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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Ratcliff, David C, M.D. 08-Dec-06

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
  9200 Corporate Boulevard
Rockville, Maryland 20850




DEC 8 2006

WARNING LETTER

VIA FEDERAL EXPRESS

David G. Ratcliff, M.D.
Chief of Medical Affairs
Washington Regional Medical Center IRB
3215 North Hills Boulevard
Fayetteville, Arkansas 72703

Dear Dr. Ratcliff:

This Warning Letter is to inform you of objectionable conditions observed during the Food and Drug Administration (FDA) inspection of your Institutional Review Board (IRB) from August 21 to August 25, 2006, by an investigator from the FDA Dallas District Office. The purpose of this inspection was to determine whether your IRB is in compliance with applicable federal regulations. IRBs that review investigations of devices must comply with applicable provisions of Tit1e 21, Code of Federal Regulations,(21 CFR} Part 56-lnstitutional Review Boards, Part 50-Protection of Human Subjects, and Part 812-Investigational Device Exemptions. This letter also requests prompt corrective action to address the violations cited.

The inspection was conducted under a program designed to ensure that data and information contained in requests for Investigational Device Exemptions (IDE}, Premarket Approval (PMA) applications, and Premarket Notification submissions [510(k)] are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.

Our review of the inspection report prepared by the district office revealed serious violations of Title 21, Code of Federal Regulations, {21 CFR), Part 50 - Protection of Human Subjects, Part 56 - Institutional Review Boards, and Part 812 - Investigational Device Exemptions. At the close of the inspection, the FDA investigator presented an inspection observations form FDA 483 for your review and discussed the observations listed on the from with you. The deviations noted on the FDA 483, and our subsequent review of the inspection report are discussed below:

The IRB failed to prepare, maintain, and follow adequate written procedures for conducting the review of research. (21 CFR 56.108, 21 CFR 56.110(c), and 21 CFR 56.115{a){6)]

You failed to ensure that the IRB prepared and followed written procedures for the conduct of IRB activities. Examples include, but are not limited to the following:

Pursuant to 21 CFR 56.108(a)(1) and 56.108(a}(2}, IRBs are required to follow written procedures for conducting its initial and continuing review of research; determining which projects require review more often than annually; ensuring prompt reporting to the IRB, appropriate institutional officials, and the FDA of any unanticipated problems involving risks to human subjects or others; any instance of serious or continuing noncompliance or the requirements or determinations of the IRB; and any suspension or termination of IRB approval. Your IRB lacked any written procedures. At the time of the inspection, you indicated that the IRB was using their bylaws and guidebook; however, you acknowledged that the IRB was operating without any type of written procedures.

The IRB failed to prepare and maintain adequate documentation of IRB activities. {21 CFR 56.115]

Purusant to 21 CFR 56.115(a)(2), an IRB shall prepare and maintain adequate documentation of IRB activities, including the following: minutes of IRB meetings which shall be in sufficient detail to show attendance at all meetings; actions taken by the IRB; the vote of these actions; the basis for requiring changes in or disapproving research; and a written summary of the discussion and the resolution. The inspection revealed several instances in which your IRB failed to prepare and maintain adequate documentation of its activities, including the following:

  • The [redacted] meeting minutes identify eleven members as present. However, the voting record for approval of the revised informed consent for protocol [redacted] notes [redacted] For [redacted] Against [redacted] Abstained, but does not account for the missing vote.
  • Minutes for the [redacted] meeting could not be located and produced during the inspection. In addition, the minutes covering continuing review approval for protocol [redacted] for 2003, 2004, and 2005 could not be located.

Please note that expedited review procedures are for certain kinds of research involving no more than minimal risk for minor changes in approved research. During the inspection, records related to expedited review could not be located. Your IRB uses the expedited review process to routinely review and approve new research studies and for the continuing review and approval of studies. Documentation is needed to evaluate the expedited review process. In addition, the lRB has not adopted a method for keeping all members advised of research proposals which have been approved under the expedited review procedure.

The violations described above are not intended to be an all inclusive list of problems that may exist at the IRB. The IRB is responsible for ensuring compliance with the Act and applicable regulations.

Within fifteen (15) working days of receiving this letter, please provide written documentation of the actions you have taken or will take to correct these violations and prevent the recurrence of similar violations. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you. Send your response to: Attention: Michael Marcarelli, Pharm.D., Food and Drug Administration, Center far DeviCes and Radiological Health, Office of Compliance, Division of Bioresearch Monitoring, 9200 Corporate Boulevard, HFZ-312, Rockville, Maryland 20850.

A copy of this letter has been sent to the Dallas District Office, District Director, 4040 North Central Expressway, Suite 300, Dallas, Texas 75204. Please send a copy of your response to that office.

If you have any questions, please contact Michael Marcarelli, Pharm.D. by phone at (240) 276-0125 or by email at Michael.Marcarelli@fda.hhs.gov.

Sincerely yours,

/S/

Timothy A. Ulatowski
Director
Office of Compliance
Center for Devices and Radiological Health

[Redacted]


Kristina C. Borror, Ph.D.
Director, Division of Compliance Oversight
Department of Health and Human Services
Office of Human Research Protections
The Tower Building
1101 Wootton Parkway, Suite 200
Rockville MD 20852.