Jeffrey A. Singer
In recent testimony before the Senate Appropriations Committee, Food and Drug Administration Commissioner Marty A. Makary, MD, said he favored streamlining the agency’s approval process for biosimilar drugs.
Analogous to generic drugs that compete with conventional, chemically synthesized pharmaceuticals, biosimilar drugs compete with biologic medicines, which are derived from natural sources, are complex, and may contain combinations of carbohydrates, proteins, nucleic acids, and even living material, such as cells or organisms.
Biological products include vaccines and blood-derived therapies. When patents for traditional drugs expire, other manufacturers typically introduce generics, sparking competition that drives prices down. Similarly, once patents on biological drugs lapse, companies can develop biosimilars, which also help lower costs through market competition.
In the US in 2023, only 2 percent of prescriptions were for biologics, yet biologics made up 46 percent of pharmaceutical spending. According to a 2022 analysis by McKinsey, developing a typical biosimilar requires an investment of between $100 million and $300 million and usually takes six to nine years, from initial analytical work through final FDA approval. That contributes to the high price of biosimilars.
To approve a biosimilar, the FDA typically requires a stepwise demonstration of similarity that includes analytical studies to compare structure and function, nonclinical (animal) studies when needed—usually for toxicity—comparative pharmacokinetic (what the body does to the drug) and pharmacodynamic (what the drug does to the body) studies, immunogenicity studies (the ability of the drug to cause an immune response), and clinical trials that often include comparative efficacy studies (CES) in one or more indications if residual uncertainty remains. Think of it as forcing a replay of a movie scene in every theater before letting it go nationwide.
As I explain in my book, Your Body, Your Health Care, when Congress passed the Kefauver-Harris Amendment to the FDCA in 1962, it required drug makers to convince the agency that a new drug was effective as well as safe. This arduous FDA approval process increases drugmakers’ research and development costs while reducing the time remaining on their patents, allowing them to recoup those costs. This is one major contributor to high prescription drug prices. It creates the phenomena of “drug lag” and “drug loss.”
“Drug lag” describes the delay consumers experience because of the FDA’s requirement to prove a drug’s efficacy before it can reach the market. Each added day in the approval process effectively withholds a potential treatment from patients who might benefit. “Drug loss” happens when companies decide not to pursue development of certain therapies because they believe the high cost and uncertainty of FDA approval make it financially unviable.
Fortunately, the FDA does not require clinical efficacy trials for generics competing with off-patent brand-name drugs. Once convinced of their safety, the FDA allows generics manufacturers to skip clinical efficacy trials based on the concept of bioequivalence.
Unfortunately, the FDA requires clinical efficacy trials for biosimilars. However, for several years now, the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) have adopted a more modern, science-based approach to approving biosimilars. They no longer require clinical efficacy trials for biosimilars if the pharmacokinetic, pharmacodynamic, and other analytical and immunogenicity assessments match the original biologic.
Thus, patients in Europe and the UK gain earlier access to biosimilars. For example, the EMA approved infliximab-dyyb (Inflectra), a biosimilar alternative to infliximab (Remicade), in 2013. The FDA approved infliximab-dyyb in 2016. These drugs are used to treat various autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Because the EMA has a streamlined process with fewer clinical efficacy trials, the EU has higher biosimilar adoption rates, along with deeper price reductions, compared to the US.
To remove some of the barriers to access to biosimilars that the FDA imposes on patients and their health care providers, Senator Rand Paul (R‑KY) has introduced S. 1414, the “Expedited Access to Biosimilars Act.”
The proposed legislation retains the FDA’s requirement for pharmacokinetic testing because of its role in evaluating safety and establishing clinical similarity. However, it eliminates the automatic requirement for pharmacodynamic and comparative efficacy studies unless there are strong scientific reasons to justify their use. Pharmacodynamic studies are rarely suitable because valid and predictive pharmacodynamic markers are uncommon and rarely recognized by the FDA as reliable indicators of effectiveness. The bill also removes the requirement for separate immunogenicity testing under comparative efficacy studies, since pharmacokinetic studies already include safety and immune response assessments, making additional testing unnecessary.
Together with a complementary bill from Senator Mike Lee (R‑UT), this effort represents a broader bipartisan push to remove unnecessary regulatory barriers. The Biosimilar Red Tape Elimination Act, initially introduced by Senator Lee in 2023, was reintroduced this year with bipartisan support. The bill would eliminate another FDA requirement, making it easier for patients to access biosimilars: a requirement that they undergo “switching” studies to demonstrate clinical interchangeability with the original biologic. The European Medicines Agency eliminated this requirement in 2022. I wrote about the proposal here.
Based on Commissioner Makary’s statements before Congress and recent podcasts, he is likely to support both of these measures. Both bills will improve access to care, increase competition to help lower prices, and steer policy in a way that respects patient autonomy.