The US Federal Trade Commission (FTC) is among those asking the US Food and Drug Administration (FDA) to reconsider its proposed guidance for naming biosimilar drugs.
What's in a name? Plenty as it relates to naming conventions for biosimilars. In August, the FDA proposed adding a four-letter suffix to nonproprietary names of biosimilar products shared with innovator products through the issuance of draft guidance. The FDA naming system follows a similar proposal in 2014 by the World Health Organization. The FTC, the USP, and others, however, object to the plan. What is being said and where does the FDA go from here? DCAT Value Chain Insights (VCI) takes an inside look.
FDA’s naming proposal
In August 2015, the FDA issued draft guidance, Nonproprietary Naming of Biological Products: Draft Guidance for Industry; Availability.The draft guidance describes FDA’s proposal that all biological products bear a nonproprietary name that includes a manufacturer-specific FDA-designated suffix. In a joint FDA blog announcing the release of the draft guidance, Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, and Karen Midthun, director of FDA’s Center for Biologics Evaluation and Research, highlighted the main issues proposed by the FDA in the draft guidance.
The draft guidance proposes that reference products and biosimilars have nonproprietary names (also called proper names) that share a core drug substance name and, in order to better identify each product, an FDA-designated suffix that is unique for each product. This suffix would be composed of four lowercase letters, and not carry any meaning. For example, the nonproprietary name of a reference product could be replicamab-cznm, and a biosimilar to that product could be replicamab-hixf.
For interchangeable biological products, FDA's proposal requested feedback from the public about whether the nonproprietary name for such a product should include a distinct suffix, or should share the same suffix as its reference product (e.g., the nonproprietary name of both the reference product and the interchangeable product could be replicamab-cznm).
In their blog, Woodcock and Midthun said that the proposed naming convention seeks to address two main issues: (1) help prevent inadvertent substitution (which could lead to medication errors) of biological products that are not determined to be interchangeable by the FDA; and (2) to support safety monitoring of all biological products after they are on the market, by making it easier to accurately track usage of biological products in all settings of care, such as outpatient, hospital, and pharmacy settings.
FDA is also considering, and requested public input on, the benefits and challenges of other naming approaches, such as a suffix derived from the name of the license holder. The FDA also is seeking public comment on what to consider to do to address previously approved biological products that have nonproprietary names without a suffix. FDA said that applying the naming convention to these products would encourage routine use of designated suffixes in ordering, prescribing, dispensing, and recordkeeping practices and avoid inaccurate perceptions of the safety and effectiveness of biological products based on their licensure pathway. Along those lines, the FDA sought comment on the best approach to implement this naming convention for previously licensed products. Along with the draft guidance, the FDA issued a proposed rule, Designation of Official Names and Proper Names for Certain Biological Products, which sets forth proposed names for six products based on the naming convention outlined in the draft guidance. The proposed rule to designate nonproprietary names that contain a suffix for six previously licensed biological products. Each of the six products is either a reference product for an approved or publicly disclosed biosimilar product application or a biological product that is either biosimilar to or related to one of these reference products.
Industry and public feedback
FDA provided until October 27, 2015 for feedback on its draft guidance and received multiple comments from other government agencies, trade associations, companies, and individuals. In its comments, the US Federal Trade Commission, raised concerns about the FDA’s proposal. “FTC staff is concerned that FDA’s proposal—to assign different suffixes to the drug substance names of biosimilars and their reference biologics—could result in physicians incorrectly believing that biosimilars’ drug substances differ in clinically meaningful ways from their reference biologics’ drug substances, especially since differences in drug substance names have traditionally connoted meaningful differences in drug substances,” said the FTC in its comments. “A misperception that the drug substance in a biosimilar differs in clinically meaningful ways from that in the reference biologic could deter physicians from prescribing biosimilars, thus impeding the development of biosimilar markets and competition,” it said. It suggested that the FDA reconsider its proposed system for nonproprietary names of biologic products in favor of other means to accomplish its purposes that are less likely to hinder competition from biosimilars.
