Preventing and reducing substance use disorders and overdose deaths remains a priority of mine and an area of major focus at the U.S. Food and Drug Administration. I would like to take this time to reflect on International Overdose Awareness Day, Aug. 31, 2023, which reminds us of what’s at stake and acknowledges people in our communities who are affected by overdose but might go unseen in the crisis.
The agency continues to take actions in response to the four priorities outlined in the FDA’s Overdose Prevention Framework one year ago, including primary prevention, encouraging harm reduction, advancing evidence-based treatments for substance use disorders, and protecting the public from unapproved, diverted, or counterfeit drugs.
While we have made progress in many areas, the crisis has grown into an even more dangerous public health challenge. Last year, we had more than 107,000 overdose deaths, which means each day nearly 300 people died from a drug overdose. These deaths are primarily driven by illicit fentanyl and its analogs. Additionally, other controlled substances, such as stimulants and benzodiazepines, are being used in combination with opioids. And new challenges continue to arise. Below is an update on some activities we are taking across the agency in each of the Overdose Prevention Framework priorities.
**Supporting primary prevention by eliminating unnecessary initial prescription drug exposure and inappropriate prolonged prescribing. **
Specific to opioid medications, the agency continues to promote primary prevention through appropriate prescribing. In April, the agency announced required changes to opioid pain medication labeling to further encourage safe use and informed decision making by patients and health care providers. These changes include stating that the risk of overdose increases as the opioid dosage increases; immediate-release opioids should generally not be used for a long time; many acute pain conditions require no more than a few days of an immediate-release opioid medication; and extended-release/long-acting opioids should be used only for severe and persistent pain. We also support the development of clinical practice guidelines for acute pain indications as a way to encourage evidence-based pain management and eliminate unnecessary prescribing of opioid pain medications. Recently, the American Dental Association and University of Pittsburgh published a guideline on the management of acute dental pain in children, the result of a cooperative grant the FDA awarded in 2020. Another set of recommendations for adolescents and adults is in development. Furthermore, we solicited applications this summer to develop guidelines for the management of acute low back pain, as well as postoperative pain in patients who have undergone laparoscopic abdominal surgeries.
Even when opioid medications are appropriately prescribed, patients may not use or need all of them. In response, the FDA continues to take measures to provide patients with expanded options to remove unused and unwanted opioids from their homes. The agency announced in April that we are requiring manufacturers of opioid analgesics to make prepaid mail-back envelopes available to outpatient pharmacies and other dispensers as an additional disposal option. We also strive to provide diverse options for disposal and ensure equitable access for patients, pharmacies, and communities. To that end, the agency recently finished collecting information and comments on in-home disposal products and participated in a June National Academies of Science, Engineering, and Medicine (NASEM) workshop on in-home disposal. We hope the workshop and request for comments will further inform us of the scientific and policy considerations surrounding potential in-home disposal product requirements so that removing unused and unwanted opioids is an easy, safe, and secure choice for patients.
We have also taken several actions to encourage the safe use of prescription stimulants, which are an important treatment option for conditions including attention-deficit/hyperactivity disorder (ADHD). In May, we announced we are requiring sponsors of stimulant medications this year to update and standardize their labeling information regarding the risks associated with these medications. We hope these updates will help inform decision making by patients and health care providers. In July, we also awarded NASEM funding to convene a workshop on the diagnosis and treatment of ADHD in adults. Additionally, we recognize that the lack of availability of certain medications in recent months has been understandably frustrating for patients and their families, and we will continue to do all we can to understand, prevent, and reduce the impact of stimulant drug shortages with a focus on availability of the medications for patients who meet the indications for use.
Encouraging harm reduction through innovation and education.
With opioid-related overdoses at an all-time high, the FDA is doing all we can to support the availability, accessibility, and development of opioid overdose reversal drugs. This year, the FDA approved the first two branded nonprescription naloxone nasal sprays, as well as a generic nonprescription naloxone nasal spray. These actions pave the way for this life-saving medication to be sold directly to consumers in places like drug stores, convenience stores, grocery stores and gas stations, as well as online. However, we understand that development of nonprescription naloxone is only part of the equation, and so we will continue to support expanded access to prescription naloxone through the Drug Supply Chain Security Act guidance, issued last September. We hope this guidance continues to help facilitate and expedite the distribution of prescription naloxone products to harm reduction programs. Additionally, the agency approved the first nalmefene hydrochloride nasal spray for health care and community use. To inform future product development efforts, we also continue to gather information from a wide variety of stakeholders, including people who use naloxone, through activities such as our March Reagan-Udall Foundation workshop on understanding fatal overdoses.
The FDA has provided premarket clearance for both visually read test strips for use in laboratories and laboratory-based tests to detect fentanyl in urine, as well as laboratory-based tests to detect fentanyl in hair. These tests require analysis of test specimens in an appropriately certified clinical laboratory. In collaboration with our federal partners, I also co-authored a commentary on testing for fentanyl, and we welcome the opportunity to work with manufacturers on point-of-care devices intended for testing human specimens suitable for use in Clinical Laboratory Improvement Amendments-waived environments.
