FDA EIR - Next Breath LLC - February 23, 2018

An FDA bioanalytical surveillance inspection of Next Breath, a Division of Aptar Group, Inc., took place in Baltimore, MD, from February 13-23, 2018. The inspection, conducted under Compliance Program 7348.001 for in vivo bioequivalence, focused on analytical records and method validations for bioequivalence studies related to ANDAs. Although no Form FDA 483 was issued, the FDA investigator discussed several critical observations with company management. Main issues identified included deficiencies in Quality Control (QC) sample representation during HPLC analysis for Aerosol Particle Size Distribution (APSD) tests, with sensitivity solution recovery outside established criteria in multiple runs. The HPLC method validation for APSD was found to have an insufficient range to cover expected sample concentrations. Additionally, a large number of manual integrations in HPLC chromatograms lacked the required justification and approval per the company’s Standard Operating Procedures. A significant compliance concern was the unblinding of test and reference product information during Droplet Size Distribution (DSD) testing by an analyst, compromising study integrity. Next Breath’s management acknowledged these findings and committed to implementing corrective actions. These include updating future HPLC analytical runs to incorporate QCs spanning the full concentration range, ensuring comprehensive method validation reports, strictly adhering to manual integration procedures with proper documentation, and maintaining product blinding in all future bioequivalence studies.