FDA Stays Mum on Interchangeable Biosimilar Guidance

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April 13 — The FDA will release a draft guidance on biosimilar interchangeability this year, the agency's biotechnology director told an April 12 conference, but he didn't address how interchangeables would be named.

The agency has released three final guidances to industry concerning these lower cost versions of biologics and will finalize five draft guidances by year's end, said Steven Kozlowski, director of the Food and Drug Administration's Center for Drug Evaluation and Research's Office of Biotechnology Products.

The agency also plans to release two additional draft guidances before the end of 2016, he said, including one on interchangeability—determining whether a pharmacist can substitute a biosimilar for the original biologic without a physician's approval. But Kozlowski didn't provide any details about the highly anticipated interchangeability draft guidance.

“I think our primary consideration there will be on the scientific basis and expectations for interchangeability, but I really can’t comment on what's going to be in it until the draft guidance is out,” he said.

Kozlowski spoke at the National Policy and Advocacy Summit in Washington that was hosted by the Alliance for Patient Access.

Relying on Comparative Data

A biosimilar is a biologic product that is highly similar to a biologic already approved by the FDA; on additional approval by the FDA, the biosimilar can be considered interchangeable with the original biologic, also known as the reference product (RP). A streamlined approval process is expected to reduce the price for biosimilars to 15 percent to 30 percent of the RP.

The FDA has approved two biosimilars since the Biologics Price Competition and Innovation Act of 2010 was passed as part of the Affordable Care Act: Zarxio (filgrastim-sndz), Sandoz's biosimilar of Amgen's cancer treatment Neupogen in March 2015 (9 LSLR 328, 3/20/15), and Inflectra (infliximab-dyyb), Pfizer's and Celltrion's biosimilar of Johnson & Johnson's arthritis treatment Remicade on April 5 (10 LSLR 08, 4/15/16).

In addition to the two approved biosimilars, Kozlowski said, a number of companies have publicly announced they have submitted biologic license applications (BLAs) under the BPCIA's abbreviated approval pathway, and, as of early April, there were 60 biosimilar product development programs.

“CDER has received meeting requests to discuss the development of biosimilars for 19 different reference products,” Kozlowski said.

For licensure, a proposed biosimilar relies on, among other things, comparative data with the RP, as well as publicly available information regarding the FDA’s previous determination that the RP is safe, pure and effective, he noted.

“The bottom line is that the goal is to demonstrate biosimilarity between the proposed product and a reference product, not to independently establish safety and effectiveness of the proposed product,” Kozlowski said.

Five Draft Guidances to Go Final

In implementing the BPCIA, Kozlowski said, the FDA has issued final guidances on scientific considerations and on qualitative considerations in demonstrating biosimilarity to an RP, as well as one on questions and answers regarding BPCIA implementation (9 LSLR 491, 5/1/15).

It has released draft guidances on the RP exclusivity period (8 LSLR 1012, 10/17/14), clinical pharmacology data to support a demonstration of biosimilarity to an RP (8 LSLR 817, 8/22/14), nonproprietary naming for biologic products (9 LSLR 1033, 9/18/15), labeling for biologic products (10 LSLR 08, 4/15/16) and additional questions and answers regarding BPCIA implementation.

“FDA expects to finalize its current draft guidances this year and to issue draft guidances on considerations in demonstrating interchangeability to an RP and statistical approaches to evaluation of analytical similarity data to support a demonstration of biosimilarity,” he said.

Step-Wise Approach

Kozlowski noted that the FDA will consider the totality of the data and information submitted in the BLA and that it intends to use a risk-based approach to evaluate all available data and information submitted.

“We will apply a step-wise approach to data generation and the evaluation of residual uncertainty, going from analytical studies to animal studies to clinical PK/PD [pharmacokinetics and pharmacodynamics] studies to a clinical immunogenicity assessment to additional clinical studies,” he said. Pharmacokinetics refers to the movement of a drug into, through and out of the body, and pharmacodynamics refers to the study of the biochemical and physiological effects of drugs on the body.

Kozlowski said this doesn't mean that all of the data types will be necessary for any given biosimilar development program. “In its discretion the FDA may determine that certain studies are unnecessary in an [abbreviated pathway] application,” he said.

Interchangeable Naming Not Set

The FDA indicated in its naming guidance that it intends to designate a proper name for all biological products, both previously licensed and newly licensed, that includes a suffix composed of four lowercase letters, with the suffix added to the core name of each product and attached with a hyphen, Kozlowski said.

A Federal Trade Commission attorney told a Feb. 23 conference audience that the FDA's biosimilar naming proposal was an “elegant” idea that is doomed to failure and should be withdrawn (10 LSLR 05, 3/4/16). The Biotechnology Innovation Organization and Pharmaceutical Research and Manufacturers of America supported the FDA’s draft guidance, but the Generic Pharmaceutical Association didn't (9 LSLR 1033, 9/18/15).

Kozlowski said proper names that contain FDA-designated suffixes should help prevent inadvertent substitution that may lead to medication errors and that the suffixes should assist in the precise identification of the biological product associated with adverse events in all settings of care. He said this can translate into an improved understanding of identified safety issues and a more targeted agency response.

“The FDA is continuing to consider whether the nonproprietary name of an interchangeable product should include a unique suffix or should share the same suffix as its reference product,” he said.

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