In Major Move on Biosimilar Interchangeability, FDA Establishes New 'Purple Book'

Posted 09 September 2014 By Alexander Gaffney, RAC


In a landmark move, the US Food and Drug Administration (FDA) has published its first-ever edition of the "Purple Book," a new list of licensed biological products and interchangeable biosimilars that is meant to be the biological equivalent of the pharmaceutical "Orange Book."


FDA's Orange Book is widely used in the regulatory community (and by doctors) for identifying which drug products are substitutable for one another.

The book contains all pharmaceutical drug products that are approved or have not been withdrawn for reasons of safety or efficacy with the exception of products marketed before 1938 (pre-Federal Food, Drug And Cosmetic Act) or products approved solely on the basis of their safety (such as those approved through FDA's Drug Efficacy Study Implementation).

The book's usefulness comes down to two main points: as a listing for therapeutic equivalence, and for patent exclusivity.

To the former, many state laws only allow generic substitution for products contained within the Orange Book and known to be therapeutically equivalent.

To that end, the book identifies products that are both therapeutically equivalent and therapeutically similar. Products that are coded as "A" (AA, AN, AO, AP, AT or AB) are known to FDA to be therapeutically equivalent, having no known or unresolved bioequivalence issues.

Products that are coded in the Orange Book as "B" (BC, BD, BE, BN, BP, BR, BS, BT, BX) are not therapeutically equivalent, and either have bioequivalence issues that are known or issues that remain unresolved (but potentially resolvable, which would allow them to be coded as AB).

To the latter point of patents, each product is also associated with the name of the holder of the application, as well as the status of the patent and market exclusivity status of the drug.

The lists are updated on a monthly basis, and FDA also publishes comprehensive yearly editions of the book.

Introducing the Purple Book

Now, FDA is adding a new edition known as the Purple Book, which, like the Orange Book, will seek to answer questions about the interchangeability of products.

That, as Regulatory Focus has reported on extensively, is shaping up to be one of the most pressing issues associated with the approval of biosimilar products.

Due to manufacturing differences, biosimilar products are not exactly the same as the products they aim to replicate.  While FDA's regulatory processes are intended to ensure that an approved biosimilar product is therapeutically similar or the same as a reference biologic product, many regulatory experts have expressed concern about how companies will be able to illustrate interchangeability without extensive testing.

To date, FDA has indicated that it will advance a four-part standard for biosimilar interchangeability:

  • not similar
  • similar
  • highly similar
  • highly similar with a fingerprint-like similarity

Purple is the New Orange

And now, just weeks after receiving two applications for approval for biosimilar products (Zarzio and Remsima), FDA is for the first time releasing a look at its Purple Book.

The book, which is actually split up into two parts—one for products approved by the Center for Drug Evaluation and Research (CDER), and the other for products approved by the Center for Biologics Evaluation and Research (CBER)—is meant to convey key pieces of information.

Information in the Purple Book includes:

  • The BLA number
  • Product Name
  • Proprietary Name
  • Date of Licensure
  • Date of First Licensure
  • Reference Product Exclusivity Date
  • Interchangeable or Biosimilar
  • Withdrawn

FDA's use of the terms "interchangeable" and "biosimilar" seems to be important, as it implies the agency will not automatically consider all products approved through the 351(k) biosimilar pathway to be interchangeable. The catch-all term for non-interchangeable biosimilar products, it seems, will just be "biosimilar."

The agency has not yet explained if it will maintain a range of "interchangeable" rankings, similar to the way it grades drugs in the Orange Book.

For now, the Purple Book is sparse, reflecting the lack of biosimilar products now on the US market. But with two biosimilar products now approaching approval, and many other products on their way, FDA's new book may soon see plenty of updates.


FDA Purple Book Announcement

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Categories: Biologics and biotechnology, Labeling, Regulatory strategy, News, US, CBER, CDER

Tags: Purple Book, Orange Book, Biosimilarity, Biosimilar, Biosimilars, Interchangeability, Biosimilar Interchangeability

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