ASHINGTON — In a bland Northern Virginia office building nestled between a Costco and a freeway interchange, a dozen government scientists have spent the past year crunching numbers and making the following determination: In 2018, drug makers will be allowed to produce no more than 98,145 kilos of oxycodone, 38,047 kilos of morphine, and 1,342 kilos of fentanyl.
The precise limits are set as part of a little-known process in which, every year, the Drug Enforcement Administration regulates the volume of controlled substances that can be produced in the United States.
The process was started nearly five decades ago to ensure that drug makers produced enough medicines to avoid shortages. But in the midst of a national opioid epidemic, fresh scrutiny of the quota system has spread to Capitol Hill, where Democratic lawmakers are pressing the DEA to use it for another reason — to help stem supply.
“It is clear that we need to reduce the amount of oxycodone and hydrocodone that DEA approves for manufacture each year and hold Big Pharma accountable for manufacturing a product that is leading to the deaths of hundreds of people every day,” said Sen. Edward Markey (Mass.), who has introduced a number of bills aimed at addressing the opioid crisis.
Rarely, however, has the quota system been used to eliminate or constrain supply for a class of drugs similar to opioids — created to fill a medical need but with consequences that, in at least some cases, have outweighed the medical benefits.
The lone historical exception is that of the sedative methaqualone, which was marketed until the early 1980s as Quaalude. The drug became so abused that it quickly fell out of favor with the medical community, and in conjunction with nose-diving prescription rates and manufacturer interest, the DEA began to lower the quota for methaqualone production in 1973. It hit zero in 1981.
But opioids are not quite analogous. No medical group thinks they are without merit when properly distributed, and a substantial number of pain patients would suffer if denied access to them.
Many experts are not sure using the quota system as a tool to constrain supply is a sound idea — and instead believe the focus should be on reducing prescriptions.
The DEA could have considered tightening quotas to address the crisis more than a decade ago, “when we were clearly already in the middle of an opioid crisis and it was clear the prescribing of OxyContin was happening at a rate much greater than could be clinically needed,” said Andrew Kolodny, the co-director of the Opioid Policy Research Collaborative at Brandeis University.
“Now,” he said, “I don’t think it makes any sense, because the prescribing peaked in 2011 and 2012.”
Still, some lawmakers say that the DEA has historically been too liberal in the setting of the quotas. In a letter to the agency’s acting administrator earlier this year, 16 Democratic senators noted that the agency allowed aggregate production quotas for oxycodone to increase thirty-nine-fold between 1993 and 2015, and quotas for fentanyl to increase twenty-five-fold.
“Further reductions are necessary,” wrote the senators, led by Sen. Dick Durbin, the chamber’s No. 2 Democrat.
Republicans have had little to say on the issue. And a Trump administration official, speaking on condition of anonymity, said the politicization of the quota system has created the potential for hospital shortages and access issues for pain patients who have legitimate medical needs.
Outside the United States, there are cautionary tales of government intervention in the supply of pharmaceutical drugs.
In Russia, for example, a heavy-handed regulatory system meant to guard against drug abuse has led to shortages, with highly publicized cases like that of a Russian naval officer with late-stage cancer who committed suicide after being unable to obtain sufficient pain medicine.
In Uganda, fear of a U.S.-style opioid crisis has left palliative care doctors without the necessary means to treat patients in their final, agonizing stage of life.
In the United States, the quota system is used for all Schedule II drugs — those that are deemed to have legitimate medical uses but that carry high potential for abuse. It also applies to a select number of stimulants, as well as research-oriented production of Schedule I drugs like marijuana and GHB deemed to have no accepted medicinal value.
To set the quotas, the DEA says it relies on estimates of legitimate medical need from the Food and Drug Administration, prescription levels from the previous year, manufacturers’ forecasts, and other data. A spokesman said the agency uses a strict formula, and does not take into account business or other circumstantial considerations.
“If any part of the steps that are taken need to be changed, or people want them to be changed, Congress has to do that,” the spokesman, Melvin Patterson, told STAT.
(A spokesman for the Food and Drug Administration, which sends information about past and projected prescription levels to the DEA each year to assist in the quota-setting process, declined to specify the source of the FDA’s data.)
The quota levels for aggregate opioid production in 2017 were lowered by about 25 percent, a move that may have helped to address political pressure to reduce the quota but had little impact on actual supply. The DEA acknowledged that the numbers appeared lower because the agency decided to eliminate a cushion it has previously included as a safeguard.
It represented “a quota that was built into the system to handle an emergency, a catastrophic event” but that was never used, said Joe Rannazzisi, who ran the DEA’s division of diversion control until 2015 and now consults with lawyers pursuing legal action against the opioid industry.
For 2018, the DEA has lowered the quota for opioids another 20 percent — a quota even Rannazzisi acknowledged is more likely to substantively reflect and impact prescription levels.
“Physicians, pharmacists, and patients must recognize the inherent risks of these powerful medications, especially for long-term use,” Chuck Rosenberg, then the DEA’s acting administrator, said in an August statement. “More states are mandating use of prescription drug monitoring programs, which is good, and that has prompted a decrease in opioid prescriptions.”
While the DEA is required to publish the aggregate quota amounts each year, it is prohibited from making public the individual quotas it awards to specific manufacturers.
That makes it difficult, Democratic congressional aides told STAT, for the public to connect the dots between manufacturers and the supply of narcotics they are responsible for on the market.
Markey has sponsored a bill that would require the DEA to release individual quota levels for manufacturers, in the hope that drug makers perceived to be contributing to the addiction crisis will become more responsible actors in the face of greater public awareness.
That could put manufacturers that obtain controlled substances for research purposes or compounding with other drugs at a competitive disadvantage. But Rannazzisi said that in most cases, the idea of forcing accountability through transparency is a sound one.
“I totally agree with that,” he said. “Mr. Markey, his theory is somewhat correct — I guess he’s looking at shaming manufacturers for how much [quota] they’re getting.”
Industry groups have not bothered to advocate against the measure — it is virtually certain to receive neither a hearing nor a vote in the Senate Judiciary Committee. But opposition, Democratic aides said, would be fierce if Democrats controlled either the House or Senate or if the bill appeared likely to become law.
Purdue Pharma, which manufactures and markets oxycodone as OxyContin, declined to comment on the Markey bill and the quota process in general. A spokeswoman for PhRMA, the drug industry lobby, said the group had not reviewed the bill or taken a position on it.
Regardless of what happens, there is consensus across industry groups and the expert community that the simplest way to reduce the supply of opioids over the long term is simply to reduce prescriptions. Already, changes to prescription practices nationwide have sapped some of the demand for the drugs.
Guidelines issued by the Centers for Disease Control and Prevention to encourage more responsible prescribing practices are also a focus. And policy staff across federal agencies agree those guidelines, coupled with a slew of state laws limiting prescription length and encouraging use of non-opioid painkillers, are the best bet when it comes to addressing the crisis.
Instead of reducing prescriptions by lowering quotas, Kolodny said, governments should work to lower quotas by reducing prescriptions. But the Pandora’s box was opened long ago.
“In 2002, there should have been a change in the way we have a quota or a cap, and a cap would have been a mechanism to prevent other pharma companies from putting other opioids on the market,” Kolodny said.
“The problem with new opioids getting approved is each time the opioids get approved, [manufacturers] have to recoup their investment,” he said. “The only way to do that is to get prescribers to prescribe your drug, which means a campaign to incentivize prescribing. Basically each new opioid is pouring fuel on the fire.”