Manufacturers Under Pressure to Manage Painkillers

Opioid abuse generates calls for efforts to curb distribution.
Apr 01, 2013
Volume 26, Issue 4

Jill Wechsler
Abuse and misuse of prescription drug painkillers is soaring, responsible for more than 16,500 deaths in 2010, according to the Centers for Disease Control and Prevention (CDC). More than 250 million opioid prescriptions were filled in 2009, fueling a $9 billion market. Limiting opioid abuse is the most crucial public health issue for the Center for Drug Evaluation and Research (CDER) at FDA, said CDER Deputy Director Douglas Throckmorton in December 2012 at an industry conference. FDA seeks stronger warning labels and is encouraging development of abuse-deterrent formulations of long-acting opioids. Yet, Throckmorton notes the challenge of assuring patient access to these crucial drugs while reducing the "epidemic of abuse and misuse." This dilemma reflects a split in the medical community: pain specialists plead for ready access to needed medications for more than 100 million adults with chronic pain, while a growing number of experts back curbs on prescribing to curtail abuse. A key question is whether long-term treatment with opioids for pain is safe and effective, compared to use of these drugs for short-term relief.

The opioid crisis also has drawn attention of Congressional leaders. The Senate Finance Committee launched an investigation in May 2012 of financial ties between opioid manufacturers and pain experts, looking for links between pharma industry money and the surge in inappropriate drug use. Sen. Joe Manchin (D-WV) sought to add stronger controls on certain opioids to last year's FDA Safety and Innovation Act (FDASIA), but backed off when FDA promised to address the issue this year. The development of new opioids with anti-abuse features also is spurring legislative proposals to block generic versions of older, easily tampered products.


FDA's immediate task is to weigh the scientific and medical merits of a proposal from the Drug Enforcement Administration (DEA) to impose stricter controls on drugs such as Vicodin (combination of hydrocodone and acetaminophen). DEA initially petitioned FDA in 2004 to evaluate evidence for reclassifying hydrocodone combination products from schedule III to schedule II under the Controlled Substances Act (CSA). This "upscheduling" would impose more stringent recordkeeping and storage requirements on 81 marketed combination medicines, virtually all of which are generic drugs. Schedule II prescriptions cannot be refilled or phoned in by doctors, and nurse practitioners and physician's assistants can't write scripts. The fear is that going to the doctor every three months for a new prescription could over-burden individuals who are coping with chronic pain.

Regulatory Roundup
FDA rejected DEA's initial proposal, questioning whether the schedule change would make a real difference, considering the rampant abuse of opioids such as OxyContin and morphine that already are schedule II. DEA has come back with additional data on the surge in opioid-related deaths and hospitalizations, which has generated a groundswell for action. FDA sought advice on DEA's proposal from its Drug Safety and Risk Management Advisory Committee at a January 2013 meeting (rescheduled from October 2012 due to Hurricane Sandy). FDA safety experts and representatives of medical organizations analyzed DEA's research, while dozens of family members and medical practitioners described their experiences with drug-induced deaths and ruined lives.

Opposition to DEA's proposal came from the Generic Pharmaceutical Association (GPhA), which predicted supply-chain problems as manufacturers and wholesalers face requirements for larger vaults and new systems for storing controlled ingredients and finished goods. Pharmacists complained about a host of costly new security procedures, while practitioners predicted access problems for patients suffering from cancer, trauma, and post-operative pain. Despite FDA skepticism about the policy change, the advisory committee voted 1910 in favor of DEA upscheduling, and FDA is expected to follow the panel's advice.

These issues were re-examined a week later at a February FDA public hearing on proposals to add stronger labeling and warnings on opioid painkillers. Physicians for Responsible Opioid Prescribing had petitioned FDA to revise labels to limit opioid treatment to 90 days and to patients with "severe" and not "moderate" pain. Again, dozens of stakeholders testified on abuse and access issues. Family members of addicts complained that existing labels fail to adequately inform doctors or patients of the severe risks of the drugs; pain specialists opposed arbitrary limits, emphasizing the need for flexibility to treat patients based on individual needs. There was discussion about whether a drug track-and-trace system, using serialization to identify individual units, could curb illegal opioid distribution. Pharmacists supported this approach, along with use of electronic medical records and drug monitoring programs to identify dangerous drug use.

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