Drug Contamination Problems Hit NIH

Serious drug quality issues have forced the National Institutes of Health (NIH) to shutter its fairly new, in-house facility for producing clinical supplies for certain clinical trials, a development that starkly illustrates the complexity of manufacturing sterile products to meet good manufacturing standards. NIH director Francis Collins announced the sudden shutdown June 4, 2015, following the discovery of fungal contamination in vials of albumin used to administer interleukin to patients. Those reports had triggered an FDA inspection of the facility in May, which cited the NIH Pharmaceutical Development Section (PDS) in the NIH Clinical Center for 17 deficiencies, including flaws in its air handling system, inadequate quality controls, insufficient staff training, and inadequate standard operating procedures. 

The PDS closure immediately affects supplies for 46 clinical studies and approximately 250 patients scheduled to participate in the trials. NIH says it’s searching for alternative supply sources to keep the trials going, as many of the study subjects are seriously ill. NIH also will engage an external group of experts in microbiology and sterile manufacturing to conduct a thorough review of the facility and its policies and procedures. Collins said that an interim corrective action plan would be prepared for FDA by June 19, 2015.

The current PDS was established in 2010, designed to be a state-of-the-art replacement for a smaller facility dating back to 1953 and no longer up to standards. NIH invested some $12 million in establishing the new operation, including an analytical unit designed to ensure the quality and purity of its products. The aim was to provide customized investigational agents not available from commercial operators to support the center’s capacity for conducting clinical trials; some commercially available products require special formulation for children and other patients. At that time, the aim was to expand its capacity to produce drugs and placebos needed by outside NIH-funded investigators as well. NIH invited the press to tour the new facility in March 2010 as it awaited final FDA inspection and approval. Program leaders described the benefits of the new operation and their vision of creating a national resource for clinical investigators, particularly those involved in research on orphan drugs and treatments for tropical diseases. The operation complemented then-new NIH initiatives to promote personalized medicine and to seek new uses for compounds that had been abandoned by pharma companies.

The problems experienced at the PDS recall similar events at drug compounding operations such as the New England Compounding Center, which was hit with criminal charges following deaths linked to contaminated injectables. FDA also gained authority to oversee large compounders more closely under a major overhaul of drug-compounding regulations.

The NIH situation highlights the inherent difficulties in producing high quality drugs, particularly injectable products that must meet high sterility standards and comply with extensive quality control requirements. As Thomas Sullivan writes in his Policymed.comblog, this should serve “as an example to academics and Pharmscolds that the government is not capable of doing everything and needs the pharmaceutical industry to do what they do best.”

But even established pharma and generic-drug makers have had serious problems with sterile drug production, as seen in plant closures and widespread shortages of important medicines.