WARNING LETTER
Sourav K. Mishra, M.D. / All India Institute of Medical Sciences
MARCS-CMS 724881 —
April 29, 2026
Delivery Method:
VIA UNITED PARCEL SERVICE AND VIA E-MAIL
Reference #:
26-HFD-45-04-02
Product:
Drugs
Recipient:
Recipient Name
Sourav K. Mishra, M.D.
Sourav K. Mishra, M.D. / All India Institute of Medical Sciences
Sijua, Patrapada
Bhubaneswar
751019
Odisha
India
Issuing Office:
Center for Drug Evaluation and Research (CDER)
United States
WARNING LETTER
FDA Ref. No.: 26-HFD-45-04-02
Dear Dr. Mishra:
This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at All India Institute of Medical Sciences in Bhubaneswar, Odisha, India, between March 17 and March 20, 2025. The investigator representing FDA reviewed your conduct of a clinical in vivo bioequivalence study (Protocol 0270-22, “A Multicenter, Open Label, Balanced, Randomized, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Crossover, Bioequivalence Study between two formulations of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (50 mg/m
2
dose) (Doxorubicin-Test compared with Doxorubicin-Reference) in Patients with Advanced Ovarian Cancer”) of the investigational product doxorubicin hydrochloride liposome injection 20 mg/10 mL, performed for Qilu Pharmaceutical (Hainan) Co., Ltd.
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, it appears that you did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in Title 21 of the Code of Federal Regulations, parts 312 (21 CFR 312) and 50 (21 CFR 50) governing the conduct of clinical investigations and the protection of human subjects.
1
We wish to emphasize the following:
1. 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 investigations are conducted in accordance with the investigational plan. The investigational plan for Protocol 0270-22
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required you to prohibit the use of cytochrome P450 CYP3A4 and CYP2D6 inhibitors to subjects during the entire study duration, and before baseline for at least five half-lives of the given drug, if given prior to the first dose of the study intervention.
You failed to adhere to this requirement. Specifically, all three enrolled subjects were orally administered Aprecap (aprepitant), a moderate inhibitor of CYP3A4, during the study. Examples of these failures include:
a. Subject
(b)(6)
signed the informed consent on October 17, 2023, and was administered investigational product on November 1, 2023 (Period I) and on December 1, 2023 (Period II). However, this subject was administered Aprecap between November 1 and November 3, 2023, and between December 1 and December 3, 2023.
b. Subject
(b)(6)
signed the informed consent on October 30, 2023, and was administered investigational product on November 10, 2023 (Period I). However, this subject was administered Aprecap between November 10 and November 12, 2023.
c. Subject
(b)(6)
signed the informed consent on November 16, 2023, and was administered investigational product on November 29, 2023 (Period I) and on December 27, 2023 (Period II). However, this subject was administered Aprecap between November 29 and December 1, 2023, and between December 27 and December 29, 2023.
During the inspection, you stated that it is the oncology department’s usual practice to administer Aprecap 125/80 capsules before a patient receives chemotherapy. You also stated that you would pay closer attention to the protocol requirements related to prohibited medication. While we acknowledge your statements made during the inspection, your statements are inadequate because you have not provided sufficient details about how you, as a clinical investigator, will prevent similar violations in the future.
We emphasize that failure to conduct the clinical investigation in accordance with the protocol raises significant concerns about your protection of the study subjects enrolled at your site, and also raises concerns about the validity and integrity of the data collected at your site. Specifically, as stated in the protocol, Cytochrome P450 CYP3A4 and CYP2D6 inhibitors were prohibited during the study as they affect the pharmacokinetics of the study intervention, which is the primary objective of the clinical trial. In addition, the prohibited medication can interfere with the investigational product metabolism, which can increase the risk of side effects and reduce investigational product efficacy. As the clinical investigator, you are responsible for ensuring compliance with the protocol requirements for prohibited and concomitant medications.
2. You failed to obtain informed consent in accordance with the provisions of 21 CFR part 50 [21 CFR 312.60 and 21 CFR 50.20].
