The Centers for Disease Control and Prevention (CDC) reports that “[t]he United States is in the midst of an opioid overdose epidemic,” noting that the rate of overdose deaths involving opioids has nearly quadrupled in the last 15 years.1 Concomitant with this increase in overdoses has been a four-fold increase in opioid prescriptions.2 Many efforts are underway to alleviate the problem, including actions by CDC, various state legislatures, the Joint Commission, the Federation of State Medical Boards and the US Food and Drug Administration (FDA).
FDA has recently undertaken an additional series of steps to address opioid abuse. In February the agency issued an action plan calling for a “sweeping review” of its opioid policies. In March FDA began formally implementing some of these action items with required class-wide safety labeling changes for immediate-release (IR) opioids.3 And at about the same time, FDA also issued a new draft guidance document to support industry in developing generic opioids with abuse-deterrent formulations (ADF), ensuring that they are no less abuse-deterrent than the corresponding brand-name drug.4 FDA’s stated goal is to reverse the opioid-abuse epidemic while still providing patients with access to effective pain relief.
Opioids Action Plan
In introducing the FDA Opioids Action Plan,5 the agency stated that it “is deeply concerned about the growing epidemic of opioid abuse, dependence and overdose in the United States” and that this is “a comprehensive action plan to take concrete steps toward reducing the impact of opioid abuse on American families and communities.” As part of the Action Plan, the agency’s actions will include the following:
- Expanding use of advisory committees and experts, particularly for approving new opioids without abuse-deterrent properties and pediatric use;
- Developing warnings and safety information for IR opioid labeling to provide doctors with better information about the risks of opioids and how to prescribe them safely;
- Strengthening post-market requirements to gather better evidence on issues such as the serious risks of misuse and abuse associated with long-term use of opioids and predictors of opioid addiction;
- Updating the Risk Evaluation and Mitigation Strategy (REMS) Program for opioids to increase the number of prescribers who receive training on pain management and to inform on the safe, appropriate prescribing of opioid drugs;
- Expanding access to ADFs to discourage opioid abuse and encourage generic ADF product development;
- Improving access to naloxone and overdose treatment, encouraging safer prescribing and use of opioids and ultimately developing new classes of pain medicines without the same risks as opioids; and
- Reassessing the risk-benefit approval framework for opioids to formally incorporate broader public health considerations of abuse in approval decisions.
Opioid Labeling Changes
Less than two months after announcing its Action Plan, FDA announced required class-wide safety labeling changes for IR opioid pain medications.6 The new labeling requirements include a boxed warning about the serious risks of misuse, abuse, addiction, overdose and death, as well as a maternal use warning. FDA also updated the indication for IR opioid products, clarifying that these products should be reserved for severe pain with no acceptable alternative treatments. The dosing information is now more specific and includes patient monitoring instructions. FDA is additionally requiring for all opioid products safety labeling changes that provide additional information about the risks associated with opioids and encourage prescribers to balance those risks when managing patients’ pain. These requirements supplement FDA’s 2013 class-wide safety labeling changes and its then-new post-market study requirements for all extended-release and long-acting (ER/LA) opioid analgesics intended to treat pain.7
Draft Guidance on Generic Opioids
Finally, in its latest action to address the opioid abuse epidemic, FDA issued a draft guidance, “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products,”8 to encourage industry to develop opioid products that are more difficult to abuse and also to ensure that generic ADF opioids are no less abuse-deterrent than their reference brand-name drugs. The draft guidance includes recommendations for studies generic drug manufacturers should conduct to demonstrate parity between the generic and brand-name product with respect to all potential routes of abuse (e.g. crushing and dissolving). The agency also acknowledged that more generic ADF opioids would improve access to abuse-deterrent opioids by lowering their cost. The public may submit comments to FDA on the document by May 24, 2016. In addition, FDA plans to schedule a public meeting on this issue later in the year to solicit feedback from outside experts and the public before finalizing the guidance.
FDA is among a growing number of agencies and organizations that are mobilizing to address, and hopefully ameliorate, the problem of opioid abuse and overdose. CDC statistics show that, concomitant with the quadruple increase in opioid overdose over the past 15 years, the amount of prescription opioids sold in the United States has nearly quadrupled during that same time.9 CDC has undertaken a number of broad steps to address the problem, including improving data quality and prevention strategies, strengthening state efforts at effective interventions and equipping health care providers with better data and tools to improve opioid prescribing. Focusing on the medications themselves and related approvals and labeling, the latest measures by FDA are another step forward in the battle against opioid abuse. Public comments may be submitted to FDA regarding the draft guidance on generic opioids by May 24, 2016.