Compelling Presentation of the Biosimilarity Assessment

by Theodor Tiko

The biosimilarity assessment report summarizes and critically presents the similarity exercise data in support of the overall biosimilarity claim, ranging from the applicable quality attributes (QA) of the target product profile up to potentially supporting non-clinical and clinical studies.

It is projected that over the next 20 years, more than 60% of all new drugs will be biopharmaceuticals. Therefore biosimilars are an important product class to satisfy the ever-increasing cost savings of healthcare budgets worldwide. Their regulation has been pioneered from EMA, who in 2005 adopted the first abbreviated regulatory pathway and guidelines for biosimilars for the European Union. Even though there are slight inherent differences in national legislations and definitions, there is constant harmonization of the regulatory requirements globally. The agencies continue to clarify biosimilar guidelines with one of the most recent ones being the " Considerations in Demonstrating Interchangeability with a Reference Product" from the FDA.

Marketing authorisation applications (MAAs) for biosimilars in the EU follow the normal structure of the CTD format, as for any other MAA. An additional element for biosimilar applications is the similarity exercise against the reference medicinal product (RMP) which is presented separately within the CTD structure as a "biosimilarity assessment report". The EMA recommends to make use of section 3.2.R for this purpose but the detailed location of the similarity data should generally be discussed with the authorities prior to submission. The aim of this analytica similarity exercise is to demonstrate that the biosimilar product and the RMP chosen by the applicant are similar at the level of the finished medicinal product. Biosimilarity can be declared when sufficient similarity in structure, function, PK/PD properties, immunogenicity, side effects, and where necessary, clinical efficacy are achieved.

The biosimilarity assessment report thus summarizes and critically presents the analytical similarity data in support of the biosimilarity claim as a whole, ranging from the applicable quality attributes (QA) of the target product profile up to potentially supporting non-clinical and clinical data. The quality target product profile (QTPP) forms the basis for the development of the biosimilar product and is based on data collected on the chosen RMP from extensive characterisation and publicly available information. According to the applicable guidelines, sensitive and orthogonal state-of-the-art characterisation studies are applied to the biosimilar (commercial scale) and RMP in parallel (i.e. side-by-side), to demonstrate with a high level of assurance that the quality of the biosimilar is comparable to the RMP. Quantitative ranges are established for the similarity exercise based on the measured QA ranges of the RMP and their relevance discussed taking into account the investigated QA, the number of RMP lots tested, the age of the batches at the time of testing and the test method used. Descriptive or inferential statistical approaches are used on a case-by-case basis based on appropriate justifications. It is not expected that all quality attributes of the biosimilar product will be identical to the RMP. However, qualitative and/or quantitative differences should be justified and, where relevant, demonstrated to have no impact on the clinical performance of the product. This may include additional non-clinical and clinical data with particular attention paid to quality attributes that might have an impact on immunogenicity or potency, or that have not been identified in the RMP.

The overall evidence for biosimilarity as described in the biosimilarity assessment report is a central element of the biosimilar registration dossier and Biopharma Excellence can support with the assessment of biosimilarity and writing of biosimilarity assessment reports in frame of your planned CTA/IND and MAA/BLA.