Monoclonal antibodies as similar biotherapeutic products - Draft Guideline

Recommendation

7/8 May 2024

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Regulatory Requirements and Practical Implementation

On 1 March, the World Health Organization (WHO) published a new guideline draft on the evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs). This product specific document is intended to provide special considerations for the evaluation of monoclonal antibodies developed as similar biotherapeutic products and to complement the existing WHO Guidelines like the guidelines on evaluation of similar biotherapeutic products (SBPs) or the guidelines on the quality, safety and efficacy of biotherapeutic protein products prepared by recombinant DNA technology.

A lot of existing recombinant deoxyribonucleic acid (rDNA)  technology derived biopharmaceutical therapeutics based on monoclonal antibodies (mAbs). Some of these products are counted among the top ten lists of annual global pharmaceutical revenue successes. For an increasing number of these "block buster" products, the expiry of patents or data protection was reached or is nearing. Therefore, more and more companies started with the development of copies (generics) of the innovator products.

But producing biosimilar copies of such highly complex biological macromolecules is a real challenge. The high variability in glycosylation patterns, N and C terminal heterogeneity, post translational modifications etc. need to be taken into consideration during the evaluation of the biosimilarity.

The first guideline on the topic were adopted by the  Expert Committee on Biological Standardization (ECBS) in 2009, but with the ongoing development of the biosimilar market, the WHO was requested to update these guideline, especially to take account of technological advances in the characterization of rDNA derived products.

Amongst the classical explanations of the background and scope of the document, the draft includes the following chapters:

Special considerations for characterization and quality assessment
- Strategy for mAb biological activity assessment
- Consideration of production cell line changes and resultant glycoform 14 differences
- Standards

Special considerations for nonclinical evaluation of monoclonal antibodies
- In vitro studies
- In vivo studies

Special considerations for clinical evaluation of monoclonal antibodies
- PK (Pharmacokinetic)
Aim of comparative PK studies
Study design and population
Regimen
PK characteristics of the reference mAb
Doses
Routes of administration
Sampling times
Specific assays for serum drug concentration
Parameters in PK
- PD (Pharmacodynamic)
PD markers and PD assay
- Primary clinical study
Clinical trial design
Study population
Primary study endpoint
Safety
- Indication extrapolation
- Pharmacovigilance and post approval consideration

More details can be found in the "Guidelines on evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs)".