Beth McGinty, chief of the Division of Health Policy and Economics and professor in the Department of Population Health Sciences at Weill Cornell Medicine, shared her perspective on some of the key discussions from the workshop.

• Evidence supporting use. The clinical trials discussed during the workshop suggest that providing an in-home disposal system increases the likelihood of disposal versus controls. McGinty noted, however, that this research is still in the early stages and more studies are needed that directly compare the uptake of in-home systems to other disposal options (e.g., mail-back envelopes).

• Barriers to use. Several potential barriers to the uptake and use of in-home opioid disposal systems were discussed, such as costs for consumers, complexity of instructions and difficulty of use, confusion about what is the “best” option to use, and public perceptions about the end product–drug mixtures (e.g., environmental impacts), McGinty said.
• Disposal system evaluation. To evaluate the safety and effectiveness of in-home drug disposal systems, it will be necessary to know the specific components of the systems, she continued. Disposal system testing will be complicated by the likelihood that patients will also dispose of non-opioid medications in these products.
• Minimum criteria for disposal systems. Should FDA decide to exercise its REMS authority to require dispensing of in-home drug disposal systems with prescribed opioids, minimum criteria for these systems will need to be determined, McGinty said. Several potential criteria were discussed, such as the extent to which a system renders opioids unusable; deters recovery of drug from the end product–drug mixture after disposal; and is safe for the user, household members, pets, and the environment.
• Overlapping regulatory authorities. The legal and regulatory landscape for in-home drug disposal systems was also discussed. McGinty recalled discussions of how requiring dispensing of in-home disposable systems might conflict with state and local solid waste regulations that would prohibit discarding the used disposal kits in the trash.

PARTICIPANT REFLECTIONS

To conclude the workshop, Laura Bix, Patrick Raulerson, Andrew Coop, Mark Bicket, and Jeff Horwitz shared their reflections on recurring themes from across the five panel sessions in an open discussion moderated by Alastair Wood.

Developing a Multipronged Approach

Throughout the workshop several speakers discussed that opioids have a role in pain management, Wood said. There are ongoing efforts to promote appropriate prescribing, but patients frequently have unused drug remaining after treatment. Workshop discussions covered a range of approaches for removing unused opioids from the home in a timely manner, with a focus on the role of in-home drug disposal systems.

A consistent message across the discussions was that a multipronged approach to removing unused opioids from the home is needed, Bix

said. There is no one system that will meet all needs. Raulerson agreed there is no single best option. The RCT evidence discussed suggests that providing patients with a disposal option and associated education promotes disposal, but evidence about which disposal option is best suited to which patient is lacking and emphasizes the need for a multipronged approach, he said. Different patients might be better served by one option over another, depending on personal needs and preferences. Raulerson pondered whether the collection of these types of data could be included in the REMS to inform future REMS modifications on the dispensing of disposal options.

Horwitz agreed that a multifaceted approach is needed, including taking all opportunities across the pathway of care to provide disposal systems and education as appropriate. William Simpson of DisposeRx expressed support for all solutions that contribute to addressing the issue of opioids in the community. He also emphasized the importance of sustained efforts to educate and raise awareness about the risks of opioids. There are opportunities to engage patients during encounters with physicians, nurses, or pharmacists, as well as through EHR systems, pharmacy apps, and the types of messaging strategies discussed by Kathleen Egan, he said.

Throughout the workshop lessons from FDA’s current REMS modification on providing mail-back envelopes were discussed. FDA has received comments raising concerns about the implementation of the opioid mail-back program, particularly about the potential for diversion by USPS employees or others.¹ However, Raulerson pointed out that mail-back for other types of medications has been used safely for some time. He added that the USPS has ensured FDA that the regulations and internal policies and practices in place that apply to current mail-back programs will also ensure the safety of the mail-back of opioids, and systems are in place for response should any issues arise. Kristen Aldred of Stericycle concurred that mail-back programs and take-back kiosks have been used successfully in some states for the collection of unused medication.

Engaging All Stakeholders

Discussions highlighted the need to engage trusted partners, such as physicians and pharmacists, in providing education and disposal solutions to patients, Bicket said, and to learn from other stakeholders, including state, Tribal, and other programs that have experience with opioid disposal programs. It was also stated, Bix said, that the perspectives of consumers

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¹ See https://www.fda.gov/drugs/news-events-human-drugs/our-perspective-cders-efforts-expand-opioid-disposal-options (accessed November 18, 2023).

need to be considered in disposal system design (to understand resources, barriers, and motivations that might impact uptake and use).

The complexities and challenges of implementing REMS requirements were discussed, and points were made about partnering with entities already involved in opioid disposal to help ensure that new requirements do not conflict with or supplant their efforts or create confusion, Bicket said. Wood added that examples of initiatives by individual states, such as those discussed at the workshop, can inform the development of federal programs. Raulerson said the agency is cognizant of this and wants to hear more from stakeholders about what has and has not worked.

