WASHINGTON, D.C.—Federal regulators are hoping that new biologics will become available to patients at a lower cost under a new act designed to facilitate the development of products intended to be biologically similar to already approved biologic therapies, U.S. Food and Drug Administration (FDA) officials said in a session titled, “Biosimilars Development: Food and Drug Administration Perspective,” at the 2012 ACR/ARHP Annual Meeting, held November 9–14. [Editor’s Note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.]
But the review and approval of such products will depend on the product, how much is known about it, and the quality of the data submitted to the FDA, the officials said.
The Biologics Price Competition and Innovation Act of 2009 (BPCI), approved as part of the Affordable Care Act, is designed to hasten development of products that are proposed to be “biosimilar” to previously approved therapies.
“Biologics have revolutionized the management of many rheumatic diseases,” said Nikolay Nikolov, clinical reviewer with the FDA’s Division of Pulmonary, Allergy and Rheumatology Products (DPARP). “However, the access to these drugs may be limited due to higher price. The abbreviated biosimilars pathway is expected to facilitate development of biosimilar products and provide additional treatment options.”
A product is considered to be biosimilar under the act if it is highly similar to the reference product notwithstanding minor differences in clinically inactive components and there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency.
The officials described the “stepwise” and “totality of the evidence” approach to the assessment and determination of biosimilarity. The foundation is the extensive analytical characterization of the structure and function of the product. Additional clinical studies might be required to resolve any residual uncertainties that might stem from limitations of the data that are presented or differences observed in the structure and function of the proposed biosimilar product and the reference product.
“The goal is to demonstrate biosimilarity—that the products are highly similar with no clinically meaningful differences,” said Leah Christl, PhD, associate director for therapeutic biologics at the FDA. “The goal is not to independently establish effectiveness and safety of that proposed product. The reference product already did that.”
She added that, “we really want folks to understand their product, their protein, the product that they’re developing, and the key to this is understanding which attributes matter and which don’t.”
More Data, Speedier Product Development?
Marjorie Shapiro, PhD, chief of the FDA’s Laboratory of Molecular and Developmental Immunology, stressed that the better the data on the nature of the product, the less additional data will likely be needed, possibly making for a speedier development.
“The more good data we have from those types of studies may reduce the need for other types of studies, additional clinical studies, and perhaps some nonclinical studies,” she said. “But there are different pathways to get to biosimilarity.”
Dr. Nikolov said that it’s possible to extrapolate clinical and nonclinical data from one indication to another, “provided there is a sufficient scientific justification.” That justification should address mechanism of action in each condition of use, pharmacokinetics and biodistribution of the product in different patient populations, and differences in expected toxicities for each condition of use and each patient population.
An FDA panel was asked how a trial could be conducted to compare a new product’s risk to an existing product, when one group of patients would be getting the established product and the other wouldn’t. Badrul Chowdhury, MD, PhD, director of the DPARP, said it’s important to remember that the premise of such a trial would be that the products are biosimilar. “One needs to conclude that, first of all, there’s biosimilarity and there’s equipoise—that we do know what the benefit or the harm is,” he said. “And then one does a study.”
The panel was also asked whether a drug sponsor could conduct a pharmacokinetic study, if called for, while doing a clinical study at the same time to resolve remaining questions. Dr. Christl said that, “there’s really no one-size-fits-all approach,” and that it depends on the risk that the sponsor is willing to absorb. But, she added, “we hope that folks will come in with some analytical characterization data before they do any clinical studies,” so that the regulators can offer suggestions on appropriate ways to design clinical studies.
In response to another question, Sarah Yim, MD, associate director of DPARP, said that biosimilars would trigger the Pediatric Research Equity Act. Dr. Christl said that when regulators review the product, it might be possible that they would consider the new product so similar to the reference product that pediatric studies wouldn’t be necessary. But there also might be enough differences that additional data, such as a pharmacokinetic study, would be needed. “We’re trying not to have to re-prove safety in every population,” she said, “if we can avoid it.”
Thomas Collins is a freelance medical journalist based in Florida.
