Biopharmaceutics Classification System (BCS) biowaivers

The BCS classifies drugs based on their solubility and permeability characteristics into four classes: I, II, III, and IV Biowaivers for BE studies may be permitted for BCS Class I drugs that have a high solubility and high permeability as these drugs dissolve and are absorbed rapidly following oral administration. Due to safety concerns with oncologic agents, these compounds may not be exempt from BE studies even if they fall into the BCS Class I category as they are cytotoxic. In these cases, additional studies may be required, and an Investigation New Drug (IND) application may be necessary prior to conducting BE studies.

● Narrow therapeutic index

Most oncologic agents have a narrow therapeutic index meaning that they have the potential to cause dose-limiting adverse effects at or near doses required to achieve the desired therapeutic effect. In such cases, the bioequivalence criteria of 90% CI with 80-125% may be insufficient. The European Medicines Agency (EMA), Health Canada, and the FDA have proposed to tighten the limits to 90-111.1% according to within-subject variability in response and perform replicate studies.

Bioequivalence studies form the basis for approval of generic products as well as approval of products following manufacturing or post-approval changes. These studies are especially critical for oncologic agents that have safety concerns and therefore should be performed with utmost care to ensure the availability of affordable medications allowing for improved patient adherence.

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