This post, Part III, of a three-part series (Part I and Part II) on FDA’s interchangeability draft guidance highlights a number of open issues that stakeholders have identified in their comments to FDA. These include the naming and labeling for interchangeable products as well as the relationship between multiple interchangeable products for the same reference product. Biosimilar makers also wanted FDA to make clear that physician-mediated switching is possible for non-interchangeable biosimilar products even if pharmacy-level substitution is not. A number of patient groups, by contrast, expressed concern that payers were in effect mandating pharmacy-level substitution for non-interchangeable biosimilars by taking innovator products off formularies.
President Donald J. Trump has now been in office for just over one hundred days. Observers have been quick to mark this milestone and assess the new administration’s performance, especially on headline-grabbing issues like immigration and foreign policy. Amidst the hubbub, however, few have commented on how President Trump’s opening moves could affect the multi-billion-dollar biologics industry. President Trump’s actions during his first hundred days on issues like trade, judges, and healthcare have the potential to shape the biologics industry for innovators and biosimilar makers alike for years to come.
Despite nearly universal opposition from both biosimilar makers and innovator companies, FDA has issued final guidance adopting its controversial August 2015 proposal for naming biologics. Under the guidance adopted by FDA, the nonproprietary name of a biologic will consist of the core nonproprietary name of the originator product plus a meaningless but distinguishable suffix of four lowercase letters unique to each product.
On August 30 FDA approved Sandoz Inc.’s biosimilar of Enbrel (etanercept), Amgen Inc.’s blockbuster biologic for treatment of moderate to severe rheumatoid arthritis and a number of other autoimmune conditions. The biosimilar, Erelzi (etanercept-szzs), is the third biosimilar approved for marketing in the US under the Biologics Price Competition and Innovation Act of 2009 (BPCIA). Erelzi has been approved for all of Enbrel’s indications and is the first U.S. biosimilar of etanercept.
Last year, FDA published a draft guidance recommending that the nonproprietary names of biologics, including biosimilars, should consist of “core names” along with unique suffixes that are “devoid of meaning.” In a recent notice in the Federal Register, FDA stated that it will allow biologics sponsors to submit ten suggested suffixes for their products under FDA’s proposed naming scheme. This new recommendation represents a change from last year’s guidance, which invited sponsors to submit three suggested suffixes.
A 70-group coalition of healthcare stakeholders urged the FDA to incorporate meaningful and therefore memorable suffixes into its distinguishable naming system for biological medicines to provide strong patient protections and provider confidence. The coalition emphasized that “meaningful suffixes are easier for patients, providers and pharmacists to both recognize and remember, thus facilitating accurate association between adverse effects and specific products.” The coalition explained that meaningful suffixes based on the name of the manufacturer, such as the “sndz” suffix used for the first approved biosimilar, Sandoz’s Zarxio (filgrastim-sndz), instead of the random suffixes proposed in FDA’s most recent draft guidance and used for the first time in FDA’s recent approval of a second biosimilar, Celltrion and Pfizer’s Inflectra (infliximab-dyyb), would promote manufacturer accountability. Notably, FDA used a random suffix for the nonproprietary name of Inflectra despite widespread criticism by innovators and biosimilar makers alike of FDA’s naming approach.
On April 5, the FDA announced the approval of Inflectra, Celltrion and Pfizer’s biosimilar of Johnson & Johnson’s Remicade (infliximab). Inflectra is now the second biosimilar approved for sale in the United States, after Sandoz’s Zarxio. Inflectra’s label and naming reflect the latest FDA guidance.
On January 26, 2016, the World Health Organization (WHO) unveiled the final version of its proposal for a worldwide biosimilar naming convention. The WHO proposes to add a “biologic qualifier” (BQ), which consists of four random consonants and an optional two-digit checksum, as an identifier that follows the nonproprietary name of each biologic and biosimilar product. This proposal resembles FDA’s biosimilar naming proposal, which adds four random consonants as a suffix to nonproprietary names. Industry and healthcare stakeholders have criticized FDA’s proposal to use random suffixes, instead of meaningful—and therefore memorable—ones, due to a greater likelihood of reporting and prescription errors with meaningless names. The WHO proposal, which uses a randomly generated separate identifier, is likely to draw similar criticism.
FDA has received comments from more than 170 groups on its proposal for naming biosimilars. Biosimilar makers, insurers and pharmacies largely oppose distinct nonproprietary names (also known as proper names) for biosimilars. By contrast, innovators (including those that develop biosimilars), healthcare providers and patient advocacy groups view them as critical to ensuring patient safety. However, most stakeholders in both camps urged FDA to use meaningful suffixes to distinguish biosimilars from originator products rather than suffixes “devoid of meaning.” FDA proposed to add meaningless suffixes to the nonproprietary names of originator products to address concerns of biosimilar makers that distinct names would discourage adoption of biosimilar products. But biosimilar makers expressed concern that such meaningless suffixes will lead to a variety of errors and ultimately endanger public safety. FDA may now revisit its proposal given the largely uniform preference of innovators and biosimilar makers alike for meaningful and memorable nonproprietary names, such as those that identify the manufacturer of the biologic.
In its draft guidance, FDA proposed distinguishable nonproprietary names for biosimilars to promote the safety of patients receiving biologic medicines and minimize inadvertent substitution of biologics that have not been determined to be interchangeable. FDA did not make a proposal for naming interchangeable biological products. Instead, FDA requested comments on how to name such products in addition to seeking comments on its approach to naming biosimilars. Stakeholders’ comments are now in. Innovator companies (including those that also develop biosimilars), healthcare providers and patient advocacy groups favor distinguishable nonproprietary names for biosimilars. Biosimilar makers, insurers, pharmacies, and the FTC, by contrast, largely fall into a different camp; they argue that distinct names are unnecessary for monitoring biosimilars and will likely bias providers against prescribing them. Notably, the two camps came together on the naming of interchangeable products. Since interchangeable products will likely first be approved as biosimilars, both camps advocated keeping the initial biosimilar name rather than changing it after approval as an interchangeable product. As a result of this unified view, FDA is likely to expand the naming approach it ultimately adopts for biosimilars to interchangeable products.
The FDA has issued a long-awaited draft guidance document and proposed rule on the nonproprietary names for biosimilar medicines. FDA proposes to give biosimilars a “core name” shared with all related biological products and a four-letter suffix, unique to each product. The four-letter suffix, unlike the placeholder name for the first US biosimilar, Sandoz’s Zarxio (filgrastim-sndz), does not identify the product’s manufacturer. Instead, it is a random collection of four letters, “devoid of meaning.” Patient groups and physicians have applauded FDA’s use of unique suffixes to differentiate biological products but innovator companies prefer meaningful suffixes, such as the one for Zarxio, and biosimilar manufacturers argue for no distinguishing names at all.
Despite its recent approval of the first biosimilar product, the FDA has yet to release a naming policy for biosimilars. With more biosimilar applications in the pipeline, a number of industry groups are taking opposing positions on the future of biosimilar nomenclature.
Today the FDA announced approval of the first ever biosimilar in the United States, Sandoz’s Zarxio, a biosimilar of Amgen’s Neupogen (filgrastim) product. Although Sandoz has cleared FDA obstacles, when Zarxio reaches the market depends on the outcome of Amgen’s lawsuit under the BPCIA.