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
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
 

Part Five. Clinically important variations in bioavailability leading to non-approval of the product

A new formulation of bioavailability outside the acceptance range as compared with an existing pharmaceutical product is by definition not interchangeable. A marketing authorization for a formulation of lower bioavailability may not be approved because of efficacy concerns. In contrast, a formulation of higher bioavailability (“suprabioavailability”) may not be approved because of safety concerns. There are then the following two options:

1. The suprabioavailable dosage form, if reformulated so as to be bioequivalent to the existing pharmaceutical product, could be accepted as interchangeable with that product. This may not be ideal, however, as dosage forms of lower bioavailability tend to be variable in performance.

2. A dosage form of increased bioavailability in which the content of active substance has been appropriately reduced could be accepted as a new (improved) dosage form, but this decision would normally need to be supported by clinical trial data. Such a pharmaceutical product must not be accepted as interchangeable with the existing pharmaceutical product, and would normally become the reference product for future interchangeable pharmaceutical products. The name of the new pharmaceutical product should be such as to preclude confusion with the older approved pharmaceutical product(s).

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