Compliance program supports IND and IDE research applications
Two-year-old program is working well
With research institutions increasingly facing vigorous regulatory scrutiny, it is a good idea to provide investigators with support in areas where they might have issues. One such area involves applications for investigational new drugs (INDs) and investigational device exemptions (IDEs).
The University of Pittsburgh in Pittsburgh, PA, established its Office for Investigator-Sponsored IND and IDE Support in August, 2007, as a combined service of Office of Clinical Research, Health Sciences, the Clinical and Translational Science Institute, and the Research Conduct and Compliance Office.
"As an institution, this gives us better oversight," says Dennis Swanson, RPh, MS, director of the IND and IDE office. The office has three employees who share time with this office and other clinical research compliance work.
"All sponsor investigator IND and IDE applications are required to be submitted to the FDA through this office," Swanson says. "Those sponsor investigator applications in process before the office opened are also required to be submitted to the office along with all subsequent FDA correspondence."
Before opening the office, there was no central office providing IND/IDE application support to investigators, Swanson says.
"Also, there was no central office within the university prior to this office that was involved with seeing all FDA communication related to sponsor investigator applications," he adds.
"Another issue that led to the establishment of this office is related to the fact that the FDA only communicates directly with the sponsor of an IND or IDE application," Swanson says.
"In the past, the FDA would perhaps put a clinical hold on the IND application or have concerns they'd communicate to the sponsor or investigator, but the university's IRB was out of that communication loop," he explains. "And so was the university, so we had certain problems and issues that the university needed to know about, but didn't."
Citations can result
In one case, the FDA had placed a clinical hold on a sponsor investigator IND application, and the investigator continued with the project anyway, resulting in an FDA citation, Swanson recalls.
"The FDA came to the university and IRB and asked why we permitted the study to go forward in face of the clinical hold, and the answer was that the university didn't know about the clinical hold," Swanson says.
The new office gives the institution immediate information that could be used to identify trends and issues of noncompliance, he notes.
"We routinely do presentations for investigators in individual departments with regard to what we've found," Swanson says.
For example, one finding was that investigators sometimes complete FDA IND or IDE applications when it is not necessary.
"Within the FDA's regulations there are several different categories of research wherein if you are doing research in that area, the submission of an IND application is not indeed required," Swanson says.
When the office opened, compliance officials found that many IND applications were unnecessary because they would have been exempted under FDA regulations and criteria, Swanson says.
"In the past, investigators would have made an assumption that an IND was required and they'd either not go ahead with the project or they'd provide a submission when it's not required," he explains.
For instance, FDA regulations exempt research studies with off-label use of approved drugs based on certain criteria, he explains.
"Primarily, this is if the off-label use does not provide significant increase in risk or decrease in acceptability of risk," Swanson says.
Also, studies involving dietary supplements may or may not require an IND application, he adds.
"Sometimes an IND is required and sometimes it's not in studies of human cells and tissue-based products," Swanson says. "So for those studies, investigators could avoid the requirement to apply for an IND if they fall under one of those exceptions or exemptions."
Now the IND/IDE office educates investigators about the exemptions and gives them advice about when it is truly necessary to submit an IND or IDE application.
Research regulatory officials also have identified a number of compliance issues related to IND/IDE applications, Swanson says.
"I don't think many investigators have a good understanding of what the responsibility of a sponsor of an IND is," Swanson says. "They understand their responsibilities as an investigator, but when they are both sponsor and investigator, they might not be familiar with the sponsor's requirements."
The IND/IDE office's role includes extensive education through its Web site (www.o3is.pitt.edu) and the one-on-one discussions with clinical researchers.
"Our Web site includes background information about this office and the university's policies and procedures governing sponsor-investigator applications," Swanson says. "And there's a section called 'General Requirements for IND and IDE submission' that addresses some of the exceptions."
The office does not have enough staff to help investigators write IND/IDE applications, but there are templates available, he notes.
"We've developed templates for the overall IND application and templates for individual components of IND/IDE application," Swanson says. "Where there is standard wording, such as in adverse event reporting, we've written those sections out for the investigator."
Typically, investigators are referred to the IND/IDE office from the clinical and translational science institute.
"We meet immediately with them to address whether an IND/IDE is required, and if it's required, we go over it with them," Swanson explains. "At the investigator's request, we will review drafts of the application and provide whatever assistance we can."
When Swanson reviews an application, he looks for statements that might raise red flags with the FDA, and he makes certain investigator sponsors have not overcommitted to activities.
For instance, an investigator might state that he will report all adverse events to the FDA within 24 hours, Swanson says.
"That's overkill," he says. "They only need to report adverse events that are both serious and expected and felt to be possibly related to the investigational drug."
Also, they need to report it within seven or 15 days, depending on whether it's life-threatening, Swanson adds.
In another example, investigator sponsors might claim that a drug is manufactured in compliance with good manufacturing practice standards, Swanson says.
"The FDA interprets that as manufacturing it in compliance with FDA's good manufacturing practice regulations at 21CFR, part 211, and that may not be the case," he explains. "The drug may have been manufactured locally at a facility that does not operate in strict compliance with these regulations."
Since the FDA does not require investigational drugs for phase I clinical investigations to be manufactured in strict compliance with the 21CFR, part 211 regulations, then claiming this on an application is unnecessary, he adds.
"You have to be careful about what you say in an IND application," Swanson says. "The FDA will hold the investigator to what's said in the IND application, and it will audit against those statements."
With research institutions increasingly facing vigorous regulatory scrutiny, it is a good idea to provide investigators with support in areas where they might have issues. One such area involves applications for investigational new drugs (INDs) and investigational device exemptions (IDEs).You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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