures Aspects of pharmaceutical production to be assessed. Includes audits of suppliers.
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

So what else is there?

???
ISO9000
HTM 2010 Validation of Autoclaves BS 6001

GAMP

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

OTHERS ISPE Publications on good Pharma Practice HTM 2010 Validation of Autoclaves
Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

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Basic Principles of GMP

WHAT ELSE IS THERE
Contract manufacture. Technical agreements. WHO 1.7 EEC 2.7 Both define contract giver and acceptor And their individual and shared responsibilities
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

WHAT ELSE IS THERE
Complaints Recalls Returns Stability programmes.

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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

Basic Principles of GMP

All the guidelines presented are objectives which are not negotiable Nowhere does it say if it costs too much one can ignore the guideline Nowhere does it say if the resources are unavailable the guideline can be ignored. Whist not negotiable, the means /ways of achieving the objectives are a matter of company style one mans solution is another mans
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Artemisinin based combined medicines February 23-27, 2009, Kampala, Uganda

disaster.