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FDA and Congress seek to limit the production and distribution of pain medicines.
Continued public alarm over opioid-related overdoses and deaths is generating additional strategies to reduce opioid prescribing and production and to crack down on firms for inappropriate marketing of these therapies. Related FDA initiatives support the development of less addictive pain therapies and new treatments for addiction, at more affordable prices.
At the same time, states and municipalities have brought hundreds of lawsuits against opioid manufacturers and distributors for aggressive promotion that spurred excessive prescribing of painkillers, and the Department of Justice recently said it would join efforts to recover costs for federal government opioid treatment programs. These actions have increased pressure on pharmaceutical companies to monitor and limit opioid production and distribution, and on physicians and other health professionals to modify prescribing.
A main initiative is to reduce individual access to large quantities of pain pills through a range of actions by FDA and other federal agencies. The Drug Enforcement Agency (DEA), which regulates production and prescribing of controlled substances, is moving to curtail the manufacture of opioids where there’s evidence of illegal diversion. Attorney General Jeff Sessions announced in April 2018 that the proposed policy would add drug abuse or diversion to the list of factors that DEA uses to set quotas for opioid production (1). DEA also would be able to obtain more information from states, FDA, Medicare and Medicaid, and the Centers for Disease Control and Prevention (CDC)-in addition to data from manufacturers-in setting annual production limits for drugs such as oxycodone and fentanyl.
The Department of Justice further stated that it is joining settlement talks with drug manufacturers, states, and other entities involving litigation over opioid production (2). Such action was spurred by reports of distributors delivering more than 20 million painkiller tablets to pharmacies in a small town in West Virginia, a visible sign of intended illegal diversion.
However, it’s not clear how the new DEA rule would affect the market. Traditionally, the DEA production quota system was designed to ensure that drug manufacturers produce enough of needed medicines to avoid shortages in needed pain therapies, and quotas have been determined largely by manufacturer projections for drug sales in coming months. Whether or not the DEA can use the same process to reduce supply remains to be seen, as it may be difficult to identify a particular manufacturer related to a broader oversupply situation.
Recent DEA moves to limit opioid manufacturing, moreover, may have contributed to ongoing reports from hospitals and clinics of serious shortages in injectible pain medicines needed for surgery and for treating cancer patients and others experiencing severe pain. The limited supplies are linked to manufacturing problems at a leading Pfizer facility producing pre-filled syringes and vials of morphine and other potent medicines. Hospitals continue to seek alternative suppliers for injectables and to use more pills and less potent analgesics where possible. Health professionals, however, fear that the need to administer unfamiliar injectables with different strengths and delivery systems may lead to dosing errors.
Congress aims to enact legislation by summer to curtail access to opioids and to expand funding for substance-abuse treatment programs. A notable provision in bills moving through the Senate and House aims to reduce opioid use by authorizing FDA to require drug manufacturers to provide oral formulations in blister packs with limited three- or seven-day supplies. FDA also could require safe disposal packaging systems that block re-use of leftover drugs. FDA and stakeholders examined these strategies at an FDA public workshop in December 2017 on the role of packaging, storage, and disposal options in addressing opioid abuse.
These provisions are part of the much broader Opioid Crisis Response Act of 2018 approved by the Senate Health, Education, Labor and Pensions (HELP) committee in April (3). The House Energy and Commerce Committee similarly has developed a comprehensive opioid package of bills that support addiction treatment, research on non-opioid pain therapies, and curbs on excessive prescribing. The legislators clarify FDA authority to remove pain therapies from the market if found less effective in limiting abuse than when initially approved, and for the agency to obtain information that can assist in detecting and seizing counterfeit and illicit drugs coming into the country.
Congress further supports the development of new non-addictive pain therapies by directing FDA to issue guidance on designing clinical trials and on developing alternative treatments. FDA would clarify how it weighs the risks and benefits of drugs with potential to be misused or abused, while also offering expedited and breakthrough pathways to manufacturers of novel pain and addiction treatments. The National Institutes of Health similarly gains authority to provide funding more quickly for promising research proposals related to treatments for pain and addiction.
These measures build on FDA initiatives to encourage innovation in developing treatments to limit the euphoric effects of opioids, in addition to methadone, buprenorphine, and naltrexone. FDA issued a draft guidance in April 2018 on developing new sustained-release buprenorphine products less vulnerable to misuse or abuse (4). The agency also proposes abbreviated development and testing programs for new therapies similar to already approved treatments that differ in delivery systems or formulations. In addition, FDA is revising the content of training information provided by manufacturers to prescribers under an expanded Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS), which now includes both immediate-release and extended-release opioid analgesics.
Democrats would like legislation to impose tougher penalties on manufacturers and drug wholesalers and distributors for marketing and distribution practices calculated to expand opioid use. At Congressional hearings, Democrats loudly criticized drug companies for promoting excessive prescribing and for channeling funds to patient pain advocacy organizations to support wider use of certain therapies. Sen. Bernie Sanders proposed a bill that levies stiff fines and prison sentences on drug company executives involved in illegal opioid marketing and distribution, along with reduced exclusivity and tax credits for firms convicted of such activities. Leading opioid manufacturers earlier this year announced plans to limit or cancel promotional activities, but still may face penalties designed to help defray public outlays for costly addiction and rehab programs.
There may be some relief ahead, as seen in reports of a sharp drop in the volume of pain medicines prescribed and dispensed to patients in 2017, according to data from IQVIA (5). The trend indicates that physicians are responding to advisories from CDC and FDA and other health authorities to reduce opioid prescribing overall and to limit the number of doses in those prescriptions considered necessary. FDA looks to continue the trend with further advice on clinical study design related to addiction treatments and the development of non-opioid pain therapies. The agency also aims to examine whether new formulations do support abuse deterrence, Gottlieb said in testimony before Congress on FDA’s budget plan (6). The commissioner urged payers and health plans to expand coverage for therapies to prevent overdoses and to treat addiction, as well as non-opioid pain medicines. To ensure that patients suffering from pain have access to appropriate treatment, FDA is holding a public meeting on July 9, 2018 to hear from patients and medical professionals on strategies to support prescribing guidelines and pathways for developing new pain threapies (7).
1. Department of Justice, “Attorney General Sessions Announces Charges in DEA Opioid Limit Rules,” Press Release, April 17, 2018.
2. Department of Justice, “Attorney General Sessions Delivers Remarks on the Trump Administration’s Response to the Opioid Epidemic,” Press Release, March 22, 2018.
3. S. 2680, The Opioid Crises Response Act of 2018.
4. FDA, Opioid Dependence: Developing Depot Buprenorphine Products for Treatment, Guidance for Industry, Draft Guidance (CDER, April 2018)
5. IQVIA, “IQVIA Institute for Human Data Science Study: US Prescription Opioid Volume Declined 12 Percent in 2017–Largest Drop In 25 Years,” Press Release.
6. FDA, President’s Fiscal Year 2019 Budget Request for FDA–House Testimony, April 17, 2018.
7. S. Gottlieb, MD, “Addressing Needs of Patients While Stemming the Tide of the Opioid Crisis,” FDAVoice blog, May 14, 2018.
Vol. 31, No. 6
When referring to this article, please cite it as J. Wechsler, "Manufacturers Under Pressure to Curb Opioid Use and Abuse," BioPharm International 31 (6) 2018.