WARNING LETTER
Louisiana State University Health Science Center IRB
MARCS-CMS 686088 —
September 27, 2024
Delivery Method:
VIA UPS and Electronic Mail
Reference #:
24-HFD-45-09-01
Product:
Drugs
Recipient:
Recipient Name
Charles C. Coleman, M.D.
Recipient Title
IRB Chair
Louisiana State University Health Science Center IRB
433 Bolivar Street, Suite 206
New Orleans
,
LA
70112
United States
Issuing Office:
Center for Drug Evaluation and Research (CDER)
United States
WARNING LETTER
FDA Ref. No.: 24-HFD-45-09-01
Dear Dr. Coleman:
This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted between July 17, 2023, and July 26, 2023, of the Louisiana State University Health Science Center, New Orleans (LSUHSC) Institutional Review Board (IRB). Investigator Koffi A. Amegadje, representing FDA, conducted the inspection to determine whether the IRB’s procedures for the protection of human subjects complied with FDA regulations contained in Title 21 of the Code of Federal Regulations (21 CFR), parts 50 and 56. These regulations apply to clinical investigations of products regulated by FDA.
This inspection is a part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.
At the conclusion of the inspection, Investigator Amegadje presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of the IRB’s August 16, 2023, written response to the Form FDA 483.
From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and the IRB’s August 16, 2023, written response, it appears that the IRB did not adhere to applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA regulations governing the protection of human subjects.
We wish to emphasize the following:
1. The IRB failed to conduct continuing review of research at intervals of not less than once per year [21 CFR 56.109(f)]
In order to fulfill the requirements of the IRB regulations, the IRB is required to conduct continuing review of previously approved research at intervals appropriate to the degree of risk, but not less than once per year [21 CFR 56.109(f)].
Specifically, the LSUHSC IRB failed to conduct continuing review of research at least once per year for the following FDA-regulated studies:
a. On August 8, 2019, the LSUHSC IRB approved Protocol
(b)(4)
, “
(b)(4)
,” at a convened meeting. Continuing review for Protocol
(b)(4)
was due by August 7, 2020. However, the IRB did not conduct continuing review for this study until August 19, 2020 (a lapse of IRB approval for 12 days). The next IRB continuing review for Protocol
(b)(4)
was due by August 18, 2021. However, the IRB did not conduct continuing review for this study until October 22, 2021 (a lapse of IRB approval for 78 days). We note that during the second lapse in IRB approval, between August 19, 2021, and September 29, 2021, study activity was ongoing, including enrollment of two subjects at clinical sites, and clinical site protocol deviations occurred.
b. On January 15, 2021, the LSUHSC IRB approved Protocol
(b)(4)
, “
(b)(4)
,” at a convened meeting. Continuing review for Protocol
(b)(4)
was due by January 14, 2022. However, the IRB did not conduct continuing review for this study until March 14, 2022 (a lapse of IRB approval for 59 days). The next IRB continuing review for Protocol
(b)(4)
was due by March 13, 2023. However, the IRB did not conduct continuing review for this study until April 28, 2023 (a lapse of IRB approval for 46 days).
We acknowledge that the studies listed above for failure to conduct continuing review of research at intervals of not less than once per year were not included on the Form FDA 483 you received, and therefore your written response does not address this violation for these clinical studies.
However, in your August 16, 2023, written response, you stated that between June 2020 and July 2021, there were three episodes when the KUALI system did not send Continuing Review reminders as scheduled (45, 30, and 15 days before the Continuing Review date), and the KUALI system has been functioning properly since August 2021. You stated that the KUALI system sent at least one reminder to each clinical investigator for most of the studies identified during the inspection. You also stated that the IRB manually identified studies requiring continuing review during the KUALI system failure, and the IRB notified clinical investigators by email; however, you also stated that all relevant studies might not have been identified. You stated that you revised the notification schedule to send alerts at 60 days, 45 days, 30 days, 15 days, 7 days, and 1 day before the Continuing Review date.
In your written response, you stated that the IRB plans to take the following corrective actions:
Performing random spot checks of renewal notification on a monthly basis
Contacting the vendor with a “high priority ticket” if notifications issues are detected, and manual scheduling; and, if the issue is not resolved within 7 days, manually sending alerts until the issue is resolved
Revision to your Standard Operating Procedure, SOP 3.02, to reflect the new notification schedule of 60 days, 45 days, 30 days, 15 days, 7 days, and 1 day before the Continuing Review date
We are unable to perform an informed evaluation of the IRB’s written response because you did not provide a corrective action plan that, if properly carried out, would prevent the recurrence of this type of violation in the future. Specifically, you did not provide sufficient details regarding how the IRB (as opposed to the clinical investigator) would ensure that the IRB will conduct continuing review of research within the required time interval. While a clinical investigator has a responsibility to ensure that an IRB will conduct continuing review and approval of their study [21 CFR 312.66], the IRB still must conduct continuing review of research within the required interval, as required under 21 CFR part 56.
