September 1, 2015

The Naming Game: FDA Releases Draft Guidance, Proposed Rule on Biological Names

Arnold & Porter Advisory

On August 27, 2015, the US Food and Drug Administration (FDA) released long-awaited draft guidance1 proposing a new system for establishing nonproprietary names for all biological products, including biosimilar and interchangeable biologics. The agency also released a related proposed rule2 setting forth specific nonproprietary names (proper names) for six biologic products under its authority under section 508 of the Federal Food, Drug, and Cosmetic Act (FDCA) and section 351(j) of the Public Health Service Act (PHSA).3 Each of the six products is either a reference product for an approved or publicly disclosed biosimilar product application or a biological product that is either biosimilar to or related to one of these reference products.

The guidance and proposed rule come roughly five months after FDA announced the approval of the first biosimilar product, Zarxio® (filgrastim-sndz), manufactured by Sandoz, Inc., which was deemed biosimilar to Amgen Inc.'s Neupogen® (filgrastim). FDA approved Zarxio for the same five indications as Neupogen. Additionally, the guidance and proposed rule come after FDA opened several dockets to solicit public comment regarding biological naming,4 as well as several citizen petitions regarding this topic.5 Comments on the proposed rule and draft guidance are due November 12, 2015 and October 27, 2015, respectively.

FDA's general naming proposal, which comes after recent pressure on the agency from industry groups and Congress, largely aligns with naming conventions recommended by the World Health Organization. Specifically, FDA proposed that reference products and biosimilars have proper names6 that share a core drug substance name and, in order to better identify each product, an FDA-designated suffix that is unique for each product. For originator products, FDA intends to use a core name7 that is the name adopted by the United States Adopted Names (USAN) Council for the drug substance, when available. If the biological product is a related biological product,8 a biosimilar product, or an interchangeable product, the core name will be the name of the drug substance contained in the relevant previously licensed product.9 The suffix, which would be proposed by the applicant, would be composed of four lowercase letters. For example, as FDA outlined in a blog post, the nonproprietary name of a reference product could be replicamab-cznm, and a biosimilar to that product could be replicamab-hixf.

FDA stated that proposed suffixes should be "devoid of meaning" and should not: (1) be promotional, such as by making representations with respect to safety or efficacy; (2) include abbreviations commonly used in clinical practice in a manner that may lead the suffix to be misinterpreted as another element on the prescription or order; (3) contain or suggest any drug substance name or core name designated by the USAN Council; (4) look similar to or be mistaken for the name of a currently marketed product (e.g., should not increase the risk of confusion or medical errors with the product and/or other products in the clinical setting); and (5) be too similar to any other product's suffix designation. FDA further recommended that applicants request FDA review of a proposed suffix during the IND phase or at the time of BLA submission; otherwise, a prior-approval labeling supplement would be required.

For interchangeable biological products, FDA requested feedback from the public on whether the nonproprietary name for such a product should include a distinct suffix or should share the same suffix as its reference product (e.g., the nonproprietary name of both the reference product and the interchangeable product could be replicamab-cznm).

With respect to previously licensed products, FDA's guidance explains that the revised proper name generally would be the product's original proper name plus the designated suffix attached with a hyphen.10 The draft guidance explains that in the "near term," FDA intends to assign distinguishing suffixes to a limited group of (1) biological products that are referenced by approved or publicly announced pending biosimilar applications and (2) any related products to those reference products through rulemaking. Accordingly, FDA is seeking comment on the best approach to implement this naming convention for previously licensed products, including what criteria FDA should use to prioritize retrospective application of the proposed naming convention.

As described in greater detail in the draft guidance and proposed rule, FDA's rationale for the designation of distinguishable names in the proposed rule focused on two primary areas: (1) safe use; and (2) pharmacovigilance. Under this rationale, FDA proposed the official name designations for the six products as follows: filgrastim-bflm (BLA125553), filgrastim-jcwp (BLA 103353), filgrastim-vkzt (BLA 125294), pegfilgrastim-ljfd (BLA 125031), epoetin alfa-cgkn (BLA 103234), and infliximab-hjmt (BLA 103772). FDA stated that the addition of the suffix to the names would avoid confusion regarding the products' relationships with related products and allow originators, related products, and biosimilars to be grouped together in electronic databases, yet remain distinguishable to help health care providers identify these products.

