Graph with number of biosimilar approvals on the X axis and years from 1970 until 2018 on the Y axis. The line on the graph represents a generally upward trend.

The Rise of Biosimilars: Success of the BPCIA? (Part III)

By Jonathan Darrow

This is Part III in a series exploring the history, challenges, and opportunities in the regulation of biosimilars, or biologic medical products that are very similar to already approved biological medicines.  Part III considers a path forward in the regulation of biologics.  For Part I, click here.  For Part II click here.

A Path Forward

The small number of biosimilar approvals compared to generic drug approvals cannot establish the failure of the BPCIA due to differences in industry familiarity with each follow-on pathway, the number of reference products available for copying, patient population sizes, patent barriers, and drug costs. The later arrival of US laws and guidance documents—not inadequate legal design—is the most straightforward explanation of why the first US biosimilar approvals were delayed compared to those in Europe.

Rather than dismantling a biosimilar framework more than a decade in the making, Congress should exercise restraint until it determines that these efforts are unlikely to bear fruit. Although early skepticism was to be expected, several indicators suggest the market has already reached a turning point. Chief among these is the steeply upward trend in approvals since the first approval in 2015 (Exhibit 1). The large price discounts seen in a few foreign markets are encouraging, and there is a robust pipeline of biosimilars currently in development. Several biosimilar guidance documents have been issued in draft form, suggesting an ongoing commitment of the FDA to reduce technical and regulatory uncertainty. FDA guidance on interchangeable biosimilars, a more stringent classification that facilitates automatic pharmacy substitution, was finalized only in May 2019, paving the way for future products in this class.

As industry and regulatory investments in biosimilars continue to mature, policymakers should consider whether minor changes could refine the biosimilar framework. For example, transparency could be enhanced by listing relevant biologics patents in advance in the Purple Book. The proposed Purple Book Continuity Act would require such listing, though only after a patent dispute is initiated. The use of four-letter suffixes that distinguish biosimilars from their reference products (e.g., “adalimumab-atto”) can facilitate pharmacovigilance, but may also engender unjustified perceptions of therapeutic inequivalence. Alternative safety monitoring systems could be considered. States retain substantial authority in matters affecting health notwithstanding FDA determinations of interchangeability and could amend their laws to encourage greater use of biosimilars. Reimbursement models could be revised to ensure there are no financial incentives to prescribers or health systems to avoid the use of biosimilars. Medical training and continuing education could address perceived differences between biosimilars and reference products that are not supported by evidence.

There are also reasons for optimism that do not depend on either agency implementation of current law or future policy changes. Although biosimilars have so far targeted only blockbuster biologics, it is natural for manufacturers to enter more lucrative markets first. As those markets become more competitive, manufacturers can be expected to enter increasingly less attractive markets. Biologic products will likely remain more complex and expensive to test, manufacture, package, store, distribute, and administer, but greater experience with the biosimilar approval process and technological advances may gradually reduce the disparity between generic and biosimilar input costs. If biosimilars prove to be reasonable substitutes for their reference products, skepticism of prescribers and patients will wane just as it has with respect to small-molecule drugs over the past several decades. Although it is unclear to what extent the BPCIA will ultimately prove a success, its abandonment would be premature.


Author’s note 1: This post provides updated data on biosimilar approvals through December 2019.  An original version of this article was published under the title “Biosimilar Approvals And The BPCIA: Too Soon to Give Up,” available at

Author’s note 2: The author receives grant support from Arnold Ventures and the Harvard-MIT Center for Regulatory Science. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The author gratefully acknowledges Peter Bach, Yaniv Heled, and Aaron Kesselheim for feedback on the completed draft. 



Jonathan Darrow

Dr. Jonathan J. Darrow is a an Assistant Professor at Harvard Medical School and the Program on Regulation, Therapeutics, and Law (PORTAL) at Brigham & Women's Hospital. He received his research doctorate (SJD) in pharmaceutical policy from Harvard University, where he completed an LLM program in intellectual property (waived), as well as degrees in genetics (BS), law (JD), and business (MBA) from Cornell University, Duke University, and Boston College. After qualifying for the California and Patent bars in 2001 and 2002, Dr. Darrow served as a senior law clerk at the U.S. Court of Appeals for the Federal Circuit, worked in private law practice at Cooley LLP and Wiley Rein LLP, taught on the faculties of four universities and for the World Intellectual Property Organization, authored several law textbooks, supported the intellectual property divisions of WHO and WTO, lectured widely on issues of FDA regulation, and published numerous articles on issues such as expanded access, the breakthrough therapy designation, competition policy, pharmaceutical patenting, gene therapies, drug efficacy, biological products, therapeutic vaccines, and expedited development and approval programs. He is an author of several textbooks, including Cyberlaw: Management & Entrepreneurship (Cengage 2012; Aspen 2015), The Legal and Ethical Environment of Business (Aspen 2014 and Wolters-Kluwer 2d ed. 2018), and Business Law and Management for Entrepreneurs (Edward Elgar, forthcoming). He has lectured widely on issues of FDA regulation, and published numerous articles on issues such as expanded access, the breakthrough therapy designation, competition policy, pharmaceutical patenting, gene therapies, drug efficacy, biological products, therapeutic vaccines, and expedited development and approval programs.

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.