FDA and industry need to work out the science of generic biologics before a legislative debate would be useful, FDA Principle Associate Commissioner Murray Lumpkin, MD, suggested.

"This is not something that FDA can make a decision on its own about. There are clearly science issues that have got to be answered, and there are very clear law issues that have got to be answered," Lumpkin said during the National Organization for Rare Disorders conference on "Exploring the Pathway to Generic Biologics" March 19 in Washington, D.C.

Lumpkin argued that the debate surrounding the creation of a regulatory path for generic biologics is the argument of what comes first: the legislation or the science.

"Is it worth going down the path of figuring out what the law says, yes or no, if the science hasn't been answered...or do we need to figure out the science first, and then once that's figured out say 'okay, now how do we get there because this...is the right public policy to follow at this point in time?'" Lumpkin asked.

"At the end of the day, it's going to be coming up with a body of scientific evidence that says 'we are at this point with the science that we think we need to now have a public policy discussion,'" Lumpkin said.

Though a generic biologics policy would not be created by FDA alone, Lumpkin said, it would surely be the "fulcrum" of debate and the enforcer of any future law.

"Just like we enforced the 1984 law, we will do what Congress tells us to do. But I think we need to have the science debate. We need to get the science part figured out," Lumpkin said.

FDA Commissioner McClellan has said that generic biologics are inevitable but has not proposed a timeline for creating a mechanism.

The Center for Drug Evaluation & Research is considering seeking legislative changes to allow it to review biologics and drugs under the same application format following the consolidation with the Center for Biologics Evaluation & Research (¹ 'The Pink Sheet' March 10, In Brief). Such a move would not create a generic biologics pathway per se, but could have regulatory implications.

US Pharmacopoeia CEO Roger Williams, MD, told the NORD symposium that USP is focused on developing the science of generic biologics, in accordance with a resolution from its 2000 Quinquennium (² Also see "Bioequivalence Methods For Modified-Release Drugs To Be Examined By USP" - Pink Sheet, 1 May, 2000., p. 31).

"I think of it in terms of the 'if' question, the 'how' question, and the 'will' question. I think we're sort of moving past the 'if' question to the 'how' question. I was trying to deal with the 'how' question," Williams said.

"If you were going to try to do it from a scientific standpoint, here's how you might think about it: will people do it? Will people generate the necessary data to make a compelling case to the agency, the government, payors, practitioners? I can't say, that's certainly not in my court. I think certainly where USP wants to focus is on the 'how' questions," he added.

USP organized an expert panel of 13 scientists from industry, academia and FDA to evaluate the equivalence of complex active ingredients and products, including peptides, non-glycosylated proteins, glycosylated proteins and monoclonal antibodies.

USP has also organized a council of experts to examine complex actives on vaccines, virology and immunology; blood and blood products; biotechnology and natural therapeutics and diagnostics; and cell therapy and tissue engineering. The vaccines and blood committees have six members each; the biotechnology and cell therapy committees have nine.

In the fall, USP will hold a conference in Crystal City, Va. on biologics with one day dedicated to the equivalence of biologics. The goal of the conference will be to create official USP reference standards for generic biologics.

Biogen VP-Preclinical & Clinical Development Sciences James Green, PhD, argued that variable standards would be needed for generic biologics.

"Each product is going to have a different product comparability program, and each product, at the end of the day, is probably going to have a different level of clinical assessment...because the safety bar has to remain high," Green said.

"It really has to remain high because the unmet need is being met by the product that was there, and all we're trading, really, is health care dollars," Green added.

Biogen is understood to be spearheading development of a position paper on generic biologics for the Massachusetts Biotechnology Council (³ Also see "Generic Biologics Are Coming, Commissioner McClellan Tells MBC" - Pink Sheet, 24 February, 2003., p. 11).

Barr Research President Carol Ben-Maimon, MD, expressed confidence that scientific issues could be resolved because of the background of the generic companies involved. "Companies like Sicor...are extremely experienced manufacturers of biologics; they have been manufacturing biologics for more than ten years."

A Sicor subsidiary in Lithuania has been selling both human growth hormone and interferon alfa-2b in the Baltic countries and developing nations for 12 years.

Support for generic biologics depends on more than "good science," Ben-Maimon added. "Much of the confidence is dependent upon the physicians who often don't speak to the generic industry at all and are very unaware of the...kinds of regulatory hoops we jump through in order to get our products approved."

Sicor is exploring possible pathways for submitting abbreviated biologic license applications in the U.S. "We are working closely with FDA and EMEA in the European Union in structuring submissions for this product area," a statement from Sicor CEO Marvin Samson said.

"This program necessitates complete analytical testing of the protein, clinical safety and a demonstration of clinical efficacy. We believe that these requirements will create barriers to entry for some companies, but are achievable for us," the statement continued.

Sicor anticipates a preliminary meeting with FDA to take place in the next couple of months with agency representatives from manufacturing, clinical, and toxicology participating. Sicor expects the meeting to start a dialogue about what would be required for an abbreviated approval process for biologics in the U.S.

The Croatian pharma company Pliva plans to file its application for generic erythropoietin in the EU in the near future. For the submission, Pliva conducted abridged preclinical and clinical studies in addition to other standard generic requirements. Pliva expects its generic version of erythropoietin to reach the markets in the UK, Spain, and Germany in 2006.

Generic Biologic Science Must Evolve Before Legislative Debate – Lumpkin

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