The US biosimilars market is at an interesting juncture. While the EU has been approving these lower-cost copies of biotech drugs for more than a decade, and now has 27 biosimilar products available on the market, the US has been much slower to embrace this trend.

The US Food and Drug Administration (FDA) only approved its first biosimilar in 2015, with three more approved in 2017, including Amjevita, a biosimilar to Humira – though none of the last three have been launched. At least five more could gain US licensure in 2017’s first-cycle review.

These numbers suggest that the biosimilar market is finally poised to take off in the US, which can translate to significant new revenue opportunities for biopharma companies in the region. QuintilesIMS predicts the global biologic medicines market will exceed $390 billion by 2020 and account for up to 28 percent by value of the global market for pharmaceuticals. The growth of biosimilars could also substantially cut healthcare costs for the country. Estimates suggest the United States Germany, France, Italy, Britain, and Spain will save as much as $110 billion by 2020.

As more biosimilars become available, the savings should continue to grow.

But for all the opportunities that biosimilars bring to the development space, there are also many roadblocks. These drugs can be difficult and expensive to develop and face many regulatory and market challenges. It can be useful for biopharma companies to review the challenges faced by biosimilar developers in other markets as they craft their development strategies.

  • Safety. In the late 1990s, developers of an early biologic using a erythropoietin product made a small manufacturing site change that lead to a significant immune response in some patients causing some to need blood transfusions and dialysis. The problem was subsequently resolved, but it led the European Medicines Agency (EMA), and the FDA to establish strict rules for the similarity of both structure and functional activity of biosimilars to those of the innovator/reference product. Developers moving into this space need to be certain their project plan aligns with these rules or risk failing to secure regulatory approval. 

  • Extrapolation. Early concerns related to developers’ ability to fully mimic an originator biologic caused some products not to be granted approval for all indications and factors. This extrapolation uncertainty, coupled with physicians’ initial reluctance to accept biosimilars for certain indications, led some sponsors to question whether it was worth the extra capital to study their biosimilars in multiple indications. However, extrapolation appears to be less of an issue than it used to be. Regulators are becoming more comfortable approving indications that were approved for the originator, as long as the most sensitive indication has been studied in a Phase III trial.  

  • Reference products. Minor differences between reference products can impact the development of the biosimilar and the conduct of the similarity study, making the appropriate selection of reference product an important aspect of successful biosimilar product development. To avoid complications, companies interested in developing a biosimilar should first establish a global regulatory and commercialization strategy, then use a tiered approach to addressing the specific needs of outlier countries that may not accept US/EU requirements.  

  • Recruiting for trials. Patient recruitment for biosimilars can be particularly challenging. Given the choice, many physicians and research sites prefer to work on novel compounds rather than generic versions of biologic products. As more companies enter the biosimilar arena, this challenge will only grow as they will be competing with one another for the same patients, as well as competing with sponsors of New Chemical Entity (NCE) treatments for the same indications. Working with a research partner that has access to networks of trial sites and strategies – including the use of prescription and real world data - to help ramp-up novel sites interested in pursuing these projects can mitigate the risks related to recruiting for these trials.  

  • Confusion about interchangeability. Interchangeability remains a concern for sponsors of biosimilar products, but this problem is being addressed differently in different parts of the world. In the US, draft interchangeability guidelines have only recently been issued. If this designation is granted, the successful developer gains one year of regulatory exclusivity. To date, no sponsor of a biosimilar product has sought the interchangeability designation. In the US, many states have promulgated regulations on whether the pharmacist can substitute the biosimilar for originator product. Indeed, CVS recently announced it will no longer reimburse certain originator products when biosimilar versions are available on the market in the US.  

  • The price of advice. One important lesson learned from working with biosimilar developers in Asia is the need to obtain regulatory buy-in first, before commencing a clinical program. Although novel and innovative solutions can be proposed, regulators will decide whether a program is acceptable for an approval in a particular country. Typically, the FDA and EMA will work with biosimilar sponsors to accommodate a Phase III program satisfying both agencies. But it won’t be cheap. One of the biggest financial hurdles to obtaining regulatory advice is the cost of regulatory meetings involved in the submission process, which may be upward of $1 million in the US. If specific regulatory guidance is not available in the market of interest, this must be obtained via consultancy with a resource or partner that has access to the regulators.


Many of the obstacles in the biosimilars marketplace will dissipate over time as developers regulators, payers and providers grow more comfortable with the biosimilar development process. However others, like the challenge of recruiting for these trials, may continue to get worse as competition for patients increases. Despite the challenges, the huge economic potential of this space cannot be ignored.

To navigate the marketplace, sponsors should engage with partners who understand the best ways to motivate investigators, and have experience shepherding these products to market outside of the US. With the right team and strong plan, this development path offers significant potential for decades to come.

About The Authors

Vice President, Global Strategic Drug Development and Head of Global Biosimilars Strategic Planning

Recent thinking: Biosimilars or biobetters?

Vice President Strategic Drug Development, Head, Biosimilar Center of Excellence

Recent thinking: Biosimilars or biobetters?