As a clinical investigator, you are required to obtain informed consent in accordance with 21 CFR part 50. FDA’s regulations at 21 CFR 50.20 state that, except as provided in 21 CFR 50.22, 50.23, and 50.24,
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no investigator may involve a human being as a subject in research covered by the regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative. Under 21 CFR 50.20, “an investigator shall seek…[informed] consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence”.
You failed to seek informed consent for the above-referenced clinical investigation under circumstances that provided the prospective subject or the representative sufficient opportunity or information to consider whether or not to participate and that minimized the possibility of undue influence. Specifically, Section 1 of the informed consent form (ICF) stated that all reference to the words “study drug” throughout the ICF can mean Doxorubicin-Test and Doxorubicin-Reference. Section 10 of the ICF stated, “There is evidence that this study drug is effective and indicated in your disease condition.” In addition, Section 4 stated that liposomal doxorubicin is already approved by various regulatory authorities to treat the disease condition. Sections 4 and 10 also did not specify whether “liposomal doxorubicin” or “study drug”, and the statements concerning their approval or effectiveness, respectively, were applicable to the reference product or the test product. The lack of clarity may lead individuals to mistaken conclusions about the investigational product and whether it had already been demonstrated to be effective. Further, statements that overstate the possible benefit of the investigational product may unduly influence individuals to agree to participate when they might not otherwise do so.
During the inspection, you stated that you understood the FDA investigator’s statements that you are ultimately responsible for all documentation provided to study subjects, regardless of who authored the informed consent form, and that safety or efficacy claims of the test drug were not allowed in the informed consent form. While we acknowledge your statement of understanding, your statement is inadequate because you have not provided sufficient details about how you, as a clinical investigator, will prevent similar violations in the future.
We emphasize that as the clinical investigator, you are responsible for ensuring that legally effective informed consent is obtained from subjects before their enrollment. Your failure to obtain informed consent before involving subjects in research jeopardizes the rights, safety, and welfare of subjects and raises concerns about whether subjects had an adequate opportunity to fully assess the risks and benefits of their participation in the clinical investigation.
We acknowledge that a Form FDA 483 citing the inspectional findings described in this letter was not issued, however, these concerns were discussed with your staff at the conclusion of the inspection.
We emphasize that as the clinical investigator, you are ultimately responsible for compliance with all applicable FDA regulations governing the conduct of clinical investigations and the protection of human subjects, both to protect the rights, safety, and welfare of subjects and to ensure the integrity of study data. Your failure to conduct the clinical study in accordance with the protocol, and your failure to seek informed consent in accordance with the requirements in 21 CFR part 50, raise significant concerns about your protection of study subjects enrolled at your site and raise concerns about the reliability of the data collected at your site.
This letter is not intended to be an all-inclusive list of deficiencies with your clinical study of an investigational product. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address any deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations.
This letter notifies you of our findings and provides you with an opportunity to address the deficiencies noted above. Within 15 business 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 this matter adequately may lead to regulatory action without further notice to you. If you believe that you have complied with the FD&C Act and relevant regulations, please include your reasoning and any supporting information for our consideration.
Your written response, and any questions or concerns about this letter or the inspection, should be sent via email to the FDA at CDER-OSI-Communications@fda.hhs.gov.
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
David Burrow Digitally signed by David Burrow
Date: 4/29/2026 01:48:38 PM EDT
_________________________
1
In accordance with 21 CFR 320.31(c), the provisions of 21 CFR parts 312 and 50 are applicable to this bioequivalence study in humans because Protocol 0270-22 was conducted under an Investigational New Drug application (IND).
2
Protocol 0270-22 (Version: 2.1, Document Release Date: 29-Nov-2022) was effective when the prohibited medication and study intervention were administered to the subjects.
3
The exceptions provided in 21 CFR 50.22, 50.23, and 50.24 are not applicable here.
Content current as of:
05/19/2026
Regulated Product(s)
Drugs