Presentation:
FDLI Conference, Washington DC
April 16, 2004
The Division of Bioresearch Monitoring Case Studies
Case Study #1
- An IDE was submitted to treat infants with hydroplastic left heart syndrome by Have a
Heart Incorporated (HAH).
- HAH reported several emergency uses of the device to the FDA.
- However, these devices had been modified substantially which caused the FDA to request
that a separate IDE be submitted by HAH.
Case Study #1
- An IDE was submitted as the FDA had requested, which was conditionally approved.
- Due to data integrity concerns of the FDA, a "for cause" inspection was
completed.
- Numerous deficiencies were noted during this inspection which warranted a Warning Letter
to be issued.
Case Study #1
The Warning Letter notified HAH of the following:
- Failure to maintain accurate records of adverse events.
- Failure to notify the FDA of emergency uses within five working days.
Case Study #1
- Failure to ensure proper monitoring of clinical investigation and secure
investigator compliance.
- Failure to select qualified monitors.
- Failure to maintain complete records of shipment and disposition of devices.
Case Study #1
- HAH responded by submitting a Corrective Action Plan which addressed many
of the violations cited and appeared to be adequate if followed.
Case Study #1
- As a follow up to the first inspection HAH was inspected again by the FDA.
Case Study #1
HAH was found in violation of the following:
- No written SOP’s for ensuring prompt compliance and / or corrective action for
protocol deviations.
- No disciplinary action was taken by HAH when noncompliance occurred.
- Investigational sites did not document reasons for protocol deviations.
- Device accountability was not reconciled as required by HAH’s SOP’s.
Case Study #1
- The FDA sent an informational letter to HAH advising them to adhere to the
previously submitted Corrective Action Plan.
Case Study #1
- HAH notified the FDA through submission of a supplement to their second IDE that there
were three unreported emergency uses of the device that resulted in three deaths prior to
approval of the IDE application.
- In light of this information, the FDA conducted a third "for cause" inspection
of HAH in order to determine whether the compassionate/ emergency use provisions were
being abused.
Case Study #1
- The inspection revealed the following:
Case Study #1
- An additional four emergency use cases were discovered during the inspection that were
not reported to the FDA within five working days.
- Device accountability records failed to account for over twenty devices.
- Adverse events were not reported in a timely manner even though the firm had a
Corrective Action in place.
Case Study #1
- Because of the continuing nature of noncompliance observed during multiple
inspections, the FDA asked HAH to meet with FDA officials to explain their
actions.
Case Study #1
- What are the problems that you see in this case?
- What action would you take if you were representing the FDA?
- What action would you take if you were representing HAH?
Case Study #1
So what is the solution?
- Issue another Warning Letter?
- Invoke the Application Integrity Policy?
- Levy Civil Money Penalties?
- Pursue Criminal Action?
Case Study #1
- Discussion
- Ask questions of the panel members
"INSERT GRAPHIC HERE"
Case Study #2
- Two IDE’s were submitted by Geriatric Solutions, (GS) for knee and
hip replacement devices.
- GS informed the FDA that they had implanted a significant number of devices
prior to the approval of the IDE in the hip study.
Case Study #2
- These subjects did not receive informed consent nor were they aware that
they had received a investigational device.
Case Study #2
- GS stated that they sold these investigational devices by physician’s
prescription.
Case Study #2
- Based on this information the FDA decided to conduct "for cause"
inspections of GS as well as the Clinical Investigators.
Case Study #2
The inspections revealed the following:
- Failure to ensure control of the investigational device.
- Failure to document and report adverse events.
- Failure to ensure the clinical investigators obtain informed consent from subjects prior
to the use of the device.
- Failure to utilize IRB approved informed consent forms.
- Failure to adhere to study protocol.
Case Study #2
- Failure to ensure clinical investigators obtain IRB approval before initiating the
study.
- Failure to ensure maintenance of device accountability records.
- Failure to obtain IDE approval and IRB approval prior to initiating study.
- Failure to ensure proper monitoring of the clinical investigation.
- Failure to obtain financial disclosure or investigator agreements for each investigator.
Case Study #2
- Based on the inspections, the FDA took the following action:
- Issued a Warning Letter to GS.
- Issued Notices of Initiation and Disqualification Proceedings and Opportunity to Explain
Letters (NIDPOE) to the Clinical Investigators.
Case Study #2
- The FDA requested that no additional patients be enrolled in the study and that the GS
send a patient notification letter to those who had received the device without informed
consent. GS also needed to prepare a Corrective Action Plan and audit all the data from
the hip study.
Case Study #2
- GS submitted a draft Audit/Corrective Action Operating Plan, however, this
CAP was inadequate due to its lack of specificity in terms of actions to be
taken and documentation for corrective action already made.
Case Study #2
- GS then notified the FDA that one of their hip devices that was approved
in Europe not the U.S. was imported into the U.S. and implanted in 170 patients
in St. Louis, Missouri and these sales were made pursuant to the physicians’
"prescriptions" as custom devices.
Case Study #2
- The FDA’s response was the following:
Case Study #2
- GS then notified the FDA that they had found similar problems as the ones
documented in their hip study in their knee study.
Case Study #2
- What are the problems that you see in this case?
- What action would you take if you were representing the FDA?
- What action would you take if you were representing GS?
Case Study #2
So what is the solution?
- Issue another Warning Letter?
- Invoke the Application Integrity Policy?
- Levy Civil Money Penalties?
- Pursue Criminal Action?
Case Study #2
- Discussion
- Ask questions of the panel members.
Mission of the Office of Compliance
- To protect the public health by ensuring that devices and radiological health products
are safe and effective.
- To ensure compliance with applicable laws, regulations, and standards through education
and enforcement.
FDA Web Sites
- WL index by date-month/year:
http://www.accessdata.fda.gov/scripts/wlcfm/indexdate.cfm
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Updated July 8, 2004
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