Some people enrolled in clinical trials with the U.S. National Institutes of Health (NIH) are continuing the use of experimental drugs despite the possibility the compounds have fungal contaminations.
NIH suspended operations yesterday at a facility that makes experimental drugs for the agency’s Clinical Center in the wake of an investigation by the Food and Drug Administration (FDA) that revealed multiple problems that could expose sterile drugs to contamination. Forty-six trials currently underway receive materials from the facility, and NIH is searching for alternate sources of products for about 250 patients involved in the studies. In some instances, however, finding those other sources won’t be possible, and some trials will have to be delayed, says Lawrence Tabak, principal deputy director of NIH.
In addition, a few trial subjects, after being informed of the risks, have requested to continue with their experimental treatments made by the now-closed facility. NIH Director Francis Collins has granted exceptions to those whose conditions could be severely compromised if they failed to receive their next scheduled dose. They will be monitored for signs of infection. “Many of them have been taking the products for a while with no untoward effects. The likelihood of infection is small, but we still want to be cautious,” Tabak says.
“This is a distressing and unacceptable situation,” Collins said in a statement. “The fact that patients may have been put in harm’s way because of a failure to follow standard operating procedures in the NIH Clinical Center’s Pharmaceutical Development Section is deeply troubling. I will personally oversee the steps to protect the safety of patients and remedy the situation as swiftly as possible.”
In April, a Clinical Center employee had noticed what appeared to be a fungal contamination in a vial of albumin—used in the administration of the drug interleukin in experimental studies—after being unable to draw the liquid out of the vial. Visual inspection of about 650 vials from the same batch revealed one additional contaminated vial. Six patients from three studies received vials from the same lot, although it’s unclear whether those vials or others were contaminated. At this point, none of the six have developed signs of infection or illness.
Following the April episode, an internal review was conducted, says Tabak, which noted several issues with the physical facility. Although the exact timing is unknown, at some point FDA received an anonymous complaint and conducted an unannounced inspection of the NIH facility located on the Bethesda, Maryland, campus between 19 May and 29 May. Their 14-page assessment exposed a number of shortcomings, both physical and operational. An exhaust vent leading from one of the facility’s “clean rooms” to the roof lacked a filter or screen, for example, and flaws in the air handling system could expose sterile drugs to microbial contamination during processing. The report noted deficient cleaning and disinfection processes (insects were found in two of five clean room ceiling light bays), and examples of apparently inadequate employee training (lab employees with clothing that left parts of their face, neck, and arms exposed).
To date, all products from the facility have been visually inspected, and no obvious additional contamination was observed. NIH is in the process of sending the products to an outside contracting laboratory for additional testing, which could take several weeks. They are also in the process of contacting and monitoring patients in the remaining 43 studies. Studies of treatments for autoimmune and rare genetic diseases as well as for different forms of cancer are among those potentially affected.
A full review using outside experts in engineering, microbial practices, and sterility practices is planned, and NIH is scheduled to provide an interim corrective action plan to FDA by 19 June.