Last month, the former co-owner of a Massachusetts compounding pharmacy, whose tainted medicines are blamed for a deadly meningitis outbreak in 2012, was sentenced to nine years in prison.
More than 60 people died and more than 700 people became ill across the United States after receiving injections of fungus-contaminated steroids shipped by the now-closed New England Compounding Center (NECC).
Compounding pharmacies produce medications that are tailored to the clinical needs of patients when a drug approved by the Food and Drug Administration (FDA) won’t work for them.
For example, a patient may need a liquid version of a medication approved only in pill form. Or they may need a medication made without preservatives.
The NECC case raised many questions about the quality of medicines — especially those that are supposed to be sterile — coming out of the thousands of compounding pharmacies across the country.
But it also highlighted another big issue with drug safety in the United States — for both compounding pharmacies and pharmaceutical companies.
“One of the major problems that exist in terms of the regulatory system for oversight of drugs is the fact that the FDA doesn’t have the authority to order recalls of drugs. I think many people are surprised to hear that,” Dr. Michael Carome, a director of the nonprofit advocacy group Public Citizen, told Healthline.
Recalling drugs is difficult
The FDA can order recalls of medical devices, blood products, vaccines, and baby formula … but not medications.
In spite of this, Carome said that most mainstream drug manufacturers “understand the liability risk they face” when one of their drugs has a problem with quality.
When the FDA, or the drug company itself, identifies an issue, the company will almost always initiate a recall.
Drugs produced by these companies, though, are not free of problems.
The FDA website lists nine Class 1 drug recalls just last month. Four were due to problems with lack of sterility and one for concerns over manufacturing practices.
Class 1 recalls involve drugs that are likely to “cause serious adverse health consequences or death” if taken.
At the other end of the spectrum are compounding pharmacies that may not always be as cooperative.
“There have been multiple examples where the FDA has asked a compounding pharmacy to recall a product and the company has refused,” said Carome.
For example, in 2013 FDA inspectors found lack of sterility in some of the drugs made by NuVision — also known as Downing Labs — a compounding pharmacy in Texas.
The company issued a partial recall. But FDA inspectors found that the company “continued to manufacture injectable drugs under insanitary conditions,” according to an agency press release.
After that, the FDA issued a warning to healthcare professionals to stop using any sterile drug products from NuVision.
In 2015, the company finally issued a nationwide recall of all of its drugs. The next year, a judge issued a permanent injunction prohibiting the company from making or distributing drugs until it complied with all FDA regulations.
Another company, Park Compounding Pharmacy, was warned by the FDA in 2015 about lack of sterility at its facilities in California. The company stopped making sterile drugs, but it refused to recall its existing products.
In both cases the FDA was not aware of any patients who were hurt by the compounding pharmacies’ products.
But that’s not always the case.
A report by the Pew Charitable Trusts identified more than 50 reported compounding errors between 2001 and 2017, which led to 1,200 people being sickened and 99 deaths.
Who’s watching for sterility?
Mainstream drug manufacturing facilities are routinely inspected by the FDA. That’s not true of most compounding pharmacies.
After the NECC meningitis outbreak, Congress passed a law in 2013 that allowed compounding pharmacies to register with the FDA as “outsourcing facilities.”
“Once a company registers as an outsourcing facility,” said Carome, “it is required to follow certain FDA regulatory requirements and comes under the FDA’s authority.”
This includes meeting FDA regulations for ensuring compounded drugs are high quality and that sterile drugs produced in the facility are actually free of fungus, bacteria, or other contaminants.
According to the FDA website inspectors visit these facilities on a “risk-based schedule.”
The catch? Designation as an outsourcing facility is voluntary.
An FDA report showed that production conditions have improved in some compounding pharmacies.
But there is much more work to do.
The FDA currently lists more than 70 registered outsourcing facilities, of which 58 have been inspected.
FDA inspectors found “significant objectionable conditions” in all but two of the facilities that were inspected.
These included waste in sterile areas, mold contamination on ceiling tiles, and even toaster ovens being used for sterilization.
More than a dozen companies were issued warning letters by the FDA. Two companies stopped making sterile drugs and recalled all of their sterile products.
And these are just the compounding pharmacies that have voluntarily registered with the FDA.
Carome estimates that there are thousands of unregistered facilities, all of which fall into a sort of regulatory gray area.
“The FDA has authority there,” said Carome, “but state pharmacy boards are the leading regulator of compounding pharmacies that have not registered as outsourcing facilities, which is the vast majority.”
FDA inspections at some of these facilities have turned up problems. In some cases, the FDA has turned the matter over to the state pharmacy board.
However, another report by The Pew Charitable Trusts found that on average each state inspector is responsible for monitoring 230 pharmacies. Illinois inspectors handle 900 pharmacies each.
Regulations for compounding pharmacies also vary from state to state.
Because there are so many compounding pharmacies not registered with the FDA and so few inspectors, inspections may not happen regularly.
“They are generally triggered by some red flag that there’s a concern about the quality or safety of the products, or the quality of their production facilities and techniques and procedures,” said Carome.
Mandatory FDA drug recalls
These issues have prompted some to call for stronger regulation.
“What’s really needed is for the FDA to have recall authority where they can just simply order these companies,” said Carome, “rather than asking them to do so voluntarily.”
Mandatory recalls might also be more effective at alerting healthcare professionals and the public about unsafe drugs.
Without a company’s cooperation — as with NuVision — FDA warnings may be missed by the public.
But “if a company knows who its customers are, and to whom they’ve shipped potentially tainted products,” said Carome, “they’re in a much better position to initiate an effective recall.”
Earlier this year Congresswoman Rosa DeLauro (D-Conn.) introduced a bill that would give the FDA “mandatory recall authority over drugs and homeopathic products.”
The bill was referred to a House subcommittee, where it remains.
Public Citizen has previously lobbied Congress to grant the FDA this kind of recall authority, but so far these efforts have been unsuccessful.
Others worry that President Trump’s push to speed up the FDA approval process for prescription drugs might increase the risks to consumers. Whether that means cutting back on testing a drug for safety and efficacy, or eliminating some of the inspections of manufacturing facilities remains to be seen.
In the absence of strong FDA oversight of compounding pharmacies, how concerned should consumers be?
“We think that FDA-approved drug products are generally safer choices than compounded drug products,” said Carome.
These drugs undergo a lengthy review process to show that they are safe and effective for their intended use.
Also, the FDA “inspects the facilities where FDA-approved products are manufactured,” said Carome, “and those inspections are done before the first drug is sold and then periodically thereafter.”
There are times, though, when a compounded drug is the only option for patients — like for those with an allergy to one of the nonactive ingredients or who need a liquid form of the drug.
Or when there’s a shortage of an FDA-approved drug, such as a cancer medication.
In these situations, said Carome, choosing a compounded drug over an FDA-approved drug is a “reasonable” option.
But he added: “It’s preferably one that’s obtained from an outsourcing facility, which is subject to FDA inspection and must comply with Good Manufacturing Practices.”