FDA is also considering an alternative nonproprietary naming format for biological products in which the suffix attached to the core name would be derived from the name of the license holder listed on the license. Under this alternative naming format, the official names and proper names for the six products that are the subject of this proposed rule could be as follows: (1) epoetin alfa-amgn; (2) filgrastim-amgn; (3) filgrastim-sndz; (4) filgrastim-srbt; (5) infliximab-jnsn; (6) pegfilgrastim-amgn. FDA invited comments on this approach, including whether meaningful suffixes (e.g., suffixes derived from the names of the license holders) would be expected to be more memorable or useful to health care providers or patients than suffixes devoid of meaning, and therefore be more useful for facilitating the safe use and appropriate pharmacovigilance of these products. FDA also requested comment on whether meaningful suffixes derived from the name of the license holder might create inappropriate market advantages that would impede biosimilar products' acceptance in the market.11

FDA proposed that any final rule that may be issued based on this proposal would become effective 90 days after the date of its publication in the Federal Register. During the 90-day period after publication of any final rule, FDA expects that BLA holders for these six products would submit a prior approval supplement to their BLA to update the labeling of their product. After approval of the supplement, FDA intends to work with sponsors to minimize any manufacturing and distribution disruptions related to the implementation of new labeling and any related marketing materials. FDA expects that manufacturers will implement the new labeling at the time of their next manufacturing run, and the Agency does not intend to object to manufacturers exhausting existing inventories of finished product that is not labeled with the official names and proper names designated by this rule.

Although FDA is continuing to consider the appropriate naming convention for biological products, including how such a convention would be applied retrospectively to currently licensed products, FDA proposed to take action with respect to these six products because of the need to encourage routine usage of designated suffixes in ordering, prescribing, dispensing, recordkeeping, and pharmacovigilance practices for the biological products subject to this rulemaking, and to avoid inaccurate perceptions of the safety and effectiveness of biological products based on their licensure pathway.

  1. Available here.

  2. Available here.

  3. The six products constitute the sole biosimilar product licensed to date (i.e., filgrastim-sndz (BLA 125553)), and reference products for which there are approved or publicly disclosed biosimilar applications (i.e., filgrastim (BLA 103353), epoetin alfa (BLA 103234), infliximab (BLA 103772), and pegfilgrastim (BLA 125031)), as well as a biological product related to such a reference products (i.e., tbo-filgrastim (BLA 125294)).

  4. See, e.g., notices that published in the Federal Register "Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request for Comments" (75 FR 61497, October 5, 2010) and "Draft Guidances Relating to the Development of Biosimilar Products; Public Hearing; Request for Comments" (77 FR 12853, March 2, 2012) and other public dockets established by FDA.

  5. One citizen petition requested that FDA require biosimilar products to bear nonproprietary names that are similar to, but not the same as, those of their reference products or of other biosimilars (See Docket No. FDA-2014-P-0077). Other citizen petitions requested that FDA require biosimilar products to be identified by the same nonproprietary name as their reference products (See Docket Nos. FDA-2013-P-1153 and FDA-2013-P-1398).  Additionally, another citizen petition proposed a unique name for all biologics and biosimilars, such that if a biosimilar sponsor elected not to use a unique proprietary name for its product, FDA should assign a unique nonproprietary name composed of the reference product nonproprietary name supplemented with a distinguishable suffix linked to the biosimilar sponsor so that it can be differentiated from the reference product.

  6. The proper name of a biological product reflects certain scientific characteristics of the product, such as chemical structure and pharmacological properties.  This name is different from a proprietary name, which generally is trademarked and registered for private use.

  7. FDA's guidance explains that the core name is the component shared among all related biological products as part of the proper name. Two examples of a core name are filgrastim and epoetin alfa.

  8. A "related biological product" is described in the guidance as a biological product submitted in a BLA under section 351(a) of the PHSA (i.e., a "stand-alone" BLA) for which there is a previously licensed biological product submitted in a different section 351(a) BLA that contains a drug substance for which certain nomenclature conventions (e.g., USAN Guiding Principles) would be expected to provide for use of the same drug substance name. An "originator biological product" is defined as a biological product submitted in a BLA under section 351(a) of the PHS Act (i.e., a "stand-alone" BLA) for which there is no previously licensed biological product submitted under section 351(a) that is a related biological product. FDA uses these definitions for purposes of this notice.

  9. FDA explained that use of a shared core name would indicate a relationship among products. The placement of the identifier as a suffix should result in biological products with the same core name being grouped together in electronic databases to help health care providers identify these products.

  10. FDA explained that there may be limited exceptions, such as for tbo-filgrastim, which FDA proposed to change the proper name by attaching a distinguishing suffix to the core name of "filgrastim," rather than attaching a distinguishing suffix to the original proper name of "tbo filgrastim." See Section IV of the draft guidance.

  11. While FDA is proposing to designate distinguishable nonproprietary names for these six biological products, FDA explained that it is continuing to consider the issues raised by these citizen petitions and the comments submitted to the corresponding public dockets with respect to establishing a general naming convention for biological products.

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