Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1
(1997; 248 pages) [French] View the PDF document
Table of Contents
Open this folder and view contentsIntroduction
Open this folder and view contents1. National drug regulation
Close this folder2. Product assessment and registration
View the documentGuidelines for the assessment of herbal medicines1,2
Open this folder and view contentsStability of drug dosage forms1
Open this folder and view contentsGuidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms1
Close this folderMultisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability1
View the documentIntroduction
View the documentGlossary
Close this folderPart One. Regulatory assessment of interchangeable multisource pharmaceutical products
View the document1. General considerations
View the document2. Multisource products and interchangeability
View the document3. Technical data for regulatory assessment
View the document4. Product information and promotion
View the document5. Collaboration between drug regulatory authorities
View the document6. Exchange of evaluation reports
Open this folder and view contentsPart Two. Equivalence studies needed for marketing authorization
Open this folder and view contentsPart Three. Tests for equivalence
View the documentPart Four. In vitro dissolution tests in product development and quality control
View the documentPart Five. Clinically important variations in bioavailability leading to non-approval of the product
View the documentPart Six. Studies needed to support new post-marketing manufacturing conditions
View the documentPart Seven. Choice of reference product
View the documentAuthors
View the documentReferences
View the documentAppendix 1. Examples of national requirements for in vivo equivalence studies for drugs included in the WHO Model List of Essential Drugs (Canada, Germany and the USA, December 1994)
View the documentAppendix 2. Explanation of symbols used in the design of bioequivalence studies in humans, and commonly used pharmacokinetic abbreviations
View the documentAppendix 3. Technical aspects of bioequivalence statistics
Open this folder and view contents3. Distribution
Open this folder and view contents4. The international pharmacopoeia and related activities
Open this folder and view contents5. Basic tests
Open this folder and view contents6. Laboratory services
Open this folder and view contents7. International trade in pharmaceuticals
Open this folder and view contents8. Counterfeit products
Open this folder and view contents9. Training
View the documentSelected WHO publications of related interest
View the documentBack cover
2. Multisource products and interchangeability

Economic pressures often favour the use of generic products, and this can sometimes result in the purchase on contract of such products by procurement agencies without prior licensing by the appropriate drug regulatory authority. However, all pharmaceutical products, including generic products, should be used in a country only after approval by that authority. Equally, pharmaceutical products intended exclusively for export should be subjected by the regulatory authority of the exporting country to the same controls and marketing authorization requirements with regard to quality, safety and efficacy as those intended for the domestic market in that country.

Nominally equivalent interchangeable (generic) pharmaceutical products should contain the same amount of the same therapeutically active ingredients in the same dosage form and should meet required pharmacopoeial standards. However, they are usually not identical, and in some instances their clinical interchangeability may be in question. Although differences in colour, shape and flavour are obvious and sometimes disconcerting to the patient, they are often without effect on the performance of the pharmaceutical product. However, differences in sensitizing potential due to the use of different excipients, and differences in stability and bioavailability, could have obvious clinical implications. Regulatory authorities consequently need to consider not only the quality, efficacy and safety of such pharmaceutical products, but also their interchangeability. This concept of interchangeability applies not only to the dosage form but also to the instructions for use and even to the packaging specifications, when these are critical to stability and shelf-life.

Regulatory authorities should therefore require the documentation of a generic pharmaceutical product to meet three sets of criteria relating to:

- manufacture (GMP) and quality control;
- product characteristics and labelling; and
- therapeutic equivalence (see Part Two).

Assessment of equivalence will normally require an in vivo study, or a justification that such a study is not required in a particular case. Types of in vivo studies include bioequivalence studies, pharmacodynamic studies, and comparative clinical trials (see sections 10-12). In selected cases, in vitro dissolution studies may be sufficient to provide some indication of equivalence (see section 13). The regulatory authority should be in a position to help local manufacturers by advising them on drugs that pose potential bioavailability” problems so that in vivo studies are therefore required.

Examples of national requirements for in vivo studies for drugs included in the WHO Model List of Essential Drugs are given in Appendix 1.

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