Policy considerations for originator and similar biotherapeutic products

Abstract

Biotherapeutic products (BTPs), also known as biotherapeutic medicines, contain structurally complex active substances produced by living organisms. Due to their complexity and method of manufacture BTPs require distinct regulatory approval standards relative to chemically-synthesized small molecule medicines. This is also relevant for licensing copied versions of a BTP, or similar biotherapeutic products (SBPs) made by a different manufacturer where regulatory concepts developed for generics should not have been applied. In all these licensing scenarios regulators need to evaluate the results of comparability exercises, including sensitive head-to-head analytical, pre-clinical and clinical comparisons with the original product as a basis for approval. SBPs do not contain chemically identical active substances, and may have slightly different benefit-risk profiles, therefore it is necessary to monitor post-approval safety on a product-specific basis. Policymakers may therefore emphasize the need for product-specific identification in patient records and safety reports using either a unique trade name or a distinguishable non-proprietary naming system. The unique nature of BTPs also informs the nature and degree of interchangeability between the originator and SBPs versions. Many policymakers also emphasize that switching between SBPs should only occur with the involvement of the prescriber. It is recommended that pharmacy substitution would only be appropriate when there is a robust framework for a competent authority to assess product-specific evidence of interchangeability. Another challenge is posed by the historical existence in some jurisdictions of copy BTPs that were not assessed according to current regulatory standards. To address this situation the World Health Organization has proposed a regulatory assessment framework wherein the status of such products can be normalized via the orderly submission and review of supplementary data.