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.