Inspections, Compliance, Enforcement, and Criminal Investigations

St. Joseph Mercy Oakland Instiutional Review Board 9/15/15

  

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

Public Health Service
Food and Drug Administration
 10903 New Hampshire Avenue
Silver Spring, MD 20993 

 

WARNING LETTER
SEP 15, 2015 
VIA UNITED PARCEL SERVICE
 
Jack Weiner, Pharm.D.
President and Chief Executive Officer
St. Joseph Mercy Oakland Health System
44405 Woodward Avenue
Pontiac, MI 48341
 
Dear Dr. Weiner:
 
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 April 8, 2015 to April 21, 2015, by an investigator from the Detroit District Office. FDA previously issued your IRB a Warning Letter on August 1, 2013 for objectionable conditions observed during an inspection from April 17, 2013 to April 22, 2013. This follow-up inspection was conducted to determine whether your IRB is in compliance with applicable federal regulations. IRBs that review clinical investigations of medical devices and drugs must comply with applicable provisions of Title 21, Code of Federal Regulations (CFR) Part 56 - Institutional Review Boards, Part 50 - Protection of Human Subjects, Part 812 - Investigational Device Exemptions for devices, and/or Part 312 - Investigational New Drug Application for drugs. This letter also requests prompt corrective action to address the violations cited and discusses your IRB’s written response dated May 5, 2015 to the noted violations.
 
The inspection was conducted under a program designed to ensure that data and information contained in applications or submissions to the FDA 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 severalviolations of 21 CFR Part 56 - Institutional Review Boards, which concerns requirements prescribed under section 520(g) of the Federal Food, Drug, and Cosmetic Act (Act), 21 U.S.C. § 360j(g). At the close of the inspection, the FDA investigator presented an Inspectional Observations Form FDA 483 and discussed the observations listed on the form with (b)(4), IRB Chair. The deviations noted on the Form FDA 483, your IRB’s written response dated May 5, 2015, and our subsequent review of the inspection report, are discussed below:
 
1.  Failure to conduct continuing review of research at least annually. [21 CFR 56.109(f)]
 
An IRB is responsible for conducting continuing review of research covered by these regulations at intervals appropriate to the degree of risk, but not less than once per year.
 
Your IRB failed to conduct continuing review of research at least annually.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Examples Examples of this failure include, but are not limited to, the following:
 
a.  Your IRB did not approve study (b)(4) prior to the expiration date of April 14, 2015.  An FDA investigator attended your IRB’s April 13, 2015 meeting and confirmed that the study was not reviewed by the IRB members. In addition, the minutes recorded during the meeting show that this study was not discussed. Yet, the IRB issued an approval letter to renew the study.
 
Afterwards, on April 21, 2015, your IRB presented draft meeting minutes to the FDA investigator. The draft minutes which were composed from memory a day later, indicate that the study was reviewed at 8:09 and 8 members voted at the April 13, 2015 IRB meeting.  The draft minutes are contrary to the FDA investigator’s observations and the minutes recorded during the IRB’s meeting.
 
b.  Your IRB approved renewal of study (b)(4) (also referred to as (b)(4)) on October 8, 2012.  However, the IRB did not conduct the next continuing review of this study until October 14, 2013.
 
This noncompliance is a repeat violation that was identified during the last FDA inspection in 2013.
 
Your failure to conduct continuing review at least annually delays or prevents the IRB from considering any changes in the research or research-related events. Continuing review is required to ensure that appropriate human subject protection measures are in place throughout a study’s duration.         
 
In addition, the discrepancy between the minutes created during the April 13, 2015 meeting and the minutes composed a day after the meeting calls into question the validity and reliability of the Board’s documentation practices, and meeting minutes of activities conducted at IRB meetings.
 
Your IRB’s response states that the IRB will shorten the interval for renewal to 11 months and send correspondence to the principal investigator at least two months prior to the expiration date of each study’s approval period.  The response also states that the IRB intends to purchase or lease an electronic IRB management system to aid in managing time frames for renewals.  
 
Your IRB’s response is inadequate because it lacks sufficient detail to ensure that the IRB will conduct continuing review of research at least once per year.  The response also does not explain the corrective actions taken for Study (b)(4) or the preventative actions taken to avoid recurrence of such violations in the future.  Your IRB’s 2013 Warning Letter response stated that the IRB would use an IRB software program to assist with monitoring and conducting continuing review in a timely manner. However, during the inspection it was noted by IRB members that funds were not allocated by the hospital administration for this purchase.
 
In your response to this letter, please provide a detailed explanation of the actions that the IRB has taken or plans to take to ensure that the IRB conducts continuing review at least once per year.  The response should provide documentation of actions taken for Study (b)(4) and actions taken to ensure that current IRB Standard Operating Procedures (SOPs) are accurate. Please provide copies of new or revised SOPs that your IRB has implemented or plans to implement with the expected completion dates.  The response should also provide documentation of retraining on current SOPs, training on new or revised SOPs and any other training taken by your staff. Please include a list of staff trained and the training dates.  
 
