USP Position
Provision that Removes Biologics and Biosimilars Quality Protections in Senate Innovation Legislation
On April 6, 2016, language that would remove a 100-year-old patient protection in federal drug law that requires
biological products, including biosimilars, to adhere to public quality standards was amended into the FDA and NIH
Workforce Authorities Modernization Act (included in innovation or “Cures” legislation). The language was inserted at
Senate Health, Education, Labor and Pensions (HELP) Committee. If enacted, this policy change will reduce certainty,
transparency, and predictability in the biosimilars area.
While the provision would enact a significant departure from current law, many key stakeholders were not consulted on
its likely substantial impact medicines quality and patient safety, supply chain integrity, competition, and patient
access. It could also thwart implementation of the bipartisan Biologics Price Competition and Innovation Act of 2009.
The proposed provision represents a major policy change and should be not implemented without robust stakeholder
consultation; stakeholders affected by this provision include healthcare practitioners, payers, pharmacists, industry and
patients.
The proposal represents a major change in public health policy, despite it being presented as technical in nature.
1. It exempts biologics from the requirement that all medicines marketed in the United States comply with USP’s
public standards for quality.
2. It is an unprecedented departure from over 100 years of the legal, public policy and patient protection
framework that has ensured quality medicines for Americans.
3. These provisions in the Federal Food, Drug, and Cosmetic Act have been part of the safety net that makes
medicines in the United States among the safest in the world and undoing them will create unknown and
potentially significant risks to patient safety.
4. Eliminating these provisions for biologics undermines a long history of collaboration between FDA and USP1 in
developing and updating public quality standards for medicines—working closely with industry, the scientific
community, and other stakeholders—something FDA recognizes as vital to strengthen efforts to protect the
public health.2 USP has always worked closely with FDA and leading scientists in this ongoing public health
dialog—USP remains committed to do so, working with policymakers and the Agency to find the best solutions.
5. Sets US apart and behind all developed countries,3 and most emerging countries,4 which have a system of drug
regulation tied to pharmacopeial public standards that is intended to protect patients and facilitate availability
of high quality and safe medicines.5 More than 40 countries outside the US have written USP’s quality standards
into law as part of such a system. This proposal’s language would gut that system in the United States for
biologics.
1
http://www.usp.org/sites/default/files/usp_pdf/EN/aboutUSP/fdaand_usp_exhibit.pdf
http://www.fda.gov/drugs/resourcesforyou/industry/ucm357661.htm
3
Including Europe, UK, Japan, Australia, Canada, and others
4
Including India, China, Brazil, Mexico, Turkey, and others
5
More than 40 countries outside the US have written USP’s quality standards into law as part of such a system.
2
1
If enacted, this provision could have broad impact on quality and safety.
1. Unlike a private specification developed by an individual company with a financial interest, public standards are
developed through an open, collaborative and transparent process and are utilized to test quality at many points
in the supply chain. This is increasingly important in today’s global pharmaceutical marketplace, where the
majority of drugs consumed in the US come from outside the country through fragmented and difficult to trace
supply chains.
2. In addition to removing the requirement of compliance to public quality standards, the provision also would
eliminate adherence to standards for storage and labeling for biologics, which are the most sensitive to
environmental conditions of all medicine classes.
3. The provision would affect lifesaving or other significant biologics like insulin and human growth hormone,
where USP standards are used daily in quality compliance actions by FDA, manufacturers and in other
independent testing situations that safeguard the US medicine supply. Many of these medicines in the current
environment have international supply chains where the ability of testing at entry into the United States or at an
overseas manufacturing site to a common standard provides a critical safeguard.
While positioned as a measure to advance innovation, the provision could negatively impact biosimilar product
development and competition.
Biosimilars developers use public quality standards to establish the key quality attributes of their products. In
this way, USP’s public standards facilitate the entry of products from multiple manufacturers. USP’s processes
provide a unique mechanism to bring manufacturers to the table and accelerate that development process.
Moreover, public quality standards facilitate the application process for NDAs and BLAs. Industry utilizes USP’s
public standards in applications or licenses to set forth the quality, purity, and strength of their product or substance;
thereby minimizing the necessity to establish these themselves.
USP’s standards-setting process is collaborative and iterative to account for changes in innovation. These
standards are flexible to evolve with public health needs and advances in quality expectations.6
To augment USP’s ongoing revision processes, the Pending and Accelerated Monograph Revision processes have been
implemented within the past few years to allow USP to work quickly and proactively to update standards to reflect
new technology in product specifications.
One recent example is USP’s monograph for the blockbuster drug enoxaparin sodium. It has been revised
several times, including through Accelerated Revision, to accommodate subsequent US market entries for this
product.
In monograph development, USP routinely engages with our broad array of scientific experts on the USP Council of
Experts, the stakeholders in the USP Convention and regulators from around the world to ensure that USP monograph
development is aligned with technology advances.
6
USP’s product specific standards are reflective of the approved medicine in the marketplace and evolve as the quality specifications
for the products evolve. The insulins, glucagon, and growth hormone are well documented examples, but even for the recent
biosimilar approvals like Filgrastim, USP has shown that the applicable official standard is appropriate and reflective of both the
innovator and the biosimilar product on the market.
2
In most cases for biologics, a monograph is not based on a single manufacturer’s submission, but rather developed with
broad input from industry and vetted in USP’s own laboratories to develop robust approaches that support a multimanufacturer environment for biologics.7
Without having USP public standards, industry might have to look to public standards from outside the US to facilitate
product development—it might rely on the public standards from other regions such as the European, Chinese, or Indian
Pharmacopeias.
USP monographs are not a requirement for regulatory approval.
Action Requested
A policy change of this significant magnitude warrants a transparent and thorough discussion. USP and its more than
900 Convention Members and scientific experts8 were not collectively aware of the amendment or its implications or
reach. While presented as technical, the removal of this long-standing patient protection has a very large substantive
implication. And, while positioned as advancing innovation, this provision could conversely slow the development of
new biosimilar products, reducing market competition, and provider and payer choice and ultimately decreasing access
for patients to lower-cost biosimilars. This outcome would be contrary to the intent of Congress in enacting the
Biologics Price Competition and Innovation Act of 2009.
USP respectfully requests that this provision not be advanced for consideration on the Senate floor without a
transparent and thorough discussion about the role of science-based, public quality standards for biologics and
biosimilars that engages appropriate stakeholders, including the scientific, patient, practitioner, pharmacy, payer and
industry communities.
US Pharmacopeial Convention
USP is a nongovernment, nonprofit scientific organization which was founded in 1820 with the objective of bringing
uniformity to medicine and pharmacy in the United States through the establishment of a compendium of drug
standards. Today, USP continues to set public standards for the identity, strength, quality, and purity of medicines, as
well as for food ingredients and dietary supplements—and for practice and healthcare quality standards, such as those
involving drug labeling and the safe compounding of preparations. USP has a close relationship with FDA, dating back to
the Pure Food and Drug Act of 1906, when FDA was known as the Bureau of Chemistry. Today our compendial standards
are connected to FDA through the 1938 Federal Food, Drug, and Cosmetic Act.
7
Recent examples include Enoxaparin sodium (brand name Lovenox) monographs; Epoeitin monograph and Chapter; Glucagon
monograph revision and chapter; monoclonal antibody test Chapter <129>; Glatiramer (brand name Copaxone).
8
The USP Convention includes membership from leading scientific, patient, pharmacy, provider, consumer and industry associations
as well as public health and regulatory agencies from the US and from around the world.
3