Biosimilars and Interchangeability

Topic Information

Dear Colleagues,

Biological products include medications for treating many serious illnesses and chronic health conditions. A biosimilar is a biological product that is highly similar to, and has no clinically meaningful differences from, a biological product already approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA), which is also termed the reference product. All biological products are only approved after meeting both agencies’ rigorous approval standards. This definition is based on a comprehensive review of scientific evidence, which demonstrated that the biosimilar is highly similar to the reference product and that there are no clinically meaningful differences between the two products in terms of safety, purity, and potency (i.e., safety and efficacy). This evidence included comparisons of the products at an analytical level, using a comprehensive battery of chemical and biological tests and biological assays to confirm the similarities in the structural and functional characteristics of the two products (including those known to influence safety and efficacy).Additionally, it was supported by comparative data concerning human pharmacokinetics, clinical immunogenicity, safety, and overall effectiveness.

Nevertheless, an outstanding debate surrounds the question of whether biosimilars can be regarded as interchangeable with their reference biological products (and vice versa), or with biosimilars of the same reference product.

The EMA has not issued any official position or guidance on the interchangeability of biosimilars, as prescribing and advising physicians is the responsibility of each Member State of the European Union (EU). In Europe, a biosimilar that meets the rigorous regulatory requirements of the EU Biosimilar Approval Pathway may be considered interchangeable; however, it is at the discretion of each Member State to establish prescribing and dispensing protocols for the interchangeable use of biosimilars. In the United States, the regulatory assessment of biosimilar interchangeability differs from other approaches. The Biologics Price Competition and Innovation Act of 2009 (BPCIA) legally defines it, and biosimilars that are granted interchangeability status may be substituted for the reference biological product at the pharmacy level, subject to state laws, without the prescribing physician's intervention.

The development of biosimilar products may involve various facets, such as enhancing the recognition and evaluation of product attributes, defining acceptable differences in attributes more accurately between the reference product and the suggested biosimilar product, devising analytical methods to detect relevant disparities, and undertaking comparative analytical evaluation with advanced statistical methodologies. Additionally, exploring the use of in vitro and in silico methods to assess immunogenicity could potentially support demonstrating interchangeability between the reference product and the proposed interchangeable product. In this context, the “switching design” could be of interest.

We are pleased to invite all researchers and research teams that are interested in the field of biosimilars and interchangeability to contribute to this Topic with their manuscript(s). Full original research papers, short communications, and reviews regarding this topic are all welcome.

Dr. Alexis Oliva
Prof. Dr. Shein-Chung Chow
Dr. Joao Goncalves
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biologics biologics	-	-	2021	26.9 Days	CHF 1000	Submit
Molecules molecules	4.2	7.4	1996	15.1 Days	CHF 2700	Submit
Pharmaceuticals pharmaceuticals	4.3	6.1	2004	12.8 Days	CHF 2900	Submit
Pharmaceutics pharmaceutics	4.9	7.9	2009	14.9 Days	CHF 2900	Submit

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Open AccessArticle

Characterization of Critical Quality Attributes of an Anti-PCSK9 Monoclonal Antibody

by Thayana A. Cruz, Nicholas R. Larson, Yangjie Wei, Natalia Subelzu, Yaqi Wu, Christian Schöneich, Leda R. Castilho and Charles Russell Middaugh

Biologics 2024, 4(3), 294-313; https://doi.org/10.3390/biologics4030019 - 11 Sep 2024

Viewed by 839

Abstract

During early development of biopharmaceuticals, suboptimal producing clones and production conditions can result in limited quantities of high-purity products. Here we describe a systematic approach, which requires minimal amounts of protein (~10 mg) to assess critical quality attributes of a monoclonal antibody (mAb). [...] Read more.

During early development of biopharmaceuticals, suboptimal producing clones and production conditions can result in limited quantities of high-purity products. Here we describe a systematic approach, which requires minimal amounts of protein (~10 mg) to assess critical quality attributes of a monoclonal antibody (mAb). A commercial anti-PCSK9 IgG2 (evolocumab, Repatha^®) and an early-stage biosimilar candidate were compared head-to-head using a range of high-throughput physicochemical and in-vitro binding analytical methods. Overall, both mAbs were shown to be highly pure and primarily monomeric, to share an identical primary structure, and to have similar higher-order structural integrity, apparent solubility, aggregation propensity, and physical stability profiles under temperature and pH stress conditions. Low levels of dimers were detected for the innovator (1.2%) and the biosimilar candidate mAb (0.3%), which also presented fragments (1.2%). Regarding charge heterogeneity, the amount of the main charge isoform was 53.6% for the innovator and 61.6% for the biosimilar candidate mAb. Acidic species were 38% for the innovator and 30% for the biosimilar candidate. Variations in the relative content of a few N-glycan species were found. The in-vitro binding affinity to PCSK9 was monitored, and no differences were detected. The mathematical approach called “error spectral difference” (ESD), proposed herein, enabled a quantitative comparison of the biophysical datasets. The workflow used in the present work to characterize CQAs at early stages is helpful in supporting the development of biosimilar mAb candidates. Full article

(This article belongs to the Topic Biosimilars and Interchangeability)

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