7 questions you might have about biosimilarity, answered
David Rosen, FDA practice group leader and co-chair of the Life Sciences Industry Team at Washington, D.C.-based Foley and Lardner, LLP, has more than 35 years of experience in various aspects of biopharmaceutical regulation, with a strong focus on generic drugs.
During his tenure at the FDA, which dates back to 1978, Rosen was one of the principal Commissioned Officers in charge of creating the Orange Book, also known as "Approved Drug Products with Therapeutic Equivalence Evaluations." The Orange Book also contains therapeutic equivalence evaluations for approved multisource generic prescription drugs.
BioPharma Dive spoke to Rosen about the evolving role of biosimilars as an important part of the therapeutic landscape. Here, he weighs in not only on the new legislation, but also issues related to biosimilar approval, as well as naming conventions and how ultimately, the most important factors are safety, efficacy, and overall patient well-being.
1) What is it in the first new guidance from the FDA "Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009 Guidance for Industry" that represents new information, specifically a point on which industry players were seeking clarification?
David Rosen: FDA’s guidance entitled "Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act (BPCIA) of 2009 Guidance for Industry" provides comprehensive information on the indications, routes of administration, the reference product that can be used in studies, among other areas. It provides information in a concise manner in a single location, again to help Companies understand FDA’s expectations. While, in my view, there was no new information in the Q&A guidance, the information is set out in a comprehensive and organized fashion that should prove to be useful for Companies desiring to develop biosimilar products.
2) How similar are Hatch-Waxman and the BPCIA?
Rosen: These two pieces of legislation have a lot of similar features. However, biologics are different from generic small molecules and need to be regulated differently. Therefore, it’s important to make sure that there are important standards in place and that both the FDA and industry do things to ensure biosimilar products meet appropriate standards.
3) What types of lobbying efforts are underway on the part of brand-name biologics manufacturers to create barriers of entry for biosimilars?
Rosen: The 12-year period of exclusivity, which is afforded to new biologics continues to be highly contested. One reason is that it seems long, compared with small-molecule generics, which get five years of exclusivity.
People must take into consideration the intensive financial costs and the timeframe associated with biosimilar development. For every biologic that gets approved, many more are not. There is an added level of complexity in terms of the analytics and extensive clinical trials that elevates product-development costs.
In addition, there are concerns around the issues of notice requirements and exchange of patent information. Companies are currently in the process of seeking ongoing clarification, and these issues will most likely be played out in court and then integrated into the BPCIA as some type of amendment.
There are also concerns about establishing biosimilarity. People are lobbying the FDA to set standards to demonstrate high similarity. And the interchangeability is a huge concern. The FDA has not provided guidance on the studies necessary to establish interchangeability. We hope that this will be the subject a guidance in the not to distant future.
4) Some of the things used to justify indication extrapolation include demonstration of analytical and functional similarity between biosimilars and the original biologics. What are examples of other factors that are used to justify indication extrapolation?
Rosen: The FDA has set forth guidance noting that a company does not have to demonstrate that a biosimilar product has activity for all approved indications. As a company developing a biosimilar, you can pick one indication to base trials on. The company does not have to conduct studies in all indications.
As a general proposition, if the biosimilar product works for one indication, and the company has established through rigorous analytical methods that the biosimilar product is highly similar to the approved innovator biologic product, there’s no reason to believe that the biosimilar product shouldn’t function as expected for the other indications.
5) Given the different data requirements of different regulators, how likely is it that biosimilar companies developing biosimilars will be able to use data used to support approval in the E.U. or any other regulatory market?
Rosen: Highly likely. There is a lot of data on biosimilars in the E.U., and based on guidelines, companies can use E.U. data. That’s a big deal. This means that companies can use the data to bridge to additional data that may be required for US approval. The ability to use data from approvals in the E.U. offers companies marketing biosimilars outside of the U.S. the opportunity to leverage the clinical data and analytics.
6) Where are we with respect to naming conventions for biosimilars? And why is this a contentious issue?
Rosen: Naming of biosimilars has also been a big deal. The question is: “How do I know which product it is if two products have the same non-proprietary name?” In this case, it’s going to be harder to track what’s going on, and if safety issues emerge, then it could complicate the clinical situation.
Several key ideas about naming have been put forth, including having completely separate names for the products; having the same name or maintaining the naming convention that FDA is currently using, i.e., adding a company suffix designation to the non-proprietary name.
7) What’s the ulimate takeaway from all this?
Rosen: In the end, it’s about what’s best for patients and for public health. Public health, safety and efficacy has to come first. Biologics are used to treat patients that often have more serious diseases. And if a biosimilar drug does not work as well as the innovator product, there might not be another chance to adequately treat the person’s illness.
We want to be sure that these biosimilar products are achieving their intended therapeutic effect and are as safe and effective as the innovator biologics.