FDA Requests Comments on Potential Modification to Opioid Analgesic Risk Evaluation and Mitigation Strategy

On April 21, 2022, the United States Food and Drug Administration (FDA) filed a Notice and Request for Comment regarding a potential modification to the Opioid Analgesic Risk Evaluation and Mitigation Strategy (OA REMS) to require that mail-back envelopes be dispensed and education on safe disposal provided with opioid analgesics dispensed in an outpatient setting. FDA believes that such a requirement might “reduce the amount of unused opioid analgesics in patients’ homes, thereby reducing opportunities for nonmedical use, accidental exposure, and overdose, and possibly reducing the development of new opioid addiction.”

The Notice states that while the volume of prescription opioid analgesics dispensed has been trending downward since 2012, there were still an estimated 140.6 million prescriptions, resulting in an estimated 8.7 billion units (e.g., tablets or capsules) dispensed in 2021 from U.S. outpatient retail and mail order pharmacies. Additionally, despite the decline in opioid dispensing, as of 2020, prescription opioids were involved in more than 16,000 fatal overdoses per year, higher than the number seen at the peak of opioid analgesic dispensing in 2012.

The FDA notes that patients frequently report having unused opioid analgesics after treatment of acute pain, such as pain following surgical procedures. Opioid analgesics prescribed to treat chronic pain conditions can also result in unused drugs. When not properly disposed, these “extra” opioid analgesics provide opportunities for nonmedical use, accidental exposure, and overdose. Most of those who reported non-medically approved use of prescription pain relievers obtained them through friends, relatives, or their own prescription. Therefore, FDA’s efforts to address the opioid crisis include a focus on encouraging appropriate disposal of unused opioid analgesics.

As noted above, the FDA is currently investigating whether mail-back envelopes and education on safe disposal would help alleviate the opioid crisis. FDA notes that this is just “one possible application of FDA’s new authorities” in the Federal Food, Drug, and Cosmetic Act (FD&C Act) related to packaging and disposal and that if there are other possible applications of these applications – including novel packaging or other safe disposal options that would meet standards found in the SUPPORT Act.

FDA also noted in the Notice that it is “actively encourag[ing]” drug manufacturers to innovate in this space and that the Agency does recognize that there are organizations (public and private) that have ongoing efforts to increase the safe disposal of opioids. To that end, the Agency believes that it is important for patients to have a variety of options when it comes to disposing of unused opioids, including kiosks, take-back events, and in-home disposal options.

While FDA seems to be a proponent of the mail-back envelope REMS, the Agency is seeking comments for and against the idea, and already recognizes that there are some potential burdens placed on pharmacists and pharmacies with the mail-back envelope REMS requirement, including possibly: (1) completion of any REMS-mandated training and certification; (2) implementation of REMS-compliant processes in pharmacies; and (3) documentation of compliance with REMS requirements by pharmacies.

Comments Requested

FDA is soliciting comments from stakeholders regarding all aspects of the potential mail-back envelope REMS mandate described in this document.

Some of the specific topics FDA is interested in hearing about include:

1. The potential safety advantages and public health impacts of providing mail-back envelopes with opioid analgesics dispensed in an outpatient setting.
2. Whether there are specific opioid analgesic drug products for which requiring mailback envelopes is more important from a public health perspective and, if so, which products.
3. How pharmacies could identify those patients who are most likely to have unused opioids to optimize provision of mail-back envelopes to these patients and potentially positively impact the share of mail-back envelopes that are utilized to safely dispose of opioid analgesics.
4. How pharmacies could develop and implement algorithms to determine when to provide a mail-back envelope, including how feasible or practical it would be for pharmacies to do so.
5. What key educational messages regarding secure storage and safe disposal should be included in any patient education component of the potential OA REMS requirement described in this notice, including educational messages to increase uptake and use of mail-back envelopes, as well as what form that education should take (e.g., handouts, pharmacist counseling of patients).
6. Any existing programs that provide mail-back envelopes, especially programs that provide patient counseling on disposal and that operate in retail pharmacies, including any data on the effectiveness of these programs.
7. Other actions FDA could take in addition to, and in support of, a mail-back envelope disposal REMS requirement to increase safe disposal of unused opioid analgesics.

If you would like to submit comments, you can submit written or electronic comments by June 20, 2022.