n December 2025, just ahead of the new year, the US FDA published a Questions and Answers Guidance for Industry, addressing questions manufacturers, packers, and distributors (“firms”) may encounter when developing FDA-regulated promotional labeling and advertisements (i.e., promotional communications).

• Prescription biological reference products licensed under section 351(a) of the Public Health Service (PHS) Act (42 U.S.C. § 262(a)), and
• Prescription biosimilar and interchangeable biosimilar products licensed under section 351(k) of the PHS Act (42 U.S.C. § 262(k))

The guidance outlines considerations for how data and information about reference products and biosimilar products should be rendered in promotional communications. For purposes of the guidance, a biosimilar product is one licensed under section 351(k) of the PHS Act as either biosimilar to, or interchangeable with, a reference product. The guidance seeks to reduce likely confusion among healthcare practitioners and patients—particularly around biosimilarity, interchangeability, and appropriate product use—by outlining how data and comparative information should be presented as “accurate, truthful, and non-misleading.” Note that recommendations for nonprescription products are not included in this guidance.

The global biosimilars market value is expected to more than double from $35.04 billion in 2025 to approximately $72.29 billion by 2035. The US and Europe together account for the bulk of this market. While market estimates vary by vendor, the market situation highlighted in the December guidance remains unchanged: increasing approvals and competitive entry are driving both opportunity and regulatory focus.

There are three ways in which this December guidance—applicable to all FDA-regulated promotional labeling and advertising, regardless of communication medium—is intended to support manufacturers: 1. to help firms develop compliant promotional materials; 2. to increase confidence in the FDA’s biosimilar framework; and 3. to underpin informed prescribing and substitution decisions.

Regulatory Context

This all traces back to section 351(k) of the PHS Act, which created an abbreviated licensure pathway for biosimilar and interchangeable biological products. To count as a biosimilar, a product must be highly similar to a reference product, with no clinically meaningful differences in safety, purity, or potency. To have interchangeable status under section 351(k)(4), the product must produce the same clinical result in any patient, and switching or alternating with the reference product can’t increase the risk to safety or efficacy. Only then can it be substituted at the pharmacy without the prescriber’s sign-off, subject to state law. FDA laid out its original expectations for meeting this standard in its May 2019 guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” which generally called for switching-study data. FDA’s thinking has since shifted. A 2024 draft update allows applicants to instead submit an assessment explaining why their existing analytical and clinical data already meets the standard without dedicated switching studies—and FDA has signaled plans to finalize this shift in 2026.

Once licensed, biosimilar and interchangeable products may be prescribed to both treatment‑naïve and treatment‑experienced patients and are held to the same rigorous standards as reference products, providing the context for the FDA to issue this guidance addressing questions related to FDA‑regulated promotional communications.

FDA’s activities in early 2026 have reinforced that the agency continues to refine its thinking and expectations regarding biosimilar development and acceptable comparative evidence. In March 2026, the agency announced further steps to improve biosimilar development, including the publication of draft Q&As and the withdrawal of certain previous scientific guidance—part of the same broader push that includes the interchangeability update discussed above, with FDA officials signaling that both are on track for finalization in the first half of 2026. Separately, FDA’s legislative materials (April 2026) included a proposal to eliminate the statutory distinction between “biosimilar” and “interchangeable”; if adopted, this policy could materially change how firms communicate about interchangeability and substitution. Since this distinction is written into the PHS Act itself, only Congress can eliminate it; the FDA does not have authority to make this change unilaterally through guidance or rulemaking. Right now, this is still just a budget proposal, not law, and therefore it will need congressional action before anything changes.

At the DIA Global Annual Meeting 2026, Peter Richardson of the European Medicines Agency (EMA) raised a useful point: the EU has largely moved away from comparative clinical efficacy studies, leaning instead on analytical and quality data to establish biosimilarity, and EU biosimilars are treated as interchangeable by default, with no separate designation required. FDA is already moving toward the switching-study side of that picture on its own, as noted above. What Congress alone can still do is erase the legal category itself—which is exactly what FDA’s own proposal is now asking it to do. The EU is functionally already there; the US still needs an act of Congress to fully catch up.

