WARNING LETTER
Adnan Dahdul, MD
MARCS-CMS 719607 —
March 12, 2026
Delivery Method:
UPS Express Mail & Electronic Mail
Reference #:
CBER-26-719607
Product:
Biologics
Recipient:
Recipient Name
Adnan Dahdul, MD
Adnan Dahdul, MD
95 Frank B Murray Street
Springfield
,
MA
01103
United States
adahdul@sisuhealth.com
Issuing Office:
Office of Compliance and Biologics Quality
United States
Secondary Issuing Offices
United States
March 12, 2026
WARNING LETTER
Dear Dr. Dahdul:
This Warning Letter informs you of objectionable conditions observed during a U.S. Food and Drug Administration (FDA) inspection conducted at your clinical study site between May 6, 2024, and June 20, 2024. FDA Investigators met with you during the inspection to review your conduct as the clinical investigator for the clinical study entitled: “
(b)(4)
.” Protocol Number
(b)(4)
(hereinafter, the protocol). FDA conducted this inspection under the Bioresearch Monitoring (BIMO) Program, which includes inspections designed to review the conduct of research involving investigational products (IPs) and to help ensure that the rights, safety, and welfare of human subjects are being protected.
At the conclusion of the inspection, a Form FDA 483, Inspectional Observations, was issued and discussed with you. We acknowledge receipt of your written responses dated July 11, 2024, Aug 29, 2024, and September 27, 2024, to the Form FDA 483 (“Response Letters”).
Based on our review of the Establishment Inspection Report (EIR), documents accompanying that report, the Form FDA 483, and your Response Letters, you violated regulations governing the proper conduct of clinical studies involving investigational products, including regulations published in Title 21 of the Code of Federal Regulations, parts 312 (21 CFR 312) and 50 (21 CFR 50) (available at https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312?toc=1). The applicable provisions of the CFR are cited for each violation listed below. The violations include but are not limited to the following:
1. You failed to obtain legally effective 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 regulations at 21 CFR 50.20 state that, except as provided in 21 CFR 50.23 and 21 CFR 50.24, 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.
For at least three subjects enrolled in the study, you failed to obtain legally effective informed consent from the subjects prior to performing study related procedures and as required by the protocol and in each of these instances, an exception was not applicable.
A. Parental consent was obtained from Subject
(b)(6)
at 15:42 on
(b)(6)
, and study records show that the subject had a urine pregnancy test performed at 14:13, vital signs taken at 14:19, and blood samples drawn at 14:21.
B. Informed consent was obtained from Subject
(b)(6)
at 16:42 on
(b)(6)
, but screening confirmation on
(b)(6)
at 16:30 indicated that all screening procedures were complete.
C. Informed consent was obtained from Subject
(b)(6)
at 16:48 on
(b)(6)
, but screening confirmation was documented on
(b)(6)
at 16:31, indicating that all screening procedures were complete.
In your response letter dated July 11, 2024, you stated: “We believe that the time discrepancies are due to research staff utilizing personal cellular phones and watches to document the time instead of a centralized clock system in addition to not following ALCOACCEA (Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring and Available) processes.” While we acknowledge the corrective and preventative actions (CAPA) that your site has taken, including refresher training on ALCOACCEA principles and informed consent, reviewing binders for research participants in accordance with ALCOACCEA and correcting discrepancies and/or quality issues, and installing synchronized individual clocks in all patient rooms, laboratories and the IP preparation room, we find your response to be inadequate because the staff received initial protocol training on January 18, 2023, which covered these areas, and similar issues were identified during a Sponsor monitoring visit (audit) between September 12 and 15, 2023 and addressed by a CAPA signed by you (Dr. Dahdul) on October 4, 2023 that the Sponsor deemed adequate. We are still not convinced that the violations observed, including the issue with miscalculating the times and synchronization of the clocks have been satisfactorily addressed and remediated, because the objectionable conditions persisted after the protocol training was completed and the CAPA was implemented, and especially because these observations seem related to the broader issue of proper investigator oversight and supervisory reviews that have not been addressed.
We emphasize that as a 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. Your failure to obtain legally effective informed consent before involving subjects in research, and your failure to review and address the violations within a reasonable timeframe raises significant concerns about your oversight of the study, supervision of study staff, and protection of the study subjects enrolled at your site.
2. You failed to ensure that the investigation was conducted in accordance with the signed statement of the investigator and the investigational plan. [21 CFR 312.60].
