Dr. Sundar Ramanan, Global Head of Regulatory Affairs, Biocon Biologics

Dr. Sundar Ramanan, Vice President & Head, Global Regulatory Affairs, Biocon Biologics, presented on behalf of the Company at the public meeting for the reauthorization process for the Biosimilar User Fee Act (BsUFA III) program organized by the U.S. Food and Drug Administration (FDA) on November 19, 2020.

Dr Ramanan is an internationally recognized expert in biologics, including biosimilars, for science-based policy engagement with regulators, health ministry and industry trade organizations.

The public meeting was held to collect a wide variety of stakeholder perspectives on the broad goals laid out by the U.S. FDA for the FY2023-2027 program.

Dr Ramanan from Biocon Biologics was among the select presenters at the meeting, which included representatives from pharma trade associations, patient groups and physician groups who shared their wish lists for the third iteration of the agency’s biosimilars review program.

Starting with BsUFA I and subsequently through BsUFA II, the U.S. FDA has improved the biosimilar regulatory process by providing greater clarity around the regulatory framework, as well as, expectations from the industry through timely guidance and communications. The agency has done a great job of evolving the regulatory requirements with emerging scientific evidence.

Dr Ramanan suggested that in BsUFA III, the agency should further evolve the regulatory framework based on emerging cumulative scientific evidence.

He started by saying, “The basic premise in the practice of medicine is that evidence must precede practice; and needless to say we continue to accumulate positive evidence for the safety, efficacy and value of biosimilars to U.S. patients. It’s time to consider further evolution in the regulatory framework and processes.”

Dr Ramanan put forth the following recommendations, which could further facilitate efficiency in the regulatory process.

1. Biosimilar Review Timelines

Currently the biosimilar review process has a fixed timelines regardless of (a) the quantity of data being reviewed and (b) a reference product with lack of biosimilars. We request the agency to address these two areas by evolving the review process from one of a fixed timeline to an adaptive timeline.

Specifically, for a product which may not have or require comparative clinical trials the review burden is likely to be substantially lower than for a product that requires a full comparative clinical trial for safety and immunogenicity. Therefore, the agency should consider the differences in review burden for deciding timelines, i.e. create an adaptive timeline as opposed to the current fixed timeline (i.e. lower timeline) proportional to the regulatory review burden. 

Not all originator biologics have biosimilars developed referencing them. To spur further competition for molecules with limited or no biosimilars, the agency should consider a lower review timeline for the first biosimilar application, much akin to the accelerated review process for drugs with breakthrough therapy designation under PDUFA. Of note, there is precedent in the regulations for generics.

Given that biosimilars have demonstrated value to society, it is important to broaden the value impact and eliminate pockets of inefficiencies. 

2. Incremental Evidence to Establish Interchangeability

Globally, for every originator monoclonal antibody for which biosimilars have been approved, there are four approved biosimilars each with U.S. FDA and European Medicines Agency (EMA) nods. 

There is robust real world evidence today that shows that there is no impact on safety and immunogenicity due to switching, not only between the reference product and a biosimilar, but also between biosimilars. The agency should take this emerging scientific and clinical evidence in consideration in terms of incremental clinical evidence as is currently required for interchangeable biosimilars. 

Taking this into account can have a widespread positive impact on patients, as interchangeable biosimilars can be substituted for their reference product without prescriber intervention.

3. Naming Convention for Biosimilars

The agency needs to look at the he naming convention for biosimilars, which currently requires a four-letter suffix at the end of a biosimilar’s non-proprietary name to distinguish between it and its reference product.

During the early days of biosimilars both paper-based systems and electronic systems were present. Currently, with the emergence of mainly electronic systems, there are adequate guard-rails built into the system to ensure track and trace for pharmacovigilance purposes. Therefore, the agency should consider doing away with the need for a suffix for naming biosimilars. 

It can ensure better uptake of biosimilars.

A patients-first, science-based approach will enhance regulatory predictability and efficiency while facilitating more efficient biosimilar development.

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