In submitted comments, the Biotechnology Industry Organization (BIO) noted its support for a nonproprietary naming convention that ensures all biological products are distinguishable. “BIO believes that a distinguishable nonproprietary naming convention would best facilitate robust pharmacovigilance, ensure accurate attribution of adverse events to the correct product, mitigate the risk of inappropriate or unintended substitution and unintended switching, and support tracing of products in the event of a recall,” said the association.” “In short, BIO strongly believes that distinguishable nonproprietary names enhance and protect public health, and serve as another important step in developing a transparent and effective regulatory framework for the review and approval of biosimilars. Thus, BIO supports the development of a system under which nonproprietary names of biological products that are highly similar to each other in structure and function are distinguishable, but morphologically related, and easy to recognize, remember, and report accurately.”
In commenting on what those nonproprietary names should be, BIO said that nonproprietary names must be easily recognizable and non-confusing to physicians, nurses, pharmacists, and patients. It said that suffixes be “memorable” in order to allow healthcare practitioners to understand the distinct identity of each product and to enable pharmacovigilance. To promote memorability, and thereby encourage uptake of the proposed naming convention, BIO recommends that the suffix for a biological product be unique to each license holder (or the entity responsible for pharmacovigilance, if different from the license holder). Further, BIO recommends that license holders be afforded the option of using the same suffix for each biological product from that license holder. It said that the use of a memorable suffix unique to a license holder will provide a biological naming convention that reduces confusion and enables effective pharmacovigilance and that it will also permit healthcare practitioners to associate the particular suffix of each biological product with the identity of that product. BIO said that assigning a unique suffix to each individual biological product would result in a dramatic increase in the number of suffixes over time, increase the review workload on FDA to review the significantly greater number of suffixes, and considerably increase the complexity and potential for confusion by healthcare practitioners.
“Simplifying the naming convention to, in general, provide for a suffix that is unique to each license holder and shared by each biological product from that license holder will promote better understanding by health care practitioners,” said BIO in its comments, which added that such naming conventions be used for interchangeable biological products. The association said in its comments that each interchangeable biological product also should have a unique suffix to facilitate pharmacovigilance and advance recognition that interchangeable biological products are not identical. In certain circumstances, BIO recommends that sponsors be permitted to request or use a separate suffix, subject to the same evaluation factors, for an individual biological product where the use of their “primary” suffix is insufficient to adequately distinguish the biological product or to promote adequate pharmacovigilance.
BIO said it also supports the concept of retrospective application of the naming convention to previously licensed biological products, but recommends that the agency consider the potential impact to healthcare practitioners and patients that have become familiar with the marketed biologic products over the years. In its comments, BIO requested that FDA investigate and then subsequently outline additional details, including timelines and process for application and implementation, about the retrospective application of the nonproprietary naming convention by publishing guidance and allowing for public comment by stakeholders.
BIO added that its supports global harmonization and the efforts of the World Health Organization (WHO) to facilitate a distinguishable suffix that can be used globally, but that it can support harmonization only for a naming convention that uses memorable and meaningful suffixes, instead of random suffixes as is currently proposed. “A naming convention premised on the use of random suffixes would undermine the very goals that the Agency is seeking to achieve related to patient safety, adoption and uptake, and pharmacovigilance,” said BIO in its comments. “Accordingly, we strongly urge FDA, in its discussions with the WHO, to encourage the WHO to implement a BQ system in which suffixes are memorable and meaningful, and in which a suffix may be unique to a license holder and shared across multiple biological products offered by that license holder. If WHO decides to take another approach, the suffix adopted in the US can be easily mapped to the suffix assigned by the WHO. The US can most effectively assist WHO and other jurisdictions by demonstrating successful adoption of a suffix framework, including meaningful and memorable suffixes.”
