FDA’s Revised Draft Guidance on Biological Product Promotion Provides Additional Recommendations/Clarifications

On April 24, 2024, the FDA issued a revised draft guidance, Promotional Labeling and Advertising Considerations for Prescription Biological Reference Products, Biosimilar Products, and Interchangeable Biosimilar Products – Questions and Answers, (the “Revised Draft Guidance”) which replaces the Agency’s initial draft guidance issued in February 2020 (the “Initial Draft Guidance”).

This Revised Draft Guidance provides considerations for manufacturers, packers or distributors (dubbed “firms”) of prescription biological reference products, biosimilar products, and interchangeable biosimilar products presenting data and information about such products in promotional materials in a truthful and non-misleading way.  Promotional labeling is generally any labeling other than FDA-required labeling that is devised for the promotion of a product, as well as other functions, and can include printed, audio, or visual matter that describes the product. While the Federal Food, Drug & Cosmetic Act does not explicitly define “advertisement,” FDA provides several examples in its regulations at 21 CFR § 201.1(l)(1) (e.g., “advertisements in published journals, magazines, other periodicals, and newspapers, and advertisements broadcast through media such as radio, television, and telephone communication systems”).

Major differences between the Revised Draft Guidance and the Initial Draft Guidance include additional recommendations, an example of a misleading promotional communication for interchangeable biosimilar products, and clarifications on postmarketing reporting requirements.

The Revised Draft Guidance emphasizes that where multiple products are licensed as biosimilar to and interchangeable with or biosimilar to but not interchangeable with the same reference product, promotional communications should avoid suggesting that any of the products are less safe or effective than each other for their approved uses. To emphasize this point, the Agency provides one new example of a promotional communication for interchangeable biosimilar products where it would consider the presentations described to be misleading (see Example 4 in Q7). In the example, it would be misleading for a product that is an interchangeable biosimilar to suggest superior safety and efficacy to a  non-interchangeable biosimilar product solely based on the product’s status as an interchangeable biosimilar product. Relatedly, promotional communications for a biosimilar product that suggest that a finding of biosimilarity means that the FDA determined the reference product and biosimilar product are identical to each other would not be accurate, and therefore misleading, because “biologics generally cannot be copied exactly” and typically have even minor differences between batches of the same product.

The Revised Draft Guidance also further clarifies postmarketing reporting requirements for submitting promotional communications to the FDA do apply to promotional communications for biological reference products, biosimilar products, and interchangeable products under 21 CFR § 601.12(f)(4). The FDA specifically notes that “specimens of mailing pieces and any other labeling or advertising devised for promotion of the reference product or biosimilar product [including an interchangeable biosimilar product] must be submitted to FDA at the time of initial dissemination of the labeling or at the time of initial publication of the advertisement, as applicable” and be accompanied by a completed Form FDA 2253 (emphasis added). We note this clarification is helpful given the modification to the definition of “promotional labeling” in the Revised Draft Guidance as part of footnote 4.  In the new definition, FDA removed the phrase, “that is devised for the promotion of a product,” broadening the definition of “promotional labeling” to potentially encompass any labeling other than the FDA-required labeling.  The restatement in text that postmarketing reporting requirements apply to labeling devised for promotion is supportive of our original understanding.

As a reminder, manufacturers, packers or distributors of prescription biological reference products, biosimilar products, and interchangeable biosimilar products may voluntarily seek FDA feedback on their proposed promotional communications before dissemination by following the current process outlined in FDA’s draft guidance Providing Regulatory Submissions in Electronic and Non-Electronic Format – Promotional Labeling and Advertising Materials for Human Prescription Drugs (April 2022).

Comments to the revised draft guidance are due to the docket by June 25, 2024.