Clinical safety is critically important during the development of a biosimilar. An overview of the main aspects of safety assessment of biosimilars has been prepared to assist all those interested in this area of growing importance [1].
In June 2013, the European Medicines Agency (EMA) released its ‘Guideline for similar biological medicinal products containing biotechnology-derived proteins as active substances: non-clinical and clinical issues’ for a six-month consultation [2]. The guideline, which forms the basis of this overview by Dr Thijs J Giezen of the Foundation Pharmacy for Hospitals in Haarlem, The Netherlands, and Dr Christian Schneider of the Danish Health and Medicines Authority, Denmark, lays down the non-clinical and clinical requirements for marketing authorization of a biosimilar claiming to be similar to a biological product already marketed.
The authors note that safety data should be collected throughout the complete clinical development programme of a biosimilar, and should be compared between the biosimilar and the reference product. Assessment of immunogenicity is especially important in this context due to the potential impact of changes in the production process and consequently on clinical safety. Differences in the safety profile will question biosimilarity and will require appropriate in-depth assessment and evaluation. Although differences in the safety profile are to be avoided, there is a possible exception when the biosimilar has a lower immunogenicity than the original reference product.
Extrapolation of safety data from one indication to the other is possible and should be justified, especially with regard to immunogenicity and potential differences in the characteristics of the patient population and the disease in which the biological is used.
The same rules and obligations apply for biosimilars as for any other biological, note the authors, which means that a Risk Management Plan (RMP) must be submitted as part of the application procedure as well as Periodic Safety Update Reports (PSURs) and the collection of adverse events identified and reported after approval.
Within the RMP, the knowledge obtained with the reference product should be the basis for the content of the RMP and the obligatory post-marketing requirements, including risk minimization measures.
Traceability is of paramount importance, conclude the authors, and all measures should be implemented to improve traceability.
Editor’s comment
Readers interested to learn more about the safety of biosimilars are invited to view the following manuscripts published in GaBI Journal:
Safety and toxicity of biosimilars—EU versus US regulation
WHO leadership in public safety on biosimilars to be commended
Readers interested in contributing a research or perspective paper to GaBI Journal – an independent, peer reviewed academic journal platform – please send us your submission here.
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References
1. Giezen TJ, Schneider CK. Safety assessment of biosimilars in Europe: a regulatory perspective. Generics and Biosimilars Initiative Journal (GaBI Journal). 2014;3(4):180-3. doi:10.5639/gabij.2014.0304.041
2. GaBI Online – Generics and Biosimilars Initiative. EU guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 12]. Available from:www.gabionline.net/Guidelines/EU-guidelines-for-biosimilars
Source: www.gabionline.net
