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Training Module 4
Quality Assurance
Learning Objectives
Upon completion of this module, you will be able to
Explain the need for a systematic quality assurance process for pharmaceutical products Describe key elements of the quality assurance process for pharmaceuticals Discuss the procedures and standards for prequalification of suppliers of pharmaceuticals Apply quality assurance and supplier selection principles to case discussions
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Quality Assurance
A process, not an end-point Must be independent of financial pressures Must ensure that quality policies are followed Must have final authority in product acceptance, rejection and release to public Integral to production, not an add-on Responsible for day-to-day operations and for longer term goal settings Quantitative discipline with specified parameters
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DEFINITIONS
QUALITY
The totality of features and characteristics of a medicinal product and its ability to satisfy stated and/or implied needs
QUALITY ASSURANCE
The sum total of the organized arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use.
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DEFINITIONS
GOOD MANUFACTURING PRACTICE (GMP)
That part of QA which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use.
QUALITY CONTROL
That part of GMP which is concerned with sampling, specifications and testing.
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Quality relationships
QA GMP QC
Quality relationships
Quality Management Quality Assurance GMP Quality Control
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PACKAGING
STORAGE
Quality Assurance
Primary Functions Quality Control
Analytical testing of products
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Safety measures
CONSEQUENCES OF QA BREACHES
Poor Treatment outcomes High Health Bills Treatment Failures & Deaths Loss of Confidence in the Health Services Enormous Economic Losses National Security Issue
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Source: (WHO)
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GMP Principles
Must be built into manufacturing process Prevents errors that cannot be eliminated through quality control of finished product Ensures all units of a medicine are of the same (within specified parameters) quality Poor medicines leads to loss of credibility for everyone: manufacturers, health care workers and governments WHO Guidelines for GMP
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Action of proving (in accordance with principles of GMP) that any procedure, process, equipment, material, activity, or system actually leads to expected results
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Associated Concepts
Good Laboratory Practice (GLP) Good Clinical Practice (GCP) Clear language use Effective record keeping Design, installation, operational and process qualification (DQ, IQ, OQ and PQ) Self-inspection and self-regulation Good Distribution Practice (GDP)
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Documentation
Premises
(Equipment)
Materials
(Supplies, Ingredients)
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(Cont.)
Selection of product and goal of treatment may vary depending upon patient group Infected adults Infected women (who may be/may become pregnant) Infected children (blood-borne or sexual transmission) Emergency workers Victims of sexual assault
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14%
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Clinical Outcomes
Successful treatment for HIV with quality medicines will:
Improve general health status/well-being Reduce viral load to <20 cells/mL Maintain CD4 within normal range (550-1400 cells/mL) Prevent/reduce drug resistance Manage and minimize drug-related side-effects Reduce need for medical intervention
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Combination Products
More convenient, improve adherence, reduce pill burden for patient E.g. Triomune (NRTI-NNRTI triple combination therapy consisting of stavudine, lamivudine, and nevirapine) Product formulations to allow twice daily (or even once daily) dosing
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Suppliers/Manufacturers
Many reliable manufacturers, both innovator and generic companies, can offer quality productsthe aim is sustained, consistent and acceptable quality rather than high or better quality, terms that are impossible to quantify
Battling HIV/AIDS, World Bank 2004
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Single source
Newer products still subject to patent protection in many countries (e.g. Saquinavir)
Limited source
More than single source/supply possible (e.g. AZT); may be difficult to manufacture (e.g. amphotericin); may be unprofitable drug with limited market potential
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Comparison of Sources
Mu lti- s o u r c e # o f m a n u fa c tu r e rMa ny s W o rld-w id e Pu b lic in fo r m a tio nA v a ila b le C o m pe nd ia Pu b lic e x p e r ie n c e Lo ng -sta nding A cce ssible S in g le / lim ite d s o u r c e Inno v a to r m a nufa cture r Lim ite d lo ca l g e ne ric No t a v a ila ble In-ho use spe cifica tio ns V e ry lim ite d No t e a sily a cce ssible
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Prequalification Verifications
Compliance with GMP Inspections and certification of facilities or reliance on national regulatory authorities Compliance with good distribution practices Quality assurance methods for selection of raw material suppliers, storage of products, transportation delivery of final product, etc. 55
Perform Inspections
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Pharmaceutical Stability
GMP state there must be a written testing program designed to assess stability characteristics of drugs. Results of stability testing are used to determine appropriate storage conditions and expiration dating
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Stability Issues
Time-related harmful events include a) Deterioration of therapeutic activity below specified threshold b) Potentiation of therapeutic activity above specified threshold c) Appearance of toxic substance forming as a degradation by-product
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Bioavailability
Measurement of both the rate of drug absorption and total amount (extent) of drug that reaches the general systemic circulation from an administered dosage form
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Equivalence
More general, relative term indicating a comparison of one drug with another along a set of established standards/criteria Bio-equivalence Clinical equivalence Therapeutic equivalence Pharmaceutical equivalence
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Therapeutic Equivalence
Two different brands of a drug product are expected to yield the same clinical result For therapeutic equivalence Pharmaceutical, chemical and bioequivalence must be demonstrated Product must be appropriately labeled Product must be manufactured in compliance with GMP
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Bio-Equivalence
Indicates that a drug in two or more similar dosage forms reaches the general circulation at the same relative rate and the same relative extent Does not necessarily demonstrate clinical or therapeutic equivalence (but does not necessarily rule it out either!)
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Evaluation of Equivalence
Products frequently tested in small samples, not whole populations Individual variations may emerge Must adhere to GMP Appropriate and accurate labeling (e.g. generic or brand-name product)
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Conclusions
GMP as a quality management system Ensure appropriate infrastructure encompassing organizational structure, procedures, processes, and resources Ensure systematic actions necessary to provide adequate confidence that product will meet quality standards and expectations
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Conclusions
Good Manufacturing Practices are Pivotal to quality assurance Everyones responsibility (manufacturers, purchasers, distributors, consumers) Clear, transparent, documented, readily observable On-going, consistent, reproducible
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Conclusions
GMP are aimed at reducing risks inherent in pharmaceutical production Qualification and validation provides confidence in manufacturers processes Prequalification provides greatest assurance regarding quality of pharmaceutical products, based on GMP and product dossier
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Case Study
In your small groups, review the case study which you have already read. As a group, identify critical issues raised by this case study. Use the guided discovery questions to prompt discussion.
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