“Follow-On” Biologics Guidance Will Limit Use Of Data To “Public Domain”

FDA's upcoming draft guidance on follow-on biologics will allow use of data that are in the public domain only, Center for Drug Evaluation & Research acting Director Steven Galson, MD, told the Schwab Soundview Washington Research Group health care conference May 5.

"The information referenced must be in the public domain," Galson declared. "FDA does not have the legal authority to reference information in an innovator company's BLA submission."

FDA's development of a guidance on follow-on biologic products is of intense interest to the biotech industry - and its sources of capital on Wall Street.

Acting Commissioner Lester Crawford, PhD, told a recent Bear Stearns conference that FDA hopes to have a "structure" for considering the issue in place soon - prompting a new round of concerns in industry about the direction of FDA's effort (¹ (Also see "FDA Generic Biologics “Structure” To Come Soon; Policy Debate In 2005" - Pink Sheet, 5 Apr, 2004.), p. 7).

Galson used the Schwab conference to deliver a carefully crafted and nuanced statement on the upcoming guidance (see ² (Also see "FDA “Follow-On” Biologics Guidance: A Preview" - Pink Sheet, 10 May, 2004.)).

During the section of his presentation covering follow- on biologics, Galson read prepared remarks, rather than following his usual off-the-cuff presentation style.

[Editor's note: A transcript of Galson's statement on generic biologics appears in this edition of "The Pink Sheet."]

The overall tone of Galson's remarks was to reassure investors that FDA is not planning any radical steps (like creating a true "generic biologics" process) on its own initiative. "The development and potential submission of applications for most potential follow-on biologics is really many years away," Galson said.

However, the draft guidance will be very broad in scope, with the clear intent of moving the debate forward on how abbreviated pathways could be created for "follow-on products."

The scientific pathway covered in the guidance is "conceptually separate" of what is - or what should be - permitted by law, Galson said. "These critical issues must also be addressed in detail by Congress before any large scale development of follow-on biologics will be possible".

"The legal framework only exists today" for the "limited number of proteins that are regulated as new drugs under Sec. 505 of the FD&C Act," Galson said. He specifically cited human growth hormone and insulin.

Nevertheless, "to encourage consistency, we are developing a guidance that will provide a general framework for the scientific approaches that could be used to demonstrate similarity or sameness between...a broader spectrum of therapeutic peptides and proteins, including vaccines, human blood-derived products and certain other products."

Galson offered a definition of a "follow-on" product as "a protein product with the same amino acid sequence and a similar enough production process and overall structure to appear on its face to be very similar to an already approved product or products."

"As a general rule, the more complex the biologic is in the production process, the more scientific studies required to establish this sameness principle," he said.

"It is currently not really scientifically possible to establish that two proteins are exactly the same, even for two batches of the same product made by the same manufacturer," Galson said. "However, it is possible to assess how similar the two proteins are; current manufacturers must make that assessment every time they change their production process."

As a result, "there may be some qualities that could be characterized as similar to those innovator products in order to allow some abbreviation in the pathway for follow-on versions, but not getting rid of most of the process like we have for the current generic process."

For example, Galson suggested, a follow-on product could use the same surrogate endpoint as a previously approved agent.

Galson said that the draft guidance would come out "this spring." The agency plans to hold public workshops as part of the comment process (³ (Also see "FDA “Follow-On” Biologics Framework Development Will Become More Public" - Pink Sheet, 26 Apr, 2004.), p. 41).