The investigational plan (the Protocol) required you to ensure that eligibility screening was conducted and documented to determine if subjects were healthy, stable, and did not have any medical or psychiatric issues that may make them ineligible for the study. Study records indicate that you did not conduct a complete and adequate review at the time of initial eligibility screening to ensure that these subjects were stable, did not have an increased risk of injury/worsening of their condition from study participation, and were eligible for enrollment in the study. Subjects were enrolled and participated in the study despite documented evidence of medical histories and active unstable conditions such as bipolar disorder, schizoaffective disorder, schizophrenia, and illicit drug use/alcohol abuse. The Protocol provided for exclusion of subjects based on specific criteria, including such medical histories and conditions.
For example:
A. Subjects
(b)(6)
presented with conditions that could increase the subjects’ risk from study participation. Protocol exclusion criteria #12 states “
(b)(4)
.” Subject
(b)(6)
was in remission from opioid dependence, subject
(b)(6)
’s substance abuse ended in 2013, and subject
(b)(6)
presented with anxiety, depression, schizoaffective disorder, post-traumatic stress disorder (PTSD), and opioid use disorder, and later left the study due to unstable mental health issues. We assert that the above listed conditions present an increased risk of study participation and make the subjects’ participation inappropriate for the study.
B. For at least two study subjects, a complete medical history was not obtained at Visit 1, as directed by the protocol. For example, Visit 1 for subjects
(b)(6)
and
(b)(6)
was conducted on
(b)(6)
, at which time both subjects were dosed with the IP. The Relevant Medical and Surgical History documents for these subjects were not properly evaluated until 8/15/2023 for Subject
(b)(6)
and showed opioid dependence in remission, and 11/09/2023 for Subject
(b)(6)
and showed anxiety and substance abuse. The protocol required that a complete medical history is obtained at Visit 1, and the conditions later added and/or evaluated may increase the risk of study participation and make the participant inappropriate for the study.
C. There are at least three instances where the protocol was not followed for the IP dose preparation and administration. The protocol required that subjects were administered the IP Kit number assigned at randomization. Subject
(b)(6)
was administered the incorrect IP. The subject was assigned IP kit number
(b)(4)
but was administered kit number
(b)(4)
. Subject
(b)(6)
, was assigned the IP kit number
(b)(4)
but the subject was administered the IP from kit number
(b)(4)
. Subject
(b)(6)
was dosed with an expired IP. The IP was prepared at 4:00 pm without the use of a
(b)(4)
, as directed by the IP manual, giving it an expiration of
(b)(4)
after preparation, as stated in Appendix 5 of the Investigational Product Manual. The subject was dosed at
(b)(4)
. We also note that the original expiration time documented on
(b)(6)
was
(b)(4)
, but this was changed to
(b)(4)
on 10/03/2023, without explanation.
In your response letter dated July 11, 2024, you acknowledge an “insufficient number of well experienced site staff” and also note a lack of consistency as well as oversight of those staff performing IP duties. In addition, you asserted that “research participants inclusion/exclusion criteria data has been thoroughly evaluated by the investigators for eligibility and have been found to be appropriate for inclusion in the research study and no subjects should have been excluded.” For the reasons specified in Section 2.A. of this letter, we do not agree with your assertions. During the inspection, you informed the FDA Investigator that the clinical site was not aware of subjects with known substance abuse problems, but if you were aware, you would have excluded those subjects. Your written response conflicts with information you gave the FDA investigator during your inspection, and it fails to adequately address the observation where subjects were enrolled in the study despite an increased risk from study participation.
We emphasize that as a clinical investigator, it is your responsibility to ensure that clinical studies are conducted in accordance with the investigational plan to protect the rights, safety, and welfare of subjects. Your failure to ensure that enrolled subjects met protocol-specified eligibility criteria and were given the correct IP at the right time, as required by the protocol and your obligation under 21 CFR 312.60 to conduct the investigation according to the protocol, jeopardized the rights, safety, and welfare of enrolled subjects. Additionally, your lack of supervision and oversight, and failure to conduct the clinical studies in accordance with the protocol raises significant concerns about the validity and integrity of all the data collected at your site in the course of your investigations.
3. Failure to prepare and maintain adequate and accurate case histories with respect to observations and data pertinent to the investigation. [21 CFR 312.62(b)]
A Clinical Investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational product or employed as a control in the investigation.
For the first 196 subjects enrolled in the study between 6/26/2023 and 6/30/23, entries in subjects’ source record forms did not include study staff initials, signatures, or any information identifying who completed the entries for protocol required activities. Examples of such records include but are not limited to:
-
(b)(4)
risk determination assessments.
