FDA 483 - Alvotech HF - March 17, 2022

The FDA Form 483 documents observations from an inspection, indicating a lack of procedural control for qualifying incoming materials. The firm has not initiated an investigation in its deviation management system (Veeva) regarding a progressively increasing trend of critical quality defects in incoming mL stopper lots. Since August 2020, 14 out of 20 stopper lots (70% failure rate) were rejected or failed AQL inspection. Quality Assurance has not been involved in release or reject decisions for raw materials failing acceptance criteria outside the Veeva system, with release decisions pending for 8 of the 14 failed lots.

Despite critical defects being found since August 2020, only one defect type has been placed on a tightened inspection level. Three stopper lots received in August 2020 were rejected in October 2020 due to splits/cuts, potentially caused by a lack of plug concentricity. The supplier, , reportedly lacks a process to measure eccentricity, and their visual inspection equipment, Envision system, may not detect splits. Inspection criteria for splits and cuts were not changed.

Since October 2020, six other stopper lots were inspected, with three lots ( ) released in October and November 2020 without tightened inspection, subsequently found to have critical defects. Document Change Control # DCC-003069, approved June 2021, implemented tightened inspection criteria for Defect # DEF3