Biosimilars Forum Comments on FDA Naming Guidance

October 27, 2015

Dr. Stephen Ostroff
Acting Commissioner
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

Re: Comments to August, 2015 Proposed Guidance: “Nonproprietary Naming of Biological Products” (Docket No. FDA-2013-D-1543)

Dear Acting Commissioner Ostroff:

The Biosimilars Forum appreciates the opportunity to comment on the Food and Drug Administration (“FDA”) proposed guidance regarding the nonproprietary naming of biological products, as published in Docket No. FDA-2013-D-1543.

The Biosimilars Forum is a non-profit organization whose mission is to advance biosimilars in the United States with the intent of expanding access and availability of biological medicines and improving health care. The Forum works on a consensus basis to develop policy positions to ensure the United States has a competitive, safe and sustainable biosimilars market, providing more options to patients and physicians.

Summary of the Proposed Guidance

In the draft guidance, the FDA proposes to designate a nonproprietary name for biological products licensed under the Public Health Service Act (“PHSA”) that includes a suffix composed of four lowercase letters. The draft guidance proposes assigning a “proper name” which consists of a core name (the component shared among all related biological products) and the four letter suffix. The FDA believes this naming convention will improve pharmacovigilance and clearly differentiate among biological products that have not been deemed to be interchangeable, ensuring safe use. The FDA states that it intends to apply this naming convention to both newly licensed and previously licensed biological products. The FDA also is considering whether for interchangeable products, the designated suffix should be unique or should be the same as the reference product.

General Comments to the Proposed Guidance

The Biosimilars Forum applauds the FDA for advancing an approach in this proposed guidance and the related proposed rule designating official names and proper names for certain biological products that recognizes that each biosimilar is a unique, single source drug and that the naming convention for biosimilars should be the same as that applied to all biologics.

Specific Comments to the Proposed Guidance

While the Biosimilars Forum takes no position on whether a suffix should be included in the U.S. proper name, the Forum believes that should the FDA go forward with the proposed addition of a suffix, (1) the suffix should be affixed to all biological products developed by a given company, and (2) the four letter suffix should be unique to the original product sponsor and meaningful, as opposed to random, and preferably derived from the company name. This approach would ensure that the name is more easily remembered, which in turn would better meet the stated FDA goals of safety and enabling enhanced pharmacovigilance. The FDA should also support the implementation of meaningful suffixes in its discussions with the World Health Organization (WHO) and other global regulatory bodies, in order to align biologic naming policies, to the extent possible.

With regard to interchangeability, the Biosimilars Forum does not believe that the naming convention should be used to designate whether or not the product is interchangeable, nor should the name match the reference product. Rather, interchangeability should be addressed in the Purple Book, label, and summary basis of approval that is published on the FDA website.

The Biosimilars Forum also believes that the FDA must ensure there is flexibility in the implementation of this system to address case by case situations that may arise as experience is gained. For example, the Forum feels that the FDA must provide a process that allows a company to change its suffix in the event of a safety need or business consideration.

Similarly, the Forum requests that the FDA provide specific guidance to industry on how currently marketed and future biologics and biosimilars are to be converted to this new naming scheme. As the agency moves forward with this process, it would be useful for the FDA to articulate how the FDA will actually execute the suffix change; for example, will there need to be a rulemaking to change suffixes? The guidance should address time frames for both of the following scenarios: 1) timeframe for naming of products already on the market when the guidance is finalized and 2) forward planning for when biosimilars are approved and the reference biologics on the market need to implement their changes. In both scenarios, the Forum encourages the FDA to support a “level playing field” for biosimilars and reference biologics and ensure implementation does not disrupt supply or cause delays in applications.

Forum members are also concerned about ensuring the protection of a company’s trademark and avoiding misrepresentation in the assignment of meaningful suffixes. The Forum urges the FDA to develop a system for ascribing meaningful suffixes that would be fair, equitable and reliable, and would prevent application of a suffix that may be misleading or confusing to practitioners and consumers, potentially undermining the goal of distinguishing biological products, and discouraging the uptake of safe and effective biosimilars in the U.S.

Responses to Questions Posed by the FDA

The Biosimilars Forum’s responses are below to the questions posed by the FDA in the August 28, 2015 Federal Register notice of availability of the draft guidance.

What are the potential benefits and challenges of designating a suffix in the proper name of a biological product that is: (1) Devoid of meaning versus meaningful, and (2) unique to each biological product versus unique to each license holder, and shared by each biological product manufactured by that license holder.

In your comments, please address how each option would impact the following: Safe use of biological products; pharmacovigilance; and market acceptance and uptake for certain products.