-    Clinical Assessments
-    Medical History
-    Physical exam assessment determinations
-    Laboratory sample collection
-    Vital signs
A. At times, source data did not match information in the Electronic Data Capture (EDC) system, source records were missing, and data entries (including late entries) in source documents and the EDC system were nonattributable, with no documentation or explanation for the changes and/or discrepancies. In addition, late entry corrections were consistently made to source data with no supporting documentation or explanation for the changes. This included but was not limited to late entry corrections for protocol required data points. For example:
1) For Subject
(b)(6)
, the time initially entered for signing the ICF was 15:38 on
(b)(6)
. Multiple corrections and changes were made to source documents after the ICF was signed several days and weeks later by a different coordinator. Specifically, the post-dose observation time was changed from 17:22 to 17:27 on 7/14/2023 (
(b)(6)
days after the original observation and by a different coordinator). There is no documentation or explanation for the time change, the length of time between the original entry and the change, or why the change was made by a different coordinator.
2) For Subject
(b)(6)
, the time for obtaining informed consent was changed from 9:55 to 9:00 with no documentation or explanation for the change. It appears that the change was made to align with the study activities times which are documented as occurring between 09:00 and 09:55.
3) For Subject
(b)(6)
, source documents noted that the subject decided not to participate after signing the ICF and had a blood draw performed. There should be nine pages to the intake form, but four pages (Pages 2, 3, 5, and 7) are missing and unaccounted for. The missing pages include:
- inclusion/exclusion (page 2/3)
- medical history (page 5)
- blood sample collection (7)
- IP temperature records for shipments on 3/30/23
- Page 2 of Visit 1 source document is missing and not found, documentation of the blood draw was not present, and the Inclusion/exclusion criteria review worksheet was also missing.
B. Study subject
(b)(6)
listed homeless shelters as a primary residence. The subject died during the course of the study from an alcohol and fentanyl drug overdose. The Subject’s death was documented in the EDC as a death due to cardiac arrest. However, the death certificate for the subject describes the cause of death as fatal intoxication of fentanyl and ethanol.
C. Shipment confirmation for shipment identifier S-94-03-1760 was assessed on 3/30/2023 at 1110. The corresponding temp tale placed with the shipment has a stop date of 3/22/2023. There is no confirmation as to whether this was the correct temperature probe or explanation of what happened to the investigational product between 3/22/2023 and 3/30/2023.
In your response letter you state that the errors occurred in part due to your staff not fully adhering to ALCOACCEA principles, high volume of subjects during the screening period, and other workflow constraints. You also stated that as a corrective action measure, source documents were updated to ensure that all sections are fully ALCOACCEA-compliant, all staff completed retraining on GCP and Good Documentation Practices, and that implementing a comprehensive training material and quality assurance process will equip your staff with the necessary skills and knowledge to maintain the highest levels of data integrity and compliance. We remind you that even with the most skilled staff, proper supervision and oversight, review and prompt attention to errors, omissions, and deviations are critical to a clinical investigator’s conduct of a study, and that as an investigator, you are required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation.
Because of the above violations, we are not confident that your study was conducted in accordance with the investigator agreement and the investigational plan, and in accordance with good clinical practices. Additionally, we are not convinced that the study was adequately supervised. Without documented evidence, we are still not assured of the quality, integrity, and accuracy of the data collected during this study, that the rights and welfare of research participants were protected, and that your corrective action is targeted and fit for purpose.
In your response to this letter, please explain how you intend to rectify the issue of lack of investigator oversight and proper supervision of research staff and detail your procedure to ensure contemporaneous review and remediation of the observations impacting the accuracy and adequacy of data and information necessary to reconstruct a complete picture of your study conduct. In addition, please provide us with documentation of your processes for verifying the accuracy and completeness of the data, including how you identified or resolved the missing pages and data and erroneous data, and how you changed/corrected data where no attributable source data was available as a reference. Additionally, please provide documented examples of your actions to reconcile source and EDC data.
Neither this letter nor the observations noted on the Form FDA 483, which were discussed with you at the conclusion of the inspection, are 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 all applicable requirements in the FD&C Act and all applicable 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 or plan to take to correct the listed violations and prevent similar violations in the future. Include any documentation necessary to show that the matters have been appropriately addressed and mediated. If you cannot address these matters within fifteen (15) working days, please explain the reason for your delay and the timeframe for completion.
Failure to address this matter adequately may lead to regulatory action. 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. FDA has several references available at http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm for more information on human subject protection and the conduct of clinical research.
Your response should be sent via email to CBERBIMONotification@fda.hhs.gov and cc OIIBIMODivision1Correspondence@fda.hhs.gov. If you have any questions regarding this letter, please contact the Division of Inspections and Surveillance, CBER at 240-402-8979.
Sincerely,
/S/
Melissa J. Mendoza, JD
Director, Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
CC:
Mishelle Harriger, SCSO, OII, OBMI Division 1
OIIBIMODivision1Correspondence@fda.hhs.gov
Content current as of:
05/26/2026
Regulated Product(s)
Biologics