Guidelines on procedures and data requirements for changes to approved biotherapeutic products. WHO Expert Committee on Biological Standardization, Sixty-eighth Report; WHO Technical Report Series No. 1011, 2018, Annex 3
(2018; 99 pages)


This document is intended to provide guidance to national regulatory authorities (NRAs) and manufacturers on regulating changes to already licensed biotherapeutic products in order to assure their continued quality, safety and efficacy, as well as continuity in supply and access. The term “biotherapeutic products” as used in this document collectively includes the originator products and SBPs (also called “biosimilars”).

Changes are essential for the continual improvement of the manufacturing process and for maintaining state-of-the-art control of biotherapeutic products, and often need to be implemented after the product has been approved (that is, when it has been licensed or when marketing authorization has been received).

The regulation of changes to approved biotherapeutic products is key to ensuring that products of consistent quality, safety and efficacy are marketed after they receive authorization or licensure. Many NRAs of Member States have requested guidance on the data needed to support changes to approved biotherapeutic products in order to ensure comparability of the pre-change and post-change products with respect to quality, safety and efficacy. Although it is difficult to provide a set of guidelines that apply to all national situations, an attempt has been made to cover a range of possible changes in manufacture, quality control, safety, efficacy and product labelling information.

This document is intended to serve as a guide for establishing national requirements for the regulation of post-approval changes to biotherapeutic products. The categories of changes and reporting procedures are provided in the main body of the document and the data requirements to support the proposed changes are provided in the appendices.

These WHO Guidelines provide guidance for NRAs and marketing authorization holders on the regulation of changes to the original marketing authorization dossier or product licence for an approved biotherapeutic product in terms of: (a) the procedures and criteria for the appropriate categorization and reporting of changes; and (b) the data required to enable NRAs to evaluate the potential impact of the change on the quality, safety and efficacy of the product. Additionally, the purpose of these WHO Guidelines is to assist NRAs in establishing regulatory procedures for post-approval changes to such products.

Related documents
The WHO Essential Medicines and Health Products Information Portal was designed and is maintained by Human Info NGO. Last updated: December 1, 2019