1. FDA’s Role in Addressing the Opioid Epidemic
Ellen Fields, MD, MPH Deputy Director, Division of Anesthesia, Analgesia, and Addiction Products Office of New Drugs, CDER, FDA
Association of University Anesthesiologists
International Anesthesia Research Society
Annual Meeting, Washington, DC
May 6, 2017

2. The opinions and information in this presentation are my own and do not necessarily reflect the views and policies of the FDA

3. Outline
Federal Context for FDA Efforts to Address Prescription Opioid Abuse
Other Federal Efforts
FDA Action Plan
Types of Activities FDA is Undertaking
Selected examples

4. Overall Message
The FDA work to improve the safe use of opioids is taking place within a larger policy framework aimed at addressing opioid abuse while assuring appropriate access to pain treatment
Ongoing and planned activities reflect the commitment by FDA to integrate the use of all of our available tools to achieve our goals related to the safe use of prescription opioids.
Collaboration with many different stakeholders is critical for addressing the prescription opioid crisis

5. Prescriptions for Opioid Analgesics Dispensed by US Retail Pharmacies
Unprecedented US Population Exposure to Rx Opioid Drugs; We know from research on ethanol that access and availability correlate with behaviors related to abuse and to alcohol-related deaths; we can certainly see the increases in availability of opioids over the past 25 years. We also know that a large majority of prescription opioids involved in abuse were obtained, bought, or stolen from friend or relative; about 20% prescribed by person’s single physician
Most opioid analgesics prescribed by primary care physicians and dentists, not specialists
Majority of exposures from IR forms
From: 5

6. Marked Increases in Prescription Opioid and Heroin Overdose Deaths in the USA 2000 to 2015
Other Synthetic Opioids
(e.g. fentanyl, tramadol)
Commonly Prescribed Opioids
(natural and semi-synthetic opioids and methadone)
Heroin
Any Opioid
USA 2015 Overdose Deaths:
52,404 Any Drug
33,091 Any Opioid

7. FDA is a Part of a Larger Governmental Response to Opioids Abuse
Office of the National Drug Control Policy (ONDCP) Plan
Health and Human Services (HHS) Secretary’s Plan

8. ONDCP National Drug Abuse Prevention Plan
Issued April 2011
Four major areas of focus to reduce prescription drug abuse and other harm from drugs
Education
Monitoring
Proper medication disposal
Enforcement

9. HHS Secretary’s Initiative to Combat Opioid Abuse
Improving opioid prescribing practices to reduce opioid use disorders and overdose
Expanding use and distribution of naloxone
Expanding medication-assisted treatment (MAT) to treat opioid use disorders and reduce overdose --

10. Other Critical U.S. Governmental Efforts FDA is Supporting
National Pain Strategy
Focuses on key areas of pain and pain care, including professional education and training, public education and communication, service delivery and reimbursement
National Pain Research Strategy
Strategic plan under development for pain research across federal agencies
Surgeon General’s Call to End the Opioid Crisis
Launched a new prescriber education campaign, Turn the Tide
Issued the first-ever Surgeon General’s Report on Alcohol, Drugs and Health: Facing Addiction in America
CDC Guidelines for Prescribing Opioids for Chronic Pain
Provides recommendations for the prescribing of opioid pain medication focused on the use of opioids in treating chronic pain

11. FDA Response to Opioids Abuse

12. FDA Action Plan (February 4, 2016)
In response to the opioid abuse epidemic, FDA leadership called for a far-reaching action plan to reassess the agency’s approach to opioid medications. The plan focused on policies aimed at reversing the epidemic, while still providing patients in pain access to effective relief. --

13. FDA Opioids Action Plan
Expand the use of advisory committees
Develop warnings and safety information for immediate-release (IR) opioid labeling
Strengthen postmarket requirements to get needed data
Update Risk Evaluation and Mitigation Strategy (REMS) Program for Prescription Opioids
Expand access to abuse-deterrent formulations (ADFs) to discourage abuse
Support better treatment for prescription opioid abuse and overdose
Reassess the risk-benefit approval framework for opioid use --

14. Tools Available to FDA to Carry Out the Action Plan
Improving the use of opioids through careful and appropriate regulatory activities
Improving the use of opioids through careful and appropriate policy development
Improving the treatment of pain through improved science
Improving the safe use of opioids through communication, partnership and collaboration

15. Expanded Public Engagement by FDA is a Critical Part of FDA Response
In 2016, FDA held 9 public meetings about opioids
7 Advisory Committee meetings (topics included REMS, ADFs, pediatrics, and naloxone)
Science Board meeting and generic ADF public meeting
Several more meetings are planned for 2017
Participated in numerous public meetings held by others
ECRI Institute Public Meeting on Healthcare Systems and Drug Abuse
National Prescription Drug Abuse & Heroin Summit
3 public NASEM meetings devoted to opioid abuse issues

