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
Open this folder and view contentsPart Two. Equivalence studies needed for marketing authorization
Close this folderPart Three. Tests for equivalence
View the document10. Bioequivalence studies in humans
View the document11. Pharmacodynamic studies
View the document12. Clinical trials
View the document13. In vitro dissolution
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
13. In vitro dissolution

Comparative in vitro dissolution studies may be useful in the documentation of equivalence between two multisource pharmaceutical products. However, because of the many limitations associated with the use of in vitro dissolution in the documentation of equivalence it is recommended in these guidelines that its application for this purpose should be kept to a minimum. In vitro dissolution testing as the sole documentation of equivalence is therefore not applicable to the drugs and dosage forms listed as examples (a) - (e) on In vivo studies (9), but should be reserved for rapidly dissolving drug products.1 When the multisource test and reference products both dissolve with sufficient rapidity (e.g. >80% in 15 minutes), their in vivo equivalence may be presumed. Approval of multisource formulations by the use of comparative in vitro dissolution studies should be based on the generation of comparative dissolution profiles rather than single-point dissolution tests, as described in various pharmacopoeial compendia and other publications. Multiple dissolution test conditions and physiologically relevant media are recommended.

1 Where a drug substance and drug product do not dissolve with sufficient rapidity, as noted above, in vitro dissolution methods may still be used to document equivalence using appropriately validated dissolution methodology including an in vitro/in vivo correlation. Such methodology should be derived from the development and application of specifications and statistical methods to define non-equivalence. This may require formulations with different in vivo performance characteristics. With such formulations, discriminatory in vitro dissolution tests for use in equivalence studies may be developed. With these additional requirements, however, a standard in vivo bioequivalence study as described in section 7 may be preferable.

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