sábado, 29 de agosto de 2015

FDA Law Blog: FDA Semi-Decides the Biosimilar Naming Issue; Issues Draft Guidance and a Proposed Rule

FDA Law Blog: FDA Semi-Decides the Biosimilar Naming Issue; Issues Draft Guidance and a Proposed Rule

Posted: 28 Aug 2015 01:42 AM PDT
By James C.  Shehan –

On August 27, 2015, FDA published its much–anticipated views on the non-proprietary naming of biological products.   Set forth in a proposed rule, a draft guidance, and a blog post, FDA proposes that a four letter suffix “devoid of meaning” be part of the name of all biological products, including reference products and biosimilar biologics.  The proposal solicits public feedback on whether in the alternative the suffix should not be meaningless but instead be derived from the name of the license holder.  The proposal also states that the four letter suffix will be different for each product except perhaps interchangeable products.  For interchangeable products, FDA declines to make a naming decision but instead solicits feedback on two alternatives: whether interchangeable products should also have distinct suffixes or share the same one.   By largely taking the position advocated by the makers of reference products, the proposal has already elicited negative comments in some quarters.

How a biosimilar should be named has been one of the hottest issues in biosimilars (see our previous posts hereherehere, andhere), despite it being an issue upon which the BPCIA is silent.  Advocates for unique non-proprietary names insist that they are necessary to ensure safety, accurate adverse event reporting and the preservation of physician and patient choice.  On the other hand, advocates for use of the same name argue that the safety and pharmacovigilance concerns are minimal and that different names will be a major barrier to marketplace acceptance of biosimilars.  The European Union long ago decided that distinct names were necessary, and the issue has been squarely in front of FDA since the BPCIA’s passage.   In addition, FDA has on two occasions approved biologics with unique non-proprietary names: (1) tbo-filgrastim for a Teva product approved before the BPCIA was passed; and (2) filgrastim-sndz, approved in March for Sandoz’s Zarxio but with a specific FDA notation that the non-proprietary name was a placeholder subject to change.

The draft guidance leads off with a simple summary of the Agency’s position: “FDA’s current thinking is that shared nonproprietary names are not appropriate for all biological products. There is a need to clearly identify biological products to improve pharmacovigilance and, for the purposes of safe use, to clearly differentiate among biological products that have not been determined to be interchangeable.”  FDA further explains that it hopes to avoid “inadvertent substitution” of products, facilitate pharmacovigilance “when other means to track a specific dispensed product are not readily accessible,” encourage routine use of suffixes in ordering, prescribing, dispensing, and recordkeeping,  and “avoid inaccurate perceptions of the safety and effectiveness of biological products based on their licensure pathway.”

Under the new system, FDA’s naming convention for biological products will be to assign a proper name that will include a “core name” and a designated suffix.  For originator biological products, FDA will make the core name the name adopted by the USAN Council  for the drug substance.  For other biological products (e.g., “related,”  biosimilar, and interchangeable products), the core name will be the name of the drug substance contained in the relevant previously licensed product.

FDA believes that use of a shared core name will indicate a relationship among products.  FDA chose to use a suffix instead of a prefix so that products with the same core name will be grouped together in electronic databases and thereby to help health care providers identify products.

FDA intends to apply this naming convention to both newly licensed and previously licensed biological products.

A few products will be exempt: biological products for which a proper name is provided in the regulations (e.g., 21 C.F.R. part 640), and “certain categories of biological products for which there are well-established, robust identification and tracking systems to ensure safe dispensing practices and optimal pharmacovigilance (ISBT 128 for cord blood products).”  For previously licensed products, in most cases FDA will simply attach a hyphen and the four letter suffix to the product’s original proper name, one exception being the tbo-filgrastim product mentioned earlier, which will lose its prefix and gain a suffix.

As for the selection of those suffixes “devoid of meaning,” for new products FDA wants the sponsors of full BLAs to propose a suffix during the IND phase.  For existing products, FDA is considering the most effective regulatory approach and intends to provide will provide additional information.  In the near term, however, FDA is using the proposed rule to assign distinguishing suffixes to six products, including the Amgen, Teva and Sandoz filgrastims, Neulasta, Epogen, Procrit and Remicade.  These products were selected because either they are referenced by approved or publicly announced pending biosimilar applications, or are related products to those reference products.  FDA advises applicants for new biosimilar products to also propose a four letter suffix.

FDA mandates that the proposed suffix should be four lowercase letters, be unique and be “devoid of meaning.”  The proposed suffix should not be promotional, “such as by making misrepresentations with respect to safety or efficacy,” not include abbreviations commonly used in clinical practice and therefore subject to misinterpretation,  not contain or suggest any drug substance name or core name, not look similar to the name of a currently marketed product or to any other product’s suffix.  FDA encourages applicants to conduct due diligence on their proposed suffixes.

FDA’s non-decision on interchangeables is set forth very simply:

FDA intends to apply the naming convention described in this guidance to interchangeable products licensed under section 351(k) of the PHS Act in an original application or a supplement and is considering two alternative approaches:

1. Distinct from the reference product: An applicant for a proposed interchangeable product submitted in an original application under section 351(k) of the PHS Act would propose a unique suffix composed of four lowercase letters for use as the distinguishing identifier included in the proper name designated by FDA at the time of licensure (see section V of this guidance). An applicant seeking a determination of interchangeability in a supplement to its 351(k) application would keep the existing suffix.

2. Shared with the reference product: An applicant for a proposed interchangeable product submitted in an original application or a supplement under 351(k) of the PHS Act would be assigned the same proper name and suffix as its reference product.
FDA's proposal elicited at least one immediate negative reaction.  In a statement, Dr. Bertrand C. Liang, Chairman of the Biosimilars Council (a division of GPhA), stated: “The FDA’s proposals today on naming conventions for biosimilars warrant serious scrutiny for their potential to erect barriers to patient access to new, more affordable medicines, and jeopardize their safety.  Because the Biosimilars Council shares the agency’s deep commitment to patient safety, we believe that biologics and biosimilars should be required to have the same International Nonproprietary Name (INN) with no added 'FDA-designated suffix.'”

The comment period on the draft guidance is open for 60 days, and the comment period on the proposed rule is open for 75 days

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