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Biosimilars Law Blog
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EMA takes steps toward facilitating global clinical trials for biosimilars

Applicants for marketing authorisation for biosimilars in the European Union (“EU”), under certain conditions, will be able in the near future to use batches of reference biological medicinal products sourced from outside the European Economic Area (“EEA”) in pre-clinical and clinical studies that are part of the comparability exercise preceding authorisation of biosimilars. On 28 September 2012, the European Medicines Agency (“EMA”) announced that it has updated its procedural advice document for applicants for marketing authorisation for biosimilars to reflect this change.

As a result, pharmaceutical companies developing biosimilars in multiple jurisdictions both within and outside the EU would be permitted to conduct related comparability studies with batches of the reference medicinal product sourced from outside the EEA without the need to repeat the studies with EU-sourced reference product batches. This would simplify the global development of biosimilars and would avoid the duplication of studies. The requirement that the reference biological medicinal product is authorised to be placed on the market in the EU is, however, maintained. Applications for marketing authorisation in the EU for biosimilars relying on a reference medicinal product which is not authorised in the EU would not be permitted.

The new regime will apply after the adoption of the revised EMA Guideline on similar biological medicinal products (CHMP/437/04) (“EMA Biosimilars Guideline”). The draft of the revised Guideline is expected to be published and released for public consultation in the beginning of 2013. The expected date for the adoption of the revised EMA Biosimilars Guideline is not yet announced.

What is the practical impact of this update?

In practice, this means that applicants for marketing authorisation for biosimilars in the EU could demonstrate the comparability of their biosimilars with reference biological medicinal products through pre-clinical and clinical studies using batches of the reference medicinal products manufactured and released outside the EEA. The EEA includes the EU Member States, Norway, Lichtenstein and Iceland. As a result, the batches of the reference medicinal product could be manufactured and released by a manufacturer other than the manufacturer referenced in the marketing authorisation for the reference medicinal product in the EU.

This is a departure from the current position of the EMA reflected in the EMA Biosimilars Guideline. The Guideline provides that it is mandatory that the batches of the reference medicinal product used in the comparability exercise for the biosimilar are sourced within the EEA.

The change in the EMA’s position reflects the intention of the European Commission to accept the use of batches of reference medicinal products sourced from outside the EEA in the comparability exercise conducted for the purposes of applications for marketing authorisation for biosimilars. The aim is to facilitate the global development of biosimilars and to avoid unnecessary repetition of clinical trials.

Conditions for the use of batches of reference medicinal products sourced from outside the EEA

The use of batches of reference medicinal products sourced from outside the EEA would, however, be subject to certain conditions. The applicant for marketing authorisation for a biosimilar will be required to provide an extensive analytical comparison in order to establish that the reference product batches sourced from outside the EEA are representative of the reference medicinal product authorised in the EEA. The suitability of the reference product batches sourced from outside the EEA will be ascertained on case-by-case basis by the EMA. The applicant for a marketing authorisation for a biosimilar may be required to provide comparative pharmacokinetic and pharmacodynamics data.

Moreover, the exclusive use of reference medicinal product batches sourced from outside the EEA should also be justified. The justification should be based on a comparability data for the biosimilar, the reference medicinal product manufactured in the EEA and the reference medicinal product sourced from outside the EEA.

Next steps

As a next step, the European Commission, the EMA’s Committee for Medicinal Products for Human Use (“CHMP”) and the CHMP Working Parties will discuss and establish the comparability data requirements and the conditions under which the use of batches of reference medicinal products sourced from outside the EEA would be permitted. This process will also involve a close cooperation with the United States Food and Drug Administration (“FDA”) in relation to the acceptance of batches of reference medicinal products sourced from the US.

Once established, the new conditions and requirements applicable to the use of batches of reference medicinal product sourced from outside the EEA will be reflected in the revisions of the EMA Biosimilars Guideline. As discussed above, the draft version of the revised Guideline will be released for public consultation in early 2013.