The FDA Gets Moving (A Bit) on Biosimilar Guidance

The FDA Gets Moving (A Bit) on Biosimilar Guidance

Mark Crawford

On February 9 the U.S. Food and Drug Administration (FDA) released three draft guidance documents to assist biosimilar product development in the U.S.

The FDA guidance recommends a stepwise approach toward demonstrating biosimilarity that could ease trial requirements if biosimilarity can be demonstrated in earlier steps—such as a comparison between the proposed biosimilar and reference product on structure, function, animal toxicity, human pharmacokinetics and pharmacodynamics, clinical immunogenicity, and clinical safety and effectiveness. 

“These draft documents are designed to help industry develop biosimilar versions of currently approved biological products, which can enhance competition and may lead to better patient access and lower cost to consumers,” says Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research.

The new guidance was created in response to the Patient Protection and Affordable Care Act, which called for an abbreviated approval pathway under section 351(k) for biosimilars that are interchangeable with FDA-licensed biological products.

Biological products are therapies used to treat diseases and health conditions. They include a wide variety of products including vaccines, blood and blood components, gene therapies, tissues, and proteins. Unlike most prescription drugs made through chemical processes, biological products generally are made from human and/or animal materials.

Biosimilars (also known as follow-on biologics) are biological products that are highly similar to an already approved biological product, for which there are no clinically meaningful differences between the biosimilar and the approved biological product in terms of the safety, purity, and potency.

The three guidance documents are:

  • “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product”—intended to assistcompanies in demonstrating that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submitting an application, called a “351(k)” application, to the FDA
  • Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product”—provides an overview of analytical factors to consider when assessing biosimilarity between a proposed therapeutic protein product and a reference product for the purpose of submitting a 351(k) application
  • “Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009”—provides answers to common questions from people interested in developing biosimilar products

Jumping In

This new approach could speed the development of cheaper versions of top-performing drugs, but it’s too early to tell how many companies want to assume the risks of making biosimilar drugs at this early stage.

“Copying biological molecules is a stickier proposition than making ordinary generic medicines because proteins are typically much larger and more complex than small-molecule drugs,” writes Heidi Ledford on the Nature Blog. “They are also often produced in cell cultures, and even small variations in how the cells are grown can change the properties of the protein produced. As a result of this complexity, it has been unclear just how ‘abbreviated’ an abbreviated approval process for biosimilars could be. Would clinical trials in humans be mandatory? How large would those clinical trials need to be?”

Ledford also indicates the FDA has committed to providing a guidance document that shows what standards need to be met for a biosimilar drug to be considered interchangeable with the original drug. “That designation may allow pharmacists to substitute the biosimilar drug when a doctor has prescribed the original medicine, a move that historically has allowed generics to whittle away more of a branded drug’s market,” she adds.

Will They Save Money?

As Woodcock mentioned, the FDA hopes this accelerated pathway will lead to lower costs for consumers.

So does Novation, a leading supply contracting company for VHA, UHC, and Provista. Novation has been actively monitoring the development process for biosimilars, especially inEurope. Based upon the European market, Novation reports that these “highly similar” versions of reference biologics could result in price decreases of 20% to 30%.

“However, adoption of biosimilars will be a more complex process and will require greater physician involvement in contrast to what traditionally happens with small-molecule generics,” says Steven Lucio, director of pharmacy clinical solutions for Novation.

A possible downside to this streamlined approval process is reduced innovation as companies scramble to get their piece of the biosimilar market.

In an interview with Mass High Tech (, Konstantin Linnik, an intellectual property attorney at Nutter McClennen & Fish inBoston, sees potential risk in creating this legislation to save money. “It could drag the whole industry down,” he cautions. “People are focused on me-too drugs instead of innovation, though it does generate competition.”

“While the issuance of these guidances is an important and meaningful first step in FDA’s implementation of the law, the guidances themselves are at a very high level of generality,” adds James N. Czaban, attorney and partner with Wiley Rein LLP inMcLean,Virginia. “Moreover, some of the most interesting and challenging legal and procedural issues under the BPCIA [Biologics Price Competition and Innovation Act],   such as exclusivity standards for reference products, interchangeablility standards for biosimilar products, and issues surrounding the patent litigation procedures established by the BPCIA—remain unaddressed by the agency. For the most part, the guidances do not provide any clear road maps for the development and approval of any particular biosimilar product.”

For an excellent overview of the guidances, read Czaban’s “First Biosimilars Guidances Issued by FDA” at:


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