(1997; 248 pages) [French]
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.