The Forum believes that ascribing a meaningful suffix in the proper name of a biosimilar will decrease the likelihood of transcription errors, medication errors and unplanned substitution of products, which in turn will increase physician and patient confidence in biosimilars. As mentioned above, the Forum believes that the suffix should be meaningful and derived from the company name. If the FDA implements a policy allowing for suffixes based on the company name, it should provide a process that allows a company to change the suffix of a product in the event of a safety need or business consideration.

What would be the potential benefits and challenges for an interchangeable product to share the same suffix as designated in the proper name of the reference product? Your response should consider that FDA’s publicly available electronic resource, the Purple Book, will identify biological products determined by FDA to be biosimilar to or interchangeable with a reference product. If an interchangeable product does share the same suffix as the reference product, how would this impact your responses to question 1, including pharmacovigilance?

The Forum believes that a designation of interchangeability does not negate the need to clearly identify biological products made by different manufacturers. Further, incorporating the reference product suffix into the name of an interchangeable product would pose significant challenges. For example, when a biosimilar product becomes interchangeable, it would be difficult and costly to change the name of the product to incorporate the reference product suffix without causing confusion among health care professionals and patients. There are additional concerns regarding trademarks and proprietary naming conventions that would need to be addressed under this potential scenario. The Forum believes that information about interchangeability will be adequately conveyed in the Purple Book and that sponsors will be able to communicate this information to physicians as well.

Would there be additional benefits or challenges if the suffix designated in the proper name of a biosimilar product that is subsequently determined to be interchangeable were changed to that of the reference product upon a determination of interchangeability? Would there be benefits or challenges to allowing the manufacturer of the biosimilar product that is subsequently determined to be interchangeable to have the option of retaining its original suffix or adopting the same suffix as the reference product?

As noted in Question 2, the Forum believes that the name and suffix should remain the same upon a finding of interchangeability and that the interchangeable product should not be required to incorporate the reference product suffix. Requiring a name change or the addition of the reference product suffix would be a lengthy and costly undertaking for the biosimilar(s) each time a product was determined to be interchangeable. The Forum considers the Purple Book, the label, and the summary basis of approval to be the appropriate places to provide an interchangeability designation.

How could FDA and/or other Federal partners improve active pharmacovigilance systems for purposes of monitoring the safety of biological products? For example, because NDC numbers are not routinely recorded in billing and patient records in many clinical settings in which biological products are dispensed and administered, are there other identifiers besides distinguishable nonproprietary names that are routinely accessible by active pharmacovigilance systems and could enable as good as or better pharmacovigilance? How can FDA and/ or other Federal partners help ensure that a distinguishable identifier for each biological product would be captured at the point of dispensing or administration to the patient and be routinely accessible in systems used for pharmacovigilance?

The Forum respectfully requests that the Agency consider the need for additional input to garner a full response to this question. There are multiple stakeholders who will be engaged and responsible for 1) the process implementation of suffixes to the current on-market biologics and biosimilars, and 2) implementing the changes to the current reference biologic’s naming as new biosimilars enter the marketplace. The Forum recommends that the Agency host an external stakeholder workshop to discuss how to effectively implement this policy in a timely manner that is least disruptive to health care administration, patient access, and the marketplace. Physicians, payers, PBMs, manufacturers and others should be invited to participate.

In addition, the Forum notes that while the FDA has identified the need for distinguishable names to prevent medication errors and to promote pharmacovigilance (supporting the fact that each biologic is unique), the CMS proposed payment rule includes all biosimilars of the same reference product (interchangeable and non-interchangeable) within the same HCPCS/ J-code. We urge FDA and CMS – its “Federal partner” and sister agency at HHS – to work together to ensure a distinguishable identifier for each biological product that can be routinely accessible in systems used for administering, billing and pharmacovigilance. The naming and identification policies for biologics should be aligned across HHS agencies and, due to the FDA’s scientific expertise, should reflect the FDA’s regulations for biologics and biosimilars as the foundation for these policies.

What process and reasonable timeframe should FDA use to designate a suffix to include in the nonproprietary name of a previously licensed biological product?

The Forum believes that if the FDA decides to incorporate suffixes into the non-proprietary names of biologics, it should provide guidance to sponsors regarding how on-market reference biologics might implement a suffix prior to the approval and launch of a biosimilar. The Forum believes that any naming and/or suffix policy for biosimilars should also be required of the reference biologic and should promote a level playing field for both products. The Agency’s guidance should be specific enough to avoid disadvantaging the biosimilar in the marketplace, but also should allow sponsors some discretion regarding their own implementation of naming previously-licensed products. Providing the sponsor flexibility in implementation will ensure that the requirement is manageable rather than arbitrary. There are multiple steps the sponsor would need to implement and the process must be sufficiently flexible to accommodate the risks involved, such as possible delays, and the impact on and education of health care providers. Additionally, name changes will require other stakeholders – including compendia, electronic medical record systems vendors, electronic prescribing systems vendors, payment systems vendors, and health systems with standing treatment orders – to make changes.

