FDA EIR - Applied Therapeutics, Inc. - May 03, 2024

An FDA inspection of Applied Therapeutics Inc. was conducted from April 29 to May 3, 2024. This high-priority surveillance inspection, under the Prescription Drug User Fee Act (PDUFA) and Compliance Program 7348.810, identified significant deficiencies in data integrity, study conduct, and oversight.Key violations cited in a Form FDA-483 included the deletion of source data for 11 subjects' clinical assessments by a service provider, preventing verification. Substantial discrepancies were found between source and submitted efficacy endpoint datasets post-submission, with error rates up to 36%. The company also failed to obtain signed data change forms for approximately 128 rater score modifications, violating standard operating procedures.Further concerns involved the sponsor's exclusive control over critical clinical data, denying investigators access needed for regulatory record retention. The widespread use of easily modifiable .csv files for data transfer was deemed unacceptable due to potential for untraceable changes. Inadequate monitoring of efficacy data, undocumented data hardcoding, and unblinding of key personnel before critical protocol changes, raising bias concerns, were also noted. An investigational product dosing error affecting 16 subjects was identified.Applied Therapeutics was required to submit a written response to the FDA-483 observations within 15 business days. Corrective actions are necessary to enhance data integrity, improve quality management systems, ensure data traceability and investigator access, and align all aspects of study conduct with regulatory standards for clinical trials.