USP Standards For Biological Drugs Would Restrict Innovation, US FDA Says
Executive Summary
Top officials at the US FDA explain why the agency opposes USP monographs for biological products as a Senate committee proposes to disallow them and the USP launches an advertising campaign in their favor.
Leading US Food and Drug Administration officials are explaining why the agency opposes USP compendial standards for biological drug products as the USP launches a print and digital advertising campaign in favor them.
The United States Pharmacopeia is campaigning against proposed Senate legislation that would exclude biologics from requirements to meet USP quality standards. (Also see "USP Rivalry With US FDA Over Compendial Standards Provision Busts Into Open Legislative Fight" - Pink Sheet, 11 Jun, 2019.)
The USP placed advertisements in Roll Call, The Hill and Politico that say the measure "threatens public safety by removing the requirement that biologic medicines meet public quality standards." The standards provide transparency on quality, enable accountability and foster competition that reduces prices, the advertisement says.
The USP’s main mission and source of revenue are the written compendial standards, or monographs, and physical reference materials it develops to help the pharmaceutical industry ensure the quality of drug products.
What Woodcock And Marks Say
FDA officials provided a different perspective.
These standards work well for small molecule drugs, but “when it comes to biological products (including biosimilars) – the requirement to adhere to a monograph may actually hinder progress while not offering additional quality assurances,” Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, and Peter Marks, director of its Center for Biologics Evaluation and Research, said in a 13 June “FDA Voices” post.
Such monographs can force sponsors to comply with two standards when only one is needed, causing delays and potentially reducing competition and restricting innovation, they said.
Woodcock and Marks called attention to a more detailed explanation of the issue that Steven Kozlowski, who heads the CDER quality office that reviews biotechnology drug applications, provided in a 12 June “CDER Conversation” online post.
What The Draft Legislation Says
Section 207 of a drug pricing bill drafted by the Senate Health, Education, Labor and Pensions Committee would exclude all biological products regulated under the Public Health Service Act from requirements to follow USP compendial standards, according to the committee’s section-by-section analysis of the bill.
The committee notes that USP standards originally applied only to drugs regulated under Section 505 of the Food, Drug and Cosmetic Act, and asserts that the proposed change “prevents delays related to compliance with USP standards in the licensure of biosimilar and interchangeable products.”
Why FDA Says Monographs Are Bad For Biologics
Kozlowski said that in the years since the 1997 FDA Modernization Act extended to biologics a requirement that small-molecule drugs adhere to USP monographs, USP has established very few monographs for biological drug products.
He said in FDA’s view, biologics are so complex that USP monographs would not help on quality like they do for chemical drugs and would constrain innovation.
Biological products are complex, with many attributes that must be examined using analytical methods that also are complex. Kozlowski said their “sameness” cannot be defined with the specificity that USP monographs do for small-molecule drugs.
The Difference With Similarity
When the 2009 Biologics Price Competition and Innovation Act established a pathway for follow-on versions of biologics, approval was based on similarity rather than sameness.
Congress recognized in the law that the inherent variability of biosimilars calls for a “highly similar” standard for biosimilars instead of the traditional “sameness” standard for generic drugs.
“While there is generally one way to show sameness, the approach to demonstrating highly similar may vary from product to product, and still meet all safety and efficacy criteria,” Kozlowski said.
The Risk To Competition
He posited that if the USP adopts one biosimilar developer’s approach in a compendial monograph, other firms that win US FDA approval of their biosimilars with other approaches would be unable to meet the monograph criteria, and would be blocked from the US market.
Competition would be further restricted if a firm had patented characteristics of their product included in a monograph.
“The BPCI Act was designed to ensure a clear pathway for approval of biosimilars and interchangeable products and is intended to balance innovation with consumer interests," Kozlowski said. "Monographs for biological products do not align with these goals and may serve to burden competition for biological product development.”
Why FDA Review Is Enough
Kozlowski added that FDA review of biological products suffices to assure safety, efficacy and quality and that USP monographs would not provide any additional assurance.
The FDA reviews more information about a biological product than USP can access, including proprietary data, which he said allows the agency to assess each product individually instead of relying on compliance with pre-specified standards.
The flexibility of the agency’s approach to review enables it to accommodate improvements in manufacturing processes that could safely and effectively increase access, but that could fail to meet rigid monograph criteria developed based on increasingly obsolete manufacturing processes.
What USP Does That FDA Supports
Kozlowski underscored the FDA’s continuing support for monograph standards for small molecule drugs.
He also signaled support for optional standards for biological products that align with the agency’s flexible approach.
“Any mandatory standards, however, would impede innovative technologies, as well as place unnecessary burdens on industry and on FDA reviewers,” he said.