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¹ See https://sfenvironment.org/sites/default/files/fliers/files/medicinedisposalproducts_march2019.pdf (accessed November 18, 2023).

Key Performance Questions

Is the Disposal System Safe for the User?

For the disposal systems available at the time of the review, Shield found that assessment of safety was a challenge as ingredients were often not fully disclosed. Examples of ingredients listed included activated carbon, bentonite clay (an ingredient of kitty litter), and calcium hypochlorite (a concentrated, solid form of chlorine and a powerful oxidizer), as well as non-descript ingredients such as “denaturing agents” and “organic plant-based powder.” Some systems had strong chemical

odors. She noted that the use of child-resistant packaging by disposal systems was variable.

Disposal systems required dissolving the drug in water or unknown solvents that were provided. Shield found that there was a potential for spills from pouch-type disposal systems, and some product labels warned of the potential for foaming or release of gas, but there were no label warnings regarding the safety of the resulting product–drug mixture for exposed skin and no clean-up instructions for spills.

Shield offered several recommendations to address some of the user safety concerns identified in the report. These included

• improving labeling to clarify non-specific and confusing instructions (e.g., “not for use with drugs known to react with each other”) and to warn users to avoid skin contact with contents;
• listing all product ingredients and identifying those that are hazardous;
• addressing the potential for leakage (e.g., by adding absorbents or solidifying agents) and including instructions for cleaning up spills; and
• using child-resistant packaging.

Does the Disposal System Render the Drugs Undesirable?

Shield found that “deterrence impact does vary by product.” She suggested that the noxious nature of some system ingredients might make them less desirable for misuse. Other systems state their ingredients are “plant-based” or safe for use in food, which could be interpreted as edible. She also observed that when ready for disposal in the trash, all but one of the systems had labels that clearly indicated there was medication inside, making it easy for someone seeking drugs to find it.

Does the Disposal System Render the Drugs Non-Retrievable?²

Data on testing for retrievability of disposed drugs were not available for all systems assessed in the 2019 review at the time of publication, Shield said. Some systems advertise that they “deactivate,” “destroy,” or “degrade” drugs, but laboratory testing results available in 2019 indicate that some active pharmaceutical ingredient is still retrievable. Other available testing indicated that washing the product–drug mixture with water was sufficient to desorb some of the drug from an activated charcoal dis-

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² The non-retrievable requirement was removed from the SUPPORT Act in the Consolidated Appropriations Act of 2023.

posal system. Shield also noted that complete adsorption of the drug to be disposed can take several hours to several days, and adsorption is impacted by chemical properties of the drug (e.g., solubility). Importantly, testing of disposal systems for non-retrievability was generally done for a small quantity of an individual drug. Actual consumers are likely to use the system to dispose of a combination of different drugs, and types of drugs, at once.

Summarizing her findings from the 2019 review, Shield said that “overall, the available testing data [were] not convincing that any of the systems demonstrated irreversible physical or chemical destruction of controlled substances.”

Is the Combined Product–Drug Mixture Safe for Solid Waste Disposal?

Various concerns regarding disposal in the solid waste system are discussed in the 2019 report. The product–drug mixture for disposal could be “in liquid or slurry or wet gel form,” and “liquid waste is typically not accepted in the garbage or in landfills,” Shield said. The packaging containing the product–drug mixture is subject to damage in the trash can or garbage truck, resulting in leaks (which Shield pointed out could occur before the drug has been fully adsorbed/becomes non-retrievable). In 2019, the resulting product–drug mixtures had not been fully characterized as non-hazardous and non-toxic, she continued. Drug disposal systems might be labeled as safe for trash disposal, but the burden is on residents to determine if local solid waste regulations permit disposal in their trash. Furthermore, local regulators might find it challenging to assess the acceptability of these systems for solid waste disposal given the limited information available about their ingredients, mechanisms of action, and performance, she said.

Performance Testing and Regulatory Oversight of In-Home Opioid Disposal Systems

Shield shared her recommendations on performance testing of drug disposal systems that are discussed in the 2019 report. She said these recommendations are relevant to in-home opioid disposal systems and would be “the minimum basic analysis that FDA needs to assess the utility and impacts of these products.”

• “Require independent laboratory analysis and full disclosure of analytical reports.”
• “Test drug mixtures [and] combinations of different dosage forms to better represent ‘real world’ consumer use. Consumers generally do not just dispose of opioids.”

• “Use appropriate analytic designs to assess deterrence and to assess non-retrievability of pharmaceuticals.”
• “Conduct complete waste determination of the product with treated drugs to assess if appropriate for solid waste disposal. A variety of tests will be required to assess compliance with diverse state, local, and Tribal regulations.”

