Following on from an announcement last week, regulators in Europe have issued draft guidelines for the approval of biosimilars containing monoclonal antibodies.

The EMA guidance notes that "the focus of the biosimilarity exercise is to demonstrate similar efficacy and safety compared to the reference product, not patient benefit per se," which has already been shown. It adds that in principle, the most sensitive model and study conditions (pharmacodynamic or clinical) should be used in "a homogeneous patient population, since this reduces variability and thus the sample size needed to prove similarity, and can simplify interpretation".

It goes on to say that in cases where "comparative pharmacodynamic studies are claimed to be most suitable to provide the pivotal evidence for similar efficacy, applicants will have to choose clinically relevant markers and also provide sufficient reassurance of clinical safety, particularly immunogenicity". The guidance also notes that "extrapolation of clinical efficacy and safety data to other indications of the reference mAb", not specifically studied during the clinical development of the drug, is possible, based on the results of the overall evidence provided".

The EMA concludes that post-authorisation follow-up "may have to exceed routine pharmacovigilance and may have to involve more standardised environments". The guidance is now open for consultation up to the end of May next year.

Emmanuel Papadakis, an analyst at Collins Stewart, said that Europe "has produced a set of biosimilar-friendly guidelines that clearly confound the until-recently entrenched expectations of unfeasibly high regulatory requirements". He claims it indicates "not only do you not need the original cell lines, you don’t even need the same cell system, though higher data requirements may result".

Mr Papadakis added that the guidelines outline a requirement for an abbreviated Phase I-III trial programme "as expected", and also "clearly endorse the use of extrapolation (automatic approval in multiple settings after showing biosimilarity in just one, within an indication) which will massively reduce development costs". He said the plan confirms Collins Stewart's assumption of a $100 million per-product per-indication biosimilar development cost and "an expectation of three or four bona fide biosimilars launching per brand, creating price-pressure (not commoditisation) and 10%-15% annualised brand regional sales revenue erosion post-patent expiry.