FDA EIR - Charu Aggarwal, MD, MPH, Hematology-Oncology Division - March 28, 2017

The FDA conducted a for-cause inspection of Dr. Charu Aggarwal, Principal Investigator at the University of Pennsylvania, Hematology-Oncology Division, from March 16 to March 28, 2017. This initial inspection, guided by regulatory framework CPG 7348.811 (Clinical Investigator) and 21 CFR Part 312, followed a serious non-compliance report from the University's Institutional Review Board regarding protocol C15010, a Phase 1b study involving MLN4924 in solid tumor patients. The inspection identified significant violations documented in an FDA Form 483. Main issues included failure to conduct the investigation according to the investigational plan. Specifically, prohibited concomitant medications were administered to subjects, and one subject was consented by a physician not formally listed on the study team. A subject with elevated liver function tests received the investigational product at an incorrect dose, and required time intervals between drug infusions were not consistently followed. There was also a lack of written procedures for calibrated equipment use and maintenance, and initial concerns about a missing temperature log for the investigational product. Additionally, the inspection noted inadequate and inaccurate case histories, with EKG prints often containing incorrect dates/times, manual corrections, and insufficient subject identifiers, violating 21 CFR 312.62(b). Management acknowledged these findings, stating that some issues like the temperature log and SOPs were 'miscommunications' and provided documentation. Corrections were promised for the identified deficiencies, including the medication errors, consenting procedures, dosing deviations, and record-keeping inaccuracies.