FDA Off-Label Drug Guidance: 3 Things to Know

New guidance from the U.S. Food and Drug Administration walks back constraints the agency previously laid out on how drugmakers and other companies communicate with healthcare providers about off-label uses of approved treatments.

The final guidance, released Monday, outlines the agency’s enforcement policy regarding the sharing of scientific information on unapproved uses of drugs and medical products, also known as “SIUU” communications.

The update comes roughly a year after a draft version of the guidance received heavy pushback from pharmaceutical companies and trade groups, which argued that it would interfere with their First and Fifth Amendment rights and overly restrict communications with providers.

While it remains to be seen what impact the final guidance will have on industry policy, experts told Law360 that the guidance addresses industry concerns and points to a shift in agency thinking on what standards SIUU communications must meet to be considered non-promotional and backed by science.

Here are three things to know about the FDA’s final guidance on SIUU communications.

Firm-generated presentations

The SIUU guidance clarifies what kinds of information medical products companies can draw from when creating presentations on off-label uses of drugs and devices.

It also cements the FDA’s recent shift toward allowing firms to summarize and depict scientific findings when disseminating medical journal articles to healthcare providers.

Prior to the FDA’s 2023 draft guidance, the agency had advised drug and device manufacturers not to emphasize portions of scientific articles suggesting the safety or efficacy of off-label uses when disseminating medical publications.

While the shift was welcomed by industry players, pharmaceutical companies and trade groups also raised concerns at the time that the guidance only allowed firms to create presentations based on article reprints.

Monday’s final guidance clarifies that, in addition to article reprints, firms can also use clinical resources such as medical reference texts and clinical practice guidelines.

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While this shift may be welcomed by the medical products industry, public health advocate Diana Zuckerman said it also raises concerns over the quality of information in firm-generated presentations.

“I say this as a peer reviewer and as somebody who publishes in medical journals and reviews articles that other people have submitted — there’s [an] enormous disparity between some journals and others and what they’ll publish and what others won’t,” said Zuckerman, president of the National Center for Health Research, a medical safety think tank.

In a comment letter on the draft guidance last year, the NCHR emphasized the potential for firms to “unintentionally misrepresent or manipulate results [by] using figures and graphs that do not fully represent the data.”

“Because there is rarely enough time to carefully examine the evidence in PowerPoint or other oral presentations, they are unlikely to present information in the full context needed for healthcare providers to interpret the strengths and weakness of the data provided,” the NCHR said.

Promotion vs. scientific information

Another key section in Monday’s guidance concerns the FDA’s definition of the boundary between SIUU communications and promotional activities. While the FDA allows companies to share certain scientific information on off-label drug uses with providers, laws concerning product misbranding and FDA premarket review requirements leave companies open to prosecution if the agency considers their communications promotional in nature.

In the final guidance, the FDA clarified that communications that “encourage the unapproved use of the firm’s medical product based on elements other than the communication’s scientific content” do not fall within the FDA’s enforcement policy on SIUU communications.

The agency mentioned celebrity endorsements, premium offers and promotional tag lines as examples of techniques used by firms to “influence decisions based on elements other than the communication’s substance.”

“In general, in the context of any communication from a firm to [a healthcare provider] in support of an unapproved use, the firm’s choice to use these communication techniques suggests an effort to convince the [healthcare provider] to prescribe or use the product for the unapproved use, rather than providing the [healthcare provider] with scientific information to evaluate and make their own clinical decisions,” the guidance said.

This language marks a shift from the FDA’s 2023 draft guidance, where the agency stated that SIUU communications “should not use persuasive marketing techniques” and recommended that firms differentiate channels for those communications from promotional activities to reduce the risk of providers “conflating” information about approved and unapproved uses.

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Scientific standards

Industry players will also welcome certain clarifications in the guidance regarding the scientific standards that should be met by source publications.

Notably, the final guidance did not preserve language from the 2023 draft dissuading companies from relying on scientific data generated in the “early stages” of product development.

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The final guidance also did not preserve the 2023 draft standard that source publications included in SIUU communications must — in addition to being “scientifically sound” — provide “clinically relevant” information pertinent to how providers make clinical practice decisions in caring for patients.

Instead, the guidance maintained only the “scientifically sound” standard.

“To be scientifically sound, the studies or analyses should meet generally accepted design and other methodological standards for the particular type of study or analysis performed,” the guidance said, providing examples of types of research considered valid for human and animal drugs as well as devices.

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Zuckerman raised concerns about examples provided by the FDA, saying some were “inconsistent with what a scientist would consider scientifically valid.”