EU Sets Guidelines for Biosimilar Monoclonal Antibodies - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

EU Sets Guidelines for Biosimilar Monoclonal Antibodies
The European Medicines Agency has added granularity to its biosimilars approval pathway by releasing a guideline on biosimilar monoclonal antibodies (mAbs).


Pharmaceutical Technology
Volume 36, Issue 11, pp. 42-45

Biosimilar mAb development clarified

The mAb guideline's overall aim is to lay down general principles for nonclinical and clinical studies on any potential differences between a biosimilar mAb and a reference mAb and how much these differences may amount to a dissimilarity between the two products. The guideline recommends a step-wise approach, with both in vitro and in vivo studies being conducted on a case-by-case basis. For example, comparative in vitro studies would be conducted first to assess differences in binding or function, with the necessity for additional steps involving in vivo work being determined by the need for additional information.

Extrapolation of clinical efficacy and safety data to other indications of the biosimilar, based on the overall evidence from the comparability exercise, would be acceptable, according to the guideline.

In its draft guideline on quality of biosimilars, EMA states that, "it is not expected that all quality attributes (between the biosimilar and the reference product) will be identical and minor differences may be acceptable, if appropriately justified" (2). In the mAb guideline, the agency points out that assays have been developed in recent years allowing more in-depth characterization of complex proteins both at the physicochemical and functional levels. These assays have enabled more effective assessment of minor quality differences in manufacturing processes for mAbs. Nonetheless, EMA warns that "in the current state of knowledge it may be difficult to interpret the relevance of minor quality differences" when comparing a biosimilar with a reference mAb (1) .

Pharmacovigilance requirements

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.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
27%
Oversee medical treatment of patients in the US.
12%
Provide treatment for patients globally.
8%
All of the above.
46%
No government involvement in patient treatment or drug development.
7%
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
Source: Pharmaceutical Technology,
Click here