CHEE 440 1

Introduction to GMPIntroduction to GMP

CHEE 440 2

ObjectivesObjectives

Acquire basic knowledge of Good Manufacturing Practices (GMP) What are GMPs ? Why are they important ?

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History of Food and Drugs ActHistory of Food and Drugs Act

Government Authorities Canada: Health Canada

Health Products and Food Branch (HPFB)

USA: Food & Drug Administration (FDA)

Europe: EC Directives

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HistoryHistory Food and Drugs Act Food and Drug Regulations

Division 2 : Good Manufacturing Practices 1900’s- Adulterated Food

First purity laws enacted

1930’s- Sulfanilimide Drugs had to be proven safe

1960’s- Thalidomide Drugs had to be proven safe and effective through

clinical trials

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Why are GMPs important?Why are GMPs important?

Government requirement

Ensure quality product

Reduce rejects, recalls

Satisfied customers

Maintain manufacturing consistency

Company image and reputation

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DrugsDrugs HPFB Definition: Any substance or

mixture of substances manufactured, sold or represented for use ina) the diagnosis, treatment, mitigation or prevention of a

disease, a disorder, an abnormal physical state or the symptoms thereof in humans or animals

b) restoring, correcting or modifying organic functions in humans or animals

c) “disinfection” in premises in which food is manufactured, prepared or kept

DIN Label Claim

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Food and Drugs ActFood and Drugs Act

Establishment license Site Reference File HPFB Inspections

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Production GoalsProduction Goals Safety

Product is free of unwanted side effects when used appropriately by patient

Identity Product exactly matches the labelling and related documents

Strength Product has correct concentration, potency or therapeutic

activity of active ingredient

Purity Product is free from contamination

Quality Product meets all standards, expectations; performs as claimed Product made consistently

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GMP CategoriesGMP Categories Sale Premises Equipment Personnel Sanitation Raw Material

Testing Manufacturing

Control

Quality Control Department Packaging Material Testing Finished Product Testing Records Samples Stability Sterile Products Medical Gases

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Sale C.02.003Sale C.02.003

No distributor … and no importer shall sell a drug unless it has been fabricated, packaged/labeled, tested, and stored in accordance with the requirements of this Division

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PremisesPremises C.02.004C.02.004Equipment Equipment C.02.005C.02.005

Permits effective cleaning Prevents contamination Orderly conditions Good state of repair

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PersonnelPersonnel C.02.006C.02.006

Appropriate education, training and experience

Sufficient number of people Receive GMP training

Initial and continuing training as relevant to job responsibilities

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SanitationSanitation C.02.007 - .008C.02.007 - .008

Sanitation Program to prevent contamination Limit the sources and types of

contamination» Cleaning procedures for facilities &

equipment» Pest control» Environmental monitoring

Documented evidence

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SanitationSanitation C.02.008C.02.008

Hygiene Health and eye examinations Report adverse health conditions Clothing requirements

» No direct skin contact with product

» Wash hands

» No jewelry or excessive makeup No smoking, eating, drinking, chewing, or

keeping of plants in operations areas

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Raw Material Testing C.02.009 Raw Material Testing C.02.009 - .010- .010

each lot or batch of raw material is tested three objectives

confirm the identity of the raw materials provide assurance that quality of the drug in

dosage form will not be altered by raw material defects

assure that raw materials have the characteristics that will provide the desired quantity or yield in manufacturing process

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Raw Material, Packaging Material Raw Material, Packaging Material and Finished Product Testingand Finished Product Testing

Samples of incoming materials are collected and tested before use

Approved test methods and specifications are used

Results must conform to specifications for release for use or sale

Transportation and storage records

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Manufacturing Control Manufacturing Control C.02.011C.02.011

Written procedures are established and followed Master formulae, manufacturing order and

packaging order

Critical processes are validated 2nd person verification of activities Quarantine system Labelling requirements

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Manufacturing Control Manufacturing Control C.02.012C.02.012

Recall Programme Self-Inspection Programme Ensure compliance with

vendors/contractors

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Manufacturing ControlManufacturing Control (cont’d)(cont’d)

Validation: the documented act of demonstrating that

any procedure, process, equipment, material, activity, or

system will consistently lead to the expected results

» TPP 1998 Edition

Design Qualification (DQ) Installation Qualification (IQ) Operational Qualification (OQ) Performance Qualification (PQ)

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Quality Control DepartmentQuality Control DepartmentC.02.013 - C.02.015C.02.013 - C.02.015

Quality Control Responsibilities Testing of bulk components prior to use by

production Testing of finished product prior to release

for sale Stability program (in association with QA)

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Quality Control DepartmentQuality Control DepartmentC.02.013 - C.02.015C.02.013 - C.02.015

Quality Assurance Responsibilities Ensure GMP compliance Review batch records, labels Release product, based on QC test results Authorize all master documents and SOPs Training, auditing Customer complaints Recall

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Key Quality TermsKey Quality Terms

CHANGE CONTROL written procedure that describes the action to be

taken if a change is proposed to facilities, etc. used in fabrication, packaging, and testing of drugs or any change that may affect quality or support system operation

DEVIATION Planned or unplanned temporary departure from an

approved process, specification or procedure with the potential to impact product quality

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RecordsRecords C.02.020 - C.02.024C.02.020 - C.02.024

Document all GMP activities Use Good Documentation Practices

(GDP) Records must be readily available Needed to prove activities were

done

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Good Documentation PracticesGood Documentation Practices

Documentation must be: permanent (black or blue ink) legible, clear, concise accurate timely consistent complete

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Samples and StabilitySamples and Stability

Samples Retain samples of each lot of raw material

and finished product for specified period of time

Stability Establish the length of time in which the

product meets all specifications Monitor the drug for this period of time

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Sterile ProductsSterile Products C.02.029C.02.029

Sterile Products Packaged in separate enclosed area by

trained personnel using method to ensure sterility

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Summary Summary

Pharmaceutical Industry is regulated by GMPs

Good Manufacturing Practices must be followed

GMPs ensure drug products are safe, pure and effective.