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
Open this folder and view contentsPart One. Regulatory assessment of interchangeable multisource pharmaceutical products
Close this folderPart Two. Equivalence studies needed for marketing authorization
View the document7. Documentation of equivalence for marketing authorization
View the document8. When equivalence studies are not necessary
View the document9. When equivalence studies are necessary and types of studies required
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
7. Documentation of equivalence for marketing authorization

Pharmaceutically equivalent multisource pharmaceutical products must be shown to be therapeutically equivalent to one another in order to be considered interchangeable. Several test methods are available for assessing equivalence, including:

• Comparative bioavailability (bioequivalence) studies in humans, in which the active drug substance or one or more metabolites is measured in an accessible biological fluid such as plasma, blood or urine.

• Comparative pharmacodynamic studies in humans.

• Comparative clinical trials.

In vitro dissolution tests.

The applicability of each of these four methods is discussed in subsequent sections of these guidelines and special guidance is provided on assessing bioequivalence studies. Other methods have also been used to assess bioequivalence, e.g. bioequivalence studies in animals, but are not discussed here because they have not been accepted worldwide.

The acceptance of any test procedure in the documentation of the equivalence of two pharmaceutical products by a drug regulatory authority depends on many factors, including the characteristics of the active drug substance and the drug product, and the availability of the resources necessary for the conduct of a specific type of study. Where a drug produces meaningful concentrations in an accessible biological fluid, such as plasma, bioequivalence studies are preferred. Where a drug does not produce measurable concentrations in such a fluid, comparative clinical trials or pharmacodynamic studies may be necessary to document equivalence. In vitro testing, preferably based on a documented in vitro/in vivo correlation, may sometimes provide some indication of equivalence between two pharmaceutical products (see section 13).

Other criteria that indicate when equivalence studies are, or are not, necessary are discussed in sections 8 and 9 below.

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