(1997; 248 pages) [French]
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).