Shield also emphasized the need for appropriate regulatory oversight and enforcement authority, reiterating the point by Patrick Raulerson that consumer drug disposal systems are currently unregulated. Monitoring is needed to ensure consumer safety and system performance relative to what is claimed. In addition, “any new federal regulatory structure needs to respect local authority for waste management practices,” she said. In this regard, Shield emphasized the need to engage “local solid waste agenc[y], local wastewater, local public health, [and] local law enforcement” professionals who have been working for many years to provide safe drug disposal options that meet the needs of their communities. She observed that there was a lack of local expertise represented at the workshop and said these technical and regulatory experts from local agencies “can help define the analysis that is needed to fully evaluate these medicine disposal products.”

In addition to the four key performance questions for disposal systems previously discussed, Shield suggested that in-home opioid disposal systems be evaluated relative to take-back programs as a standard. Specifically, she proposed the following questions for assessment of in-home opioid disposal systems before implementation in a REMS:

• “Is it a better solution for residents than a comprehensive drug take-back program?”³
• Who should use it? (e.g., everyone or primarily those unable to use an available drug take-back option).
• “For what drugs and dosage forms?” (e.g., all drugs or only opioids; pills, patches, liquids).
• Will it complement or interfere with “the convenient, safe and secure, and environmentally sound drug take-back programs that are already operating?”
• Will public messaging align with or conflict with recommendations from state and local governments and community groups to bring unused drugs to local drug take-back programs?

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³ Shield clarified that a comprehensive drug take-back program incorporates “pharmacy-based drop boxes, prepaid return mailers on demand, and periodic collection events” that are free to consumers and equitably distributed. Unified opioid education and promotion of take-back services are also essential elements of a comprehensive plan.

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⁴ See https://www.aapcc.org/national-poison-data-system (accessed November 18, 2023).

disposal system itself. For most of the cases the route of exposure is ingestion, but there are also thermal and ocular exposures, and an individual might report multiple routes of exposure. “Most cases are resulting in no effect or only minimally bothersome symptoms,” Brown said. Although about 15 percent sought medical attention, there were no significant effects or deaths.

Pediatric Opioid Exposure Data

Brown also provided a brief overview of registry data on pediatric opioid exposures. She said that reports of pediatric opioid exposure to poison centers declined from 2019 to June 2023. One possible explanation for this decline, she suggested, is that increased awareness about opioids might be motivating parents to take their child directly to a hospital rather than calling a poison center for advice. Another possibility is that health care providers are now more informed about opioid exposures and are less likely to consult a poison center for guidance. She noted that voluntary reporting is a limitation of the poison center data.

Although overall exposure reports have declined, the different types of opioid drugs involved in accidental pediatric exposures have expanded. Buprenorphine is the most common opioid exposure in children from birth to age 5, Brown said, “followed by oxycodone alone or in combination [and] hydrocodone alone or in combination with other products.” She added that accidental exposure in young children is generally “exploratory ingestion” of drugs they encounter in their environment. Of the more than 3,100 accidental exposures in this age group in 2022, 80 percent sought medical attention, and “10 percent of those cases resulted in a major effect or death,” Brown said.

Efficacy Considerations for Drug Disposal Systems

To test the effectiveness of drug disposal systems in preventing the environmental release of drugs, it would be necessary to know the components of the system, Bradley said. Then it might be possible to identify a tracer to detect signals in the water environment. However, nothing in current disposal systems allows for detection in the environment.

Coop acknowledged that companies are unlikely to release proprietary information about specific components of their disposal systems (e.g., exactly what their “cross-linking polymer” is). He suggested following a model like that used for tobacco products, in which manufacturers make their ingredients known to FDA. Without knowing what the components are, it is not possible to determine their toxicity or their efficacy in making the drug unusable. Ultimately, “nothing is ever completely

non-retrievable,” Coop said. But perhaps it could be difficult enough to retrieve to deter attempts. He likened this approach to the development of abuse-deterrent formulations for opioids.

Shield agreed and said her review of the available testing data raised many additional questions. She reiterated that disposal system testing is generally done one drug at a time, when in real-world use people are likely to dispose of multiple drugs in one disposal system. “Drugs have different hydrophobic and hydrophilic properties,” she said. Some are not readily dissolvable, which she said was noted in some testing results she reviewed. In some cases, it was not clear if the testing of disposal systems could distinguish between when a drug was adsorbed to the charcoal and when it was simply not in solution. She highlighted the need for testing of drug disposal systems to be done by accredited laboratories using appropriate controls. Her review found that pure active pharmaceutical ingredient was frequently used as a control for the testing. The most appropriate control, however, would be the actual dosage form of the drug (i.e., the active pharmaceutical ingredient and excipient components). Coop added that the active pharmaceutical ingredients are usually in powder form, but opioids can be in abuse-deterrent formulations that are specifically designed to prevent isolation of the active pharmaceutical ingredient. He agreed with the importance of looking at efficacy of disposal systems with the actual dosage forms (e.g., capsule, tablet, liquid, patch) and not just the active pharmaceutical ingredient. Sokolowska noted that the vast majority of opioids currently found in homes are not in abuse-deterrent formulations.

