An internal task force at the National Institutes of Health (NIH) has found “widespread and longstanding” problems at its now-suspended pharmaceutical compounding arm, though the deficiencies were not found to have any direct harm on past or current clinical trial participants.
The problems were unveiled in a new report from the task force late Thursday, which also includes more information on how NIH is addressing what was first uncovered by a US Food and Drug Administration (FDA) inspection.
Last June, NIH suspended operations at its Pharmaceutical Development Section (PDS), which is run by about 20 staff and acts as a compounding pharmacy with specialized capabilities to provide drugs for NIH clinical trial participants.
Later in June, NIH released two interim corrective action plans, and then more recently in October, the House Energy and Commerce Committee raised numerous concerns over how this temporary suspension might impact patients in NIH trials, which the task force has now responded to.
The task force, co-led by NIH Principal Deputy Director Lawrence Tabak and NIH Deputy Director for Science, Outreach, and Policy Kathy Hudson, was tasked with monitoring the status of protocols and research participants receiving PDS products for safety, identify alternative product sources to minimize research interruptions, work with FDA on corrective actions, and examine the root causes of failures at the PDS and the sterile portion of the Clinical Center Pharmacy, called the Intravenous Admixture Unit (IVAU).
The task force also contracted with Tunnell Consulting to independently assess the PDS and IVAU and make recommendations for remediation.
“Our investigation revealed that the underlying issues were more serious and widespread than was initially understood,” the task force said in a new report. “We learned that there was a prior history of contamination events and a systematic failure to adhere to a set of standard safety and compliance principles. Instead, priority had been put on producing a high volume of products to meet the requests of intramural investigators. Overall, we found that there was insufficient cGMP and regulatory expertise within the Pharmacy Department.”
As far as the clinical trials impacted by the suspension, about half of the affected protocols were cell therapy studies that used a cryopreservative dispensed by the PDS, but which is also available commercially, so there was no interruption in the supply, according to the report.
For the cell therapy research participants who required immediate treatment, FDA allowed “use of the quarantined PDS product (i.e. with cells already mixed with the PDS-dispensed cryopreservative) on a case-by-case basis for individual research participants.”
For the remaining protocols, clinical investigators switched to commercial sources when available and NIH is establishing an ongoing contract to vet external compounding facilities for products that are not commercially available. The task force is also assessing the capacity and timeframe for production of some of the PDS-formulated products in the Frederick, MD-based National Cancer Institute’s Pharmaceutical Management Branch (PMB).
In addition, Tunnell Consulting found that the extent of the problems would necessitate significant facility construction for both the PDS and IVAU to meet modern requirements for good manufacturing practice compliance, though the task force said that other decisions still need to be made about how to address long-term remediation of facilities, including the potential need for new construction.
In response to the task force’s findings, NIH Director Francis Collins said he will establish a new Office of Research Support and Compliance within the NIH Office of Intramural Research to improve the agency’s ability to maintain the highest levels of compliance with research regulations and standards.
He’s also decided to form a new Clinical Center Working Group of the Advisory Committee to the Director, chaired by former Lockheed Martin CEO Norm Augustine.
“Its charge is to examine the structural and cultural issues and make recommendations to improve the organization, financing, and management of the NIH Clinical Center. This Working Group has extraordinary experience in managing complex clinical research organizations and will deliver its recommendations to the ACD in the spring of 2016,” Collins said in a statement.
NIH Director Statement on Remediation of NIH Clinical Center Pharmaceutical Development Section
NIH Task Force on the Clinical Center Pharmacy Department