FDA EIR - Dana-Farber Harvard Cancer Center - April 25, 2018

An FDA analytical BIMO inspection was conducted at Dana Farber Harvard Cancer Center (DFHCC) from June 11-15, 2018. This surveillance inspection, performed under FACTS assignment 2018-005118 and related to BLA 761044 for an Asparaginase injection study (DFCI-2016), focused on bioanalytical method validation and sample analysis. The inspection revealed several significant issues, many of which were recurring from a previous inspection. Main violations included the failure to reject analytical runs despite failed quality control samples, insufficient documentation of sample movement and stock solution preparation, and reporting data below the lower limit of quantitation. The facility also failed to fully validate its analytical methods, specifically lacking assessments for stability, accuracy, precision, recovery, and stock solution stability. Other issues included a lack of selectivity assessment, the inclusion of subject samples that did not meet acceptance criteria in the final study report, inconsistent use of error codes, and a failure to assess the impact of hemolysis on samples. New stock solutions were also used without proper qualification against existing ones. As a result of these findings, a three-item Form FDA 483 was issued. The observations primarily cited the absence of selectivity assessment, the use of non-conforming subject sample data, and the improper use of calibration points, which led to unreliable data reporting. While DFHCC agreed to revise standard operating procedures for error codes, no immediate corrective actions were proposed during the inspection regarding the critical issues of stability assessments, hemolysis evaluation, or stock solution qualification.