WHO revised guidelines for biosimilars: scientific background

Biosimilars/Research | Posted 08/07/2022 post-comment0 Post your comment

A study carried out by Kurki P et al. in 2022 reviewed the current clinical experience and scientific evidence to provide an expert perspective for updating the World Health Organization (WHO) guidelines on evaluation of similar biotherapeutic products (SBPs; also called biosimilars) to increase flexibility and clarity.

Guidance V13F21

The original WHO guidelines were adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2009. In 2019, the Committee considered that a more tailored and potentially reduced clinical data package may be acceptable in cases where this was clearly supported by the available scientific evidence.

Firstly, the authors reviewed relevant newer guidelines issued by other regulatory bodies to identify issues that might help updating the WHO guidelines. This review suggested that the WHO guidelines may need more emphasis on the importance of the state-of-the-art physicochemical and structural comparability exercise and in vitro functional testing. In contrast, current non-clinical in vivo toxicological tests are not useful in the development of biosimilars. The use of ‘foreign’ reference product will also need clarifications. The concepts of ‘totality of evidence’ and ‘residual uncertainty’ are still relevant for the development of biosimilars [1].

Secondly, a literature search was conducted for long-term efficacy, safety, and immunogenicity of biosimilars to identify possible long-term problems that some stakeholders anticipated at the time of licensing. The study review confirmed the robustness of the current biosimilar development concept. Thus, the initially perceived residual uncertainty regarding safety, immunogenicity, and efficacy of biosimilars that shaped the original regulatory guidelines is now substantially reduced.

Finally, a search for articles concerning the role of clinical studies in the benefit-risk evaluation of biosimilars was conducted. The analyses of the roles of different development phases suggested that the large confirmatory efficacy, safety, and immunogenicity studies are, in most cases, redundant. 

The authors concluded that current data suggest that state-of-the-art analytical and functional testing and robust head-to-head pharmacokinetic and/or pharmacodynamic studies are sufficient to demonstrate biosimilarity in most cases. In vivo animal studies and large confirmatory efficacy and safety studies should be considered only on a case-by-case basis [1]. 

The review provided an opportunity to identify areas where the current guidance could be more permissive without compromising safety and efficacy. Consequently, WHO guidelines for biosimilars were revised and the ECBS adopted the revision in April 2022 [2].

From public health perspective, this is considered as an important step towards a better access to biotherapeutic products and a contribution to the implementation of the World Health Assembly Resolution WHA67.21 on access to biotherapeutic products including similar biotherapeutic and ensuring their quality, safety, and efficacy.

Back in early 2019, the WHO’s Regulation of Medicines and other Health Technologies (RHT) Department detailed a Q&A document, which is an additional guidance that complements the existing guidelines and deals with a number of issues regarding licensing SBPs, reference biological products, quality, non-clinical and clinical evaluation and pharmacovigilance [3].

Conflict of interest
This research paper [1] was funded by Ministry of Health and Welfare of the Republic of Korea; and the open access of the research paper [1] is also supported by the Norwegian Agency for Development Co-operation.  For full details of the authors’ conflict of interest, see the research paper [1].

The authors of the research paper [1] declared that there was no conflict of interest.

Abstracted by Adjunct Professor Pekka Kurki, MD, PhD, University of Helsinki, 19 Lukupolku, FI-00680 Helsinki, Finland.

GaBI Journal Citation Impact
2.2 – CiteScore 2021 (calculated on 5 May 2022)
2.3 – CiteScoreTracker 2022 (Last updated on 6 June 2022)

Submit a manuscript to GaBI Journal

Related articles
Europe’s IP framework should support earlier authorization of biosimilars, review finds

Differences in immunogenicity, pharmacovigilance and legal documents in biological products in Latin America

FDA issues new guidance on biosimilar development and the BPCI Act

LATIN AMERICAN FORUM

The new section of the ‘Latin American Forum’ on GaBI has been launched. The objective of this new section is to provide you with all the latest news and updates on developments of generic and biosimilar medicines in Latin America in Spanish.

View this week’s headline article: Directrices revisadas de la OMS para los biosimilares: antecedentes científicos

Browse the news in the Latin American Forum!

Register to receive the GaBI Latin American Forum newsletter. Inform colleagues and friends of this new initiative.

LATIN AMERICAN FORUM

Se ha lanzado la nueva sección del ‘Foro Latinoamericano’ sobre GaBI. El objetivo de esta nueva sección es brindarle las últimas noticias y actualizaciones sobre desarrollos de medicamentos genéricos y biosimilares en América Latina en español.

Vea el artículo principal de esta semana: Directrices revisadas de la OMS para los biosimilares: antecedentes científicos

!Explore las noticias en el Foro Latinoamericano!

Regístrese para recibir el boletín informativo GaBI Foro Latinoamericano. Informe a colegas y amigos sobre esta nueva iniciativa. 

  

References
1. Kurki P, Kang H-N, Ekman N, et al. Regulatory evaluation of biosimilars: refinement of principles based on the scientific evidence and clinical experience. BioDrugs. 2022;36(3):359-71.
2. World Health Organization. Guidelines on evaluation of biosimilars. Replacement of Annex 2 of WHO Technical Report Series, No. 977 [homepage on the Internet]. [cited 2021 Jul 8]. Available from: https://cdn.who.int/media/docs/default-source/biologicals/bs-documents-(ecbs)/annex-3---who-guidelines-on-evaluation-of-biosimilars_22-apr-2022.pdf?sfvrsn=e127cbf4_1&download=true
3. GaBI Online - Generics and Biosimilars Initiative. WHO releases Q&A on biosimilars evaluation [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Jul 8]. Available from: www.gabionline.net/reports/WHO-releases-Q-A-on-biosimilars-evaluation

Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.

Copyright – Unless otherwise stated all contents of this website are © 2022 Pro Pharma Communications International. All Rights Reserved.

comment icon Comments (0)
Post your comment
Most viewed articles
About GaBI
Home/About GaBI Posted 06/08/2009
EU guidelines for biosimilars
EMA logo 1 V13C15
Home/Guidelines Posted 08/10/2010