On April 25, 2024, the U.S. Food and Drug Administration (FDA) issued and requested public comment on a revised draft guidance (Draft Guidance) providing recommendations related to promotional labeling and advertising that manufacturers, packers, and distributors (collectively "Firms") should consider when promoting or advertising biosimilar products, including interchangeable biosimilar products, and their reference products. Stakeholders had until June 24, 2024 to submit comments on the Draft Guidance.
Key Takeaways
The Draft Guidance replaces a 2020 draft guidance (FDA-2019-D-5473) and is meant to address questions that Firms and their representatives had around the promotion of biosimilars. While the updated Draft Guidance remains largely similar to the previous version, it notably includes under its scope interchangeable biosimilar products. The 2020 draft guidance expressly excluded "considerations unique to promotional materials for interchangeable biosimilars." Additional changes include an example for interchangeable biosimilar products (i.e., Question 7) in addition to a number of editorial changes. The main difference from the 2020 draft guidance is the inclusion of interchangeable biosimilars, as FDA had committed to releasing such guidance in the "Biosimilar Biological Product Reauthorization Performance Goals and Procedures" for fiscal years (FYs) 2023-2027.
FDA's release of the Draft Guidance also demonstrates its continued focus on streamlining the development and distribution of biologics and biosimilars. In 2018, FDA created an Office of Therapeutic Biologics and Biosimilars and developed the "Biosimilars Action Plan" to identify key agency actions to encourage innovation and competition among biologics and the development of biosimilars. Moreover, as part of the "Biosimilar Biological Product Reauthorization Performance Goals and Procedures" for FYs 2023-2027, FDA stated its intention to release the Draft Guidance and committed to issuing final guidance within 18 months after the close of the public comment period on the Draft Guidance.
Guidance Summary
The Draft Guidance is set forth in a question and answer (Q&A) format and contains nine Q&As. We summarize the recommendations included in the Draft Guidance below:
- General requirements: As required by the Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA's implementing regulations, prescription drug promotional communications must be truthful and non-misleading about the drug's safety and effectiveness. To this end, promotional communications must convey information about a drug's effectiveness and its risks in a balanced manner and reveal material facts about the drug. Applicants must promptly revise promotional labeling and advertising for their biological products upon certain changes to the FDA-approved labeling, including changes to risk information in the FDA approved labeling. For biosimilar products, this may mean that an update to advertising is required if there are updates to the reference product's label.
- Identifying reference products and biosimilar products: FDA notes the importance of properly identifying the reference product, including the proprietary name, proper name, and core name, to prevent promotional communications that are inaccurate because they attribute data or information to the wrong product. "Correctly and specifically identifying the relevant biological product or products in promotional communications can help prevent presentations that are inaccurate because they attribute data or information to the wrong product." The FDA specifically calls out the use of non-U.S.-approved biological products as an example. In cases where a study supporting a demonstration of biosimilarity or interchangeability uses a non-U.S.-approved biological product as a comparator, promotional communications should identify the product as a non-U.S.-approved biological product.
- Presenting clinical study information: FDA recommends that a biosimilar product's FDA-approved labeling incorporate relevant data and information from the reference product's FDA-approved labeling, including clinical data that supported FDA's finding of safety and effectiveness of the reference product. For example, if a biosimilar product is licensed for fewer than all conditions of use for which the reference product is licensed, the biosimilar product's FDA-approved labeling generally contains the data and information from the reference product's FDA-approved labeling that is relevant to the licensed conditions of use of the biosimilar product. As noted in the general requirements section above, this would require monitoring of labeling information of the reference product and updating the biosimilar product's promotional materials to ensure it accurately reflects such clinical information.
- Presenting information related to safety or effectiveness: FDA states that Firms have expressed interest in developing promotional communications that include data or information related to the safety or effectiveness of their biosimilar product. These include studies that supported the demonstration of biosimilarity between the biosimilar product and the reference product are generally not included in the FDA-approved labeling for the biosimilar product. FDA requires that such promotional communications be consistent with the principles outlined in the June 2018 guidance for industry Medical Product Communications That Are Consistent With the FDA-Required Labeling: Questions and Answers.
- Comparing a reference product to its biosimilar product: FDA recommends that Firms carefully evaluate promotional communications and avoid presentations that 1) represent or suggest that a licensed biosimilar product is not highly similar to the reference product or that 2) represent or suggest that there is a clinically meaningful difference in terms of safety, purity, or potency exists between the reference product and biosimilar product.
- Additional considerations: FDA states that when multiple products are licensed as biosimilar to and interchangeable/non-interchangeable with the same reference product, promotional communications should avoid representing or suggesting that a reference product or an interchangeable/non-interchangeable biosimilar product are less safe and effective than each other based on their licensure pathway.
Promotional communications should not undermine FDA's finding of biosimilarity, including its finding that the products are "highly similar," including through comparisons of the products in promotional materials. Additionally, FDA expects minor differences between biosimilar products and biological reference products and, thus, cautions against promotional communications that suggest a biosimilar is less safe or less effective than its reference product simply because it is not identical to the reference product.
- Examples: FDA provides four examples of promotional communications where the FDA would object to and not object to promotional communications for fictional biologics, biosimilar products, and interchangeable biosimilar products. FDA provides these examples in order to illustrate some of the general considerations outlined in the Draft Guidance. As noted previously, FDA extends the Draft Guidance to include interchangeable biosimilar products and provides a new example for interchangeable biosimilar products. Example 4 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. Part of the emphasis of the Draft Guidance is the FDA's desire to move away from the use of "interchangeable" and "biosimilar" in promotional materials as a means to avoid confusion that an interchangeable drug may somehow be more effective or safer than a biosimilar product. The additional examples help to reinforce that idea.
- Request for FDA review: The FDA wants to promote honest and truthful promotion and advertising around biosimilar products, and encourages Firms to voluntarily seek FDA feedback on promotional communications for reference products or biosimilar products before dissemination of those communications. The current process for submitting draft promotional communications for comment provides companies an opportunity to seek such FDA feedback.
Conclusion
Stakeholders that are developing and disseminating promotional materials for biosimilar products, and also interchangeable biosimilar products, should review the Draft Guidance and consider its recommendations. In particular, the FDA has made clear that any promotion that attempts to imply that an interchangeable product is safer or more effective than a biosimilar product would be misleading. The release of the updated Draft Guidance also provided an opportunity for stakeholders to provide comments on the entire guidance, not just the updates related to interchangeable biosimilar products.
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