On Thursday, September 17, 2015, the United States Senate Subcommittee on Primary Health and Retirement Security held a hearing on the progress the Food and Drug Administration (FDA) has made on biosimilar implementation. Janet Woodcock, M.D., the director of the FDA’s Center for Drug Evaluation and Research answered questions about the agency’s implementation of the new approval pathway for biosimilar products created under the Biologics Price Competition and Innovation Act (BPCIA), and why there has been such a lengthy delay in offering guidance on interchangeability and labeling.
Why the Delay in Biosimilar Guidance?
One of the main concerns voiced by many Senators on the committee is the lengthy delay in receiving any kind of insight on how the biosimilars can be produced and how they will be interchangeable with the reference drugs, and potentially with other biosimilars. Senators are concerned because the pathway that the Affordable Care Act opened up has been open for over six years now, in an effort to reduce pharmaceutical costs to the patients, and every day that goes by without guidance from the FDA on how pharmaceutical companies can produce these biosimilars is another day patients are left with less pharmaceutical options.
Dr. Woodcock testified that they have fifty-seven products currently in development and have been giving the sponsors of those fifty-seven products one-to-one advice on developing their products, as necessary.
Senator Elizabeth Warren compared the FDA’s almost six year delay to the progress made by European Medicines Agency and Health Canada, both of whom approved a pathway for biosimilars years ago, and both of whom have made significant progress in getting biosimilars on the market for patients. Senator Warren criticized the FDA for having nearly a decade of experience to learn from the biosimilar approvals of those entities, and yet there are no guidelines out to help pharmaceutical companies understand what is required if they are interested in entering the biosimilar market.
Dr. Woodcock did state that the FDA has issued three final guidances, one of which is a foundational guidance for how to develop a biosimilar and which puts forth the necessary scientific framework a company needs to do to start development. However, part of the delay has been a result of the statutory wording, which requires a comparison be done with a U.S.-listed drug, which might be different from the European-listed drug, and requires additional time and research. (The three final guidances can be found here, here, and here.)
Dr. Woodcock further testified that while it may seem as though the European and Canadian health markets are moving faster than the United States in approving biologics, it is not that simple. Some of the biosimilars that have been approved in Europe have been approved in the United States, not as biosimilars but as drugs, such as growth hormones and insulin.
Negative Perceptions
Senator Warren also introduced concerns about the negative perceptions that some physicians and patients still have about the efficacy and quality of generic drugs as compared to name-brand drugs and drew a parallel between the thirty-year history of generic medicine and the emerging biosimilar market. Dr. Woodcock assured her that they are getting the biosimilar science right and that the funding is not currently there for a large educational campaign to the outside world to assuage those concerns, but once additional biosimilars have been approved, the FDA will focus on educating physicians, patients, and the general public.
Unique Biosimilar Identifiers
Senator Hatch, who was at the forefront of the generic drug market thirty years ago, was interested in the naming of biosimilars and tracking of adverse events that stem from the use of biosimilars.
Dr. Woodcock testified that the FDA needs to have unique identifiers and a way to tell who received which form of the biosimilar, so if there is a severe problem, they will not have to take all of the biosimilars off the market, just the one causing the problem.
The concern is that by uniquely identifying each specific biosimilar, interchangeability is implicated. The FDA is trying to determine whether they want the company contraction as the identifying suffix, or a random four letter grouping, by asking for input from industry professionals. Dr. Woodcock did signal that if the FDA agrees to put the suffix of the company on the drugs, the innovators will bear some of that cost, which could possibly raise the prices of the biosimilars as a pass-through cost.
View our article on FDA’s biosimilar naming guidance here.
Interchangeability and the Purple Book
Senator Cassidy was concerned about pharmacists being able to speak with the patients, review what other medication the patient might be on from other physicians, and make a determination as to whether the specifically prescribed biosimilar is safe for the patient or if there is a safer alternative. Dr. Woodcock stated that there are two tiers to that analysis, the first of which requires the biosimilars to be interchangeable, and the second is the state law that governs pharmacy substitutions.
Dr. Woodcock compared the current orange book – which is used for ratings on interchangeability for generic drugs – to a purple book the FDA will publish, which is to be used by pharmacists to determine which biosimilars are interchangeable to make the most-informed decision for the patient.
State Regulatory Concerns
Thirty-one states currently have, or are currently considering, state laws that regulate how biosimilars should be provided to patients. According to Dr. Woodcock, some of those state laws are helpful to the promotion of biosimilars and yet others have the potential to create significant barriers to biosimilar success.
The FDA has asked for explanations of each state’s programs for handling biosimilars and has an intergovernmental affairs office that interacts with each of the states. Dr. Woodcock cautioned against states erecting barriers to the use of biosimilars, stating that the FDA has started to see those issues in the European Union and it has the potential to stunt the economic and healthcare benefits of biosimilars as a whole.
Global Solutions
Dr. Woodcock testified that the FDA is working with the International Nonproprietary Names (INN) committee at the World Health Organization and they are aware of a desirability of a common global standard for how biosimilars are named. However, in practice, different countries and health organizations have shifted to utilizing different conventions. For example, in the EU, prescribers are required to identify the product by the brand name and lot number in each patient’s chart. Dr. Woodcock opined that this is not an acceptable solution in the United States because of the likelihood that it would heighten the workload of our busy doctors and medical professionals.
Global Safety Concerns
Lastly, there was some discussion of concern about the history of poor standards at certain drug manufacturing plants in India, but not much follow-through from the FDA on a solution to increase standards at those plants. As such, it is only natural that those concerns will spill over into the biosimilar world. Dr. Woodcock assured the senators that there are no biosimilars currently produced in India that are destined for the United States markets. Additionally, the laws that surrounds regulations for biologic products are extremely strict on manufacturing because of the long-checkered history of problems that originated with the Public Health Service Act. All facilities that produce a biologic or biosimilar product are inspected, unless they have recently passed inspection by an FDA official.
Conclusion
Overall, Dr. Woodcock and the FDA will continue working on affirming the scientific framework and the efficacy of the fifty-seven products they are currently working on, in addition to creating guidelines pharmaceutical companies can refer to in creating biosimilars of their own. Dr. Woodcock hopes to have other draft guidances out regarding the naming and interchangeability within the next six months.
View Woodcock’s testimony here.