Guidelines on Evaluation of Monoclonal Antibodies as Similar Biotherapeutic Products (SBPs). WHO Expert Committee on Biological Standardization, Sixty-seventh Report; WHO Technical Report Series No. 1004, 2017, Annex 2
(2017; 35 pages)


Monoclonal antibodies (mAbs) are a major class of recombinant deoxyribonucleic acid (rDNA) technology-derived biotherapeutic products that have achieved outstanding success in treating many life-threatening and chronic diseases. Some of these targeted therapy products are ranked in the top-10 lists of annual global pharmaceutical revenue sources. As patents and data-protection measures on mAb products have expired, or are nearing expiry, considerable attention has turned towards producing similar biotherapeutic products (SBPs, also termed “biosimilars”) based upon the approved mAb innovator products, with a view to making more affordable products that could improve global access to these so-called blockbusters.

The WHO Guidelines on evaluation of similar biotherapeutic products (SBPs) were adopted by the WHO Expert Committee on Biological Standardization in 2009 (1). This document set out the scientific principles, including the stepwise approach, which should be applied for the demonstration of similarity between an SBP and the reference biotherapeutic product (RBP). High similarity at the quality level is regarded as a prerequisite for enabling the use of a tailored nonclinical and clinical programme for licensure. The goal of the clinical comparability exercise is to confirm the similarity established at previous stages of development and to demonstrate that there are no clinically meaningful differences between the SBP and the RBP – and not to re-establish safety and efficacy, as this has been done already for the RBP. The decision on licensure of the SBP should be based upon evaluation of the totality of evidence from quality, nonclinical and clinical parameters. It should be noted that clinical studies cannot be used to resolve substantial differences in physicochemical characteristics and biological activity between the RBP and the SBP. If substantial differences in quality attributes are present, a stand-alone licensing approach may be considered.

Biosimilar comparability studies between a candidate biosimilar mAb and a reference product mAb are challenging for both developers and regulators. Consequently, in 2014, WHO was requested to update its 2009 SBP Guidelines to take into account technological advances in the characterization of rDNAderived products, and particularly mAbs.

The intention of this class-specific document is to set out the specific considerations involved in the evaluation of mAbs developed as SBPs. These WHO Guidelines cover rDNA-derived biosimilar mAbs used in the treatment of human diseases. The principles discussed in this document also apply to mAb-derived proteins – for example, mAb fragments and Fc fusion proteins.

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