EU Sets Guidelines for Biosimilar mAbs - The European Medicines Agency has added granularity to its biosimilars approval pathway by releasing a guideline on mAbs. - BioPharm International


EU Sets Guidelines for Biosimilar mAbs
The European Medicines Agency has added granularity to its biosimilars approval pathway by releasing a guideline on mAbs.

BioPharm International
Volume 25, Issue 11, pp. 24-26


Regulators expect that during the postauthorization pharmacovigilance stage, unpredicted adverse results from differences in manufacturing process could be detected. Incorrect extrapolations from nonclinical or clinical data during comparability assessments could also be revealed.

The EU's pharmacovigilance legislation, approved in 2010, simplifies reporting of adverse drug reactions and the submission of periodic safety update reports (PSURs), data from both of which will be held centrally.

Postauthorization safety and efficacy studies can be requested from drug-licence holders by the authorities. Applicants for marketing approvals of medicines will have to submit postauthorization risk-management plans.

For biosimilars, particularly mAbs, pharmacovigilance requirements will be tougher than for conventional medicines. "The pharmacovigilance system is an essential part of monitoring biosimilars after approval," says Morrison. "[The legislation] provides for additional monitoring for biological products, including biosimilars."

The mAb guideline states that applicants for marketing authorization of their mAbs or other biosimilars will have to provide a "comprehensive concept" of how further postauthorization safety studies will be carried out. The safety plan will cover safety claims based on extrapolations of efficacy and safety data during the comparability exercise and occurrences of rare and particularly serious adverse effects.In addition, because adverse reactions to biosimilars could be due to defects in manufacturing processes, the products should be clearly identifiable by name and batch number, according to the mAb guideline.


Because of the high expenditure necessary on manufacturing facilities, development, and pharmacovigilance activities, biosimilar producers are looking for ways of curbing costs. Merck Serono and Dr. Reddy's are among pharmaceutical companies that have formed an alliance in the production and development of biosimilars, mainly mAbs, to spread the risk. DSM of the Netherlands and Crucell, a Dutch subsidiary of Johnson & Johnson, have reduced the scope of Percivia, their US-based joint venture in biosimilars by ending in-house product development.

"In order to reduce the overall development costs, we need in the EU and in the US a scientific framework which allows global development," says Kox. The European Commission has appeared to be acknowledging the need for global development of biosimilars when it recently announced it would accept applications for approvals of biosimilars containing data from reference products that come from outside the EU.

"[With this announcement] a new regulatory paradigm is born, which is a great achievement after years of discussion," says Kox. "The issue of the reference product is not the only one to achieve global development. But for companies to be able to use data from tests from reference products that are not sourced from the EU constitutes a major and far-reaching regulatory breakthrough."

The European Commission has yet to finalize details on how a comparability exercise with a reference product outside the EU would work. But the decision does seem to show that the EU is intent on continuing to take a lead on biosimilar regulatory matters without waiting for US guidance on the development of biosimilars to be formally adopted. FDA issued three draft guidance documents earlier this year to assist companies in developing biosimilars for the US market (5–7). Under the Patient Protection and Affordable Care Act of 2010, biosimilars are due to be allowed to be marketed in the country by 2014.

Sean Milmo is a freelance writer based in Essex, UK,


1. EMA, Guideline on Similar Biological Medicinal Products Containing Monoclonal Antibodies—Non-Clinical and Clinical Issues (London, June, 2012).

2. EMA, Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues, revision 1 (London, May 2012).

3. EMA, "Multidisciplinary: Biosimilar,", accessed Oct. 13, 2012.

4. EMA, Guideline on Immunogenicity Assess-ment of Monoclonal Antibodies Intended for In Vivo Clinical Use (London, June, 2012).

5. FDA, Guidance for Industry: Q & As Regarding Implementation of the BPCI Act of 2009 (Rockville, MD, Feb. 2012).

6. FDA, Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (Rockville, MD, Feb. 2012).

7. FDA, Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product (Rockville, MD, Feb. 2012).

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