USP Decides Not to Develop Biological Product MonographsBy
The USP, a standard-setting organization, has stated that that it will not develop a new monograph for a biologic unless there is stakeholder consensus supporting its creation, including support from the FDA.
In making that decision, the USP addressed concerns by the FDA and other stakeholders that biological product monographs could impede or delay licensure of biosimilars and other biological products.
The issues involved
USP, a standard-setting organization, issued a statement on April 2, 2018 that it will not develop a new monograph for a biologic unless there is stakeholder consensus supporting its creation, including support from the US Food and Drug Administration (FDA). In making the decision not to develop a new monograph for a biologic unless there is stakeholder consensus, USP took into account concerns raised by the FDA that efforts to develop biological product monographs could impede or delay licensure of biosimilars and other biological products.
USP had considered changes to the United States Pharmacopeia (USP) and the National Formulary (NF), the USP–NF to align compendial names with FDA’s biologics naming approach and avoid potential issues for manufacturers and other stakeholders, according to USP. The proposed change had been open for comment in the USP Pharmacopeial Forum, which enables the organization to incorporate feedback from the FDA as well as a wide variety of stakeholders, including industry, researchers, health providers, and others. The comment period ended March 30, 2018.
The USP–NF is a combination of two compendia, the United States Pharmacopeia (USP) and the National Formulary (NF). Monographs for drug substances, dosage forms, and compounded preparations are featured in the USP–NF. A monograph includes the name of the ingredient or preparation; the definition; packaging, storage, and labeling requirements; and the specification. The specification consists of a series of tests, procedures for the tests, and acceptance criteria. These tests and procedures require the use of official USP Reference Standards. Medicinal ingredients and products will have the stipulated strength, quality, and purity if they conform to the requirements of the monograph and relevant general chapters. The US Federal Food, Drug, and Cosmetics Act designates the USP–NF as the official compendia for drugs marketed in the US. A drug product in the US market must conform to the standards in the USP–NF to avoid possible charges of adulteration and misbranding.
USP said it is currently reviewing stakeholder comments to its proposed change to Section 2.20 Official Articles of the General Notices and Requirements to add the following language at the end of the second paragraph: “For a biologic product licensed under the Public Health Service Act, the official title shall be the title specified in the relevant monograph plus any suffix designated by FDA unless otherwise specified in the applicable monograph.” The General Notices provide definitions for terms used in the monograph, as well as information that is necessary to interpret the monograph requirements.
In a letter dated March 28, 2018 to the USP, Janet Woodcock, Director of FDA’s Center for Drug Evaluation and Research, and Peter Marks, Director of FDA’s Center for Biologics Evaluation and Research, raised concerns that efforts to develop biological product monographs could impede or delay licensure of biosimilars and other biological products. The FDA said that it understood that USP’s initial proposal regarding the issuance of monographs for biological products was intended to harmonize biological product monographs with the FDA guidance, Nonproprietary Naming of Biologic Products, the agency’s so-called Naming Guidance. Under this guidance, the nonproprietary named designated for each originator biological product, related biological product, and biosimilar product would consist of a combination of the core name (i.e., the active pharmaceutical ingredient) and a four-letter lowercase suffix devoid of specific meaning to the product. The Naming Guidance points out that the FDA is continuing to consider the appropriate suffix format for interchangeable products and the approach to implementing the naming convention for previously approved biologic products that are deemed to be licensed under Section 351 of the Public Health Services Act on March 23, 2020.
FDA’s concern of biological product monographs focused on the possibility that a sponsor of a proposed biosimilar or interchangeable product could be deterred from seeking licensure under the abbreviated pathway created by Congress under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which was passed as part of healthcare reform (Affordable Care Act) that President Obama signed into law on March 23, 2010. The BPCI Act creates an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed reference product. Those measures do not require the biosimilar applicant to demonstrate that the same drug substance as the reference product using the same tests and assays. The FDA raised concerns that the USP’s initial approach could complicate licensure of a biosimilar that meets the requirements of 351 (k) of the Public Health Services Act, which established the regulatory pathway for biosimilars, but did not match the standards used in a USP monograph associated with the reference product.