Alastair Wood agreed that it is unlikely consumers will only use disposal systems for removing opioids from the home. He pointed out that it is not possible to conduct safety and performance testing of disposal systems for all possible combinations of drugs that might be disposed along with opioids. Coop said activated charcoal is effective for adsorption of drugs because it has a large surface area per weight⁵ and has long been used to adsorb ingested drugs. He suggested that the use of activated charcoal could be highly effective for disposing of multiple drugs if there were a way to immobilize the drug-carbon complex and prevent desorption. Shield added that “consumers are not chemists,” so it would be challenging to develop chemical methods “that people can do in their kitchens that would successfully denature or degrade all the different medicines that we use in our homes.”

Given the scientific challenges discussed, Shield urged FDA to consider a range of drug disposal options for opioids. Sokolowska agreed

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⁵ Coop clarified that adsorption is when one component sticks to the surface of another. Absorption is when one component soaks into the other.

that a “multipronged” approach is needed to be able to reach all patients with drugs in the home. Sokolowska said FDA “strongly support[s]” the range of efforts being undertaken to remove unused opioids from the home, including take-back days, disposal kiosks, and mail-back envelopes. Yet, more than half of unused opioid prescriptions are still in patients’ homes. The task at hand is to understand why people are not discarding these drugs and find ways to better educate and motivate people to remove them from their homes. In doing so, she said it is important not to let perfect be the enemy of good. She suggested that the removal of the non-retrievable standard from the SUPPORT Act by the Consolidated Appropriations Act was done in “recogni[tion] that leaving opioids in homes is a greater risk than removing them with less than perfect options.”

Shield also suggested looking to pharmacy-based drug return programs in other countries as models. These are long-standing programs, she said, while pharmacy take-back of controlled substances in the United States has only been allowed under DEA regulation since 2014. She mentioned the Cyclamed take-back program in France as an example, which she said has high rates of return.⁶ Sokolowska agreed there are lessons to be learned from regulatory authorities in other countries. However, the ability to implement similar models could be impacted by differences in regulatory frameworks and payment structures between the United States and other countries.

Minimum Requirements for In-Home Opioid Disposal Systems

Participants discussed minimum requirements for an in-home disposal system from a scientific perspective. Coop said an in-home disposal system should ideally be non-toxic. “We cannot have the solution worse than the problem,” he said. Still, people are used to using bleach in their homes and calcium hypochlorite is similar. If it were to be used, there would need to be safety education for users (lest they inadvertently create chlorine gas). He also reiterated the need for all components of disposal systems to be identified.

Brown called for minimum packaging standards that could reduce the occurrence of inadvertent exposures to both the disposal system and the product–drug mixture. This would include child-resistant closures and “clear, non-deceptive labeling,” she said. For example, users need to understand how long it will take for the drug to be fully inactivated after adding it to the disposal system, and that some drug could still be accessible and pose a risk until that point. Labeling should also emphasize that

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⁶ See https://www.cyclamed.org/english/ (accessed November 18, 2023).

the used system that then contains the drug should be kept secure until it can be properly disposed of, Brown said, and that it should be disposed of promptly and not be retained in the home.

Shield agreed that understanding the timing of inactivation of the disposed drug is important, especially if systems are reaching the landfill before inactivation is complete. She also raised the issue of package integrity for product–drug mixtures that are in liquid form. She noted that disposal systems in the form of resealable plastic bags or plastic bottles are likely to break open in the trash before reaching the landfill. Furthermore, as discussed, local solid waste regulations might prohibit disposal of liquid waste in the trash. She suggested that a solidifying agent might be added after an appropriate time for deactivation. Young added that liquid in disposal systems can leach out over time in landfills and contaminate the environment.

Shield also said that two disposal systems reviewed in her report were designed to be used until full, and the label listed the number of solid form dosages the bottle could contain. She raised concerns about where in the home one would keep this disposal system, which would be partially filled with disposed drugs mixed in some liquid or other medium.

Echoing Sokolowska, Jeff Horwitz said, “We cannot wait for perfection.” Opioids in the home are a known ris,k to people and to the environment. Horwitz summarized what he perceived from the discussions as the main takeaway points on minimal criteria for in-home opioid disposal kits. The disposal system should “change the physical integrity of the drug,” “render the active ingredients unusable to mitigate the risk of non-medical use or overdose,” “be non-toxic and non-hazardous or pose no threat to the consumer and reduce drug exposure to the environment,” and “be a deterrent to … misuse [of the drug].” Coop agreed and said rendering the drug unusable will help stem the diversion of opioids. Coop added that there is a need for disposal systems to address the issue of leaching into the environment.

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