FDA Overhauls Pharmacokinetic Study Requirements in New Biosimilar Draft Guidance
The US Food and Drug Administration (FDA) has overhauled biosimilar pharmacokinetic study requirements in new draft guidance issued on 9 March 2026, aimed at further reducing the time and cost of bringing biosimilar medicines to market. The guidance, titled “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4),” introduces significant changes to how these pharmacokinetic (PK) studies are conducted as part of the biosimilar approval process, and forms part of the current administration’s wider push to lower drug costs for American patients.
The fourth revision to the FDA’s official biosimilar guidance framework, this update revises Q&As I.8, I.10, and I.19, which had been withdrawn from the agency’s existing final guidance. Comments on the draft are being accepted until 11 May 2026.
Streamlining Pharmacokinetic Testing
PK studies evaluate how the body absorbs, distributes, metabolises, and excretes a drug. They have traditionally played a central role in demonstrating that a biosimilar behaves comparably to its reference product. Under the previous framework, developers were required to conduct at least one clinical PK study that directly compared their proposed biosimilar against the US-licensed reference product. The revised guidance moves away from this requirement.
Under the updated approach, a PK study may now use a non-US-licensed comparator product, provided this is scientifically justified. Critically, biosimilar applicants will no longer be obliged to conduct a three-way PK study comparing their product with both a US-licensed reference product and a non-US-licensed comparator. Instead, a single comparison against a non-US equivalent may suffice where the scientific rationale supports it. The FDA also confirmed that developers can incorporate clinical data obtained outside the United States without the additional burden of a separate bridging study against the US reference product.
The FDA stated that these changes could reduce PK study costs for biosimilar developers by up to 50%, equating to savings of approximately $20 million per programme. FDA Commissioner Marty Makary commented: “Streamlining biosimilar development reflects our ongoing commitment to lowering drug costs for everyday Americans. Using common sense, we are embracing more precise analytical testing approaches than have been used in the past.”
A Pattern of Regulatory Reform
The March guidance follows directly from a broader reform programme the FDA launched in October 2025, when Commissioner Makary announced draft guidance targeting comparative efficacy studies (CES) – another costly and time-consuming component of the biosimilar development pathway. Those studies, which assess whether a biosimilar produces clinical outcomes comparable to its reference product, can take between one and three years to complete and cost an estimated $24 million. The October guidance proposed that CES requirements could be waived in cases where analytical and PK data are sufficiently robust.
As part of the March update, the FDA is also retiring a 2015 final guidance document that was issued following the agency’s approval of its first biosimilar product. The agency stated that this earlier document “no longer represents the FDA’s current thinking,” noting that having now approved 82 biosimilars to date, it has “gained significant experience” in this area and that its “scientific thinking has evolved.”
The Biosimilar Spending Imbalance
The urgency driving these regulatory changes is rooted in a stark mismatch between biosimilar adoption and healthcare expenditure. Biologic medicines currently account for approximately 51% of total drug spending in the United States whilst representing only 5% of all prescriptions. Branded biologics can cost patients hundreds of thousands of dollars per year, and biosimilars, which are generally available at considerably lower prices, have the potential to ease that burden substantially.
Congress established the biosimilar approval pathway in 2010 through the Biologics Price Competition and Innovation (BPCI) Act, and the FDA has since approved products covering conditions including cancer, rheumatoid arthritis, diabetes, Crohn’s disease, and osteoporosis. Despite this progress, the approved total remains a modest fraction of the overall biologics landscape. According to data from Samsung Bioepis, 118 biologic medicines representing nearly $232 billion in combined US sales are expected to lose patent protection between 2025 and 2034. Yet only around 10% of those reference biologics currently have a biosimilar in active development, a gap that has been described in industry circles as the “biosimilar void.”
Industry Responds and the Void Persists
Industry stakeholders and patient advocates have broadly welcomed the guidance. The Biosimilars Forum characterised the October 2025 guidance as directly addressing the affordability crisis in prescription medicines. Leading biosimilar manufacturer Sandoz has described the coming years as representing a “golden decade” for patient access, with medicines worth more than $650 billion set to lose exclusivity over the next decade. In a January report, the company argued that streamlined regulatory pathways that “retain rigorous analytical studies and pharmacokinetic characterisation while eliminating expensive, time-consuming phase 3 trials” are a primary lever in closing the biosimilar void.
Yet observers caution that regulatory reform alone will not close the gap. Manufacturers face a range of additional barriers, including limited return on investment for medicines targeting rare diseases or small patient populations, the manufacturing complexity inherent in advanced biologics such as bispecific antibodies and cell-based therapies, and prolonged development timelines that can still span nearly a decade even under a streamlined regulatory framework. Market uncertainty linked to the Inflation Reduction Act, which has introduced new dynamics around Medicare price negotiations, has also created fresh disincentives for some biosimilar programmes.
Analysts have further noted that without complementary reforms addressing rebate structures, patent thickets, prescriber incentives, pharmacy benefit manager transparency, and gaps in biosimilar education, the full potential of biosimilar competition may not be realised. The benefits of the current regulatory reforms are also expected to take several years to materialise in terms of new product approvals and patient access.
International Context: Closing the Gap with Europe
The FDA’s actions are in part a response to a persistent approval gap between the United States and Europe. The European Medicines Agency (EMA) approved 22 more biosimilars than the FDA in 2025, reflecting the EMA’s longer track record with streamlined approval criteria. The FDA approved 19 biosimilars in 2024, a notable increase from the five approved in 2023, suggesting that the agency’s reform programme is beginning to bear fruit. The EMA has been pursuing its own parallel modernisation efforts through a draft reflection paper suggesting that structural and functional comparability, combined with PK data, may be sufficient to demonstrate biosimilarity, without the need for large-scale clinical efficacy trials. The FDA’s Revision 4 draft guidance signals a clear intent to align more closely with this international direction of travel.
The global biosimilars market reached approximately $30 billion in 2024 and could generate savings of over $180 billion in US healthcare costs in the coming years, according to industry estimates. Whether the FDA’s regulatory modernisation can help unlock that potential will depend on how swiftly the complementary structural and commercial challenges are addressed alongside the scientific ones.
Public comments on the March 9 draft guidance are open until 11 May 2026. Developers, payers, and patient groups are expected to respond in detail before the agency begins work on the final version.
