Alvotech HF – FDA 483, Mar 17, 2023

This FDA Form 483 was issued to Alvotech Hf, a Drug Substance and Drug Product Manufacturer located in Reykjavik, Iceland, following an inspection from March 6-17, 2023. The report identifies eight observations regarding deficiencies in their quality system and manufacturing practices.

**Key Observations:**

1. **Inadequate Quality Unit Responsibilities and Procedures:** The Quality Unit (QU) failed to ensure drug products were manufactured according to cGMP. This includes issues with laboratory data review, investigations, and adherence to written procedures. Examples include: * Quality Assurance (QA) approving Process Performance Qualification (PPQ) despite out-of-trend results for drug substance batches leading to out-of-specification (OOS) drug product batches. * QA approving PPQ reports where specified drug substance batches were not used in drug product PPQ. * QA approving a change control allowing secondary packaging and labeling before drug substance release, with plans to continue this practice. * Deficient supervisory oversight over quality/production unit operations and laboratory electronic systems/data, including "Data Incomplete" and "Bad Checksum" chromatography data not being adequately investigated, unrestricted access to original electronic test data, and inadequate review of all generated electronic test data. * Failure to follow established QU procedures, such as not completing a trend report and user access/system audit trail reviews. * Failure to