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  5. Balamurali K. Ambati , M.D., Ph.D. - 585585 - 08/13/2019
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Balamurali K. Ambati , M.D., Ph.D. MARCS-CMS 585585 —

Delivery Method:

Recipient Name
Balamurali K. Ambati, M.D., Ph.D., MBA
Balamurali K. Ambati , M.D., Ph.D.

1125 Darlene Lane, Suite 100
Eugene, OR 97401
United States

Issuing Office:
Center for Drug Evaluation and Research

10903 New Hampshire Avenue
Silver Spring, MD 20993
United States


Ref: 19-HFD-45-08-01


Dear Dr. Ambati:

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 March 25 and April 4, 2019. Julian C. Hanson, representing FDA, reviewed your conduct as the sponsor-investigator of a clinical investigation (Protocol (b)(4), “(b)(4)) of the investigational drug (b)(4).

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.

From our review of the FDA Establishment Inspection Report and the documents submitted with that report, we conclude that you did not adhere to the applicable statutory requirements and FDA regulations contained in Title 21 of the Code of Federal Regulations, part 312 [21 CFR 312] governing the conduct of clinical investigations. We are aware that at the conclusion of the inspection, Mr. Hanson presented and discussed with you the Form FDA 483, Inspectional Observations. We wish to emphasize the following:

Failure to submit an IND for the conduct of clinical investigations with an investigational new drug that is subject to 21 CFR 312.2(a) [21 CFR 312.20(a) and 312.40(a)].

In relevant part, the Federal Food, Drug, and Cosmetic Act (FD&C Act) defines the term drug as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals” [21 U.S.C. 321(g)].

As a sponsor-investigator, you studied the safety and efficacy of (b)(4) in combination with (b)(4), for the (b)(4) As a result, because the (b)(4) was intended for the (b)(4) meets the definition of a drug under the FD&C Act.

To market a new drug lawfully, a sponsor or sponsor-investigator must obtain approval of a new drug application or an abbreviated new drug application under Section 505 of the FD&C Act [21 U.S.C. 355]. An Investigational New Drug (IND) application allows a sponsor to obtain an exemption from this requirement to distribute an investigational drug [21 U.S.C 355(i)]. FDA regulations require a sponsor to submit an IND application before conducting a clinical investigation of a drug in human subjects, unless the clinical investigation qualifies for an IND exemption.

A marketed drug product is exempt from the IND requirements if all of the following exemption criteria are met:

• The drug product is lawfully marketed in the United States
• The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication for use, and there is no intent to use the investigation to support any other significant change in the labeling of the drug
• In the case of a lawfully marketed prescription drug, the investigation is not intended to support a significant change in the advertising for the drug
• The investigation does not involve a route of administration, dosage level, use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product
• The investigation is conducted in compliance with the requirements for institutional review (set forth in 21 CFR 56) and with the requirements for informed consent (set forth in 21 CFR 50)
• The investigation is conducted in compliance with the requirements of 21 CFR 312.7 regarding the promotion of investigational drugs (that is, the investigation is not intended to promote or commercialize the drug product)

A person planning to conduct an in vivo bioavailability or bioequivalence study is not required to submit an IND when certain criteria under 21 CFR 320.31 are met. Your investigational drug, (b)(4), is not a lawfully marketed drug product in the United States, nor is it exempt from the IND requirements. As a result, before using (b)(4) in a clinical investigation, you were required to submit an IND for the drug to FDA, and to have an IND in effect under 21 CFR 312.40.

FDA records indicate that you failed to submit an IND before conducting a clinical investigation of (b)(4) under Protocol (b)(4). The FDA inspection at your site identified that twelve human subjects were enrolled and treated with the unapproved drug, (b)(4) in combination with (b)(4), from April 2017 to December 2018.

We acknowledge that your April 7, 2019, written response indicated that you would submit an IND to the FDA. We recognize that you subsequently submitted an IND on April 26, 2019. However, your response is inadequate because as a sponsor-investigator, you should have obtained an IND before initiating Protocol (b)(4) and treating human subjects with the investigational drug, (b)(4) in combination with (b)(4).

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 explain the violations noted above adequately and promptly may result in regulatory action without further notice.

If you have any questions, please call Sherry G. Bous, Pharm.D., at 240-402-8176. Your written response and any pertinent documentation should be addressed to:

Sherry G. Bous, Pharm.D.
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 5364
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002

Sincerely yours,
{See appended electronic signature page}
David C. Burrow, Pharm.D., J.D.
Office of Scientific Investigations
Office of Compliance
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

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.
08/13/2019 10:10:17 AM

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