FDA Advances its Biosimilar Policy Framework

December 17, 2018

On Tuesday, December 11th, FDA made large strides to advance its biosimilar policy framework, including the release of four guidance documents and a proposed rule.  Through these guidance documents, FDA intends to maintain efficient regulatory processes for innovative and generic drug products. The first draft and final guidance documents provide “greater clarity on scientific and regulatory considerations for the development of biosimilar and interchangeable products,” while the second set identifies how the Agency will implement the intent of Congress’ direction to transition products from the drug pathway to the biologics pathway. The release of these documents begins the effort to transition approved marketing applications for a subset of biological products to biologics licenses starting in March 2020.

In a recent press release, Scott Gottlieb, M.D., FDA Commissioner, mentions that insulin products and human growth hormone are known for their higher price tags. However, he goes on to state that the new pathway “should help usher in a new era of competition for these products that’ll lead to lower prices and better access.”  This would be a monumental step that would help improve access to these products for so many Americans suffering from conditions requiring these life-saving medications.

History of Generic Biologics

The 1984 Hatch Waxman amendments to the Federal Food, Drug and Cosmetics (FD&C) Act established the current abbreviated new drug application (ANDA) pathway, creating a “streamlined” approval pathway for generic drugs. However, until recently there was not an abbreviated pathway to bring generic biologics to market which has subsequently led to decreased competition amongst these products.

On March 23, 2010 the Patient Protection and Affordable Care (PPAC) Act was signed into law, amending the Public Health Service (PHS) Act. The statutory provisions of the PPAC Act, which are also referred to as the Biologics Price Competition and Innovation Act of 2009 (BPCIA), created an abbreviated licensure pathway for biological products that are biosimilar to or interchangeable with FDA approved “innovator” biological products. The BPCIA also helps save Sponsors’ resources by eliminating duplication of human and/or animal testing. With approval from the FDA, and significant evidence that the product meets statutory standards, a Sponsor can develop a product at a lower cost than the original referenced product.

In July of this year, FDA released the Biosimilars Action Plan, which continues to advance BPCIA by increasing scientific and regulatory clarity for biosimilar development. The action plan generates increased communication and outreach for the education of biosimilars for patients, clinicians, and payors. In 2018, seven biosimilar products have been approved by the FDA, bringing the total of approvals to 15.

Recently Released Draft & Final Guidance Documents

Last week, FDA issued four guidance documents aimed at advancing its biosimilar policy framework.  These include two draft and two final guidance documents:

  1. Questions and Answers on Biosimilar Development and the BPCI Act, Guidance for Industry

In this final guidance document, FDA provides Sponsors with answers to commonly asked questions regarding the BPCIA.  The Agency states that the Q&A format “is intended to inform prospective applicants and facilitate the development of proposed biosimilars and interchangeable biosimilars, as well as to describe FDA’s interpretation of certain statutory requirements added by the BPCI Act.” The document includes various questions and their accompanying answers regarding biosimilarity, provisions related to the requirement to submit a BLA, and exclusivity.

  1. New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2), Guidance for Industry (Draft)

This draft guidance serves as a comparison to the final guidance, mentioned above, which is Revision 1. The draft guidance provides additional information on the variety and type of information that should be included to support a post-approval manufacturing change for a licensed biosimilar product.

  1. Interpretation of the “Deemed to be a License” Provision of the Biologics Price Competition and Innovation Act of 2009, Guidance for Industry

For complex historical reasons, certain biological products such as insulin and human growth hormone are currently approved as drugs under section 505 of the FD&C Act.  Starting in 2020, the approved marketing application for these products will be deemed to be biologics licenses under section 351 of the PHS Act.  Last week’s guidance document outlines the Agency’s policy on how this transition from the drug to the biologics pathway will take place and how FDA intends to use this new framework to promote competition amongst these products.

  1. The “Deemed to be a License” Provision of the BPCI Act Questions and Answers Guidance for Industry (Draft)

This draft guidance, issued in concert with the above-mentioned final guidance document, provides answers to commonly asked questions regarding the transition period for applicable products.  Some of the topics covered include: how to identify products subject to the transition, statutory and regulatory requirements for BLA submissions, how to transition applicable biological products from the Orange Book to the Purple Book, and how to designate the proper name.  The draft guidance also outlines FDA’s compliance policy for requirements related to labeling of these products.

Proposed Rule

On December 11th, the FDA also issued a proposed rule in which the Agency suggests amending “its regulation that defines ‘biological product.’”  If finalized, the new rule would incorporate the changes made by the BPCI Act, as well as clarify FDA’s interpretation of the terms ‘protein’ and ‘chemically synthesized polypeptide.’

The proposed rule states that “the term protein would mean any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size. A chemically synthesized polypeptide would mean any alpha amino acid polymer that is made entirely by chemical synthesis and is greater than 40 amino acids but less than 100 amino acids in size.”

FDA is seeking feedback on the proposed rule and is asking any interested parties to submit written or electronic comments by February 25, 2019.

What’s Next?

The regulatory actions taken by the FDA last week are huge steps for the Agency and the biologic community. As the number of approved biosimilar products continues to increase, it is only natural that competition amongst the products will follow suit. Furthermore, these regulatory actions began setting the stage for the approval of a generic insulin product that the FDA could designate as interchangeable with a reference insulin product, which would greatly improve the quality of life for so many American’s who rely on this high priced, life-saving product on a daily basis.

Are you in the process of developing a biosimilar or other FDA-regulated product? We can work with you to determine the best regulatory pathway for your product and help ensure compliance with all FDA regulations and requirements.  To learn more about our services and how we can help you, contact us today.


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