WASHINGTON - To try and get a handle on the biogeneric drug debate, the FDA recently held a scientific workshop on follow-on protein pharmaceuticals. The three-day event in Arlington, Va., included representatives from innovator drug companies and generic firms, as well as FDA personnel, and was meant to educate and prompt discourse.
Ajaz Hussain, the deputy director of the office of pharmaceutical science at the FDA's Center for Drug Evaluation and Research, reminded all in attendance that approved follow-on products should demonstrate the same safety and efficacy profile when given to patients under the conditions specified in the labeling of an innovator product.
But getting to that equivalency is another matter. And Hussain's suggestion of shortening the regulatory pathway for follow-on proteins by identifying and eliminating or minimizing unnecessary clinical and preclinical testing, fragmented attendees throughout the meeting.
"BIO has said for a long time that you need to do clinical trials to demonstrate safety and efficacy, because of the nature of the science," Michael Werner, the Biotechnology Industry Organization's chief of policy, told BioWorld Today.
On the other side, the Generic Pharmaceutical Association (GPhA) argued in favor of reduced regulation.
"There is no reason to delay consumer access to affordable medicines when sound science supports the approval of biopharmaceuticals under a shortened and less costly pathway," GPhA President and CEO Kathleen Jaeger said. "It is possible to permit approval and marketing of a vast array of biopharmaceuticals with relatively low to modest complexity, and to expand that system in the coming years to permit the approval of more complex products."
GPhA representatives could not be reached for comment, but Jaeger added that other countries already have approved biogeneric products, such as clearance of a human growth hormone in Australia.
The FDA, which remains under fire regarding drug safety oversight issues, is not speeding its decision in the wake of its meeting, which was co-sponsored with the Drug Information Association.
The seminar addressed methods of assessing the quality, safety and efficacy of follow-on protein products, but presenters and speakers at the meeting did not agree as to whether pharmacokinetic studies are necessary, and some suggested that pharmacodynamic studies might prove useful as an adjunct. Relative to immunogenicity, other speakers said that no animal study is an adequate substitute for a human study, while others said that a single-arm immunogenicity trial of a follow-on product could be sufficient as it can assess immune response and its impact on safety and efficacy. Most speakers agreed on a need for post-approval surveillance.
But issues related to manufacturing remained a source of disagreement. While Werner acknowledged that generic firms don't expect a shortened regulatory pathway to be equivalent to the abbreviated new drug application process by which chemically synthesized generic drugs are approved, he said no generic companies specified what kind of clinical trials would be needed.
"It's our view that it has to be pretty substantial, because the manufacturing process and molecules themselves are pretty complex," he added. "And that's partially why we think you can't really separate the scientific and legal issues. If the FDA is going to develop a process by which they're going to try to determine the similarity or sameness of these proteins that are being manufactured, the proprietary information from the innovator companies is implicated there potentially, because that's the frame of reference that the FDA has."
He contended that the agency would have a difficult time determining equivalence without using and disclosing information that was submitted to the FDA under assumed confidentiality.
"There was no discussion on the legal issues [at the workshop]," Werner said. "We see those as equally important in terms of needing resolution."
The GPhA expects eventual approval of biogenerics to address economic needs for more affordable biopharmaceuticals, though the organization acknowledged that follow-on biologicals would not be as inexpensive as chemically synthesized generic drugs. Still, the GPhA contended that even if generic biopharmaceuticals represented savings of only 10 percent to 20 percent, that cost differential would create billions of dollars in savings for consumers, the government and health care providers.
The FDA said findings stemming from the workshop would contribute to a foundation it is developing for future regulation, adding that it plans to issue a background document and draft guidance documents for public comment.
"I think the real question is going to be, What does the FDA do next?'" Werner said.