The “Purple Book” Makes Its Debut!September 9, 2014
By Kurt R. Karst –
If you guessed that the cover of the publication listing biological products licensed under the Public Health Service Act (“PHS Act”), including licensed biosimilar and interchangeable biological products, would be “purple,” then you guessed correctly. The “Purple Book,” which is more formally known as “Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations,” and that shares a shorthand name with other government publications (see, e.g., here and here), made its debut on FDA’s website on September 9, 2014. And why purple? Is it because the cover of the printed edition of the 2014 Code of Federal Regulations is purple (see here)? No. According to FDA:
The “Purple Book” is an easy-to-remember nickname . . . . Using a color for the nickname of the list draws upon FDA’s long-held practice of using “The Orange Book” to refer to “Approved Drug Products with Therapeutic Equivalence Evaluations” . . . . Over the years, health care professionals and other stakeholders have come to use the term “Orange Book” in place of this longer, official title. FDA wanted a similarly user-friendly term for a reference listing biologics, biosimilars, and interchangeable products. During a meeting, a staff member said, “how about purple?” Ever since, we’ve called it the “Purple Book.”
Unlike the Hatch-Waxman Amendments, which require the publication of “a list” (i.e., the Orange Book), see FDC Act § 505(j)(7), as well as monthly updates to that list, the Biologics Price Competition and Innovation Act (“BPCIA”) does not require FDA to publish a list of licensed biological products, including applicable patent and non-patent exclusivities. Nevertheless, FDA has taken the initiative to create a reference guide. In fact, FDA’s decision to publish the Purple Book is not unlike FDA’s initial, pre-Hatch-Waxman decision to create the Orange Book. At the time it was created, the Orange Book contained only minimal information – see, e.g., the First Edition (1980) of the Orange Book.
As the formal name of the Purple Book says, it is a compilation of lists. Two lists in fact: (1) Center for Biologics Evaluation and Research (“CBER”) List of Licensed Biological Products; and (2) Center for Drug Evaluation and Research (“CDER”) List of Licensed Biological Products. As FDA explains:
The lists include the date a biological product was licensed under 351(a) of the PHS Act and whether FDA evaluated the biological product for reference product exclusivity under section 351(k)(7) of the PHS Act. The Purple Book will also enable a user to see whether a biological product licensed under section 351(k) of the PHS Act has been determined by FDA to be biosimilar to or interchangeable with a reference biological product (an already-licensed FDA biological product). Biosimilar and interchangeable biological products licensed under section 351(k) of the PHS Act will be listed under the reference product to which biosimilarity or interchangeability was demonstrated.
As you peruse the lists, you’ll notice that a lot of information seems to be missing. For example, there’s nothing in the “REFERENCE PRODUCT EXCLUSIVITY” or “EXPIRY DATE DATE OF FIRST LICENSURE” columns in the CBER List, and only three entries under those columns in the CDER List – for NEUPOGEN (filgrastim) (BLA No. 103353), PERJETA (pertuzumab) (BLA No. 125409), and GRANIX (tbo-filgrastim) (BLA No. 125294). Both columns are related, as FDA previously indicated in a draft guidance on Reference Product Exclusivity (see our previous post here). FDA explains these blanks in a backgrounder on the Purple Book:
Although FDA has not made a determination of the date 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 exclusivity. A determination of the date of first licensure and of when any remaining reference product exclusivity will expire for a biological product submitted under section 351(a) of the PHS Act will generally be made for reasons of regulatory necessity and/or at the request of the 351(a) application license holder.
Once a date of first licensure is determined, then FDA will presumably add that date to the Purple Book, along with any Reference Product Exclusivity (and any attached pediatric exclusivity). One type of exclusivity that is specifically not included in the new Purple Book is orphan drug exclusivity. Instead, FDA refers to the Agency’s searchable database for Orphan Designated and/or Approved Products for that information.
As an aside, we note that the exclusivity listing for NEUPOGEN, with an expiration date of “02/20/03,” resolves the question of whether or not FDA believes the BPCIA's exclusivity provisions apply to reference products licensed prior to the 2010 enactment of the law. The listing might also provide yet another clue as to how FDA will ultimately rule on a pending Citizen Petition on pre-PBCIA-licensed products (see our previous post here).
There’s no mention from FDA on how the Agency will identify Interchangeable Biological Product Exclusivity under PHS Act § 351(k)(6). That’s not surprising though. FDA has not yet approved a highly similar biosimilar product let alone approved an interchangeable biosimilar product. So, the Purple Book will ultimately need to be changed to accommodate for any such exclusivity.
Similar to the Orange Book, which includes therapeutic equivalence evaluations, the Purple Book includes (again, as the formal title of the publication states) biosimilarity or interchangeability evaluations. Those evaluations will be identified in a column titled “INTERCHANGEABLE (I)/ BIOSIMILAR (B).” According to FDA, “[b]iosimilar and interchangeable biological products licensed under section 351(k) of the PHS Act will be listed under the reference product to which biosimilarity or interchangeability was demonstrated” (emphasis added). Does this mean that FDA is more or less likely to adopt distinguishable non-proprietary names (see here) for biosimilars? The tea leaves are not clear on this point. The CBER and CDER Lists do identify products in alphabetical order by non-proprietary name – and including where a prefix is used (e.g., filgrastim and tbo-filgrastim, both of which are reference products, are not near one another) – but who knows whether that will apply throughout the lists when biosimilars are added. Hmmm . . . . Just out of the box and already a possible Purple Book controversy?