FDA will distinguish most innovator biologics and biosimilars with a suffix added to their nonproprietary name, but the long-awaited plan leaves some important questions unanswered.

The agency intends to add the four-letter code to newly approved biologics as well as already-approved products.

A draft guidance released Aug. 27 outlines the agency proposal and reasoning. It was accompanied by a proposed rule implementing it for six products, including the first FDA-approved biosimilar, Sandoz Inc.’s Zarxio (filgrastim-sndz) along with its reference product, Amgen Inc.’s Neupogen (filgrastim).

The naming plan does not apply to biologics that have a proper name provided in federal regulations or certain biologic categories where “there are well-established, robust identification and tracking systems to ensure safe dispensing practices and optimal pharmacovigilance,” such as the ISBT 128 coding and labeling system for blood products.

The agency wrote in the draft guidance that the distinguishable names are intended to enhance pharmacovigilance efforts. It also should help prevent confusion among providers and dosing errors, especially since some biosimilars may not be approved for all of the stated indications of their reference products.

FDA said that requiring all biologics to have a distinguishable name will ensure the suffix does not gain a negative connotation.

“FDA anticipates that use of proper names with designated suffixes for biological products, irrespective of licensure pathway and date of licensure, will avoid any inaccurate perceptions of their safety and effectiveness,” the agency said in the guidance.

Janet Woodcock, director of the Center for Drug Evaluation and Research, also told stakeholders during a briefing on the guidance and proposed rule that the agency did not want multiple naming systems lingering once the new proposal goes into effect.

“We don’t want to have two different naming conventions with a sudden break for biological products,” she said. “We think it would be best for them to be uniform.”

FDA wants sponsors to request a proper suffix (see sidebar).

[Sidebar#14150827003]

Debate about whether biosimilars should have the same name as their reference product or a unique name now appears to be settled. FDA seems to have staked out a middle ground in the argument.

If all products have suffixes, innovator sponsors cannot market their products as preferable to a biosimilar because they don’t have a suffix. And biosimilar sponsors cannot market their products like small molecule generics because they share the nonproprietary name.

Kay Holcombe, senior VP of science policy at the Biotechnology Industry Organization, said in a statement that the organization was “encouraged by the FDA’s proposal to include a unique suffix” because distinguishing the products would prevent inappropriate substitution and facilitate post-marketing surveillance.

The Biosimilars Forum, a group of biosimilar sponsors, applauded FDA for “reinforcing within the proposed regulation the approach that each biosimilar is a unique drug.” The group said in a statement that the guidance strengthens its argument that biosimilars should have separate CMS J-codes.

CMS has indicated that it may place all biosimilars under the same J-code as their reference products ([A#14150507004]).

Bertrand Liang, chairman of the Biosimilars Council, part of the Generic Pharmaceutical Association, said in a statement that FDA’s proposal warrants “serious scrutiny” for its “potential to erect barriers to patient access to new, more affordable medicines, and jeopardize their safety.”

The council favors biosimilars sharing their reference product’s nonproprietary name and said adding a suffix “confers no additional safety benefit, and in fact would require the healthcare professional to be armed at all times with a code-breaking reference.”

Anticipation of the naming convention’s release escalated when the Office of Management and Budget completed its review of the proposed rule ([A#14150826001]).

The US Adopted Names Council, of which FDA is a member, also released a statement recently supporting a suffix-like proposal made by the World Health Organization. It was another clue of FDA’s decision ([A#14150826002]).

Filgrastim Harmonization

A number of questions remain to be answered, both related to the overall naming policy and specifically for the products changing names in the proposed rule.

The proposed rule announces the new names for Zarxio and Neupogen as well as for Amgen’s Epogen and Procit (epoetin alfa) and Neulasta (pegfilgastim), Janssen Biotech Inc.’s Remicade (infliximab), and Sicor Biotech’s Granix (tbo-filgrastim).

FDA intends to drop the prefix from the Granix nonproprietary name, change the suffix for Zarxio, as well as add random suffixes to the other products (see chart).

