President Obama has urged the American Medical Association to support the introduction of biosimilar drugs into the U.S. market to help lower health-care costs. These generic versions of protein-based drugs have been unavailable in the United States because legislators and the U.S. Food and Drug Administration (FDA) have struggled to agree on a regulatory path for approval. Dr. Barry Karger, director of the Barnett Institute of Chemical and Biological Analysis at Northeastern University, spoke to the issues involved and to the role the institute can play.

Q: What is the difference between current generics and biosimilars?

A: Most drugs developed by pharmaceutical companies are manufactured by chemical synthesis and are known as small-molecule pharmaceuticals. We’ve had a legal framework for the FDA to approve generic versions of these pharmaceuticals since 1984. Today, there are many generic versions of pharmaceutical drugs available at significantly lower cost than the original drugs.

On the other hand, biotechnology companies typically manufacture protein drugs made from living organisms, with sizes that are 100-fold or greater than those manufactured by chemical synthesis. Biosimilars are to these drugs what generics are to pharmaceuticals.

Because of the differences in manufacturing and in complexity, the FDA uses different groups to evaluate drug applications for pharmaceuticals and biotechnology products, and currently, there is no legal framework to guide the FDA on the approval of biosimilars. However, it is anticipated that Congress will provide legislation by the fall or early next year. Approval guidelines already exist in Europe. A major issue in the U.S. legislation is how many years the original biotechnology drug—the so-called innovator product—can be on the market before the biosimilar version can be sold.

Q: What are the challenges to getting approvals before biosimilars can enter the market?

A: Once [federal] legislation has passed, the ball will be in FDA’s court. Among other things, it will need to decide how comparable the biosimilar product is to the innovator product. The need for detailed structural analysis of the protein will be great. Then, the extent of the clinical trial and the end points will need to be decided. There is no doubt that FDA will be cautious.

Q: President Obama praised biosimilars as a way to lower health-care costs. What impact will they have in your view?

A: Biosimilars will cost less than innovator products; however, the cost differential will be much smaller than we find in the market for small-molecule generics today. The reason is that much more will be required for biosimilar approval than has been the rule for generic drugs. Nevertheless, with the emergence of biosimilars, there will likely be some downward pressure on the prices of innovator drugs.

Q: What role will the new Center for Advanced Regulatory Analysis (CARA) in the Barnett Institute play in the development of biosimilars?

A: CARA is developing powerful new approaches to determine the structure of the biosimilar relative to the innovator product. Our goal is not only to demonstrate the feasibility of our methods and technologies, but also to validate them for use in a regulatory setting. We plan to develop methods that assess the biological impact of differences in structure between the biosimilar and innovator product. The question is always, how important are the differences?

Q: As a center that focuses on the regulatory analysis of biotechnology products, how can CARA help ensure drug safety and quality?

A: For all biotechnology products—innovator products and biosimilars—our goal is to provide powerful new tools for analyzing the products. This is important not only for commercial products per se, but also for analysis of raw materials and additives to the drugs. We are all aware of the heparin and melamine problems that occurred this past year. [Additives to the blood thinner heparin as well as to wheat gluten and infant formula caused thousands of illnesses and some deaths in 2008.] We believe the tools we are developing will reduce the potential for such problems in the future.

Also, starting at the end of summer, CARA will offer short courses to the industrial and regulatory communities. Improving the technology of biopharmaceutical analysis and a better understanding of the role of structure with biological function should provide a strong basis for regulatory decisions on protein products. That is our goal.