When the Senate Committee on Health, Education, Labor, and Pensions released bipartisan legislation aimed at lowering the cost of healthcare in the United States in May, biosimilar stakeholders had some cause for optimism. However, one provision of the bill that has garnered significantly less attention from the broader healthcare community has raised concerns among many biologics stakeholders.
When the Senate Committee on Health, Education, Labor, and Pensions (HELP) released bipartisan draft legislation aimed at lowering the cost of healthcare in the United States in May, biosimilar stakeholders had some cause for optimism.
The proposed legislation—the Lower Health Care Costs Act—includes some provisions that advocates for biosimilars have long asked law makers to address, including providing generic and biosimilar developers with recourse in cases in which reference product sponsors fail to make drug samples available for testing. According to the nonpartisan Congressional Budget Office (CBO), the provisions of the act, taken together, could save the United States $7.6 billion over the next 10 years.
However, one provision of the bill that has garnered significantly less attention from the broader healthcare community has raised concerns among many biologics stakeholders: Section 207 of the bill, titled “Biological Product Innovation,” would make biologics, including biosimilars, exempt from meeting standards set by the United States Pharmacopeial Convention (USP).
The Role of the USP’s Quality Standards
The USP is an independent, not-for-profit, nongovernmental pharmacopeia whose experts are volunteers from academia, healthcare, government agencies, and other areas. The body develops public quality standards that are used as benchmarks that determine a medicine’s identity, purity, quality, potency, and consistency.
Using these standards allows for a determination that a medicine meets quality attributes regardless of which manufacturer makes a product, or which manufacturing process is used. USP also sells reference standards of products that can be used in processes that include biosimilar development.
According to law makers, exempting biologics from these standards would prevent delays to the licensure of biosimilars and interchangeable products. However, the USP says that the removing requirements for biologics to meet quality standards would put patients at risk, and it has called on Congress to reject the provision.
The Problem With Rolling Back Standards
In a June 11 letter to the HELP Committee, the USP’s chief executive officer, Ronald T. Piervincenzi, PhD, and chair of the board of trustees, Susan C. Winckler, RPh, JD, wrote that the rollback of requirements to adhere to public quality standards would jeopardize patient safety, and would “represent a shift from providing the public with access to the expectations for a quality biologic…to keeping specifications private between only the biologic manufacturer and regulator that grants market approval. We believe that the public should have transparency on the quality of biologic medicines.”
Piervincenzi and Winckler also wrote that, if drug developers do not have access to consistent public standards—which are broadly used in research and development processes—they will lack clarity on the regulatory pathway, and approvals of biosimilars could, in fact, be slowed down.
In a separate letter, issued in May 2019, organizations including the Academy of Managed Care Pharmacy, the American Diabetes Association, the American Society of Health-System Pharmacists, the Arthritis Foundation, and other organizations also voiced their concerns about a move away from required adherence to public quality standards.
In their letter to the HELP Committee, the organizations noted that, while the proposal is framed as being one that will accelerate biologic and biosimilar development, there are “no data or rationale to support such a statement,” and the group pointed to the USP’s commitment, announced in 2018, not to publish new biologic monograph standards as official and enforceable without the FDA’s support as evidence that the USP is not standing in the way of product development or licensure.
In the absence of a clearly articulated rationale for the Section 207’s inclusion in the proposed legislation, and given the fact that the CBO’s cost estimate did not address whether the USP-specific provision would have an impact on the cost of prescription drugs, some stakeholders are asking why the bill targeting healthcare costs includes a provision that could muddy developers’ understanding of the biosimilar development pathway.
According to experts who spoke with The Center for Biosimilars®, the provision at Section 207 could be linked with a long-running conflict over the naming of biosimilars.
The Federal Food, Drug, and Cosmetics Act (FFDCA) gives the USP the authority to develop official and nonproprietary names for drugs and biologics; unless the FDA has designated an official nonproprietary name for a drug, including a biologic, by notice and comment rulemaking, then the name designated by the USP applies to the drug. The FDA typically defers to the USP on creating official nonproprietary names for drugs, and the USP in turn works with the United States Adopted Names Council on these matters, after which the USP codifies the name of a drug in the USP national formulary (USP-NF).
When the idea of using a meaningless 4-letter suffix to identify biosimilars first emerged, experts told The Center for Biosimilars®, it raised the question of whether the FDA could be causing biosimilars to be labeled in a way that could be construed as misbranded, as the proper name—with its suffix included—would not match the name codified in the USP-NF.
To deal with such a possibility, in September 2017, the USP said that, for biologics, it planned to give monographs “the title specified in the relevant monograph plus any suffix designated by FDA” in order to obviate any potential compliance issues related to the potential for misbranding.
Then, after receiving stakeholder comments, many of which called into question the wisdom of using 4-letter suffixes appended to the names of biologics, the USP decided not to move ahead with the new naming requirements for its monographs.
The FDA, in its own comments, signaled that it saw a solution to the problem, and to its other stated concerns about USP monographs, in making USPs standards optional and “consistent with the flexible approach FDA uses to properly account for the complex nature of biological products.”
Notably, one expert pointed out, products (such as insulin) that will transition from regulation as drugs to regulation as biologics in March 2020 currently have binding monographs, given that they are, for the time being, drugs. To date, the FDA has not challenged the binding nature of these monographs, so the call for optional standards for biologics raised questions among stakeholders about whether the FDA’s flexible approach to biologics is in fact the driving force behind the effort to relax quality standards.
Then, in March of this year, the FDA updated its draft guidance on the naming of biologics, biosimilars, and interchangeable biosimilars, and indicated that the agency no longer plans to retrospectively assign 4-letter suffixes to already approved products (including transition products like insulins), though it will require newly approved biologics and biosimilars to carry those suffixes.
The naming decision put the FDA squarely at odds with other regulatory territories, such as Canada, which have expressly opted not to use suffixes. The decision also sparked criticism from biosimilar industry groups including the Association for Accessible Medicines, which called the guidance a “direct blow” to biosimilars in the United States.
According to experts, the FDA’s decision to move ahead with the use of suffixes is a major factor in the push to strip the USP’s biologics standards of their binding nature. Yet while such a move would solve any potential legal challenges to the use of suffixes under the FFDCA, those who support mandatory quality standards say that the change would put American patients at significant and unnecessary risk.