January 31, 2014

Chetan Javia is ELC Group’s regulatory affairs expert in India. Javia is well-versed in every aspect of the submissions process, from the development of a regulatory strategy to providing regulatory and scientific advice on applications for Europe and ‘rest of the world’ countries. A qualified pharmacist, he has extensive experience in overseeing new and re-registration submissions in variety of international geographies, including the Middle East and Central America.

The Biopharmaceutical Classification System (BCS), introduced in 1995, provides a framework for classifying the drug substance based on its aqueous solubility and intestinal permeability. It allows for the prediction of in-vivo pharmacokinetics of oral immediate-release drug products by classifying drug components based on their solubility related to dose and intestinal permeability, in combination with the dissolution properties of the dosage form.

The objectives of BCS are to:

• improve the efficiency of the drug development and review process by recommending a strategy for identifying expendable clinical bioequivalence test

• recommend a class of immediate release solid dosage forms for which bioequivalence may be assessed based on in-vitro dissolution tests

• recommend methods for classification accordingly to dosage form dissolution, along with solubility-permeability characteristics of the drug product.

At first, the BCS Biowaiver was only applied for secondary strengths, scale-up and post-approval changes, although recently the BCS Biowaiver principle has been extended for the approval of new generic drug products, thereby avoiding unnecessary human experiments and reducing time and cost involved in the development.

The BCS Biowaiver for secondary strengths, scale-up and post-approval changes is widely accepted by almost all regulatory agencies, but the agencies’ position on granting generic approval solely on the basis of BCS Biowaiver — i.e. without providing any in-vivo data — is variable.

Regulatory submissions based only on BCS Biowaiver are possible only for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) drug substances. When making such applications, discussion and consideration should be given to the similarity and differences in the excipients used in the generic formulation against the chosen reference product, the possible drug — including excipient — interaction and the effect of manufacturing process variables affecting drug bioavailability and/or solubility characteristics.

The BCS-based waiver for exempting in-vivo study, although a risky approach, should be explored with the agency by seeking pre-submission scientific advice.

Chetan Javia, chetan.javia@elc-group.com.

January 31, 2014

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