WARNING LETTER

Sohail M. Khan, M.D. MARCS-CMS 539274 — October 10, 2017

Delivery Method:: UPS

Recipient:: Recipient Name

Sohail M. Khan, M.D.; Sohail M. Khan, M.D.; 118 Cottonwood Circle
Lynn Haven, FL 32444
United States

Issuing Office:: Center for Drug Evaluation and Research; United States

10903 New Hampshire Avenue
Silver Spring, MD 20993

WARNING LETTER

OCT 10, 2017

VIA UNITED PARCEL SERVICE

Sohail M. Khan, M.D. Ref.: 17-HFD-45-10-01

118 Cottonwood Circle

Lynn Haven, Florida 32444

Dear Dr. Khan:

This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at your clinical site on July 14, 2017. Ms. Cynthia Rakestraw, representing FDA, reviewed your conduct of the following clinical investigations:

Protocol CQVA149A2336, “A 12-week Treatment, Multi-Center, Randomized, Double-Blind, Parallel-Group, Placebo and Active Controlled Study to Assess the Efficacy, Safety and Tolerability of QVA149 (indacaterol maleate/glycopyrronium bromide) in COPD Patients with Moderate to Severe Airflow Limitation,” of the investigational drug indacaterol maleate/glycopyrronium bromide (QVA149), performed for Novartis
Protocol (b)(4), “(b)(4),” of the investigational drug (b)(4), performed for (b)(4).
Protocol (b)(4), “(b)(4),” of the investigational drug (b)(4), performed for (b)(4).

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, Ms. Rakestraw presented and discussed with you Form FDA 483, Inspectional Observations. We acknowledge receipt of your July 25, 2017, 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 25, 2017, we conclude that you did not adhere to the applicable statutory requirements and FDA regulations governing the conduct of clinical investigations. We wish to emphasize the following:

You failed to retain records required to be maintained under 21 CFR Part 312 for a period of two years following the date a marketing application is approved for the drug for the indication for which the drug is being investigated; or, if no application is filed or if the application is not approved for such indication, until two years after the investigation is discontinued [21 CFR 312.62(c)].

As a clinical investigator, you are required to retain records of the disposition of the drug, including dates, quantity, and use by subjects, and to retain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. You are required to retain these records for a period of two years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or the application is not approved for such indication, until two years after the investigation is discontinued and FDA is notified.

You failed to adhere to these requirements. Specifically, for Protocols CQVA149A2336 and (b)(4):

You failed to retain records of the disposition of the drug, including dates, quantity, and use by subjects.
You failed to retain adequate and accurate case histories, including signed and dated informed consent forms, case report forms, and all supporting data.

You were required to retain the study records for both protocols because two years had not passed following approval of the indication under study for Protocol CQVA149A2336, and two years had not passed since the sponsor discontinued the study for Protocol (b)(4), at your site. Specifically, for Protocol CQVA149A2336, the New Drug Application (NDA) for the drug under investigation was approved on October 29, 2015. For Protocol (b)(4), the sponsor notified you on October 14, 2015, that the study was being discontinued at your site.

During the inspection, you stated that all study records related to Protocols CQVA149A2336 and (b)(4) had been shredded or destroyed by your staff. You stated that you did not have any paper or electronic records for any study you had conducted.

During the inspection, you stated:

“I do not have any paper or electronic study records related to [Protocols CQVA149A2336 and (b)(4)], including but not limited to source documents, case report forms, signed informed consent forms, and investigational drug disposition records. I believe these records have been shredded or destroyed by my staff.”

In your July 25, 2017, written response, you stated that your understanding was that records were to be retained for 2 years following study termination at a site. You indicated that you kept the records 2 years from the date of site closeout, after which the records were destroyed, and that the sponsor did not inform you of “any extension to the two-year record keeping period.” In addition, you stated that you will follow the document retention guidelines in the future. Your response is inadequate because we remain concerned that you do not understand your record retention requirements, and because you did not provide any documentation that you retained the required records. Specifically, it is unclear whether you understand that you are required to retain records for studies conducted at your site for 2 years from the date of application approval or study discontinuation. We are also concerned that your plan to follow document retention guidelines is insufficiently detailed to prevent similar violations in future studies.

Failure to retain study records as required by FDA regulations compromises the validity and integrity of data significantly. Because you failed to retain drug accountability records and case histories for both studies, we consider the data generated at your site for Protocols CQVA149A2336 and (b)(4) unreliable in support of a research or marketing application.

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 will 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 Adam Donat, M.S., at 301-796-5316. Your written response and any pertinent documentation should be addressed to:

Adam Donat, M.S.

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.

Acting 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 and this page is the manifestation of the electronic signature.
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/s/
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DAVID C BURROW
10/10/2017