Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

At present, there are no approved generic inhaled corticosteroids available in the US market. This is surprising since this indication represents a multi-billion dollar market and the patents of some of the market leaders are already expired. The reason for this situation is the lack of a regulatory guidance that will enable generic manufacturers to submit an ANDA for approval of a bioequivalent product. The concern, as with any topical product, is that the conventional bioequivalence study based on a comparison of drug exposure in plasma may not be appropriate and not correctly reflect the relative availability at the site of action in the lungs. Hence, the only way that a generic company can get a product approved is to undergo expensive clinical trials, which defeats the purpose of the generic drug product concept. Interestingly, the approach of the EMA in Europe has been exactly the opposite. The EMA has issued a guidance document that may allow generic approval based on in-vitro equivalence alone. However, the detailed criteria are so strict that this scenario seems not very realistic. If in-vitro equivalence is not achieved, then a pharmacokinetic study based on drug exposure in plasma can be submitted. Interestingly, even if the pharmacokinetic studies come out to be not able to show equivalence, generic approval is still a possibility if clinical equivalence can be shown. It can be shown that of the three different measures (in-vitro performance, pharmacokinetics and clinical study) the pharmacokinetic approach is the most sensitive. Hence, it is proposed to harmonize the equivalence criteria world-wide and base the approval on both in-vitro studies and pharmacokinetic studies but not require any clinical studies.

Biography

Email: hartmut@cop.ufl.edu