On May 31, the U.S. Food and Drug Administration (FDA) published a proposed rule to amend its regulations regarding prescription drug product labeling regulations.[1] Under the new rule, each time a prescription drug products is used, dispensed, or administered in an outpatient setting, the patient would receive a one-page “Patient Medication Information” (PMI) Medication Guide that highlights essential information regarding the use of the drug. If implemented, FDA believes this rule will consolidate the various forms of prescription information that are dispensed to patients and consequently alleviate confusion for manufacturers deciding what forms are needed with particular prescriptions. Overall, it appears that the FDA’s goals are twofold: (1) standardization of patient-facing prescription drug product labeling, and (2) to expand accessibility of essential safety and efficacy information relevant to such medications. 

History and Impetus for Proposed Rule: 

This proposed rule comes as no surprise to those following the FDA’s decades-long search for the most appropriate manner of conveying prescription medication information to patients. In particular, on numerous occasions, the FDA has solicited information from stakeholders regarding the development of PMI prototypes and conducted research as to the most effective options for PMI content and organization. Currently, there are four categories of written patient prescription drug information:

1. Patient Package Insert (PPI): PPI are required under federal regulations for oral contraceptives and estrogen-containing products, and also can be submitted voluntarily by applicants or may be required as part of a risk evaluation and mitigation strategy (REMS);
2. Medication Guides: If the proposed rule is implemented, the regulations section covering Medication Guides will be revised to include PMI instead. However, currently, FDA requires a Medication Guide for certain products which present potential for serious adverse events or risks, or require adherence to ensure effectiveness. Similar to PPI, these may also be required as an element of a REMS;
3. Consumer Medication Information (CMI): CMI are privately and voluntarily developed without consultation from the applicant and without consultation or approval by the FDA;
4. Instructions for Use (IFU): IFU are another technically voluntarily created patient information guide – this time developed by the applicant and reviewed and approved by the FDA. For some drug classes, FDA will strongly suggest an IFU, especially where the medication has “complicated or detailed patient-use instructions.”[2]

As indicated by the FDA’s critical remarks, the agency views these options as failed experiments in ensuring patients are using medications safely and effectively. For example, the agency noted that “[t]his written patient information, in certain instances, has been duplicative, incomplete, conflicting, or difficult to read and understand, and has not been sufficient to meet the needs of patients.”[3]

Proposed PMI Rule – A Bird’s Eye View:

We could not possibly cram into one blog post each of the proposed attributes of the PMI rule, but the bird’s eye view, at this time, is enough to get the gist of what FDA is thinking. The proposed PMI regulations are particularly detailed, with specifications for, among other things, headings, subheadings, bold type, font size, and particular disclosure statements. All content included in the PMI will be “based on information required in the PI . . . and/or the circular of information.”[4] That means—nothing promotional and everything in a scientifically accurate, non-misleading format. However, pictograms and icons are not allowed.[5]

FDA identified the one-page requirement as one of the most important specifications of the PMI rules. For products with complicated administrations, FDA stated that if detailed instructions for use cannot be adequately conveyed in the PMI format, FDA will continue to approve the typical IFU format in the PI itself and/or a separate IFU document.[6] However, FDA intends to provide little leeway for exemption from the one-page requirement altogether. Indeed, FDA emphasized that although waivers will be available for some specifications, the agency anticipates “rarely granting a waiver to the one-page format requirement.”[7]

The proposed rule will impact all new and approved drugs approved through the New Drug Application (NDA) and Abbreviated New Drug Application (ANDA) pathways, biologics license applications (BLA), authorized dispensers of prescription drugs in outpatient settings, and blood and blood components transfusion services. In particular, NDA and BLA manufacturers would be required to obtain FDA-approval for their PMI, and ANDA manufacturers would either provide PMI that mirrors the reference listed drug upon which its approval is based, or an FDA-provided PMI template for the generic drug.

On the patient-facing side, authorized dispensers – typically retail pharmacies – will be required to distribute a paper copy (or electronic copy upon the patient’s request) of the PMI each time the drug is used, dispensed, or administered. Additionally, for transfusion services, the FDA will only require PMI-approval for licensed blood establishments. Lastly, FDA will manage an online repository of PMI that will be available to the public.

Takeaways:

One of the clearest takeaways from our review of the proposed rule and agency commentary is that the FDA is focused on both standardization and accessibility – each of which go hand-in-hand in achieving the agency’s ultimate goal of patient safety and effective use of prescription medication. At the heart of this standardization focus is the development of the one-page, fill-in-the-blank style format of the PMI, although it remains to be seen whether this truncated format will actually work for products with multiple indications accompanied by myriad risk and safety information. Curiously, FDA on this point states that the indication section of the PMI should “summarize the approved outpatient indications and uses in language that is most useful for patients.”[8] This statement itself raises far more questions than it provides answers.

As noted, FDA provided detailed specifics for these forms – down to the font size (minimum of 10-point), color (black type only), and which words are permitted to appear in bold type . Combined with the broad-reaching scope of the rule, this rule standardizes the process for patient-facing prescription information across the board. Although the final rule would be implemented over a five-year period, other patient prescription drug information options would be phased out upon PMI approval.[9]

As a consequence of this standardization, FDA believes that the proposed rule will make prescription drug product information more accessible to patients. Patients will become familiar with the format of the one-page document, which they will receive each time they are dispensed medication in an outpatient setting. Patients will know where to look for certain side effects or any particular directions for use, and will become more aware of important details associated with their medications, which in turn increases the likelihood of safe and effective use. Furthermore, FDA noted that the standardization of the PMI form will help “facilitate translation into 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.”[10] As a result, such information is able to reach a broader patient audience.

Looking forward, although FDA expects that there may be extra costs incurred in the development and approval of the PMI, the overarching benefit to manufacturers is that this rule provides clarity on what information they will need to prepare product labeling and customer facing documents that help explain the product. Additionally, it is hoped that this rule will help to shed light on what the FDA considers essential information that must be disclosed to the patient. This could be especially beneficial for manufacturers of specialty medications, as the new rule will provide a more straightforward way to navigate this process.

Nevertheless, we look forward to the notice and comment period to see how FDA weighs-in on industry concerns, and how, ultimately, the final rule and regulations take shape. Stakeholders interested in weighing in on the proposed rule must submit either electronic or written comments by November 27, 2023.

[1] U.S. Food & Drug Admin., Medication Guides: Patient Medication Information, 88 Fed. Reg. 35694 (May 31, 2023).

[2] Id. at 35697.

[3] Id. at 35695.

[4] Id. at 35704.

[5] Id. at 35706.

[6] Id. at 35708-09.

[7] Id. at 35705.

[8] Id. at 35708.

[9] However, FDA did note that “current Medication Guides would continue to be available as a potential element of a REMS.” Id. at 35703.

[10] FDA Proposes New, Easy-to-Read Medication Guide for Patients, Patient Medication Information | FDA.