Milton Dallas of Rx Destroyer noted that he and other industry attendees have significant experience to share in packaging and disposal systems. He urged decision makers to engage manufacturers of drug disposal systems in discussions about development and implementation of these systems. Dallas also suggested looking to industry for new solutions for the destruction of opioids beyond incineration (e.g., chemical digestion, other thermal destruction methods).

Bix suggested that the Consumer Product Safety Commission also be engaged in discussions, and that the issue of child-resistant packaging be discussed. Horwitz noted that some in-home disposal systems do have appropriate child-resistant closures.

Properties of In-Home Drug Disposal Systems

Minimum Criteria

Discussions of the minimum criteria that opioid disposal systems should meet emphasized the need for systems that can be “safely, effectively, and easily” used, Raulerson said, noting that ease of use is essential because “they have to be used to work.”

Some of the minimum criteria for in-home disposal systems discussed, as summarized by Coop, were clarity of instructions and ease of use; non-toxic and non-hazardous components and product–drug mixtures; ability to deter misuse; and ability to alter the physical integrity of the formulation so that the active pharmaceutical ingredient can be rendered unusable. Coop noted that clarity is needed on how non-hazardous and non-toxic would be defined and measured. Another point from the discussion was how to develop in-home opioid disposal systems that account for the fact that people will likely dispose of many different medications in the systems.

Simpson noted the challenges that overlapping regulatory authority over opioid disposal presents for manufacturers of in-home systems. He

supported the establishment of minimum criteria and said that having a clear message on standards from regulatory agencies would support innovation and better solutions.

Scientific Considerations

Summarizing the panel discussion on scientific considerations, Coop said that drugs disposed via mail-back programs are incinerated, which removes any concern about product–drug mixtures. However, ingredients in in-home disposal systems can react differently, depending on what is added to them. As discussed, for example, calcium hypochlorite is an oxidizer that can alter pharmaceuticals but can also be extremely hazardous if combined with certain substances (e.g., releasing chlorine gas or generating potentially carcinogenic compounds). It was discussed that studies are needed to understand how these disposal systems perform when various non-opioid medications are added, but that it is not practical to test against all possible medications people might choose to put in the kits. Using activated charcoal to adsorb active pharmaceutical ingredients could be a safe option, but Coop noted that a tablet or similar formulation must first be broken down to release the active pharmaceutical ingredient to be adsorbed. While he said it is unlikely that those seeking drugs would attempt to extract a small amount of opioid from a large volume of activated charcoal, concerns were raised about drug leaching into the environment in landfills.

Evaluation of Safety, Efficacy, and Effectiveness

In implementing a REMS requirement for dispensing of in-home opioid disposal systems, FDA will need information about the safety, efficacy, and effectiveness of these systems. It was noted throughout the workshop that assessing safety will require knowing all the components of an in-home disposal system, Wood said. It will also be important to evaluate the safety of the product–drug mixture because it might be retained in the home for a period of time.

Another point discussed, Wood said, was that studies of safety and effectiveness in real-world use should compare in-home disposal systems to appropriate controls (e.g., other drug removal or return options and associated educational information). As noted above, the need to understand how safety and efficacy of in-home disposal systems are affected by the concurrent disposal of both opioid and non-opioid medications in the same disposal system was also discussed.

Egan stressed the need for caution when establishing whether a disposal intervention works. When evaluating why a program has not

worked as anticipated, it is necessary to ask whether the intervention, the implementation, or the evaluation did not work, she said. For example, some participants said mail-back programs do not work while others discussed successful programs. Comments to FDA indicate that there is a public perception that diversion will occur, and she suggested that this perception could be targeted and modified to potentially enhance success of the mail-back program.

Bix reiterated the importance of understanding how people interface with information on packaging. In her work she has observed “extraneous information interfering with people’s ability to find and use information that they need.” The absence of information can also lead to user confusion. For example, products containing latex must be labeled as such, but she has observed practitioners spending critical minutes searching for latex labeling on latex-free products to be sure they have not missed it.

Implementation and Motivating Behavioral Change

The need for clear and consistent messaging about the importance of opioid disposal and the options available was reiterated throughout the workshop, Coop said. Lewis Grossman also pointed out the importance of clarity, suggesting that it needs to be clearer that mail-back envelopes are a disposal method. The phrase “mail back” could be misinterpreted by patients as returning the medication they paid for to the manufacturer, perhaps to be sold again, he said. In response, Egan said this emphasizes the points made throughout the workshop about the importance of engaging consumers in product and program development.

