For economic reasons, the use of generic substitution is increasingly being supported by health authorities. Potentially, this may be problematic for drugs with a narrow therapeutic window if quality control and/or bioequivalence is not optimal. Many developing countries do not have the resources or expertise to carry out appropriate quality control resulting in widespread distribution of substandard or even counterfeit drugs. Even in countries where procedures are well regulated, substandard drugs reach the market from time to time.
Interchangeability of drugs is determined by bioequivalence studies comparing the serum concentration versus time curves for the products following single dose administration to fasting volunteers in a randomised crossover design. A number of reports, largely anecdotal, of treatment failure or increased adverse events after switching brands has cast some doubts upon whether bioequivalence testing is sufficient in all cases. These reports have covered cardiovascular, respiratory, hormonal, psychotropic, anticonvulsant, anti-infective and anti-inflammatory drugs. Equivalence is particularly difficult to obtain with many sustained-release formulations.
The WHO has initiated programs to prevent the distribution of substandard preparations and has drafted guidelines for testing bioequivalence based on internationally accepted reference products. Until such time as means can be provided — first, to enforce internationally accepted production standards, and second, to permit uniform testing of therapeutic agents — the safest clinical choice, particularly in countries where registration requirements and quality control are minimal, must remain the branded product.
KeywordsAdis International Limited Piroxicam Generic Drug Generic Substitution Bioequivalence Study
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