The FDA granted marketing authorization for the Masimo SafetyNet Opioid System, a monitoring device intended to recognize and respond by a series of escalating notifications when an individual may be experiencing Opioid Induced Respiratory Depression (OIRD) due to opioid use or overdose. The device monitors several physiological markers to detect the impairment of oxygenation due to opioid use and uses software that can notify personal contacts and/or trigger a wellness call to the device user by an Emergency Medical Service dispatch when a person may be experiencing OIRD, to help ensure they receive necessary treatment intervention, such as naloxone.
The FDA authorized for marketing the Medasense Biometrics Ltd. PMD-200 with the Nociception Level (NOL) Index monitoring system to help health care specialists assess the physiological response to painful stimuli in anesthetized patients receiving opioid medications as part of their treatment. The PMD-200 is indicated to be used adjunctively to help health care specialists tailor the administration of opioid-based analgesics in anesthetized patients.
Advancing development of evidence-based treatments for substance use disorders.
The agency has recently approved several drugs to treat substance use disorders. We approved a generic version of extended-release injectable naltrexone for alcohol and opioid use disorder (OUD), as well as an extended-release injectable buprenorphine product to treat moderate-to-severe OUD.
We continue to work to clarify premarket expectations for medical devices intended to treat OUD. The FDA issued a draft guidance on recommendations for the design of pivotal clinical studies of devices intended to treat OUD (“Clinical Considerations for Studies of Devices Intended to Treat Opioid Use Disorder”). The FDA continues to engage with sponsors on potential or planned device submissions related to opioid use or OUD through the Q-submission program.
The agency is facilitating opportunities to incorporate stakeholder engagement into treatment product development. We have held two connected public workshops (November 7-8, 2022) to engage the stakeholder community (including patient perspectives) and facilitate innovation on developing medical devices, including digital health technologies, relating to opioid use and OUD. The November 7, 2022, workshop spotlighted devices aimed at risk prediction relating to opioid use and OUD.
We believe there are promising medical device technologies needed to enhance harm reduction, risk prediction, and the treatment of OUD and we continue to work with medical device innovators to encourage research and development of these technologies to help ensure patients have access to beneficial medical devices that address their needs. The FDA, through CDRH’s Digital Health Center of Excellence, is conducting a patient preference study to understand how people with OUD might view, use, and adhere to, digital health technologies. The FDA aims to encourage development of new digital health medical devices to diagnose, manage, or treat OUD.
Protecting the public from unapproved, diverted, or counterfeit drugs presenting overdose risks.
Sometimes, drugs of abuse come from unlikely origins. Such is the case with xylazine, an active pharmaceutical ingredient in an FDA-approved animal drug essential for veterinarians who work with horses and other large animals. However, xylazine is not safe for humans and may cause serious side effects. The chemical xylazine is increasingly being found in the illicit drug supply, mixed with other drugs like fentanyl and heroin. In recognition of the public concern, the White House Office of National Drug Control Policy has designated fentanyl adulterated or associated with xylazine as an emerging threat and released a National Response Plan to proactively address this dangerous threat head-on. The FDA is actively working with federal partners on this response effort. The agency alerted health care professionals about this issue, has an import alert in place to restrict the unlawful entry of xylazine into the U.S., and continues to take action to help ensure that any xylazine entering the U.S. is intended for legitimate use.
While we have more work to do in improving prescribing and generating alternatives to opioids, the problem has shifted towards a dominant trend of chemically synthesized opioids delivered by cartels completely outside of the medical system. We work with the Drug Enforcement Administration and other law enforcement entities to deal with this complex and difficult supply problem. For example, during Operation Opioids and Other Drugs, the FDA and the U.S. Customs and Border Protection (CBP) examined over 3,500 parcels containing opioids, controlled substances, and unapproved drugs. As a result of these examinations, refusals were issued, and some violative drug products were subject to destruction, with additional referrals to CBP for regulatory action. Around 395,000 tablets, capsules, and pieces consisting of unapproved drugs and controlled substances were refused, destroyed, or referred to CBP. We continue to use data and results from our previous operations to inform future operational targets.
As part of our efforts to protect the public from harms associated with drugs that have abuse potential, the FDA recently held our fourth summit to discuss ways to collaboratively take stronger action to reduce the illegal availability of controlled substances online. Summit attendees discussed the current landscape, the challenges ahead, and ways to develop strategic and effective solutions.
**The Future, Innovation and Collaboration **
I’m pleased that we’ve seen some important advances and policy changes addressing critical areas of need; however, we have many important actions left to take, especially given the changing nature of the crisis. We seek collaborators to quell the shifting supply chain of illicit opioids and stimulants while also supporting society-wide efforts to reduce the demand for illicit drugs. And we will continue to seek ways we can effectively embrace cutting edge science and technology to support even more powerful advances to help bring an end to this crisis.
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