In response to shortages of medicines needed for Covid-19 patients on ventilators, the Food and Drug Administration is temporarily easing its rules so that compounders can start making some of the drugs.
For as long as the nationwide public health emergency is in effect, the agency will not take action against compounding pharmacies that make a medicine that is a copy of an approved drug, use bulk ingredients not on an approved list, or fail to meet good manufacturing requirements for stability testing.
“In light of unprecedented disruptions to, and demands on, the global pharmaceutical supply chain as a result of the Covid-19 pandemic, and in order to respond to evolving regional conditions, additional flexibility is temporarily needed to ensure that treatment options are available when hospitals are unable to obtain FDA-approved drugs used for hospitalized patients with Covid-19,” the FDA said in a guidance.
The shift applies only to so-called outsourcing facilities which, unlike smaller compounders that typically fill individual prescriptions, make and sell large quantities of medicines without requiring prescriptions. Moreover, they are required to register with the FDA, and must follow accepted manufacturing practices.
The decision comes as hospitals are having difficulty receiving orders for more than a dozen sedatives, anesthetics, painkillers, and muscle relaxants, which have been in short supply. The drugs are used to help manage pain and comfort levels while a patient is on mechanical ventilation. But orders are being filled and shipped to hospitals only 53% of the time, down from 72% last month.
That’s because overall demand for these drugs has jumped considerably, rising 87% from January to March alone. And demand increased a hefty 213% from January to April, according to Vizient, a group purchasing organization that negotiates contracts for medicines on behalf of about 3,000 hospitals and health care facilities in the U.S.
The FDA move was greeted cautiously by one hospital official.
“I’m happy to hear anything that improves our supply at this point. We’ll take anything from the FDA in terms of alternatives and options,” said Chris Fortier, chief pharmacy officer at Massachusetts General Hospital in Boston. “But the question becomes how quickly can a compounder ramp up and can they get enough raw material?
“I also want to know what process is used to make sure a product is tested appropriately and is safe and effective before being shipped out. I would expect any knowledgeable hospital to ask those questions. The problem is that this could take two, three weeks, maybe a month. I don’t have that much time. I’m running out of hydromorphone [a painkiller] today, so next week is probably too late for me.”
This guidance marks the second time this month that a federal agency has attempted to ease shortages complicating the battle against Covid-19. Last week, the U.S. Drug Enforcement Administration began increasing production quotas by 15% for several controlled substances, including fentanyl and morphine, as well as certain so-called intermediates that are essential to producing these medicines.
Among the drugs the FDA will allow compounders to make are five sedatives and anesthetics – etomidate, dexmedetomidine, ketamine, lorazepam, and midazolam. There are also two analgesics – fentanyl and hydromorphone – and two muscle relaxants – cisatracurium and vecuronium, according to the FDA guidance.
The move by the FDA marks a distinct – albeit temporary – change in policy, because the agency has tried to increase oversight of compounders ever since an outbreak of fungal meningitis killed dozens of people seven years ago. More than 60 deaths around the U.S. were attributed to a quality control breakdown at the now-defunct New England Compounding Center.
As a result, Congress created two classes of compounders in 2013. One is the 503B compounder, or outsourcing facility, which ships large quantities out of state and is overseen by the FDA. The other is a 503A, or more traditional compounder, that is overseen by state boards of pharmacy. But safety and oversight remained controversial for several years, partly due to varying state inspection policies.
Since then, the FDA has labored to establish criteria for stopping compound pharmacies from functioning as unregulated drug manufacturers. For their part, compound pharmacies have argued they fill an increasingly vital role in a pharmaceutical supply chain that has been battered by quality control issues with pharmaceutical ingredients, and unforeseeable and long-lasting product shortages.
“It’s hard to tell yet whether the agency has gotten the benefit-risk calculation correct,” said Liz Richardson, director of the health care products project at Pew Charitable Trusts. “It looks like they’re trying very hard to maintain standards while allowing the facilities the flexibility to respond. But it’s hard to know, given all the other things that are happening, whether this will help address the problem.”
“They’re being flexible now, but it only applies during the emergency,” Richardson added. “What happens after the emergency has passed? We want to make sure when the emergency is over that the standards go back to where they were.”
But Scott Brunner, who heads the Alliance for Pharmacy Compounding, told us the discussion may be moot and maintained the guidance “will have little or no effect.”
“I’ve talked with several (compounders) today. It’s sort of a ‘rearranging the furniture’ move by FDA, without substantive economic or regulatory relief that will (provide incentives) to switch gears and reconfigure their facilities to make a medication that will likely only be in shortage for the next 60-90 days,” he said. “So the shortages will persist, and patients will remain at risk.”
This post was updated to note that outsourcing facilities must register with the FDA.
About the Author Reprints
It doesn’t seem feasible that that compounding pharmacies are going to shift gears for such a short time and no payback. Given the concerns about compounded drugs that led to The Drug Quality and Security Act and USP800 there are many inherent risks involved in allowing one-off manufacture in the first place. USP800 took effect in December 2019 and at this point, the FDA has failed to enforce their own regulations regarding the control of chemotherapy drugs all the way through excretion by the patient.
Hi Jim,
Thanks for writing in.
Those are good points. I would guess that, yes, there will be compounders who don’t bother unless for some reason they can get the raw materials at the right price. But in the absence of being able to strike up long-term customer relationships, there may not be enough incentive. But we will see.
Oversight and safety, as noted, are indeed watchwords. Perhaps some compounders will see this as an opportunity to convince naysayers otherwise. Another point to watch, perhaps.
Hope this finds you safe,
ed at pharmalot