The Pharmaceutical Research and Manufacturers of America (PhRMA) also specified that suffixes for non-proprietary names should be meaningful and not random as the FDA proposal suggests. “PhRMA supports the prospective assignment of distinguishable nonproprietary names—comprising a common “core name” (the United States Adopted Name (USAN) for the drug substance) and a suffix identifier connected by a hyphen—for all biological products,” it said. PhRMA recommends that the suffix be unique to the license holder and generally shared across all of the license holder’s newly approved products. In unique circumstances, it also recommends that FDA permit an individual license holder to use distinct but related suffixes for the license holder’s related, non-interchangeable products to protect patient safety.
PhRMA said it agrees with the agency that the use of distinguishable nonproprietary names will minimize inadvertent substitution, facilitate pharmacovigilance for multiple biological products containing related drug substances, and establish a consistent and recognizable mechanism for identifying biological products. In order to enhance the memorability of suffixes and thus improve pharmacovigilance, PhRMA requests that FDA require license holders to propose suffixes that are, in general, derived from the name of the license holder. PhRMA believes that adopting meaningful suffixes that are generally derived from that name of the sponsor or application holder will enhance prescriber recognition, use, and memory of suffixes and thus, the utility of suffixes for their pharmacovigilance and safety objectives. It also said that it believe that meaningful suffixes will minimize confusion and burdens associated with implementation of suffixes. “Accordingly PhRMA respectfully disagrees with the proposal that such suffixes not be meaningful and submits that FDA should eliminate that restriction,” the association said in its comments.
PhRMA added that it supports the PhRMA also supports, in principle, the retrospective application of the suffix convention (as described) to existing biologic nonproprietary names through an orderly process. “We urge FDA to implement carefully any phase-in of the suffix convention to existing nonproprietary names in a manner that minimizes confusion and regulatory burdens on the agency, avoids disruption in the healthcare delivery system, and affords license holders sufficient flexibility to make labeling changes to meet the needs of patients as well as license holders’ operational requirements,” it said in its comments.
The Generic Pharmaceutical Association (GPhA) and the Biosimilars Council, a division of GPhA, also commented on the proposed naming convention, urging that biosimilars not contain suffixes as part of its naming system. “When it comes to naming of biosimilars that have demonstrated biosimilarity to the reference protein product (RPP), both products should share the same International Nonproprietary Name (INN),” it said in its comments. “The current INN system is working well in Europe, US, and Canada for all biologics. Creating a new naming convention with unique INNs will instill uncertainty, compromise safety and limit ability to improve patient access to biologics. In the US, multiple different products share the same INN and pharmacovigilance issues have not been identified. Unique names could disrupt the current naming system and inhibit market creation for biosimilars……Biosimilar products should share the same INN or proper name. Adding a suffix to the proper name is unnecessary and does not achieve the Agency’s stated goals as it will lead to confusion among prescribers and patients, potentially resulting in medication errors and mistranscription in medical records.”
The United States Pharmacopeial Convention (USP) submitted its comments on the FDA draft guidance. USP said it acknowledges FDA’s efforts to advance the successful implementation of the Biologics Price Competition and Innovation Act. “We understand the naming approach for biologics in the Draft Guidance reflects FDA’s interest in preventing inadvertent substitution of and facilitating pharmacovigilance for biological products,” said Jaap Venema, executive vice president and chief science officer of USP, in a statement. “At the same time, USP believes it is critically important to maintain a uniform and scientifically based approach that does not create unintended risks for patients and practitioners and encourages FDA to consider alternative solutions to reach its goals.”
USP says its comment to the FDA’s draft guidance highlights the following concepts: (1) USP has a long history of setting quality standards for biologic drug substances and products; (2) the existing scientifically based nonproprietary naming system for biologics and other drugs has served patients and practitioners well for over a century; (3) the naming approach proposed in the draft guidance represents a departure from well-established scientific naming principles and could have unintended negative consequences; and (4) while USP shares FDA’s goal of improving safe medication use, the USP said it encourages FDA to consider alternative solutions to achieve this goal.
USP said it will be commenting separately on the proposed rule, Designation of Official Names and Proper Names for Certain Biological Products, which sets forth proposed names for six products based on the naming convention outlined in the draft guidance.