House to FDA: who’s in charge of clinical trial manufacturing?
The suspension of an NIH facility producing clinical trial supplies has shed light on a wider dilemma: what are the FDA’s obligations for inspecting non-commercial drug production?
The House of Representatives Energy and Commerce Committee wrote to the heads of the FDA and NIH, asking if the federal agency has a duty to scrutinise production of drugs for clinical trials just as it inspects commercial manufacturing.
The committee, led by Rep. Fred Upton, became concerned when the first ever FDA inspection of NIH’s clinical trial manufacturing site since its opening in 2010 revealed compliance problems which forced it to suspend production.
An FDA visit in late May 2015 to the NIH Clinical Center’s Pharmaceutical Development Section (PDS) found manufacturing faults, as well as fungal contamination in two vials of albumin used for administration of the drug interleukin in clinical trials. Six patients had been administered drugs from vials in the contaminated batch before the problem was discovered, and up to 46 clinical trials may be affected.
‘Serious questions about management’
The committee announced it is investigating the management of the PDS and wrote to NIH, “the severity of the deficiencies, the disruption of ongoing studies, and the resulting suspension of PDS operations raise serious questions about the management of the NIH PDS for the last several years.”
The PDS was opened in 2010 but the inspection this May was the FDA’s first. According to the Energy and Commerce committee, the FDA claims it is not required to inspect the facility because it does not routinely examine sites which manufacture drugs purely for research.
“Generally,” said the committee letter, “FDA would not conduct routine inspections of such a facility, but would conduct a for-cause inspection in response to a complaint, if warranted. However, this facility was making experimental drugs for FDA-regulated clinical trial research with human subjects.”
The Representatives said the FDA’s response “raises questions about how human subjects in these clinical trials were protected without an inspection to ensure there was sufficient information to assess the risks to subjects, or if the subjects would be exposde to unreasonable and significant risk.”
The FDA’s stance contradicts that of the NIH Clinical Director, who claimed in 2010 “the new PDS area will be fully GMP-compliant and subject to inspection by FDA.”
In their letter, Representatives Fred Upton, Frank Pallone, Tim Murphy, and Diana DeGette asked new FDA chief Stephen Ostroff to answer whether the agency had legal authority to conduct a routine inspection of the facility before May 2015.
They also asked to see all communications with NIH staff about allegations of adverse events or contaminated products at PDS, and for FDA to reveal how many Investigational New Drug (IND) submissions were filed for drugs made at PDS, and whether the applications included statements on quality and GMP.
The committee also wrote to NIH Director Francis Collins, asking him to reveal how many patients were affected by the suspension of clinical trials as a result of sterility problems at PDS, and whether any died.
The politicians also asked for the names of consultants involved in constructing the suspended facility, and documents relating to the site’s cGMP status, any previous inspections and internal audits, sterility, staffing levels, contracts, and expenditures.
It singled out PDS Section Chief George Grimes, Jr., and PDS Director Robert DeChristofaro in particular, asking for documents related to their performance since May 1, 2015.
The FDA told us it does not comment on letters from Congress but will reply directly to the committee.