Life Finds A Way: The FDA Releases Draft Guidance for Labeling and Advertising Biological and Biosimilar Products

The Food and Drug Administration (FDA) has published revised draft guidelines in the Federal Register on promotional labeling and advertising considerations for the biologic and biosimilar industry, updating guidance from 2020. The quick revisions emphasize the fast-changing and rapidly growing nature of this industry.

Biological products, or “biologics”, are a class of drugs made from natural and living sources like animal and plant cells, and microorganisms such as bacteria or yeast. Examples of biological products include vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologic medicines play a critical role in the treatment of many serious illnesses, such as cancer and genetic disorders (and, in many cases, they are only treatments available). Unsurprisingly, biologics are the fastest growing class of medications in the United States and account for a substantial and growing portion of health care costs.

Recognizing the importance of patient access to biological products, Congress passed the Biologics Price Competition and Innovation Act (“BPCI Act”) in 2010 which established an abbreviated pathway for FDA approval of “biosimilar” products. A biosimilar is a biologic that is highly similar to and has no clinically meaningful differences in terms of safety, purity, and potency (safety and effectiveness) from an existing FDA-approved biologic, called a reference product. The approval pathway for biosimilars allows sponsors to leverage the FDA’s finding of safety and effectiveness of a reference product to support approval of the biosimilar, often at a lower cost to the sponsors than the development program for the reference product, provided that the sponsor can demonstrate that the biosimilar meets the statutory standards for biosimilar approval. The goal of a biosimilar development program is to demonstrate biosimilarity between the proposed biosimilar and its reference product, rather than independently establishing the safety and effectiveness of the proposed biosimilar. To meet the standard for interchangeability, an applicant must provide sufficient information to demonstrate biosimilarity and also to demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient. The applicant must further show that if the biological product is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.

The FDA has continued to make biologics an area of focus, developing the “Biologics Action Plan” in 2018 and creating an “Office of Therapeutic Biologics and Biosimilars” whose mission is “[t]o support the development and approval of high quality, safe, and effective biosimilar and interchangeable biologic products for the American public.” The recently-revised advertising and labeling guidelines represent another means through which the FDA is working to streamline the development and distribution of biologics.

The guidelines, formally titled “Promotional Labeling and Advertising Considerations for Prescription Biological Reference Products, Biosimilar Products, and Interchangeable Biosimilar Products” are designed to “address questions firms may have when developing FDA-regulated promotional labeling and advertisements” for biologic and biosimilar prescription products. In particular, the guidelines are focused on how to present information in promotional materials “in a truthful and non-misleading way,” and are replete with footnotes citing to both FDA regulations and additional guidance documents.

Most of the document is styled in a Q&A format, and has expanded from eight to nine questions. Almost all of the answers have been rewritten for clarity. The questions pertain to promotional communications, including regulatory requirements, how to identify biosimilar and related reference products, how to present information from studies conducted to support licensure of these products, and what comparisons may be made between biosimilar and reference products without running afoul of FDA regulations. Several answers refer the reader to separate FDA guidance documents, including June 2018 guidance entitled “Medical Product Communications That Are Consistent With the FDA-Required Labeling Questions and Answers” and 2022 guidelines entitled “Providing Regulatory Submissions in Electronic and Non-Electronic Format—Promotional Labeling and Advertising Materials for Human Prescription Drugs.”

Overall, the guidelines have not changed significantly. Even the “new” question, which asks whether promotional communications are subject to postmarketing reporting requirements, had been addressed previously under a separate question. The most expanded answer falls under Question Seven, which provides examples for applying the FDA’s guidance to promotional communications. New in this version are additional hypothetical scenarios designed to illustrate considerations raised in other questions, such as the need to be accurate and to ensure that the data and studies presented in the promotional materials support the claims made. Two examples are scenarios where the FDA would not expect to object to the promotional communications, while two others are promotional communications that the FDA would consider misleading. In the latter category, one scenario claimed that patients taking one fictional product experienced a higher overall response rate than patients on another product. However, because the underlying study found that the difference in response rates was not statistically significant, this claim, according to the FDA’s guidance, misleadingly implies that there is a clinically meaningful difference between the products. Another example explains that in a scenario where Product A is licensed as interchangeable with Product B, but Product C is not, it is misleading to suggest that Product A is safer or more effective than Product C.

The agency is careful to note that the guidelines do not create “legally enforceable responsibilities” and instead simply “describe the Agency’s current thinking on a topic” with recommendations.  Comments on the new draft guidelines can be submitted via the Federal Register or mail until June 24, 2024.  Even after the agency issues final guidelines, it must allow online and written comments on any guidance at any time pursuant to 21 C.F.R. 10.115(g)(5). If you have any questions regarding the guidance or any of the products or topics addressed in this alert, please reach out to the attorneys listed below.