Multisource pharmaceutical products need to conform to the same standards of quality, efficacy and safety as required of the originator’s (comparator) product. Specifically, the multisource product should be therapeutically equivalent and interchangeable with the comparator product. Testing the bioequivalence between a product and a suitable comparator (pharmaceutically equivalent or a pharmaceutical alternative) in a pharmacokinetic study with a limited number of subjects is one way of demonstrating therapeutic equivalence without having to perform a clinical trial involving many patients. In such a pharmacokinetic study any statement about the safety and efficacy of the test product will be a prediction based on measurement of systemic concentrations, assuming that essentially similar plasma
concentrations of the drug will result in essentially similar concentrations at the site of action, and thus an essentially similar therapeutic outcome. The bioequivalence study thus provides indirect evidence of the efficacy and safety of a multisource drug product. Often this will be the only evidence that the product is safe and efficacious. It is therefore crucial that the
bioequivalence study is performed in an appropriate manner. Several guidance documents stress the importance of on-site inspections to verify compliance with standards of good clinical practice (GCP) (1, 2).
The WHO prequalification project was started in 2001 to assure that medicinal products supplied for procurement meet WHO norms and standards with respect to quality, safety and efficacy (http://www.who.int/medicines/).
Specifically it is a requirement that the submitted product dossier with all its
necessary contents is assessed and found acceptable, and that the manufacturing sites of both the finished pharmaceutical product and of the active
pharmaceutical ingredient (API), are inspected and found to comply with WHO good manufacturing practices (GMP). Because products submitted to the
prequalification project are usually multisource ("generic") products,
therapeutic equivalence is generally demonstrated by performing a bioequivalence study, for example in a contract resource organization (CRO). For prequalification of such a product it is vital that, in addition to the above-mentioned
requirements, the CRO used by the sponsor to undertake the bioequivalence studies complies with WHO GCP and considers relevant elements from WHO good laboratory practice (GLP) and good practices for quality control laboratories to ensure integrity and traceability of data. Those involved in the conduct and analysis of bioequivalence studies on products to be submitted for
prequalification therefore need to ensure that they comply with the
above-mentioned WHO norms and standards to be prepared for any inspections by WHO.
The objective of this document is to provide guidance to organizations
involved in the conduct and analysis of in vivo bioequivalence studies. Bioequivalence studies should be performed in compliance with the general regulatory requirements and recommendations on good practices as specified in
the WHO bioequivalence guidelines, good clinical practices and good laboratory