WARNING LETTER
James R. Corbett, M.D.
MARCS-CMS 603967 —
February 27, 2020
Delivery Method:
VIA UNITED PARCEL SERVICE
Reference #:
20-HFD-45-02-01
Product:
Drugs
Recipient:
Recipient Name
James R. Corbett, M.D.
James R. Corbett, M.D.
1500 East Medical Center Drive
Ann Arbor
,
MI
48109-5000
United States
Issuing Office:
Center for Drug Evaluation and Research | CDER
10903 New Hampshire Avenue
Silver Spring
,
MD
20993
United States
WARNING LETTER
Ref.: 20-HFD-45-02-01
Dear Dr. Corbett:
This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at your clinical site between June 26 and July 8, 2019. Ms. Andrace Deyampert, representing FDA, reviewed your conduct of a clinical investigation (Protocol
(b)(4)
, “
(b)(4)
”) of the investigational drug
(b)(4)
, which you performed as a sponsor-investigator.
This inspection was conducted as 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, Ms. Deyampert presented and discussed with you Form FDA 483, Inspectional Observations. We acknowledge receipt of your July 26, 2019, written response to the Form FDA 483.
From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and your written response dated July 26, 2019, we conclude that you did not adhere to the applicable statutory requirements and FDA regulations governing the conduct of clinical investigations and the protection of human subjects. We wish to emphasize the following:
1. You failed to maintain an effective IND with respect to the investigations (21 CFR 312.50).
FDA terminated IND
(b)(4)
on June 1, 2014, because FDA did not receive an annual report for your investigation for at least 2 years. As the sponsor-investigator for IND
(b)(4)
(Protocol
(b)(4)
), you were required to maintain an effective IND throughout the course of the clinical investigation. You failed to do so, and you continued to conduct the investigation even after FDA terminated the study. According to FDA’s Termination Letter, you were required to submit a new IND if the study drug was subsequently subjected to a clinical investigation.
Specifically, you continued to enroll subjects and administer study drug to 18 subjects after IND termination on June 1, 2014. Subjects were administered study drug until at least January 9, 2018. Thus, subject safety and rights were compromised for a period of more than 3 years.
In your July 26, 2019, written response, you stated that you did not fully understand that an IND was necessary for a study using an FDA-approved drug as a “stressor” in a normal healthy subject population. You stated that you further did not understand your responsibilities as a sponsor-investigator to maintain the IND throughout the conduct of this study. We acknowledge that your written response indicated that you will discontinue conduct of all FDA-regulated research as either a sponsor or clinical investigator, effective immediately. However, your response is inadequate because you failed to explain how you would conduct clinical investigations if you should undertake research in the future.
We wish to emphasize that, as the sponsor-investigator, you are responsible for ensuring that an investigational new drug be used in a clinical investigation only if you have submitted an IND to FDA and the IND remains in effect throughout the course of the investigation. Your enrollment of subjects and your administration of study drug after IND termination raise significant concerns about the adequacy of your protection of study subjects.
2. You failed to promptly report all changes in research activity to the Institutional Review Board (IRB) [21 CFR 312.66].
As a sponsor-investigator, you are required to promptly report to the IRB all changes in research activity. You failed to promptly report to the IRB all changes in research activity.
Specifically, you did not promptly report to the IRB FDA’s February 5, 2014, Pre-termination Letter or FDA’s June 1, 2014, Termination Letter.
Your failure to promptly report all changes in research activity to the IRB prevented the IRB from completing a full review of your application to conduct the clinical investigation, because the IRB was not given FDA’s Pre-termination Letter and Termination Letter. As a result, the IRB was unable to make an informed determination regarding the continued safety of the subjects enrolled in your clinical investigation.
We wish to emphasize that, as the sponsor-investigator, you are responsible for promptly reporting to the IRB all changes in research activity. Your failure to promptly report to the IRB all changes in research activity raises significant concerns about your protection of study subjects enrolled in the study mentioned above.
3. You failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60].
As a clinical investigator, you are required to ensure that your clinical studies are conducted in accordance with the investigational plan. The investigational plan requires that you exclude subjects with cardiac atrioventricular conduction abnormalities. You failed to adhere to these requirements. Specifically, Subject
(b)(6)
had first-degree atrioventricular block.
We acknowledge that your July 26, 2019, written response indicated that you will discontinue conduct of all FDA-regulated research as either a sponsor or clinical investigator, effective immediately. However, your response is inadequate because you failed to explain how you would conduct clinical investigations if you should undertake research in the future. As a clinical investigator, you are responsible for ensuring that all enrolled subjects meet eligibility criteria. Enrollment of subjects who do not meet eligibility criteria jeopardizes subject safety and welfare.
This letter is not intended to be an all-inclusive list of deficiencies with your clinical study of an investigational drug. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address these deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations.
Within fifteen (15) working days of your receipt of this letter, you should notify this office in writing of the actions you have taken to prevent similar violations in the future. Failure to address the violations noted above adequately and promptly may result in regulatory action without further notice. If you believe you have complied with FDA regulations, include your reasoning and any supporting information for our consideration.
If you have any questions, please call Mark S. Miller, Pharm.D., at 301-796-2798. Your written response and any pertinent documentation should be addressed to:
Mark S. Miller, Pharm.D., BCPS, RAC
CAPT, USPHS
Branch Chief
Compliance Enforcement Branch
Division of Enforcement and Postmarketing Safety
Office of Scientific Investigations
Office of Compliance
Center for Drug Evaluation and Research
Food and Drug Administration
Building 51, Room 5352
10903 New Hampshire Avenue
Silver Spring, MD 20993
Sincerely yours,
{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
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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
02/27/2020 03:01:57 PM
Content current as of:
03/10/2020
Regulated Product(s)
Drugs