The importance of ensuring that patients understand how to use in-home disposal systems safely and correctly was also discussed, Wood said, including the need for culturally appropriate education and implementation.

Opinions varied regarding the ability of consumers to safely follow kit instructions. Horwitz asserted that most disposal systems are quite simple to use, while Coop and Wood reiterated the concerns that were expressed about people not using kits as intended, with potentially hazardous outcomes. Wood also pointed out that it might not always be clear to patients which of the drugs they might want to dispose of are opioids and which are not (just as patients often have difficulty identifying products that contain acetaminophen, which creates the potential for acetaminophen overdose). Horwitz emphasized the importance of bringing disposal options to the public to promote behavioral change and expressed faith that the American public will be able to safely follow the instructions. He likened disposal systems to other widely used consumer products that have educational campaigns to inform consumers

of the risks if misused or not stored securely, such as laundry detergent pods.²

An element of all the disposal efforts discussed is the need to change the entrenched patient behavior of retaining unused prescribed opioids after treatment is no longer needed, Raulerson said. Various reasons why patients keep unused drugs were discussed, as well as strategies to nudge or push patients toward medication disposal. In this regard, the importance of education about the need for opioid disposal and how to dispose was emphasized throughout the workshop, Raulerson said, including the need for this information to be reinforced at as many touchpoints as possible (e.g., the practitioner/prescriber, the pharmacist/dispenser, automated text-based reminders, public health campaigns). Timely patient education is part of a multifaceted approach, and simply providing additional disposal options is not likely to significantly increase the prevalence of disposal, he said.

Horwitz agreed that promoting culture change around opioid disposal is a key element for the success of any disposal options. He said mail-back programs and kiosks “work to a point” in removing medications from homes, but they are not working in the broader sense that they are not motivating widespread behavioral change toward increased disposal of opioids.

Incentives that might motivate disposal behavior were discussed throughout the workshop. Studies suggest that financial incentives and convenience can be effective motivators to some extent. Although options such as mailing, dropping off, or flushing are all easy to do, people are still not motivated to do them, Horwitz said. In many cases, he added, disposal is unfortunately motivated by a personal opioid-related concern or loss (e.g., family member addiction or overdose).

Bicket said incentives to promote a particular clinician behavior or action in association with opioid prescribing must be carefully considered so that they do not inadvertently encourage increased opioid prescribing. He highlighted the many points made about the need for supportive materials and a team approach involving trusted practitioners along the patient’s care pathway (e.g., educational materials for use at discharge prescribing).

Covering the Costs of In-Home Opioid Disposal

Simpson said that the costs of in-home disposal systems are currently paid by the customers—that is, those who distribute the systems (e.g.,

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² See https://www.cpsc.gov/s3fs-public/390%20Laundry%20Packets.pdf (accessed November 18, 2023).

pharmacies, universities, health systems). He noted that these customers generally distribute the disposal systems for free, but there are instances in which the consumer is paying for the system. Horwitz added that there are coalitions using donor funding to purchase in-home disposal systems for distribution, and he has worked with businesses that purchase them for employees. Mary Kellington noted that the Washington state program she discussed is entirely funded by drug manufacturers.

Simpson said securing reimbursement from payers is a challenging process. In the absence of reimbursement, the costs of making in-home disposal systems available could be paid by the manufacturers of opioid analgesics; by pharmacy stewardship programs; out of opioid settlements; by government payers; by companies through their environmental, social, and corporate governance programs; or most likely, by a combination of sources. Simpson noted that manufacturer costs “trickle down to the patient eventually.”

Raulerson suggested that if in-home disposal systems were to be required under the REMS, then the costs would be paid by the opioid manufacturers. He agreed with Simpson that costs are often shifted to the consumer but added that “disposal should be considered a fundamental safety attribute of the product” similar to the manufacturing processes that ensure the quality and stability of the drug. The manufacturer bears all costs of producing the product, which is ultimately reflected in the price.

Environmental Considerations

Grossman reviewed some of the environmental considerations raised throughout the workshop, including concerns about potential contamination of water supplies stemming from flushing and from disposal in the solid waste/landfill system. It was also discussed that EPA prefers incineration for the disposal for medications, he recalled. The challenge is how to balance these environmental concerns with the urgent need to increase the timely removal of unused opioids from circulation. Wood said the risk to the environment is likely to be significantly less than the risk of overdose associated with consumption of opioids in the home. Wood, Coop, and Kristin Fitzgerald all pointed out that opioids are also released into the wastewater system via excretion.

Raulerson acknowledged the need “to consider what patients and health care practitioners and pharmacists think about the … differential environmental impacts of these various options.” Contradictory guidance from FDA versus local governments (e.g., with regard to flushing) also needs to be considered when deciding how best to reduce exposure to opioids.