2.  Failure to prepare and maintain adequate documentation of IRB activities including minutes of IRB meetings that are of sufficient detail to show the actions taken at the meeting and the vote on these actions. [21 CFR 56.115(a)(2)]
 
An IRB is required to prepare and maintain adequate documentation of IRB activities including, but not limited to, IRB meeting minutes. The minutes shall be in sufficient detail to show attendance at the meetings; actions taken by the IRB; the vote on these actions; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution. 
 
Your IRB failed to prepare and maintain adequate documentation. Specifically, your IRB’s voting records were not complete for the meeting held on June 9, 2014. The meeting minutes indicate that 16 members attended the meeting. However, the “Motions/Recommendations” section only documented a maximum of 14 members voting and/or abstaining at the meeting.
 
It is critical that your IRB maintain accurate documentation of IRB meeting activities which will assist in ensuring that your IRB’s review of research is conducted according to FDA regulations and that the rights, safety, and welfare of study subjects are protected.  The inconsistencies revealed in your IRB’s record of votes for the June 9, 2014 meeting call into question whether each member’s vote was recorded correctly.
 
Your IRB’s response states that the IRB will record all votes on a detailed template and record all attendees in conjunction with their membership status. The response also states that the IRB will confirm that a description of the rationale for approval/dismissal of an agenda item is included in IRB meeting minutes and use an audio recording device to assist with minute taking.
 
Your IRB’s response is inadequate because it lacks sufficient detail to ensure that the IRB will prepare and maintain adequate documentation of the IRB activities at convened meetings.
 
In your response to this letter, please provide a detailed explanation of the actions that the IRB has taken or plans to take to ensure that the IRB prepares and maintains adequate documentation of the IRB’s meeting activities.  The response should provide documentation of actions taken to ensure that the current IRB roster and SOPs are accurate. Please provide copies of new or revised SOPs that your IRB has implemented or plans to implement with the expected completion dates. The response should also provide documentation of retraining on current SOPs, training on new or revised SOPs and any other training taken by your staff. Please include a list of staff trained and the training dates.  
 
3.  Failure to prepare and maintain adequate documentation of IRB activities including a list of IRB members. [21 CFR 56.115(a)(5)]
 
An IRB is required to prepare and maintain a list of IRB members identified by name, earned degrees, representative capacity, employment or other relationship between each member and the institution.
 
Your IRB failed to prepare and maintain an accurate list of the IRB members. Specifically, your IRB meeting minutes dated March 10, 2014 and April 14, 2014 listed (b)(4) as an IRB member and showed her voting on IRB activities. However, your IRB rosters did not list (b)(4) as an IRB member until April 16, 2014.
 
This failure to prepare and maintain adequate documentation of IRB activities including a list of IRB members is a repeat violation that was identified during the last FDA inspection in 2013. 
 
In your response to this letter, please provide a detailed explanation of the actions that the IRB has taken or plans to take to ensure that the IRB will maintain an accurate list of the IRB members.  The response should provide documentation of actions taken to ensure that the current IRB roster and SOPs are accurate.  Please provide copies of new or revised SOPs that your IRB has implemented or plans to implement with the expected completion dates.  The response should also provide documentation of retraining on current SOPs, training on new or revised SOPs and any other training taken by your staff. Please include a list of staff trained and the training dates.
 
The violations described above are not intended to be an all-inclusive list of problems that may exist at your IRB.  Your IRB is responsible for ensuring compliance with the Act and applicable regulations.  
 
We believe a regulatory conference with you is warranted to discuss the Form FDA 483 observations, repeat observations, and the corrective actions that you have implemented or plan to implement.  Please contact Veronica J. Calvin using the contact information at the end of this letter within 2 weeks of receiving this letter with proposed dates and times for this call.
 
Within 15 working days of receiving this letter, please provide documentation of the corrective and preventative actions that you have taken or will take to correct these violations, to prevent the recurrence of similar violations, and a plan to monitor the effectiveness of your corrective actions. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you. 
 
Your response should reference “CTS #EC150018/E001” and be sent to: 
 
Attention: Veronica J. Calvin, M.A.
Food and Drug Administration
Center for Devices and Radiological Health
Office of Compliance
Division of Bioresearch Monitoring
10903 New Hampshire Avenue
Building 66, Room 3508
Silver Spring, Maryland 20993-0002
           
A copy of this letter has been sent to FDA’s Detroit District Office, 300 River Place, Suite 5900, Detroit, Michigan 48207­­­­. Please send a copy of your response to that office.
 
The Division of Bioresearch Monitoring has developed introductory training modules in FDA-regulated device clinical research practices, which are available on the FDA website. The modules are for persons involved in FDA-regulated device clinical research activities. These modules are located at the following website address: http://www.fda.gov/Training/CDRHLearn/default.htm.
 
If you have any questions, please contact Veronica J. Calvin, M.A., at (301) 796-5647 or Veronica.Calvin@fda.hhs.gov.
 
 
Sincerely yours,
/S/ 
Jan B. Welch, MHS, MT (ASCP) SBB
Acting Director
Office of Compliance
Center for Devices and
    Radiological Health

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