Currently, a “Medication Guide” is FDA-approved written patient prescription drug product information for certain prescription drug products, required only to address serious safety events that patient labeling can address, where patient awareness of risks is deemed necessary or when FDA requires one as part of a REMS.

Under the proposed rule, however, the requirement to create a PMI would apply to applicants of all new and approved new drug applications (NDAs) and biologics license applications (BLAs), including biosimilars. The proposed rule would also require applicants of new and approved abbreviated new drug applications (ANDAs) that refer to a listed drug for which FDA has approved PMI to have PMI that is the same as that of the reference listed drug (RLD), except for certain differences in labeling permitted under the law, or by waiver. Interestingly, the PMIs will be accessible online through a central repository managed by FDA.

The proposal would further require “authorized dispensers” to provide PMI to patients each time a prescription drug product for which an FDA-approved PMI exists is used, dispensed, or administered on an outpatient basis, including at retail pharmacies and hospital ambulatory care pharmacies. The proposed rule defines an “authorized dispenser” as an “individual(s) or entity who is licensed, registered, or otherwise permitted by the jurisdiction in which the individual(s) or entity practices to provide prescription drug products in the course of professional practice.” In most instances, this party would be a pharmacist, but it may also include physicians, nurses, or other licensed health care providers legally permitted under state law to provide prescription drug products to patients. We assume PMI will replace the pharmacy-generated patient information hand-outs typically provided at pharmacies, but which is not reviewed or controlled by FDA.

“Authorized dispensers” would also include providers of transfusion services each time blood or blood components are administered on an outpatient basis. The requirement to create and distribute PMI would exclude products under Emergency Use Authorization, and manufacturers of preventive vaccines that do not have a Medication Guide.

Under the proposed rule, applicants would need to submit a one-page PMI document to FDA with standardized format and content, including sections for:

1. “Important Safety Information.” This section would require specific subheadings in the following order: “Warnings,” “Do not take,” Serious side effects,” and “Tell your health care provider before taking.”

2. “Common Side Effects.” The proposed rule would require a statement of frequently occurring adverse reactions from the use of the prescription drug product. FDA proposes that the listed common side effects must focus on the “most clinically relevant and the important adverse reactions to inform the patient.”

3. “Directions for Use.” In this section, the proposed rule would require the statement “Use exactly as prescribed” to appear first after the heading, followed by a summary of how the prescription drug product must be administered and the route of administration. It would include a statement of special handling, storage conditions, and disposal information.

The proposed rule would require the PMI to be:

• scientifically accurate,
• not false or misleading,
• based on and consistent with the prescription drug product’s Prescribing Information,
• updated when new information becomes available that would cause PMI to become inaccurate, and
• not be promotional in tone.

If finalized, the proposed rule would be implemented over a five-year period following the publication of the final rule, during which time FDA would begin withdrawing current regulations that require medication guides for certain prescription drug products, as well as those that require patient package inserts for oral contraceptives and estrogen-containing products. Proposed part 208 of the rule (“Medication Guides”) would be the successor regulation to current part 208 (“Medication Guides for Prescription Drug Products”), and current Medication Guides would continue to be available as a potential element of a REMS until FDA has approved PMI for the prescription drug product.

In a press release announcing the proposed rule, FDA Commissioner Robert Califf promoted the “consistent formatting” proposed in the rule as helping to “facilitate translations to other languages and make it easier for artificial intelligence or other technologies to convert the information, where feasible, to formats that assist the visually impaired.” In support of the proposal, FDA cites data showing that patients’ nonadherence to long-term prescription drug product therapies contributes to as many as 25% of hospital admissions, 50% of treatment failures, and approximately 125,000 deaths in the U.S. annually. FDA’s notice of the proposed rule also outlines at length the history of the rulemaking, including workshops, hearings, and studies on the matter, as well as previously-debated PMI prototypes.

Analysis & next steps

If finalized, the PMI would represent a major change in Rx drug labeling. Current FDA-approved prescribing information (PI) provides information solely for healthcare professionals (HCPs) and is written for that audience. When the agency changed the PI’s format in 2006, it emphasized that the PI is drafted solely for prescribers and healthcare professionals and declined requests to include a section directed at patients, instead creating Section 17 to provide agency-approved information that HCPs could use to counsel their patients.

As a result, manufacturers have struggled to translate approved instructions for HCPs into patient-friendly language for patient brochures, direct-to-consumer advertising, and direct-to-patient communications. If finalized, a PMI could facilitate those efforts and speed the use of industry-to-patient advertising and promotion.

Of course, FDA’s efforts have failed in the past due to a variety of factors, including opposition from retail pharmacies, which are set up to provide different forms of instructions. Larger forces opposed to regulation generally have also contributed to the demise of FDA’s past efforts. And, FDA has suffered setbacks in its effort to regulate drug advertising and promotion through challenges to its authority to regulate speech. It remains to be seen whether this effort will overcome those hurdles or lead to more confusion around patients’ use and understanding of drug labeling. Other hurdles, such as the evidence required to support information in the PMI or how closely follow-on generics or biosimilars must match a reference product’s PMI, will also need to be closely monitored.

The proposed rule also raises a number of questions as to its potential impact on the existing product liability landscape for manufacturers of FDA-approved drugs and biologics. One key question surrounds the interplay of the proposed rule with the learned intermediary doctrine—a legal principle which shields manufacturers from failure-to-warn-based product liability claims on the basis that a manufacturer’s duty to warn runs to the physician who prescribes the medication, not to the individual patient or general public.

In recent years, as FDA has required more patient-oriented disclosures from drug and device manufacturers, plaintiffs likewise have increasingly attempted to circumvent the application of the learned intermediary doctrine by grounding their failure-to-warn claims in allegations of inadequate FDA-required patient medication guides. Courts in different jurisdictions throughout the country have, for the most part, rejected these attempts and continued to affirm the applicability of the learned intermediary doctrine. As one court reasoned, FDA’s Medication Guide requirement does not circumvent the learned intermediary doctrine because it was “the FDA’s intent that the Medication Guide rule not alter the duty or set the standard of care for manufacturer’s.”[1] In other words, regardless of the federal regulation requiring manufacturers to supply a medication guide to patients, federal law does not impose a duty to warn individual patients. This precedent makes sense given that it is ultimately up to the doctor to make the decision regarding whether to prescribe a medicine to a patient.

In line with such court decisions, FDA notably (and perhaps intentionally), emphasizes in its proposed rule that “PMI is not intended to be a substitute for the PI . . . (while PMI would highlight the most important information, it is not intended to and would not include all the essential scientific information needed for the safe and effective use of the drug) or to be a replacement for patient counseling by a healthcare provider.” So, though Plaintiffs surely will continue to pursue patient-information-based failure-to-warn claims in hopes of pleading around the learned intermediary doctrine — and may very well increase these attempts should the proposed rule become final — language like the above from FDA supports the continued application of the learned intermediary defense, even if the new rule is enacted.

FDA is soliciting comments on the proposal by November 27, 2023. If you are interested in submitting a comment, or have any questions on FDA drug or biologic labeling rules more generally, feel free to contact any of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.

Authored by Meredith Manning, Heidi Gertner, Lauren Colton, Julie Schindel, and Bryan Walsh