Game of Thrones: FDA is Once Again Petitioned on Biosimilar Naming; Novartis Wants Shared INNsOctober 31, 2013
By Kurt R. Karst –
The forces backing implementation of an FDA policy under which biosimilar biological products, licensed under Section 351(k) of the Public Health Service Act (“PHS Act”) as added by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), and their brand-name reference product counterparts share the same International Nonproprietary Name (“INN”) are mustering, as the civil war for a modern day (and nonfictional) Iron Throne grows. Meanwhile, a cold wind blows in from the icy North; and Daenerys Targaryen exclaims “Where are my DragINNs?” (Thanks for that last one @AlecGaffney!)
That’s the scene we envision as we watch the debate over biosimilar naming grow. And grow it has. For the second time in as many months – and for the third time overall – FDA has been asked in a Citizen Petition to address biosimilar naming. The latest Citizen Petition, submitted to FDA earlier this week by the Novartis Group of companies (“Novartis”), follows a September 2013 Citizen Petition (Docket No. FDA-2013-P-1153) from the Generic Pharmaceutical Association (“GPhA”) supporting shared biosimilar and reference product INNs (see our previous post here), and a June 2013 Citizen Petition (Docket No. FDA-2013-P-0776) from the Biotechnology Information Institute saying that “FDA must assign both unique and biosimilar/(bio)generic-type non-unique names for finished products and their active agents.” The Novartis petition, like the petition from GPhA, requests that FDA require that a biosimilar be identified by the same INN as the reference product it relies on for approval.
Novartis nicely sums up the current debate and dialogue in a single paragraph:
The BPClA is appropriately silent about the nomenclature FDA should apply to biosimilars, as such nomenclature should be self-evident from FDA’s current practice. Nevertheless, the question of whether biosimilars should share an [INN] with their reference product has been the subject of much public debate. Such debate has confused the concept and current utilization of INN by departing from the INN’s intended purpose of facilitating the identification of pharmaceutical substances. Instead the current dialogue has implied that the INN is intended to facilitate the identification of a specific product. This implication is untrue and has resulted in confusing an otherwise straightforward issue. Many products, including biologics, currently marketed in the United States share INNs [(see Table 1 attached to the Novartis petition)]. But INNs are not, and cannot be, the only or even the primary tools used for tracking and tracing. Indeed, despite their shared INNs, these products have been successfully traced for pharmacovigilance purposes.
The petition goes on to make several noteworthy points. Referencing a 2006 policy paper (included as an attachment to the Novartis petition) FDA sent to the World Health Organization (“WHO”) stating, in part, that “INNs should not be used to differentiate products with the same active ingredient(s) when credible scientific data demonstrate that no pharmacologically relevant differences exist,” Novartis comments that:
assigning unique INNs to biosimilars that FDA concurs are highly similar to a reference product would imply that INNs are intended to communicate more than just molecular characteristics and a pharmacological class. It would imply that INNs are intended to communicate an aspect of the regulatory status itself, such as interchangeability or lack thereof.
But this has not been FDA’s historical position, says Novartis:
Indeed, many biologic products on the market today share INNs even though they have never been compared directly to each other, and should a demonstration of “sameness” be required by FDA retrospectively today, many of these products would fail to meet it. Nevertheless, and most importantly, the fact that these products share INNs has not resulted in any safety issues being identified.
Assigning different INNs to biosimilar versions of reference products would result in several problems, posits Novartis:
[It] would introduce unnecessary confusion into the health care system and could unintentionally communicate increased caution, unfounded risk, or other regulatory reservations that are purely hypothetical. Significantly, it would put into question years of FDA’s practice of using the well-established analytical standard of high similarity to approve major manufacturing changes of originator biologic products without a parallel change in the originator INN, despite the fact that the manufacturing changes have altered, sometimes substantially, the originator biologics’ molecular structures. . . . Requiring separate INNs for biosimilars but not originator biologics would undermine FDA’s own approval decisions, which in both cases require FDA’s determination that the compared product (biosimilar or the post-manufacturing change originator biologic) produces the same clinical outcomes as its comparator (respectively, the reference product or the pre-manufacturing change biologic).
Novartis submits that imposing unique INNs on biosimilars would not improve any aspects of patient safety, pharmacovigilance or tracking, and would instead undermine the safe use of all biologics by introducing unfounded confusion into the health care system.
The Novartis petition comes on the heels of the WHO’s 57th Consultation on INNs for Pharmaceutical Substances at which biosimilar naming was the topic du jour, as well as a recent letter from several Members of Congress supporting shared INNs for biosimilars and their reference products.
Letters of support for shared INNs came from several sectors ahead of the WHO meeting. Hospira’s Senior Vice President and Chief Scientific Officer, Sumant Ramachandra, M.D., Ph.D., authored a paper, titled “WHAT’S IN A NAME? The Importance of Biosimilar Nonproprietary Names for Healthcare Innovation,” saying that “[i]t is imperative that the [WHO], U.S. Pharmacopeia (USP), the FDA and other international regulatory bodies support the use of the same nonproprietary names for original biologics and biosimilars.” Why? Because “using a different nonproprietary name for a biologic and the biosimilar product modeled from it will create confusion among the clinicians who rely on international and local standards to fill prescriptions for patients,“ and different INNs “may impede access to the annual $20 billion savings—in just the U.S. alone—that biosimilars have been estimated to deliver,” according to Dr. Ramachandra. In addition, a joint letter from the American Pharmacists Association, the National Association of Chain Drug Stores, and the National Community Pharmacists Association urges the WHO to adopt a shared naming policy, saying that “[t]he use of different INNs would increase the burden of being able to distinguish which products are biosimilar and interchangeable with which reference product and may pose difficulties in recognizing the best alternative product for therapeutic use in a timely manner. Such confusion may lead to medication errors.”
In an October 23, 2013 letter to FDA Commissioner Margaret Hamburg, six U.S. Senators (both Republicans and Democrats) share their concerns on biosimilar naming and urge FDA to adopt a shared naming policy, saying that “[i]f biosimilars are unable to share the same active ingredient name as the brand originator product, we believe the Congressional intent behind the BPCIA would be undermined as would the safely and accessibility of affordable biosimilars.” The Senators also question the removal of the above-referenced 2006 FDA statement to the WHO from the Agency’s website:
It was brought to our attention that the FDA has removed its 2006 statement on naming from its website. Does the removal of this statement indicate that the fDA is considering a change to its position on naming? If so, we ask that the FDA provide a briefing for our staff on this topic in advance of any changes. In particular, we would like to know what factors led to the agency’s decision to reevaluate this policy and what outreach the FDA has done to consumers, pharmacists and others to inform its assessment.
Just a few days later, the Biotechnology Industry Organization (“BIO”) issued a statement addressing the October 23rd letter. According to BIO, which “strongly opposes naming products in a way that will create confusion for physicians and patients and will hinder effective pharmacovigilance,” “Congress left it to the experts at FDA to make the decision about product names – as the agency does for every other product. Reserving this to FDA will allow for thorough consideration of technical, scientific and patient safety issues involved.”