US FDA Biosimilars Acting Director Yim ‘Not A Great Fan’ Of Suffix-Based Naming Policy
Executive Summary
Whether one accepts the view that concerns about active pharmacovigilance and the need to distinguish small molecules from biologics support the controversial nomenclature system is ‘a personal thing,’ Sarah Yim says.
The US Food and Drug Administration’s biosimilars naming policy, which has faced harsh criticism from some external stakeholders, has its internal skeptics as well, including the new acting director of the agency’s biosimilars office.
Sarah Yim, acting director of the Office of Therapeutic Biologics and Biosimilars, said at the Food and Drug Law Institute’s annual conference on 2 May that she has her doubts about the need for the suffix-based nomenclature system currently in effect for all biosimilars and newly approved novel biologics.
“I have to tell you personally that I am one of those people that is not a great fan of the naming convention,” Yim said during a panel discussion on the regulatory and legal landscape for biosimilars and biologics.
“I am one of those people that is not a great fan of the naming convention.” – Sarah Yim
Yim, an agency veteran, took over as acting head of the Center for Drug Evaluation and Research’s biosimilars program in late February upon the departure of Leah Christl, who left to join Amgen Inc. (Also see "FDA Biosimilars Chief Leah Christl Joining Amgen; Agency Veteran Sarah Yim Takes Her Place" - Pink Sheet, 3 Feb, 2019.)
“I had to really dig into the rationale to try to understand why is it that we’re doing the naming convention, because I personally felt like we have so many different identifiers for these products and none of them seem to work super well for pharmacovigilance or super consistently, so … how is this going to be different?”
Yim’s views put her in the awkward position of having to enforce a naming policy that she inherited – and one that has been strongly defended by agency leadership as necessary for pharmacovigilance purposes – but for which she is not enthusiastic. (Also see "Suffix Smackdown: Gottlieb Calls Issue 'Red Herring' For Biosimilars" - Pink Sheet, 18 Jul, 2018.)
Policy Established Two Years Earlier
Yim’s arrival in the biosimilars office came more than two years after the FDA finalized a guidance reiterating its view that all biosimilars, as well as new novel biologics, should carry a distinguishable, four-letter suffix devoid of meaning in their nonproprietary names. (Also see "Biologic Product Naming: US FDA Sticks With Suffixes ‘Devoid Of Meaning’" - Pink Sheet, 12 Jan, 2017.)
FDA asserted the suffix-based system was needed for pharmacovigilance purposes. However, some biosimilar developers, the Federal Trade Commission, insurers and pharmacy groups opposed the approach, saying that existing pharmacovigilance systems are adequate to distinguish safety concerns among biosimilars and their reference products, and the new naming convention would cause confusion, harm biosimilar uptake and increase costs. (Also see "FDA Biosimilar Naming Proposal Pits Providers, Patients Against Insurers, Pharmacies" - Pink Sheet, 16 Nov, 2015.)
Among those in the biopharma industry and health care professional groups who supported suffixes, there was strong opposition to the agency’s view that they should be devoid of meaning. (Also see "FDA's Biologics Naming Plan: Industry Wants 'Memorable' Suffixes" - Pink Sheet, 9 Nov, 2015.)
All 19 biosimilars approved to date by the FDA carry a four-letter suffix, and the agency began adding the suffixes to the names of newly approved biologics beginning in November 2017. (Also see "First Three Novel Biologic Suffixes Came Courtesy Of US FDA, Not Sponsors" - Pink Sheet, 26 Jan, 2018.)
The final guidance also called for suffixes to be retrospectively added to existing products – a policy measure that some pharmaceutical sponsors and numerous other stakeholders across the health care industry said would be burdensome and cost prohibitive. (Also see "FDA’s Burden Estimate On Biologic Naming Ignores Downstream Costs, Critics Say" - Pink Sheet, 16 Feb, 2017.)
Policy Reversal Avoids Undue Burden
Shortly after Yim’s arrival in the biosimilars office, the agency released a new draft guidance exempting previously approved biologics from having to add the suffix. (Also see "Policy Reversal: FDA Will No Longer Require Suffixes For Older Biologics" - Pink Sheet, 7 Mar, 2019.)
The agency decided against adding suffixes to names of existing biologics because “we heard all the comments, and we believe that the updated policy avoids undue burden associated with the retrospective application of the naming convention,” Yim said. “We also felt that use of the suffix on the already-licensed products was not necessary to achieve the goals of safe use and pharmacovigilance.”
Center for Drug Evaluation and Research Director Janet Woodcock has defended the policy reversal, saying biosimilar developers’ concerns about inequitable treatment in product naming are detached from the reality of what prescribers and patients really care about when it comes to using the products. (Also see "Woodcock: Concerns About US FDA's Biosimilars Suffix Policy Detached From Reality" - Pink Sheet, 20 Mar, 2019.)
