February 6, 2018
“The opioid crisis has had a tragic impact on individuals, families, and communities throughout the country. We’re in urgent need of new and better treatment options for opioid use disorder. The guidance we’re finalizing today is one of the many steps we’re taking to help advance the development of new treatments for opioid use disorder, and promote novel formulations or delivery mechanisms of existing drugs to better tailor available medicines to individuals’ needs,” said FDA Commissioner Scott Gottlieb, M.D. “Our goal is to advance the development of new and better ways of treating opioid use disorder to help more Americans access successful treatments. Unfortunately, far too few people who are addicted to opioids are offered an adequate chance for treatment that uses medications. In part, this is because private insurance coverage for treatment with medications is often inadequate. Even among those who can access some sort of treatment, it’s often prohibitively difficult to access FDA-approved addiction medications. While states are adopting better coverage owing to new legislation and resources, among public insurance plans there are still a number of states that are not covering all three FDA-approved addiction medications. To support more widespread adoption of medication-assisted treatment, the FDA will also continue to take steps to address the unfortunate stigma that’s sometimes associated with use of these products. It’s part of the FDA’s public health mandate to promote appropriate use of therapies. Misunderstanding around these products, even among some in the medical and addiction fields, enables stigma to attach to their use. These views can serve to keep patients who are seeking treatment from reaching their goal. That stigma reflects a perspective some have that a patient is still suffering from addiction even when they’re in full recovery, just because they require medication to treat their illness. This owes to a key misunderstanding of the difference between a physical dependence and an addiction. Because of the biology of the human body, everyone who uses a meaningful dose of opioids for a modest length of time develops a physical dependence. This means that there are withdrawal symptoms after the use stops. A physical dependence to an opioid drug is very different than being addicted to such a medication. Addiction requires the continued use of opioids despite harmful consequences on someone’s life. Addiction involves a psychological preoccupation to obtain and use opioids above and beyond a physical dependence. But someone who is physically dependent on opioids as a result of the treatment of pain but who is not craving the drugs is not addicted. The same principle applies to replacement therapy used to treat opioid addiction. Someone who requires long-term treatment for opioid addiction with medications, including those that are partial or complete opioid agonists and can create a physical dependence, isn’t addicted to those medications. With the right treatments coupled to psychosocial support, recovery from opioid addiction is possible. The FDA remains committed to using all of our tools and authorities to help those currently addicted to opioids, while taking steps to prevent new cases of addiction.”
Today, the U.S. Food and Drug Administration issued a final guidance, “Opioid Use Disorder: Developing Buprenorphine Depot Products for Treatment,” which outlines the FDA’s current thinking about drug development and trial design issues relevant to the study of buprenorphine depot products, such as modified-release products for injection or implantation. The guidance includes minor changes to the draft document published in April 2018.
Improving access to prevention, treatment, and recovery services, including the full range of medication-assisted treatment (MAT), is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of HHS’ Five-Point Strategy to Combat the Opioid Crisis. There are currently three FDA-approved drugs for MAT – methadone, buprenorphine, and naltrexone – that have been demonstrated to be safe and effective in combination with counseling and psychosocial support to treat opioid use disorder (OUD). Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also blocks the pleasurable effects of other opioids, making continued opioid abuse less attractive.
When combined with the right treatments and supports, novel formulations or delivery mechanisms described in the FDA guidance – including passive-compliance formulations such as sustained-release depots and implants – can provide effective treatment of OUD, and may result in less misuse, abuse, or accidental exposure compared to self-administered formulations such as transmucosal tablets and films. This guidance outlines ways that companies can more efficiently advance innovations in buprenorphine depot products – from the data needed to support approval, to the specific review pathways that are available to help streamline how sponsors consider their development plans. The guidance details the types of studies the FDA recommends for buprenorphine depot products that are similar to an approved depot product, as well as buprenorphine depot products with novel features relative to approved depot products. The guidance also includes information on efficacy studies including trial design, recommended efficacy endpoints, and novel efficacy endpoints related to buprenorphine. In addition, the guidance also describes circumstances in which an application could be submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, which can provide a more streamlined development path for these products
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products