Understand Biosimilars Better Before Seeking Approval, FDA Official Says

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By John T. Aquino

Oct. 27 — Companies applying for approval of a biosimilar drug need to better understand the definitions and key concepts for the compounds, an FDA official told a conference Oct. 27.

“The definition of a biosimilar is two-pronged: it is a biologic product that is highly similar to an already FDA-approved biologic product and it has no meaningful clinical differences from that product,” John K. Jenkins, director of the Food and Drug Administration Center for Drug Evaluation and Research’s Office of New Drugs, told the DIA Biosimilars Conference in Washington.

Biosimilars are defined under the Biologics Price Competition and Innovation Act (BPCIA), a 2010 law that created an abbreviated approval pathway for the compounds intended to be lower-cost alternatives to expensive brand-name biologic drugs.

“FDA employs a step-wise approach to generate data in support of a demonstration of biosimilarity, but some biosimilar applicants seem to want to use a shotgun approach,” Jenkins said. He added, “You cannot overcome a lack of ability to demonstrate ‘highly similar’ with a demonstration of no clinically meaningful differences. Understanding this approach is still a work in progress for some.”

Grasping Paradigm Shift

Jenkins described a number of concepts and lessons learned as a result of the FDA’s experience in working with applicants since the BPCIA became law in 2010.

The BPCIA’s abbreviated pathway for FDA approval lets the applicant rely partly on data generated by the sponsor of the original biologic, which is known as the reference product (RP).

“One key concept is that development of a stand-alone product like the reference product and biosimilar development are different,” Jenkins said. “FDA’s review of a stand-alone is to establish its safety and effectiveness, while for a biosimilar the agency is trying to establish biosimilarity.”

The FDA has learned that biosimilar review and approval represents a paradigm shift in the way the agency makes a finding of safety and efficacy, he said. “It requires a cultural and cognitive transformation. Significant progress on this shift has been made within the FDA, but it is still a work in progress for some applicants as well as for many clinicians, patients and other stakeholders,” Jenkins said.

He also noted that the FDA encourages the use of novel methods and study designs for biosimilars. “These may be different from the program that supported RP approval.”

Extrapolation Can Be Challenging

The FDA also has learned extrapolation of data for approval of a biosimilar is a novel concept that can be challenging for some to accept, Jenkins said.

“It is important to stress that it is extrapolation from the RP to the biosimilar product based on all available data, not from the indication studied for the biosimilar to other indications. For products where the approved uses are in patient populations that are very different, extrapolations raise significant concerns among physicians and patients.”

A lack of understanding about what extrapolation means can have consequences, Jenkins said. “For example, biosimilar applicants may conduct additional clinical studies that are not necessary for biosimilar approval,” he said.

Jenkins outlined some best practices for biosimilar developers:

  •  support education for your staff regarding the paradigm shift;
  •  choose and use your meeting with FDA on the biosimilar wisely; and
  •  submit a complete application, making sure your facilities are ready for FDA inspection within the necessary time-frames.

To contact the reporter on this story: John T. Aquino in Washington at jaquino@bna.com

To contact the editor responsible for this story: Randy Kubetin at RKubetin@bna.com

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