Why are there two Purple Books?
The “Purple Book” began as two lists (one for the CDER and one for CBER) that kept track of each Center’s licensed biological products. In February 2020, FDA released a searchable, online database that now replaces both lists because information about FDA-approved biological products is available in the Purple Book database. Currently, the database contains information about all FDA-licensed biological products regulated by the CDER, including any biosimilar and interchangeable biological products, licensed (approved) by the FDA and FDA-licensed allergenic, cellular and gene therapy, hematologic, and vaccine products regulated by CBER.
The Purple Book database offers information about FDA- licensed biological products. It also includes information pertaining to exclusivity if the FDA has determined that a biological product is eligible for a relevant period of exclusivity.
Will transition biological products be included in the Purple Book? If so, when?
Yes. All biological products approved in NDAs that were deemed to be BLAs on March 23, 2020 (transition biological products) are included in the Purple Book Database.
What is a reference product, biosimilar, and interchangeable product?
Under section 351(i)(4), a “reference product” is the single biological product licensed by the FDA under section 351(a) of the PHS Act against which a proposed biological product is evaluated in an application submitted under section 351(k).
Under section 351(i)(2), “biosimilar” or “biosimilarity” means that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components, and there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product.
Under section 351(k)(4), an “interchangeable” biological product is a product that has been shown to be biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. In addition, for a biological product that is administered more than once to an individual to be determined to be interchangeable, it must be shown that the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.
Please visit www.fda.gov/biosimilars for more information about biosimilar and interchangeable products.
What is reference product exclusivity?
Section 351(k)(7) of the Public Health Service (PHS) Act provides for periods of reference product exclusivity, beginning on the date on which the reference product (as that term is defined in section 351(i)(4)) is first licensed under section 351(a) of the PHS Act. Specifically, if the reference product is determined to be eligible for the periods of reference product exclusivity under this section, a 351(k) application may not be submitted for review to the FDA until the date that is 4 years after the date on which the reference product was first licensed, and approval of a 351(k) application may not be made effective until the date that is 12 years after the date on which the reference product was first licensed. For additional information on how the FDA determines first licensure and reference product exclusivity, please see the draft guidance for industry, “Reference Product Exclusivity for Biological Products Filed Under Section 351(a) of the PHS Act (PDF - 99KB).”
What does the reference product exclusivity expiration date indicate?
The reference product exclusivity expiration date indicates (1) the date that is 12 years after the date on which the reference product was first licensed as described in 351(k)(7); plus (2) any pediatric exclusivity granted pursuant to section 505(A) of the FD&C Act, if applicable. The reference product exclusivity expiration date is the date on which approval of a 351(k) application referencing the reference product may be made effective and the biosimilar or interchangeable product may be licensed, assuming it is not blocked by orphan exclusivity (or any other exclusivity) and otherwise meets the requirements for licensure under 351(k). To determine whether there is unexpired orphan exclusivity for an indication(s) for which the reference product has been previously approved, please refer to the searchable database for Orphan Designated and/or Approved Products.
For additional information on determining first licensure and reference product exclusivity, please see the draft guidance for industry, “Reference Product Exclusivity for Biological Products Filed Under Section 351(a) of the PHS Act (PDF - 99KB).”
Why is a determination of first licensure not made for every 351(a) biological product licensed and currently marketed?
Although FDA has not made a determination of first licensure for all 351(a) biological products included on the lists, it does not mean that the biological products on the list are not, or were not, eligible for reference product exclusivity. As described in the Biosimilar User Fee Act II (BsUFA II) Commitment Letter, “within 30 days after FDA determines the date of first licensure, the date of first licensure and the reference product exclusivity expiry date will be included in the Purple Book.”
How often will the list be updated?
The lists are no longer being updated. Information about FDA-licensed biological products can be found on the Purple Book Database.