Regulatory Aspects of Bioequivalence Testing | 5

ABSTRACT

In vivo and/or in vitro bioequivalence (BE) testing is required for most generic drug products

submitted for marketing approval. A proposed generic drug product must be compared in vivo

and/or in vitro to the ofﬁcially designated reference drug product. Harmonized BE criteria for

the interchangeability of pharmaceutical products address the issue of waivers for in vivo trials,

which are expensive and as recently concluded, not always discriminating enough to form the

sole basis of approval of interchangeability. As discussed below, the worldwide requirements to

demonstrate BE vary widely, mostly as a result of the ability of the regulatory authorities to

enforce such requirements, both from an economic as well as ethical perspective. Waiver for BE

testing therefore becomes a topic of great interest worldwide. Several consortiums have

debated this topic for years and a consensus has begun to develop on this topic. A large

number of policy documents address this topic and include the published Food and Drug

Administration (FDA) and International Conference on Harmonization (ICH) guidelines;

Health Canada’s Guideline on Preparation of Drug Identiﬁcation Number (DIN) Submissions;

the World Health Organization (WHO) document (1999) entitled “Marketing Authorization of

Pharmaceutical Products with Special Reference to Multisource (Generic) Products: A Manual

for Drug Regulatory Authorities; Multisource (Generic) Pharmaceutical Products: Guidelines

on Registration Requirements to Establish Interchangeability”; Note for Guidance on the

Investigation of Bioavailability and Bioequivalence, Committee for Proprietary Medicinal

(CPMP/EWP/QWP/98), Pan-American Network on Regulatory Harmonization: Bioavail-

ability and Bioequivalence Working Group 2004.