Still Applicable: Core Promotional Standards

According to the Q&A publication, reference, biosimilar, and interchangeable biological products are still subject to longstanding promotional standards, and promotional communications are still subject to existing misbranding provisions (including requirements that claims be truthful, nonmisleading, and presented with an appropriate balance between benefits and risks). Whether a communication is misleading depends on a number of factors, including: (1) the quality of the data relied upon; (2) the manner in which information is framed; (3) whether sufficient context and disclosures are provided; and (4) express and implied claims made. Firms also need to keep their promotional materials current with FDA-approved labeling changes, and to meet post-marketing submission requirements (21 CFR 601.12(f)(4); 21 CFR 314.81(b)(3)(i)).

Relevance of Precise Product Identification

FDA advises firms to clearly and specifically identify whether a promotional communication refers to a reference product, a biosimilar product, or multiple products, using appropriate nomenclature to avoid misattribution of data or confusion among audiences. This will matter most when presenting safety or effectiveness information that actually applies to more than one product; for example, a biosimilar whose FDA-approved labeling uses the reference product’s core name followed by the word “products” (e.g., “replicamab products”) to show that a risk applies to both the reference product and the biosimilar. If that is the case, it is appropriate to use the same convention in promotional communications for the biosimilar.

Presenting Reference-Product Data in Biosimilar Promotion

When data from studies supporting licensure of the reference product appear in both the reference product’s and the biosimilar’s FDA-approved labeling, FDA recommends that biosimilar promotional communications draw from the biosimilar’s own FDA-approved prescribing information (its package insert), rather than pulling from the reference product’s label directly, since the biosimilar’s own labeling includes only the data relevant to its licensed conditions of use. This means relying on the CLINICAL STUDIES section and related clinical pharmacology, immunogenicity, and toxicity studies within that document. FDA also acknowledges that firms may wish to communicate additional data not found in that prescribing information (e.g., biosimilarity studies not included in the labeling) but affirms that these communications must be consistent with FDA-required labeling, supported by appropriate scientific evidence, and presented with appropriate context.

FDA-Identified Risk: Comparative Promotion

The guidance makes an important point: a statement can be completely accurate but still be misleading when presented without the appropriate context or set up as a comparison that suggests a clinically meaningful difference in, for example, safety, purity, or potency, where none genuinely exists. That is exactly the risk with any claims implying superiority or inferiority, based on small differences, approval pathways, or dosage forms: FDA’s promotional standards prohibit implying clinical superiority devoid of substantial evidence (21 U.S.C. § 352(a)).

Enforcement Trends and Practicalities

In March 2026, FDA announced that it had issued 30 warning letters to telehealth companies for misleading promotional claims about compounded GLP-1 products marketed as equivalent to FDA-approved medications. That authority came from FDA’s oversight of compounded drugs and the FD&C Act’s misbranding provisions, not from any biosimilar-specific power under section 351(k). Still, the action shows the FDA is willing to use its enforcement tools against promotional claims it considers false or misleading. These letters were not about biosimilars, but firms developing biosimilar promotion should take heed: interpret the Q&A conservatively, document comparative claims carefully, and keep a close eye on digital channels before any promotional communication goes out.

FDA’s Q&A publication and subsequent agency actions reinforced the expectation of a heightened standard: promotional communications for reference, biosimilar, and interchangeable products need to reflect the scientific and regulatory basis underlying their licensure. Confidence in biosimilars can be undermined by ambiguity regarding biosimilarity and interchangeability (due to inconsistent or unclear messaging), which can ultimately affect prescribing and substitution decisions by healthcare providers. Avoiding that kind of ambiguity comes down to a few practical habits:

• Marketing should work with Medical, Legal, and Regulatory (MLR) review to name products precisely and frame any comparisons carefully; everything needs to remain tied to the approved labeling, so the message stays clear and does not mislead.
• Marketing and digital teams should route every digital asset (e.g., owned channels, search, paid media) through an MLR review so that labeling and product characterization remain consistent across all platforms.
• Regulatory affairs and policy teams should keep an eye on future FDA developments, including final or draft guidance, since a shift in policy on interchangeability could change what is permissible tomorrow.
• Medical affairs and regulatory teams should document evidentiary support and context for any comparative statements, particularly numerical comparisons or cross-product references.