The Forum believes the Agency should consider a tiered timeline that distinguishes the process and each of the steps necessary for reference biologic sponsors to a) implement a suffix through a change in a product’s name and label with the Agency and to b) fully implement that change throughout the marketplace. Regarding marketplace implementation at-large, FDA should solicit feedback from the multiple stakeholders who will be engaged and responsible for this implementation. This could occur at the above mentioned stakeholder workshop if appropriate. A maximum timeframe for implementation of a name change in the marketplace for the reference biologic should be determined with input from stakeholders at such public meeting. This workshop would be a precursor to determining how quickly a name change can be implemented, whether it must be a phased-in change, and what legal safe harbors are needed to accommodate this process without incurring mislabeling or misbranding charges.

What criteria should FDA use to prioritize retrospective application of this naming convention to previously licensed biological products?

The Forum supports ensuring that there is no difference between application to the biosimilar and to the reference product and that biosimilars are provided a level playing field with their reference biologics in terms of this naming policy when they come to market. In the interest of pharmacovigilance, the biosimilar and reference products name changes should be handled promptly, as once two products are on the market, there is a greater need to ensure the naming convention is consistent. Current FDA label/naming change processes should be utilized where possible and leveraged.

As mentioned above, the Forum also believes sponsors should be provided with flexibility in application of the naming convention across the supply chain and market at large, so they are not attempting to update the names of all products at once and/or disrupting the marketing of products already on the market. The Forum believes it should be up to the sponsor to manage the sequencing, prioritization, or bundling of name changes for its products to avoid unnecessary disruption of the company’s distribution of current products on market. The Forum also believes the timeframe in which the sponsor is required to implement the name change for an on-market biologic should incorporate any publicly available information on timing of biosimilar approval. Full market implementation should be within a timeframe to be determined based on feedback from the public stakeholder meeting. The FDA should reference and leverage current standards for these type of changes that are being implemented today.

With regard to the remaining products, we recommend that a future date be established after which the new name must be implemented for all biologics. Product sponsors should have the discretion to determine when and how to “roll out” the change, taking into consideration whether they have a single or multiple products to change, etc. This should be done in a manner that gives other stakeholders the opportunity to implement changes to their systems.

What are the expected time frames for sponsors of previously licensed biological products to distribute products that conform to this naming convention after approval of a labeling supplement?

FDA should rely on its current practice and experience to determine the appropriate time frames for label/name changes in the marketplace. The FDA-specific process for the change should conform to current practice/regulation as much as possible; the changes within the marketplace should be initiated by the sponsor prior to the launch of the approved biosimilar and completed within a time frame that does not create a barrier to, or confusion with, biosimilars. FDA, through an external stakeholder workshop, should solicit feedback on appropriate time frames and expectations for these changes to be implemented in the marketplace.

What strategies could FDA use to enhance stakeholders’ understanding of and education about this naming convention?

The FDA and other healthcare stakeholders have publically recognized the need for comprehensive education on biosimilars and the FDA has recently stated its intent to initiate such a program for the benefit of U.S. physicians, nurses, patients, pharmacists and health IT stakeholders.

The Biosimilars Forum recommends that education on any naming system for biologics, including biosimilars and interchangeable biologics be incorporated into future education activities that will be undertaken by the Agency. We urge the Agency to direct these activities towards physicians, nurses, patients, pharmacists and health IT professionals in programs that are tailored to the specific audiences.

FDA notes that this naming convention (i.e., use of a suffix) has some similarities to the World Health Organization (WHO) proposal, ‘‘Biological Qualifier—An INN Proposal.’’ At the time of publication of this draft guidance, WHO was still evaluating the comments received on its proposal. If WHO adopts a Biological Qualifier proposal, how should the biological qualifiers generated by WHO be considered in the determination of FDA-designated proper names for the biological products within the scope of this guidance?

In the event that suffixes are implemented in the U.S., the Forum urges the FDA to encourage the WHO to align with the FDA’s policies on meaningful suffixes, as this will help to prevent confusion and medication errors in the global healthcare arena, and to provide a level playing field for biosimilars. The FDA has been a leader in pharmacovigilance and we encourage the FDA to take the opportunity to continue to do so in the biosimilars space.

Conclusion

The Biosimilars Forum is pleased to see positive momentum in the effort to designate proper names for biological products and the effort to identify each biosimilar as a unique drug. The Forum believes that to the extent the FDA decides to include a suffix in the proper name, this suffix should be unique and memorable in order to enhance safety and pharmacovigilance. The Forum urges the FDA to carefully evaluate outstanding issues, such as suffix changes, that could affect the naming process; to seek advice on timing and sequencing of events for on-market biologics, and to do everything within its power to provide a level playing field for biosimilars in the U.S.

If you have any questions or need any additional information, please contact Michael Werner at 202.419.2515 or at michael.werner@hklaw.com.