Date: March 28, 2025
On March 28, 2025, FDA notified pharmaceutical companies that certain studies conducted by Raptim Research Pvt. Ltd., a contract research organization in Navi Mumbai, India, are unacceptable because of data integrity and study conduct concerns. The notice followed surveillance and for-cause inspections between 2019 and 2023, a general correspondence letter on August 6, 2024, and an Untitled Letter dated March 27, 2025 from CDER’s Office of Study Integrity and Surveillance and Office of Scientific Investigations. It is still the latest entry on FDA’s Notifications on Data Integrity page, which was last updated July 14, 2026.
FDA concluded that Raptim “created and caused the submission of falsified in vitro data to FDA.” The Untitled Letter cites nearly identical in vitro permeation test profiles across skin donors in different sponsors’ studies. Raptim’s in vitro studies are not acceptable and, where essential for approval, must be repeated at sites without data integrity concerns. FDA asked holders of approved ANDAs and NDAs that relied on them to respond within 30 days with a plan to repeat the studies or to request withdrawal of approval, and it is changing the therapeutic equivalence rating to BX for certain generic drugs that relied on Raptim bioequivalence data until repeat studies are found adequate.
Applications with in vivo studies from Raptim are handled case by case during review. Applicants may justify continued reliance on the data, re-analyze the study samples and re-conduct the statistical analysis, or conduct a new study.
What it means for calibration
Several of the Untitled Letter’s in vivo observations concern calibration curve standards (CCs), QCs and the internal standard (IS). FDA wrote that Raptim’s response did not scientifically justify the “retrospective rejection of runs based only on the area response of CCs and QCs” when the validated method relies on the analyte-to-IS response ratio, or accepting CCs and QCs for run acceptance while excluding them from IS response range calculations (page 15). No root cause had been given for the high percentage of samples with unacceptable IS responses (page 16). In practice, run rejection and CC or QC exclusion need predefined criteria that match the validated method: M10 expects possible reasons for reanalysis to be predefined in the protocol, study plan or SOP before the analysis starts (Section 3.3.4), and the IS responses of study samples to be monitored (Section 3.3).
FDA’s compliance program for analytical BA and BE inspections (7348.004, Part III) directs FDA investigators to determine whether the audit trail option was enabled during sample analysis, whether the site has an SOP for reintegration of chromatograms and reanalysis of samples, whether rejected runs were documented with the reason reported in the study report, and whether the calibration curve is representative of study sample concentrations.
Also see: fda.gov, Notifications on Data Integrity (content current as of July 14, 2026); fda.gov, Untitled Letter to Raptim Research (March 27, 2025); fda.gov, Compliance Program 7348.004, In Vivo Bioavailability/Bioequivalence Studies (Analytical) (May 1, 2018); ich.org, M10 Bioanalytical Method Validation and Study Sample Analysis (Step 4, May 24, 2022)
Part of the WLTR ICH M10 guide for pharmaceutical and bioanalytical labs. This is a plain-language summary, not regulatory advice. Confirm requirements with the issuing agency and your quality unit. Questions or a different read on this change? Leave a comment below.