Lyophilization Services of New England, Inc. (LSNE) D/B/A PCI Pharma Services – FDA EIR, Apr 24, 2015

This FDA Pre-Approval and Good Manufacturing Practice (GMP) inspection of Lyophilization Services of New England, Inc. (LSNE) was conducted from April 13 to April 24, 2015, in Bedford, NH. The inspection, carried out under compliance programs for Pre-Approval and Sterile Drug Process Inspections, focused on the company's manufacturing of sterile and non-sterile clinical drug products and medical devices, including pre-approval coverage for a specific sterile drug product, (b) (4).At the conclusion of the inspection, a two-item Form FDA 483 was issued. The primary violations included the firm's failure to determine actual product yields and percentages of theoretical yield at various manufacturing stages, as required by regulatory standards (21 CFR 211.103). This was specifically noted in the batch records for the (b) (4) sterile drug product, where theoretical yield specifications and actual yield calculations were absent. The second observation highlighted a failure to thoroughly review unexplained discrepancies (21 CFR 211.192), particularly concerning a visual inspection deviation where the cumulative reject rate for a (b) (4) lot exceeded established specifications.In response, LSNE management committed to submitting a written response to the FDA 483 within 15 business days. Required actions include establishing theoretical yield specifications and incorporating actual yield calculations into batch records, as well as revising visual inspection procedures to ensure comprehensive review of cumulative reject rates and further investigating process deficiencies leading to critical product defects. Additionally, discussions addressed improving sterilization cycle monitoring for sterile gowning, completing overdue temperature mapping, and conducting further filler performance qualifications.