2. Abuse-Deterrent Opioids: FDA’s Role and Emerging Challenges Jeanne Ireland Principal, Ireland Strategies, LLC 2015 CWAG Annual Meeting

3. The Opioid Epidemic  Some progress being made, but devastating effects of epidemic continue  Each day, 44 Americans die from overdoses of prescription painkillers, including opioids  In 2013, nearly 2 million Americans abused prescription pain medications and more than 16,000 died  In five of the western states, over 80 painkiller prescriptions are written per 100 residents – the second highest rate in the nation. Even in those western states with the lowest national rates, 50-70 prescriptions are written per 100 residents  2012 was the first drop/leveling off of prescription overdose deaths since the 1990s  AGs and States have played a leading role in addressing opioids abuse and overdose  Use of a broad range of approaches, including prescription drug monitoring programs, naloxone access, cracking down on “pill mills,” advocacy for abuse-deterrent technologies  Introduction of legislation in 31 states this year alone relating to abuse-deterrent opioids

4. Abuse-Deterrent Opioids – a New Tool for Reducing Abuse  Abuse-deterrent opioids (ADOs) – opioids in formulations that are designed to deter abuse by one or more routes  “Abuse-deterrent” = more difficult to abuse, not abuse-proof  Current products have properties that deter abuse, including through the often lethal routes of snorting or injecting  May never be able to completely prevent abuse since product has to deliver pain relief to patient – current products can still be abused by swallowing more pills than prescribed  But, still an important element of a comprehensive strategy for reducing misuse and abuse  Shift in landscape – now technological, as well as medical, law-enforcement, and policy tools available  Emergence of ADO products presents new challenges for policymakers, including standard-setting, labeling, data, access, and cost

5. The Federal Role in Combatting the Epidemic Many agencies with different mandates related to opioid abuse, including:  Office of National Drug Control Policy– education and training  Department of Justice/Drug Enforcement Agency – oversight of controlled substances, enforcement  Department of Health and Human Services  National Institutes of Health/National Institute on Drug Abuse - research  Centers for Disease Control and Prevention – epidemiological studies  Substance Abuse and Mental Health Services Administration/Indian Health Service/Veterans Administration/Bureau of Prisons – provider education, support for PDMPs  Centers for Medicare and Medicaid Services- coverage, oversight of utilization  Food and Drug Administration – drug approval standards, labeling and other safety measures

6. FDA’s Role in Regulating Opioids  Sets standards for the approval of opioids, i.e., what type of data is required to demonstrate safety and effectiveness, analysis of risks vs. benefits  Sets standards for the approval of brand and generic ADOs – additional element of assessment of AD properties  Can require drug manufacturers to develop education materials and train practitioners on appropriate use and to conduct postmarket studies  Determines what “labeling” a drug will carry  Informs patients, providers, and payors for which conditions/uses the drug is approved, how it should be used, safety information  Determines the type of claims that can be made by drug sponsor in marketing and promoting the product  Can mandate changes to labels of approved products if FDA becomes aware of new safety information

7. FDA’s Regulation of ADOs: Multiple and Competing Considerations FDA’s vision: “…a future in which most or all opioid medications are available in formulations that are less susceptible to abuse than the formulations that are on the market today.”  Incentivize ADO development  Incentivize progressively stronger AD properties  Set realistic expectations about limitations of current technologies  Ensure access to lower-cost generics  Maintain access to pain relief for patients in need

8. Current FDA Efforts  Since 2010, approved four opioids with AD properties  In 2012, required manufacturers to educate providers and patients on appropriate prescribing and safe use  In 2013, ordered safety changes to labels of certain opioids to clarify their use for severe pain and for patients for whom other lower-risk pain medications are not appropriate. Also required manufacturers to conduct additional postmarket studies  Issued guidance for the evaluation and labeling of branded ADOs (draft in January 2013, final in April 2015) -- sets the bar for types and strength of data needed to achieve progressively stronger AD labeling  Laboratory testing  Pharmacokinetic studies  Human abuse potential studies  Postmarket data on effect in real-world setting

9. Remaining ADO Policy Decisions For FDA  Setting the bar for approval of generic ADOs – guidance expected as soon as this year  Refuse approval of new opioids without AD properties?  Withdrawal of existing products without AD properties?  Additional labeling? Complexities  Bar will keep shifting as technologies improve  Continuing need for data

10. Remaining ADO Policy Decision Outside of FDA’s Purview - Access  Reimbursement decisions by payors, including CMS, can impact patient access to ADOs  Recent study by Avalere found Medicare Part D plans place greater restrictions on patient access to ADOs than to non-abuse-deterrent generics opioids  Considerations  Cost  Need for data

11. Conclusions  Goal remains the same – reduction in abuse  ADOs offer an important new tool, but much more needs to be done  Critical policy decisions still ahead offer opportunities for continued engagement