16. Regulatory Actions: Strengthened Warnings for RX Opioid Labeling
March 2016: FDA required additional warnings on immediate-release (IR) opioids to match ER/LA opioids
Includes boxed warning about serious risks of misuse, abuse, addiction overdose and death
Includes additional warning about neonatal opioids withdrawal syndrome
Over 125 generic and over 75 brandname products
May 2016: SLCs for methadone and buprenorphine products to include a statement about the potential risk of neonatal opioid withdrawal syndrome (NOWS) when pregnant women use these products
December 2016: FDA approved additional warnings, including boxed warning, about concomitant use of benzodiazepines and opioids

17. Regulatory Actions: Better Treatment of Opioid Substance Use Disorder and Opioid Overdose
: Approval of a new formulations of naloxone for community use, including autoinjector and intranasal products
May, 2016: Approval of Probuphine, first subdermal implantable buprenorphine for management of opioid dependence

18. Regulatory Actions: Spurring Development of Abuse-Deterrent (AD) Opioids
Incentivize the development of opioid medications with progressively better AD properties and support their widespread use
Guidance for Industry-Abuse-Deterrent Opioids-Evaluation and Labeling
Assure appropriate development and availability of generics, reflecting their importance in U.S. healthcare
Generic drugs play a critical role in U.S. healthcare, including important role in controlling costs and expanding access
Draft Guidance for Industry-General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products
Expect to publish final guidance this year

19. Results: Development of AD Formulations of Opioids
Ten opioids approved with AD labeling claims (latest April, 2017), one of which is the first IR AD formulation:
(OxyContin, Targiniq ER, Embeda, Hysingla ER, MorphaBond ER, Xtampza ER, Troxyca ER, Arymo ER, Vantrela ER, Roxybond)
Work to date has often focused on use of crush/extraction-resistant, inclusion of an antagonist, and aversion technologies but some new approaches being explored
More than 30 active investigational new drug applications (INDs) being discussed for AD formulations
New technologies being explored (e.g., pro-drugs that require activation to prevent IV abuse and snorting)
FDA is requiring post-approval studies to measure real-world effects of these new formulations

20. IR and ER/LA Opioid Prescriptions
Reformulated Oxycodone ER: 2% (4.7M TRx) of total opioid market in 2014
This figure shows the nationally estimated number of prescriptions dispensed for opioid analgesics from U.S. Outpatient Retail Pharmacies from with a breakdown between selected IR and ER/LA products.
The total number of selected opioid prescriptions dispensed increased from 149 M to a peak of 214M in 2012 and decreased to 198M in 2014
Selected IR opioid prescriptions as shown by the red line increased from 131M prescriptions to a peak of 184M in 2011 and declined to 166M in 2014.
ER/LA prescriptions as shown by the green line increased from 17M in 2005 to a peak of 22M in 2010 and slightly declined to 21M in 2014.
Focusing on abuse deterrent opioids, Reformulated Oxycontin accounts for ~2% of the total opioid market in 2014
Targiniq: not marketed in 2014
Nationally estimated number of prescriptions dispensed for selected IR and ER/LA opioid analgesics from U.S. outpatient retail pharmacies
No prescriptions captured for Hysingla ER or Embeda in 2014
Source: IMS Health, National Prescription Audit ™ Extracted May and August 2015

21. REMS Risk Evaluation and Mitigation Strategy Class-wide ER/LA
Includes voluntary prescriber education
Public workshop May 9-10, 2017, to obtain input re strengthening the REMS, including mandatory prescriber education

22. Importance of FDA Collaboration with Other Stakeholders
Serves a critical function:
Expands FDAs capacity to achieve our public health mission
Gives us access to outside expertise to help guide our actions
Examples
Collaboration with Partnership for Drug-Free Kids to help educate prescribers and patients about preventing opioid misuse and abuse
Partnership with Brandeis University in support of broadened data sharing between Prescription Drug Monitoring Programs (PDMPs)

23. Communication to Patients: What to Ask Your Doctor Before Taking Opioids
FDA Consumer Update outlines questions every patient should ask when getting a new opioid prescription.
This is especially important when your doctor, dentist, or other health care professional prescribes an opioid, such as hydrocodone, oxycodone, codeine, and morphine.

24. Summary and Conclusions
FDA working to address opioid epidemic as a part of the larger HHS response
One of the FDA’s highest priorities
FDA Opioid Action Plan provides framework for FDA response to the challenge of opioids abuse epidemic
Since the Action Plan was announced, FDA has continued to make significant progress on the items identified in the plan, applying of all of our available tools to achieve our goals
Extensive use of outside groups and expertise to provide needed data and input on decisions
FDA is one of many groups with a role to play in addressing these challenges

25. Thank you 25