Failure of the IRB to conduct continuing review at intervals of not less than once per year raises concerns about the adequacy of the IRB’s oversight of ongoing research that the IRB had previously approved.
2. The IRB failed to prepare, maintain, and follow required written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and [the] Food and Drug Administration (FDA) [21 CFR 56.115(a)(6) and 56.108(b)(3)].
An IRB is required to prepare and maintain adequate documentation of IRB activities, including written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the FDA of any suspension or termination of IRB approval. The IRB must also follow such written procedures [21 CFR 56.108(b) and 56.115(a)(6)]. Furthermore, under 21 CFR 56.113, suspensions or terminations of IRB approval of FDA-regulated research must be reported promptly to the FDA.
The IRB failed to adhere to these requirements. Specifically, the LSUHSC IRB’s written procedures fail to explicitly provide a procedure for reporting suspensions or terminations of IRB approval to the FDA. Additionally, the IRB failed to ensure that the suspension or termination of IRB approval for the following FDA-regulated studies was reported to the FDA:
a. Protocol
(b)(4)
was administratively closed by the IRB on December 20, 2021.
b. Protocol
(b)(4)
was administratively closed by the IRB on March 2, 2021.
c. Protocol
(b)(4)
was administratively closed by the IRB on January 26, 2022.
d. Protocol
(b)(4)
was administratively closed by the IRB on March 20, 2023.
e. Protocol
(b)(4)
was administratively closed by the IRB on October 4, 2022.
f. Protocol
(b)(4)
was administratively closed by the IRB on January 26, 2022.
g. Protocol
(b)(4)
was administratively closed by the IRB on October 4, 2022.
h. Protocol
(b)(4)
was administratively closed by the IRB on August 25, 2022.
However, termination of IRB approval for the above-listed studies was not reported to the FDA.
In your August 16, 2023, written response to the Form 483, you stated that the IRB failed to recognize administrative closures as instances of termination of IRB approval, and therefore did not take reporting actions as dictated by IRB policies and FDA regulations. You stated that the IRB plans to take the following corrective actions:
Educating IRB administrative staff annually on suspension and termination of IRB approval and related reporting requirements
Creating an SOP on reporting incidents to the FDA that is similar to the IRB’s SOP HRP-2.01, “Reporting Incidents to [the] Office of [for] Human Research Protections (OHRP)”
We are unable to perform an informed evaluation of the IRB’s written response because you did not provide a corrective action plan that, if properly carried out, would prevent the recurrence of this type of violation in the future. Specifically, you did not provide sufficient details on the IRB procedures you are proposing to develop, and how you will ensure that these proposed written procedures will be followed to prevent repeat violations. Without these details, we are unable to determine whether your corrective action plan is adequate to prevent similar violations in the future.
Failure of the IRB to prepare, maintain, and follow required written procedures raises concerns about the adequacy of the IRB’s review processes for ensuring the protection of the rights, safety, and welfare of human research subjects.
This letter is not intended to be an all-inclusive list of deficiencies related to the IRB’s procedures or to the IRB’s review and approval of protocols. It is the IRB’s responsibility to ensure adherence to each requirement of the law and relevant FDA regulations.
This letter notifies you of our findings and provides you with an opportunity to address the deficiencies described above. Within 15 business days of your receipt of this letter, you should notify this office in writing of the actions that the IRB has taken or plans to take, to address any violations and to prevent the recurrence of similar violations in the future. Failure to address this matter adequately may lead to regulatory action. If you believe that the IRB has complied with the FD&C Act and FDA regulations, include your reasoning and any supporting information for our consideration.
We recommend that the IRB visit the following FDA Web page for information on human subject protections that may assist the IRB in its efforts to come into compliance with FDA regulations: http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm.
If the IRB has any questions, you may email FDA at CDER-OSICommunications@fda.hhs.gov. The IRB’s written response and any pertinent documentation should be addressed to:
Brittany L. Garr-Colón, M.P.H.
Branch Chief
Compliance Enforcement Branch
Division of Enforcement and Postmarketing Safety
Office of Scientific Investigations
Office of Compliance
Center for Drug Evaluation and Research
U.S. Food and Drug Administration
Building 51, Room 5352
10903 New Hampshire Avenue
Silver Spring, MD 20993
Sincerely,
{See appended electronic signature page}
David C. Burrow, Pharm.D., J.D.
Director
Office of Scientific Investigations
Office of Compliance
Center for Drug Evaluation and Research
Food and Drug Administration
Cc:
(b)(6)
, Chancellor
Louisiana State University Health Science Center
433 Bolivar Street, Suite 815
New Orleans, Louisiana 70112
Reference ID: 5453362
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This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.
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/s/
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DAVID C BURROW
09/27/2024 11:03:55 AM
Content current as of:
10/08/2024
Regulated Product(s)
Drugs