The new guidance also states that certain protein products that will transition from regulation as drugs to biologics in March 2020 also need not add suffixes to their proprietary names. In addition, the FDA is reconsidering its previous view that suffixes are needed for vaccines.
The agency’s current policy has resulted in a mixed bag of nomenclature formats for biologics, largely depending upon a product’s date of approval and regulatory pathway.
Story continues after chart...
Daniel Kracov, a partner in the Washington, DC office of Arnold & Porter Kaye Scholer, said that he, too, was skeptical of the need for suffixes but thinks the current policy is “a reasonable place for the agency to land.”
“I’m kind of in the same place that you are on that issue in that I can understand the rationales on both sides,” Kracov told Yim. “I think that there’s some value to having, for newer products … a suffix to tell them apart for pharmacovigilance and other reasons.
“I am somewhat sympathetic to the notion that it doesn’t necessarily make a whole lot of sense, if we have other mechanisms, to retitle every existing approved biologic product. It seems like a lot of work, and I understand that those who’ve run the numbers think it could be quite costly.”
“We may find at a later date, ‘Gee, wouldn’t it have been good to have suffixes for older products.’ But I think that there’s a legitimate rationale for saying let’s do this prospectively.” – Daniel Kracov
Panel moderator Freddy Jimenez, vice president of law and compliance at Celldex Therapeutics, questioned whether the FDA has a way of evaluating the impact of a suffix-based system and “when do you sort of cry ‘uncle’ and say we’re going to move onto something else?”
“I think we need to have data to really determine what the impact of the suffix actually is,” Yim said. “We are actively looking at the effectiveness of it. Obviously, it’s still early right now, so it’s going to take some time before we see how well it’s been implemented, how thoroughly it’s been implemented, and whether we can actually do any good pharmacovigilance with it. But that is our plan to assess that via studies.”
A Pink Sheet review in fall 2018 found that biosimilars had been identified by their brand names in almost every adverse event report received by the US FDA. (Also see "Biosimilar Suffixes Appear Superfluous In Adverse Event Reporting" - Pink Sheet, 10 Oct, 2018.) However, this trend could change over time as providers become more comfortable with the naming convention for biosimilars and more data are collected.
“My perspective is you’ve got to make some tradeoffs and that’s essentially what the agency is doing with this recent change of approach,” Kracov said. “We may find at a later date, ‘Gee, wouldn’t it have been good to have suffixes for older products.’ But I think that there’s a legitimate rationale for saying, 'Let’s do this prospectively.' … If we’re worried about pharmacovigilance, I’m more worried about new biologics, new biosimilars, etc., interchangeable products eventually, as opposed to products where we have a large database” of safety and real-world experience. “I think there’s some logic to making a distinction like that.”
When the FDA approves a biosimilar, the agency is “pretty confident” there is not going to be a difference in efficacy or safety between a biosimilar and its reference product, Yim said. “My understanding with the suffix is that we really just wanted to have a way to capture the manufacturer so that we could squelch any concept that there might be a difference between the biosimilar and the reference product.”
“Obviously people sort of might take that in a different way now that reference products don’t have a suffix and biosimilars do have a suffix,” Yim said, adding, however, this perception will be diluted as more novel biologics are approved with their own suffixes.
Two Primary Reasons For Suffixes
Yim said after digging into the issue, she could find two main reasons supporting the use of a suffix-based system: active pharmacovigilance, and distinguishing between drugs and biologics.
With active pharmacovigilance, “a lot of the queries use private electronic health care systems, and those often use administrative and billing databases and for those they often just use nonproprietary names, because they don’t really care about the manufacturer in those systems,” Yim said. “They just care about the medicine because it’s just for administration and billing.”
The second reason identified by Yim was the need to distinguish between small molecules and biologics for medication error purposes, because “as we get more and more classes of biologics out there, it’s going to be more difficult to tell the difference between a small molecule and a biologic.”
“For example, right now you can tell the mabs pretty easily … you can tell a fusion protein,” she said. But, “as we have more and more classes of biologics, pretty soon it’s going to be difficult to tell which ones are biologics and which ones are small molecules.
“Why does that matter? That may matter because generics obviously are interchangeable, they’re substitutable at the pharmacy level. And for our [biosimilar] pathway, that is not automatically the case,” Yim said. “It sort of, I guess in some folks’ minds, helped to have something that would enable folks to tell the difference in nonproprietary names between biologics and nonbiologics.”
“Whether you believe that’s a sufficient rationale or not is a personal thing,” Yim said, “but that is what I could see that somewhat justifies use of a nonproprietary naming convention.”