From antiretroviral originator to generic drugs: bioequivalence and pharmacovigilance

Antiretroviral drugs have been available in generic form in developing countries, which has expanded access to treatment; they have also become available in developed countries more recently.

The validation of generic drugs (GD) compared to originator drugs (OD) is mandatory to ensure that using generics will lead to a decreased cost of treatment.

The results were obtained by analyzing published data as well as European Medicines Agency recommendations.

The GD should have the same qualitative and quantitative active principle formula, the same pharmaceutical forms, and the same criteria in terms of quality, effectiveness, and safety. This equivalence is based on bioequivalence rules: comparison of the concentration/time curves (AUC); Cmax and Tmax (90%), for which the confidence intervals in the range of 80-125% should be included. Naturally, that does not mean that the concentrations can vary from 80 to 125%: this would indicate unacceptable deviations. Conforming to these criteria allows substituting an OD by a GD. Adverse effects should not be different from those observed for the OD. Adverse effects observed when the GD is used must be notified, as is the case for the OD. Accountability is established according to 4 essential pieces of information: a prescriber, a patient, a drug, and an adverse effect. It is sometimes difficult to identify the provider of the GD that has been delivered.

The level of safety concerning effectiveness and tolerance required is identical for OD and GD, in Europe. Analyzing confirmed adverse effects and therapeutic failures is the only way to identify differences that could question a GD's effectiveness.