|Framework for Implementation of Equivalence Requirements for Pharmaceutical Products. PANDRH Technical Report Nº 8, Pan American Network on Drug Regulatory Harmonization
(2011; 38 pages)
This document has been prepared by the Working Group on BE (WG/BE) of the Pan
on Drug Regulatory Harmonization (PANDRH) with the objectives of contributing to
Authorities (DRAs) of the Region of the Americas and recommending harmonized
criteria concerning the
equivalence of drugs. The document consists of two parts:
- The first part refers to scientific criteria for implementing therapeutic
equivalence. In developing this part of the document, the WG/BE analyzed in detail the WHO document
"Multisource (Generic) Pharmaceutical Products: Guidelines on Registration Requirements to
Establish Interchangeability," prepared by the WHO Expert Committee for Pharmaceutical
Preparations. The WG/BE decided unanimously to endorse the document and to promote its
implementation in the Americas. This document recommends that the 192 WHO Member States tend to the
demonstration of therapeutic equivalence and declaration of interchangeability of all
multisource products. Also, basic criteria should be established for performing in vivo and in vitro
studies to ensure the interchangeability of multisource products without compromising the safety,
quality, and efficacy of the pharmaceutical products. The WG/BE also endorsed the criteria of the
Biopharmaceutical Classification System (BCS) for waivers of in vivo studies.
- The second part of the document refers to the strategic framework for the
implementation of studies of drug equivalence. This part describes the reality of the Region of
the Americas, serving the special features of Latin America and considering that most of the
multisource products (products of different origin and/or manufacturers) marketed in the region were approved
in accordance with the drug registration requirements of each country at the time of their
registration. The gradual implementation of equivalence demonstration requirements (BE) through in vivo
studies based on the health risk of the products is recommended, and this document describes the
methodology, which complements the biowaivers outlined in the BCS of the WHO guidelines.
Furthermore, cases are presented for which there are no valid or unified products of reference.
Finally, a flow chart is presented that integrates the requirements of meeting good manufacturing
practices (GMP), the validity and reliability of the products of reference, and the concept of
gradualism in prioritization according to health risk and biowaivers.