EMA releases biosimilar guidance

The European Medicines Agency (EMA) has released guidance explaining how medicinal products can be dubbed ‘biosimilars’, using a version of an active substance within a previously authorised biological medicinal product. Such classifications ease marketing authorisation applications and EMA has laid down guidance explaining how bio-similarity should be assessed.

The guidance stresses: 'Similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise needs to be established.'

It adds that this includes 'comprehensive physicochemical and biological characterisation and comparison and requires knowledge on how to interpret any differences between a biosimilar and its reference medicinal product'.

A special system is needed because of the complexity of biological and biotechnical products, it said, adding that ideally a single EU-approved reference medicinal product should be used throughout comparability assessments for quality, safety and efficacy.

But to help develop biosimilars worldwide and avoid clinical trials, the EMA guidance said it may be possible to compare biosimilars in certain clinical studies and in vivo non-clinical studies using reference medicines approved outside the EU 'by a regulatory authority with similar scientific and regulatory standards as EMA'.

In terms of study design, a stepwise approach is normally recommended, starting with a comprehensive physicochemical and biological characterisation. The robustness of physicochemical, biological and non-clinical in vitro data should determine the extent and nature of later non-clinical and clinical in vivo studies, said the Agency.

Clinical data should help address slight differences shown at previous steps and confirm comparable clinical performance, but it 'cannot be used to justify substantial differences in quality attributes,' said the guidance. If the biosimilar comparability exercise indicates that there are relevant differences, making it unlikely that biosimilarity will eventually be established, 'a stand-alone development to support a full marketing authorisation application should be considered instead'.

However, it added that if a study is sufficiently sensitive, a confirmatory clinical trial may not be necessary. 'This requires that similar efficacy and safety can clearly be deduced from the similarity of physicochemical characteristics, biological activity/potency, and PK and/or PD profiles of the biosimilar and the reference product,' it explained.