Proposed Biologic Nonproprietary Name Changes
Product	Sponsor	Existing Nonproprietary Name	Proposed New Nonproprietary Name
Neupogen	Amgen	Filgrastim	Filgrastim-jcwp
Zarxio	Sandoz	Filgrastim-sndz	Filgrastim-bflm
Granix	Sicor Biotech	Tbo-filgrastim	Filgrastim-vkzt
Neulasta	Amgen	Pegfilgrastim	Pegfilgrastim-ljfd
Epogen and Procrit	Amgen	Epoetin alfa	Epoetin alfa-cgkn
Remicade	Janssen Biotech	Infliximab	Infliximab-hjmt
Source: FDA proposed rule

The agency said in its description of the regulation that assigning suffixes to all filgrastim products will help “avoid a potential inaccurate perception that filgrastim-sndz, or any other biosimilar product that may be licensed in the future, differs in a clinically meaningful way from its reference product or is inferior for its approved conditions of use.”

FDA also said that although the existing nonproprietary names for Granix and Neupogen separate the products from Zarxio, “the addition of a distinguishing suffix to both names, and the elimination of the prefix from tbo-filgrastim, would avoid confusion regarding these products’ relationships to one another” and Zarxio.

The new proposed suffix for Zarxio, “-bflm” is the same that FDA recommended during its review of the product. But Sandoz wanted a suffix that was meaningful and the two sides settled on the “-sndz” suffix.

However, the nonproprietary name was considered a placeholder at the time of approval until a naming policy was completed ([A#00150427010]).

Zarxio Could Retain Existing Suffix

FDA is not completely sold on the suffixes it proposed in the regulation, or using random letter combinations.

It offered several cleared alternative suffixes in the proposed rule that it considered devoid of meaning and may be acceptable. One for filgrastim, “-zbdt” was among the suffixes offered to Sandoz during the Zarxio review.

In addition, the agency said it also is considering using suffixes indicating the product sponsor, just as it had with the Zarxio placeholder name. In fact, the proposed sponsor-derived alternative suffix for Zarxio is “-sndz,” the suffix the product now carries (see chart below).

FDA asked stakeholders in the proposed rule to comment on the benefits and challenges to using randomly generated and meaningful suffixes. The agency also wants to know whether meaningful suffixes “might create inappropriate market advantages that would impede biosimilar products’ acceptance in the market,” according to the proposed rule.

“We’re trying to figure out a way to distinguish these that is clear and that is usable and yet isn’t either completely opaque to people or completely impossible to use,” Woodcock said during the stakeholder briefing.

When agency officials added the suffix to the Zarxio nonproprietary name, they wanted to distinguish it from Neupogen, but also ensure that the products were grouped together in provider databases. There also were concerns about provider confusion should the two products carry the same nonproprietary name ([A#00150427012]).

Interchangeability Questions Outstanding

The Federal Register notice announcing the guidance, which is scheduled to be published Aug. 28, includes a number of other questions.

Among them is whether there are benefits or problems if the product suffix is changed once a biosimilar is determined interchangeable.

FDA has not made a decision on what suffix an interchangeable product would receive.

Once a determination of interchangeablity is made, considered a higher standard than approval, the biosimilar could be substituted for the reference product.

The agency said in the draft guidance that an interchangeable product could retain its existing suffix (assuming it already is an approved biosimilar) or be given the same name and suffix as its reference product.

FDA asked for comments on both ideas.

Interchangeability is highly coveted by biosimilar sponsors and it is expected that applications could arrive before FDA issues guidance on how to receive the status ([A#14150422002]).

FDA-Proposed Alternative Suffixes
Product	Non-meaningful Alternative	Sponsor-Based Alternative
Neupogen	Unspecified*	Filgrastim-amgn
Zarxio	Unspecified*	Filgrastim-sndz
Granix	Unspecified*	Filgrastim-srbt
Neulasta	Pegfilgrastim-vjbk	Pegfilgrastim-amgn
Epogen and Procrit	Epoetin alfa-mkdv	Epoetin alfa-amgn
Remicade	Infliximab-djfg	Infliximab-jnsn
FDA included three alternative filgrastim suffixes (-gknh, -kbhj, and -zbdt) but did not designate them for a particular product. Source: FDA proposed rule*

FDA Biosimilar Naming Policy Takes Middle-Of-The-Road Approach

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