FDA sees trend of unsafe compounding labs

Published on
information-circle This article is more than 3 years old

Food and Drug Administration authorities say they are seeing a trend of unsafe conditions in compounding laboratories.

Needle and syringe, and drug vialsIn announcing an injunction against one compounding laboratory, FDA Commissioner Scott Gottlieb, MD, said in February the laboratory is just one example of those with poor conditions that endanger patients.

"We continue to see concerning activity when it comes to some compounded drugs, including problems related to the conditions under which compounded sterile medicines are made, which can raise significant risks to patients," he said in the announcement. "This is an area of intense focus for the FDA.

"We're committed to making sure that compounded drugs are made under appropriate production standards and, when necessary, taking enforcement actions against compounders who fail to produce sterile drugs in compliance with the law."

FDA officials published the announcement after securing an injunction against the Pennsylvania-based Ranier's Compounding Laboratory and the pharmacist who owns it, Francis H. Ranier. He and the company are forbidden from making, holding, or distributing compounded human or animal drugs that need to be sterile, at least until the laboratory convinces FDA officials that it meets regulatory standards and adds programs to guard against lapses.

In a complaint filed Feb. 1, Department of Justice officials accused Ranier and his company of a history of making drugs that fall short of sterility requirements. The complaint says an FDA investigator found in May 2018 that pharmacy employees brought unsanitary objects into a critical processing area, failed to properly use a filtration hood, and engaged in inadequate contamination tests, cleaning practices, maintenance, and storage practices.

On July 10, 2018, the FDA warned the public against using sterile products made by Ranier's, and the company told FDA officials it halted sterile compounding that day. Ranier's issued a voluntary recall 17 days later.

In September 2018, the FDA published a draft guidance document, "Insanitary Conditions at Compounding Facilities," that describes the conditions seen by inspectors and how pharmacists and others should correct them.

"FDA has investigated numerous outbreaks of infections and deaths found to be the result of drug products that were contaminated because they were produced under insanitary conditions," the document states.

The most notable of those outbreaks occurred in 2012, when injectable drugs produced by New England Compounding Center killed 64 of almost 800 people who developed fungal meningitis, according to FDA and DOJ information. Prosecutors have secured prison sentences against pharmacists responsible for practices that include making and selling drugs without confirming they were sterile, failing to tell people when drugs were contaminated, compounding with expired ingredients, forging prescriptions to dispense drugs in bulk, ignoring mold and bacteria in what were supposed to be clean rooms, and telling staff to mislabel drugs.

Since the 2012 outbreak, the FDA has investigated other serious adverse events, including deaths, and compounders have recalled drugs that needed to be sterile, the draft guidance document states. However, the document also warns that adverse events likely are underreported.

"FDA does not inspect the vast majority of compounding facilities in the United States because they generally are not registered with FDA unless they are outsourcing facilities," the guidance states. "Therefore, unless FDA receives a complaint, such as a report of a serious adverse event or visible contamination, the Agency is often not aware of these facilities, their conditions and practices, and potential problems with the quality and safety of their drug products."

Most other compounding facilities register with states, and the FDA encourages state regulators to assess practices.

In the compounding facilities seen by the FDA, inspectors have found production areas with vermin, visible mold and bacterial growth, rust, glass shavings, hairs, paint chips, and standing water. They saw handling that could cross-contaminate sensitive or potent drugs, such as hormones. Products have contained ingredients with potentially harmful amounts of impurities, including some ingredients labeled "not for pharmaceutical use."

Employees failed to wear the right equipment to protect production or keep equipment clean. Drugs were made without proper ventilation. Tools and containers went unsterilized. Employees failed to test for contamination and ensure their safety equipment was working properly. Even those who cleaned sometimes used products that leave residues on equipment and containers that subsequently had direct contact with drugs.

Those who fail to correct the problems are subject to warning, product seizure, or injunction, the guidance states.

Since August 2017, FDA officials also have published alerts about other compounding problems in human medicine, such as a steroid and anti-infective drug that caused vision problems in cataract patients because of an unsafe excipient, an injectable fitness-related product that caused tissue erosion at injection sites of two people when a component degraded before the expiration date, and confusing labeling that led to one patient receiving 50 times the prescribed dose of fentanyl.