Observations and Implications
- Given the growth in the number of biosimilars having been approved or expected to come to market in the coming years, FDA sought to clarify direction to minimize false and misleading promotional activity, all in the name of patient safety
- Definitions and proper use of the words “interchangeable”, “identical”, and “biosimilar” are critical by all stakeholders to ensure customers are not misled
- FDA reinforces that FDA approval is limited to “highly similar” unless otherwise stated
- Comparing the reference product to the biosimilar is perilous, head to head clinical trials are still seen as the gold standard when comparing two products
- This includes making inferences across indications, as many biosimilars may not have been given approval on all indications as the originator
- The guidelines address referenced product promotions just as much as biosimilar product promotions
- Clearly the biosimilar manufacturers aren’t the only one’s looking for, or needing, guidance on how to message around the relationship between a reference product and the corresponding biosimilar product
- This guidance addresses questions firms may have when developing FDA-regulated promotional labeling and advertisements for products licensed under 351(a) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(a)) and section 351(k) of the PHS Act (42 U.S.C. 21 262(k)).
- The guidance discusses considerations for presenting data and information about reference or biosimilar products in these promotional materials in a truthful and non-misleading way.
- Although the guidance covers promotional issues involving both reference and biosimilar products, some questions and answers are focused on only biosimilar product promotional materials. This guidance does not discuss considerations unique to promotional materials for interchangeable biosimilars.
- In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word “should” in Agency guidances means that something is suggested or recommended, but not required
- To meet the standard for interchangeability, an applicant must (1) provide sufficient information to demonstrate biosimilarity to the reference product and (2) demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient and, 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.
- Once FDA licenses a biosimilar or interchangeable product, providers and patients can be assured of the safety and effectiveness of a biosimilar or an interchangeable product, just as they would be for the reference product.
- FDA expects an increase in promotion involving reference and biosimilar products. FDA is providing this guidance to address questions firms may have when developing FDA-regulated promotional materials for reference products or biosimilar products. The guidance discusses considerations for presenting data and information to help ensure that the information is accurate, truthful, and non-misleading as required under the Federal Food, Drug, and Cosmetic (FD&C) Act and FDA’s implementing regulations.
What are the general requirements for the content of FDA-regulated promotional materials for reference products and biosimilar products?
- Reference products or biosimilar products are subject to the FD&C Act and FDA’s implementing regulations, including misbranding provisions that address advertisements and promotional labeling for prescription drugs issued by or on behalf of manufacturers, packers, or distributors.
- Promotional labeling and advertising must be
- Truthful and non-misleading
- Convey information about a drug’s efficacy and its risks in a balanced manner
- Reveal material facts about the drug
- Whether a promotional presentation is truthful and non-misleading involves a fact-specific determination that takes into account such factors as
- How the information is presented
- The type and quality of the data relied on to support the presentation
- Contextual and disclosure considerations.
- FDA regulations also require that firms promptly revise promotional labeling and advertising for their biological products upon certain labeling changes, including labeling changes to risk information
How should firms identify reference products and biosimilar products in promotional materials?
- Depending on the context, reference and biosimilar products, may be identified by their proprietary name(Udenyca), nonproprietary or proper name (Pegfilgrastim), or core name.
- A biological product’s core name is the component shared among a reference product and any related biological product, biosimilar product, or interchangeable product as part of the proper names of those products.
- Firms should carefully evaluate the information presented in promotional materials for reference products or biosimilar products to ensure that in each instance where the promotional materials address a product or products, the materials correctly and specifically identify the product or products to which the information applies
- For instance, if a biosimilar product’s FDA approved labeling uses the core name of the reference product followed by the word “products” to convey that a risk applies to both the biosimilar and the reference product, it would also be appropriate for similar presentations about this risk in promotional materials for the biosimilar to use this nomenclature.
- Firms should also ensure that if promotional materials describe studies in which non-U.S.-licensed comparator biological products were used (or if promotional materials otherwise mention such products), the promotional materials accurately identify the non-U.S.-licensed comparator biological products.
- Clearly and correctly identifying the relevant biological product or products in promotional materials can help prevent presentations that are inaccurate because they attribute data or information to the wrong product. It can also help the audience identify which product or products are the subject of a particular promotional presentation.
When developing promotional materials for biosimilars, what should firms consider if presenting information from the studies conducted to support licensure of the reference product when the information is included in the FDA-approved labeling of both the reference and the biosimilar products?
- Firms should refer to the biosimilar product’s FDA-approved labeling. FDA has recommended 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
When developing promotional materials for biosimilars, what should firms consider if presenting data or information from studies conducted to support a demonstration of biosimilarity when the data or information is not included in the FDA-approved labeling for their biosimilar product?
- Those presentations should be consistent with the biosimilar’s FDA-approved labeling and be truthful and non-misleading, as described in the guidance for industry Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers (June 2018) 149 (CFL guidance).
- FDA has recommended that the FDA-approved labeling for a biosimilar product generally not include data and information from studies conducted to support a demonstration of biosimilarity between the reference product and the biosimilar product.
- However, firms developing promotional materials for their biosimilar products have expressed interest in communicating this information to health care providers or other interested parties. FDA encourages these firms to apply the principles outlined in the CFL guidance if the promotional materials for their biosimilar products include data or information from studies that supported the demonstration of biosimilarity between the biosimilar and the reference product, which generally will not be included in the biosimilar product’s FDA-approved labeling.
What should firms consider when comparing reference products and biosimilar products in their promotional materials?
- Representations or suggestions that create the following impressions are likely to be false or misleading
- That there are clinically meaningful differences between the reference product and its biosimilar
- That a reference product is safer or more effective than its biosimilar product
- That a biosimilar is safer or more effective than its reference product
- That create an impression that a biosimilar is not highly similar to its reference product
- Similarly, representations or suggestions that a biosimilar product is superior to its reference product based on a difference that is not clinically meaningful between the rates of occurrence of a particular adverse reaction from a study that supported a demonstration of biosimilarity between the reference product and biosimilar would be misleading.
- Representations or suggestions that the reference product is less safe or less effective than its biosimilar based on this study also would be misleading.
- In some cases, individual statements of accurate information about a reference product or about a biosimilar product could contribute to a misleading presentation when provided in a comparative context.
- For example, presentations in promotional materials for a reference product comparing the number of indications for which the reference product is licensed to the number of indications for which the biosimilar is licensed in a manner that creates the net impression that the biosimilar product is in general less safe or less effective than the reference product simply because the biosimilar is licensed for fewer indications than the reference product would be misleading. Where a biosimilar has not been directly studied in a particular indication (i.e., the biosimilar’s licensure for the indication is based in part on extrapolation), representations or suggestions in promotional materials for the reference product that the biosimilar is less safe or less effective than the reference product in that indication because licensure for that indication was based in part on extrapolation also would be misleading.
What else should firms consider when developing promotional materials for reference products or biosimilar products?
- Promotional materials for a biosimilar product that FDA has not licensed as interchangeable with the reference product should avoid creating an impression that the biosimilar has been licensed as interchangeable with the reference product.
- Promotional materials for a reference product should avoid representing or suggesting that a biosimilar product is less safe or effective than its reference product because it has not been licensed as interchangeable with the reference product.
- FDA also reminds firms that a biosimilar product is not required to be identical to the reference product in order to be licensed