DEA lifts production quotas to ease injectable opioid shortage

The Drug Enforcement Administration has raised production quotas for drug manufacturers Fresenius Kabi and West-Ward Pharmaceuticals to mitigate the shortage of opioid injectables, but relief is likely months away.

Federal regulators and pharmaceutical manufacturers are trying to fill a void left by Pfizer, which produces about 60% of the small-dose presentations of injectable morphine, fentanyl and other opioids. Pfizer has been mired in manufacturing hang-ups since July.

Requests for additional raw ingredients were made to the DEA Jan. 1, but partial approvals for Fresenius Kabi and West-Ward Pharmaceuticals, along with a third smaller and unidentified manufacturer, weren't granted until mid-February and mid-March. The process highlights the difficult balance regulators must strike between limiting the opioid epidemic and getting pain medication to critically ill patients. Regulatory hurdles can also throw a wrench in the entire process.

Meanwhile, providers have had to scramble to find adequate alternatives that can sedate patients before surgery and manage pain after an operation as well as treat trauma, burn and cancer patients. Or, in some cases, they have had to put off treatment altogether.

"I am shocked that the DEA raised the quota only three weeks ago after being notified of the significant shortage and inability of Pfizer to ship product," said Erin Fox, who directs the University of Utah's Drug Information Service, adding that it takes time for manufacturers to ramp up production. "The shortage was well known to the DEA, so I am unclear on why it took so long to increase the amounts to other manufacturers."

In general, there is an eight- to 12-week quarantine from the time the products are manufactured to the time they are released from quality control and ready to be shipped out, said Scott Knoer, chief pharmacy officer at the Cleveland Clinic. It then takes a couple weeks to work through the wholesale distribution supply chain.

"Bottom line, this is good news, but it will likely be summer before we have some relief and longer for full relief," Knoer said.

The supply of injectable painkillers has been hamstrung as Pfizer's upgrade of its McPherson, Kan., facility drags on. Pfizer notified customers in July 2017 that it would be unable to fulfill market demand for a prolonged period. While some production has resumed, with the first batch expected to reach wholesalers this July, finished prefilled syringes have been held back since Jan. 31 as the company tries to resolve an issue related to a third-party supplier.

Pfizer doesn't expect to reach full production capacity until the second quarter of next year. It is committed to resolving the shortages as quickly as possible, the company said in a statement.

Providers, lawmakers, group purchasing organizations and industry groups like the American Hospital Association have been lobbying the DEA to raise production quotas amid the shortage. In a survey of 116 member health systems, GPO and consulting group Premier found that nearly all of them are experiencing moderate-to-severe shortages of injectable opioids. More than half reported that the shortage affected patient care, including delaying or canceling surgeries or lowering patient satisfaction scores.

"We are encouraged that the DEA did transfer raw material allocations to the three other companies, and we applaud Pfizer for recognizing the need to transfer some of their excess raw material allocation to other suppliers to help meet the inpatient needs for injectable narcotics," Todd Ebert, CEO of the Healthcare Supply Chain Association, said in an email. "However, we hope that the DEA will develop processes and procedures to recognize and respond to these market issues much more quickly in the future, as three months seems to be too long."

Without any hiccups, it can take about four weeks to fulfill extra quota requests, which the DEA bases on demand and utilization trends. But in this case, the agency had to send diversion inspectors to the facilities to reconcile issues with the companies' year-end reports and inventory checks.

There are around 600 diversion inspectors monitoring 1.7 million registrants, according to the DEA. The goal is to ensure that manufacturers aren't stockpiling raw ingredients, of which there are limited amounts that others could use.

"When we have 600 diversion investigators overseeing 1.7 million registrants, a lot of the onus falls on doctors and distributors to do their part," DEA spokeswoman Katie Laughery said. "When they don't do their part or purposefully do bad things, that causes issues."

But opioids, for the most part, don't make their way to the black market through the manufacturing or inpatient settings, experts said. Retail pharmacies present the most risk.

The DEA couldn't definitively say if limiting the quota of raw ingredients limited the diversion of opioids.

"The potential for diversion in the institutional setting versus the retail setting is infinitesimally small," said William Larkin, executive vice president and chief pharmacy officer for the GPO Acurity.

The DEA has been under immense pressure to rein in production as the opioid epidemic has worsened.

The agency reduced its production quota of opioids by at least 25% in 2016, which was the first reduction of its kind in more than two decades. But DEA-approved opioid production volumes remain high—including a 55% increase in oxycodone levels in 2017 compared with 2007, according to a July 2017 letter to the DEA signed by 16 senators.

Between 1993 and 2015, the DEA allowed production of oxycodone to increase 39-fold, along with drastic increases for other opioids, the letter said. The number of opioid prescriptions increased from 76 million in 1991 to more than 245 million prescriptions in 2014, resulting in a dramatic rise in overdoses. More than 42,000 people died from opioid overdoses in 2016, according to the Centers for Disease Control and Prevention, a five-fold increase from 1999.

There has been finger-pointing on both sides. Regulators have accused drug manufacturers of gaming the system while manufacturers argue that the DEA hasn't been quick to respond to inquiries, and when it does, there isn't much dialogue.

The DEA said it has put together a working group that aims to improve communication between regulators, manufacturers and providers.

"We are doing our best to meet the significant need that this shortage has presented for these important injectable medicines," Daniel Motto, West-Ward's executive vice president of commercial and business development, said in a statement. "We do, however, have limitations based upon the quota granted by the DEA." He added that West-Ward has requested additional active pharmaceutical ingredients.

Part of the issue is that there are a limited number of manufacturers that produce syringes of opioids. The products are heavily regulated given the complexity of making a syringe and the return on investment is slim.

Thus, it's important to have a working dialogue between all players involved, the DEA's Laughery said.

"We need to understand what the truth on the ground is," she said.

Want to continue the conversation about opioids? Join Modern Healthcare on April 25-26 at its Opioid Crisis Symposium.