The European Medicines Agency today released a new guideline titled, Guideline on similar biological medicinal products containing interferon beta. This guideline addresses the non-clinical and clinical requirements for biosimilar interferon beta products, which are primarily used to treat multiple sclerosis (MS).
In particular, the guideline addresses recombinant interferon 1a and interferon 1b, which are similar polypeptide chains that are thought to act as an immunomodulator in patients suffering from MS.
The guideline requires the demonstration of comparable quality, efficacy and safety of the biosimilar product to the reference product authorized in the EU.
Non-clinical in vitro studies in support of a biosimilar product should be comparative in nature and detect the differences in the pharmacotoxicological response difference between the biosimilar product and the reference product. In vivo studies in animals are generally not required unless bioassays or pharmacological studies raise concerns, in which case pharmacological studies or dose toxicity studies may be required.
Clinical studies in support of a biosimilar product must involve the study of pharmacokinetic properties of the product using healthy volunteers in a crossover study. The routes of administration in this crossover study must be identical for both the originator and biosimilar product, and the dosing regimen must be justified. The design of the study must also take in to account existing guidelines and pharmacokinetic parameters of interest (AUC, Cmax, T1/2, CL/F).
Pharmacodynamics must also be evaluated, preferably in conjunction with the comparative pharmacokinetics studies. There are a number of surrogate biomarkers that can be used to support a comprehensive comparative evaluation of differences between the two products.
Studies supporting clinical efficacy should be randomized, adequately powered, double-blinded and use the same routes of administration in parallel groups. Clinical efficacy studies do not need to show patient benefit per se, as that has already been established by the reference product. The demonstration of clinical similarity and equivalence, however, is paramount.
Studies in support of clinical safety should include a minimum of 12 months of immunogenicity testing data, and a further 6 months of immunogenicity testing is required after approval. The use of a validated, highly sensitive antibody assay that is capable of detecting all antibodies is required.
In addition, a pharmcovigilance plan must be presented based on the known identified and potential risks of the product, including rare events.
The consultation on this guideline ends 31 May 2012. Comments may be sent to BMWP.firstname.lastname@example.org.