FDA Releases Three Final Guidances For Industry on Developing Biosimilar Drugs

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By Bronwyn Mixter

April 28 — The Food and Drug Administration April 28 released three final documents intended to make clear the scientific and regulatory considerations for drug companies developing biosimilars.

The guidance documents are: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; and Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.

The final guidances reflect the FDA’s consideration of comments from a broad range of stakeholders, the agency said. Draft versions of the guidance documents were released in February 2012.

The final guidance comes after the FDA approved its first biosimilar drug in March. That biosimilar, Zarxio, is a product of Sandoz (part of Novartis) that is a version of the Amgen cancer drug Neupogen (filgrastim). 

Scientific Considerations 

The guidance on scientific considerations is intended to assist sponsors in demonstrating that a proposed therapeutic protein product is biosimilar to a reference product for purposes of the submission of a marketing application under section 351(k) of the Public Health Service (PHS) Act, the agency said.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act)—part of the Affordable Care Act—amended the PHS Act and other statutes to create an abbreviated FDA approval pathway for biosimilars.

Although the 351(k) pathway applies generally to biological products, this guidance focuses on therapeutic protein products and gives an overview of important scientific considerations for demonstrating biosimilarity, the FDA said. The scientific principles described in the guidance also may apply to other types of proposed biosimilar biological products.

When it approved the Sandoz biosimilar in March, the FDA noted that the BPCI Act created an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological product, called the reference product.

Quality Considerations 

The guidance on quality considerations provides recommendations to sponsors on the scientific and technical information for the chemistry, manufacturing and controls (CMC) section of a marketing application for a proposed biosimilar product, the FDA said.

The agency said the guidance should be used as a companion to other guidances that describe the CMC information appropriate for the evaluation of protein products.

Q and A 

The FDA said the third guidance provides answers to common questions from sponsors interested in developing proposed biosimilar products, biologics license application (BLA) holders and other interested parties regarding the agency's interpretation of the BPCI Act.

The questions and answers are grouped in the following categories:

• biosimilarity or interchangeability;

• provisions related to the requirement to submit a BLA for a biological product; and

• exclusivity.


The FDA said it intends to update this guidance to include additional questions and answers as appropriate.

Some Guidance Still Lacking?

Michael Reilly, executive director of the Alliance for Safe Biologic Medicines (ASBM), told Bloomberg BNA April 28 that from ASBM's perspective, it's a “good thing that the FDA continues to put out these documents that provide transparency,” but “our particular concern has been the guidances that are not out yet” on interchangeability and naming.

Reilly said the World Health Organization has a meeting June 16, and the FDA putting out guidance on biosimilar naming is “most critical to help in that meeting.”

When the FDA approved the Sandoz biosimilar in March it said it designated “a placeholder nonproprietary name for this product as `filgrastim-sndz.'” The agency said in its March 6 statement that a placeholder nonproprietary name for that product “should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products.”

Also, Reilly said he has concerns about how the agency addresses the extrapolation of clinical data in the Q and A guidance. One question in that guidance asks about whether extrapolation is going to be possible, and the FDA response is that it will be possible provided a sponsor gives appropriate scientific justification, he said.

“Scientific justification is a little bit vague,” Reilly said. “It doesn't tell you exactly what data will be required for extrapolation.”

To contact the reporter on this story: Bronwyn Mixter in Washington at bmixter@bna.com

To contact the editor responsible for this story: Brian Broderick at bbroderick@bna.com

The scientific considerations guidance is at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf.

The quality considerations guidance is at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291134.pdf.

The questions and answers guidance is at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM444661.pdf.