Zarxio, First Biosimilar Approved in the US, Added to FDA's New 'Purple Book'

Regulatory NewsRegulatory News | 16 April 2015 |  By 

Slowly but surely, the US Food and Drug Administration (FDA) is making quiet but substantial updates to its new "Purple Book"— a list meant to describe the degree to which a biosimilar drug is equivalent to the biologic product it references.


FDA first launched its Purple Book in September 2014 in anticipation of the impending approval of several new "biosimilar" products. The first of those biosimilars, Zarxio (filgrastim-sndz), was approved on 6 March 2015. Zarxio is a biosimilar of Amgen's cancer drug Neupogen.

The book is closely modeled off FDA's existing Orange Book, a guide containing a list of all pharmaceutical drug products approved for sale in the US after the 1938 enactment of the Federal Food, Drug and Cosmetic Act (FD&C Act). Products that have been withdrawn from sale for reasons of safety or efficacy are not contained within the Orange Book.

The Orange Book is primarily used for two purposes: to describe the therapeutic equivalence between two related products and to keep track of patent exclusivity.

For example, 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).

In addition, the Orange Book also contains a list of all approved drugs and the status of their respective patents and marketing exclusivity. This makes it easier for companies to determine when a drug may be legally marketed, assuming they do not violate any additional manufacturing or process patents.

Purple Book: Similarities and Differences

FDA's Purple Book is shaping up to be similar to FDA's Orange Book, though with some key differences.

The most obvious difference relates to the therapeutic equivalence of two products. Because it is almost impossible to create a biosimilar product that is identical to the original biologic, FDA is instead concerned with biosimilar "interchangeability"—the degree to which two biological products demonstrate the same effects on a patient.

As explained by FDA:

"Under 351(k)(4) [of the Public Health Service Act], 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, to be determined to be an interchangeable biological product, it must be shown that for a biological product that is administered more than once to an individual 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.

Gone is any mention of "therapeutic equivalence" or a range of rankings.

Instead, FDA has just two grades it will give products: Biosimilar (B) or Interchangeable (I). The latter will, in most cases, be preferable to the developer of a biosimilar. It is conceivable, however, that a biosimilar that is not interchangeable but has a higher degree of safety or efficacy than its innovator may find a "B" rating preferable.

New Change: Zarxio.

Now, in one of its first updates to its Purple Book on 15 April 2015, FDA has declared that Zarxio, the first biosimilar product to obtain approval, is biosimilar—not interchangeable.

The conclusion isn't unexpected--FDA noted as much in its approval notice for Zarxio in March 2015—but the product nevertheless has the distinction of being the first biosimilar product included in FDA's Purple Book.

It is, however, unclear whether the addition of Zarxio to the Purple Book occurred in the 15 April update or during the list's last update on 17 March 2015.

At present, FDA maintains two lists of biological products: one for products regulated as drugs by its Center for Drugs Evaluation and Research (CDER), and the other for products regulated as biologics by its Center for Biologics Evaluation and Research (CBER).

Information included on the lists includes the application number under which a drug was approved, the product's trade and nonproprietary names, the dates the product was first (or subsequently) licensed, the date a product's reference product exclusivity is set to expire (if a product is tentatively approved) and whether the product's approval has been withdrawn.

At present, FDA does not make any note of which changes it makes to its Purple Book.


FDA's Purple Book


© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy