Despite biosimilars being around in the EU since 2006 physicians are still often reluctant to prescribe them. Members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) highlight what physicians need to know to make informed and appropriate treatment choices for their patients [1].
Biologicals are derived from living cells and therefore demonstrate molecular complexity and heterogeneity. This makes them very difficult to reproduce, as even very small changes in the manufacturing process can cause variations in the final drug, even between different batches of the same product.
For this reason biosimilars must be ‘similar but not identical’ to its reference biological, and for this same reason EMA requires a very thorough comparison of the structural and functional characteristics, and the product and process-related impurities of the biosimilar and the reference biological. Any differences found then have to be explained and justified with regard to the potential impact on the clinical performance of the biosimilar.
Data requirements for the development and licensing of biosimilars are considerably greater than for small molecule generics. Generics typically only require physicochemical identification and demonstration of a similar pharmacokinetic profile (bioequivalence) to the originator product. Biosimilars, on the other hand, need a more extensive head-to-head comparison with the reference product, to ensure close resemblance in physicochemical and biological characteristics, safety and efficacy.
Although a repetition of the entire development programme of the reference biological is scientifically not necessary, and could even be considered unethical, the type and extent of clinical data required for biosimilars vary and depend on:
- The complexity of the active substance and how well it can be characterized
- The availability of an accepted surrogate end point to compare efficacy
- The type and seriousness of safety concerns that have been encountered with the reference product or the substance class
- The possibility to extrapolate efficacy and safety data to other indications of the reference biological
This and the two articles that follow focus on the issues involved in and the concerns that clinicians should consider when choosing biosimilars.
Editor’s comment
If you are interested in contributing a research article in a similar area to GaBI Journal, please send us your submission here.
If you would like to receive a copy* of the Weise M et al. article, please email us.
*For profit organizations subjected to a fee
Related articles
Efficacy, extrapolation and interchangeability of biosimilars
Quality, similarity and safety of biosimilars
Small molecule versus biological drugs
Reference
1. Weise M, et al. Biosimilars: what clinicians should know. Blood. 2012;120(26):5111-7.
Permission granted to reproduce for personal and educational 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.
0
Post your comment