Biosimilar Draft Guidance Shows How FDA Approves Copies of Biologic Drugs

The Food and Drug Administration published two guidances on biosimilars on March 9, including a revised draft that would reduce the clinical pharmacokinetic testing developers are advised to do, RAPS reported. FDA said in a statement that the recommendations describe when an applicant may use clinical data from outside the U.S. "without additional data from a three-way PK study," and that a PK study can use a comparator product approved outside the U.S. "if scientifically justified."

The draft, titled "New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4)," also removes FDA's earlier recommendation for at least one clinical PK study comparing the proposed biosimilar directly with the U.S.-licensed reference product, according to a client alert from Goodwin. The firm said FDA withdrew its 2015 guidance on scientific considerations in demonstrating biosimilarity, explaining that it no longer reflects current recommendations, and that the agency estimates the change could cut PK study costs by up to 50%, about $20 million per development program.

Commissioner Marty Makary said "FDA will eliminate recommendations for unnecessary clinical trials when analytical and pharmacokinetic data can sufficiently demonstrate biosimilarity," according to RAPS, which reported that he put the number of FDA-approved biosimilars at 86 as of January 2026.

A separate pathway for biologics

Biologics such as monoclonal antibodies, insulin and vaccines are generally large, complex molecules made from living sources, and they contain slight variations from batch to batch, FDA says in its overview for health care professionals. That is why copies of them are not called generics: the active ingredients of generic drugs are generally smaller and simpler to copy.

The Biologics Price Competition and Innovation Act created an abbreviated route, section 351(k) of the Public Health Service Act, codified at 42 U.S.C. 262. The statute defines biosimilar as "highly similar to the reference product notwithstanding minor differences in clinically inactive components," with "no clinically meaningful differences" in safety, purity and potency. A 351(k) application must include analytical studies, an assessment of toxicity and clinical studies, including immunogenicity and pharmacokinetics or pharmacodynamics, sufficient to show safety, purity and potency, though the law lets FDA decide that a listed element is unnecessary. The biosimilar must also use the same mechanism of action, to the extent known, and the same route of administration, dosage form and strength as the reference product.

The law also builds in a wait: approval of a biosimilar may not take effect until 12 years after the reference product was first licensed.

Biosimilar versus interchangeable

Interchangeability is a higher bar. Under the statute, an interchangeable product "may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product." To earn that status, a product must be expected to produce the same clinical result as the reference product in any given patient, and for drugs given more than once, switching back and forth must carry no greater risk than staying on the reference product.

FDA's overview says all biosimilars, including interchangeable ones, must meet the same standard of being highly similar with no clinically meaningful differences, that pharmacist substitution depends on state pharmacy laws, and that FDA does not evaluate a biosimilar for interchangeability unless the company asks. The March document is a draft, so its recommendations are not final.