The Purple Book and interchangeable biosimilars

FDA's list of approved biosimilars had 90 entries when the agency last updated it on Oct. 28, 2026. The first, a copy of filgrastim, was approved in March 2015. The newest, a copy of the eye drug ranibizumab, came in October 2026, according to FDA's biosimilar product information page¹. Thirty-six of the 90 were approved in 2024 and 2025 alone.

Every one of those products also sits in the Purple Book, FDA's searchable database of licensed biological products. It plays roughly the role for biologics that the Orange Book plays for conventional drugs, with one large difference. The Orange Book grades generics with two-letter therapeutic equivalence codes. The Purple Book records a single status that matters at the pharmacy counter: whether FDA has found a biosimilar "interchangeable."

Rules for earning that status are in motion. In June 2024 FDA issued a draft guidance saying the switching studies that applicants have run to prove interchangeability may often be unnecessary, and in September 2026 it published a draft strategy on interchangeable products that is open for comment until Nov. 17. This explainer covers what the Purple Book holds, how its interchangeability flag differs from an Orange Book code, and what the 2024 draft would change.

What the Purple Book holds

Originally the Purple Book was two separate lists, one for biologics overseen by FDA's drug center and one for those overseen by its biologics center, FDA says². It is now one online database covering biological products licensed under the Public Health Service Act, including biosimilars, interchangeable biosimilars and the reference products they copy.

Congress wrote its contents into law in December 2020. A provision of the year-end spending act, Public Law 116-260, added a "public listing" paragraph to 42 U.S.C. 262(k)(9)³. It requires FDA to publish each licensed biological product by its proper name, with its licensure date, application number, licensure status and, as available, marketing status. The list must be revised every 30 days, must carry the patent lists that reference product sponsors hand to biosimilar applicants, and must show any exclusivity period that has not yet run out.

Some familiar medicines moved into the Purple Book from the Orange Book. Insulin and insulin analogs, human growth hormone, pancreatic enzymes and some reproductive hormones had historically been approved under new drug applications. On March 23, 2020, at the end of a 10-year transition written into the 2009 biosimilars law, those approvals were deemed to be biologics licenses⁴ and taken out of the Orange Book, which opened them to biosimilar competition. GxRadar's explainer on the Biologics Price Competition and Innovation Act covers that law.

Two books, two answers to the substitution question

Orange Book codes rest on sameness. FDA rates two products therapeutically equivalent when they contain identical amounts of the identical active ingredient in the same dosage form and route and are bioequivalent. Such products "can be substituted with the full expectation that the substituted product can be expected to have the same clinical effect and safety profile," the Orange Book preface⁵ says. Products coded A are rated equivalent. Products coded B are not. GxRadar's guide to therapeutic equivalence codes lists all 16.

A biologic made in living cells can't be reproduced molecule for molecule, so a biosimilar is held to a different test. It must be highly similar to its reference product, notwithstanding minor differences in clinically inactive components, and show no clinically meaningful differences in safety, purity and potency, FDA's 2024 draft guidance⁶ restates. The two databases reflect that split.

Sources for the table are the Orange Book FAQ⁷, the Orange Book preface and 42 U.S.C. 262.

What "interchangeable" means in law

Its statutory definition is one sentence. An interchangeable product "may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product," 42 U.S.C. 262(i)(3)³ says.

Earning it takes more than biosimilarity. FDA must find that the product can be expected to produce the same clinical result as the reference product in any given patient. For a product given more than once, the agency must also find that the risk of alternating or switching between the two is no greater than the risk of staying on the reference product, the draft guidance explains⁶. FDA calls the second test the switching standard.

Interchangeability is optional. FDA does not evaluate a biosimilar for interchangeability unless the company requests it, the agency tells clinicians⁸, and some makers skip it, for example when a product is given in a hospital or clinic and would never be dispensed by a pharmacy, according to FDA's consumer explainer⁹. FDA also says the extra data do not make an interchangeable product safer or more effective than other biosimilars; its fact sheet¹⁰ describes the data as a way to judge the safety of pharmacy-level substitution.

Being first carries a reward. For the same reference product, FDA may not make a later interchangeability approval effective until the earliest of several dates: one year after the first interchangeable is marketed, 18 months after a final court decision or dismissal in patent litigation against it, or 42 or 18 months after its approval depending on whether it was sued, under 42 U.S.C. 262(k)(6)³. A December 2022 amendment specified that every product approved as interchangeable on the first day shares first-interchangeable status.

The 2024 draft guidance on switching studies

FDA's interchangeability guidance, finalized in May 2019¹¹, recommended switching studies, in which patients alternate between the reference product and the proposed interchangeable. The agency wrote it before it had received or reviewed any application for an interchangeable product, FDA acknowledged in the June 2024 update⁶.

That update, announced in the Federal Register on June 21, 2024¹², says experience with approved biosimilars has shown "the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches." It also cites analytical methods that can characterize purified proteins with high sensitivity. Under the draft, an applicant may submit an assessment of why its comparative analytical and clinical data meet the switching standard, and a company with a pending biosimilar application may amend it to ask for interchangeability.

That guidance is still a draft. FDA's guidance listing labels it "Not for implementation" (FDA guidance page¹³), while the agency's consumer page says it is updating its guidance "to recommend fewer tests to demonstrate interchangeability" (FDA⁹). FDA moved the same way on biosimilarity itself in November 2025 with a draft guidance on comparative efficacy studies¹⁴, which says a comparative analytical assessment "is generally more sensitive" than such a study at finding differences between products.

Approvals have climbed over the same period. The count below comes from FDA's list as of Oct. 28, 2026, and includes products with and without the interchangeable designation.

Where state law takes over

An interchangeable designation permits substitution. State pharmacy law decides how it happens. A study of the laws in all 50 states and Washington, DC, as of Sept. 1, 2019, published in JAMA Internal Medicine¹⁵, found that 45 states set stricter conditions for substituting interchangeable biologics than for substituting generics. The most common was a requirement to notify the prescriber. The same study counted 19 states that required pharmacists to substitute an equivalent generic for a small-molecule brand. GxRadar's pieces on state generic substitution laws and the pharmacist's role in substitution cover the drug side, and our glossary defines interchangeable biosimilar.

Whether a particular biologic has an interchangeable version, and what a given state requires before a swap, are questions a pharmacist or prescriber can answer. For the regulatory background, see GxRadar's comparison of biosimilars and generics.

Two comment deadlines fall this month. Comments on FDA's draft strategy for interchangeable products, which summarizes a September 2025 public workshop, are due Nov. 17, 2026, according to the Federal Register notice¹⁶. Comments on renewing the biosimilar user fee program, whose current authority expires in September 2027, are due Nov. 25, a separate notice says¹⁷.