FDA 483 - Shire Human Genetic Therapies, Inc. - April 22, 2022

An FDA Form 483 was issued to Shire Human Genetic Therapies, Inc. in Lexington, MA, following an inspection conducted from March 29 to April 22, 2022. The inspection identified a significant concern regarding the company's quality control processes for active pharmaceutical ingredients. The primary observation noted that the Quality Unit inadequately assessed the impact of two High-Performance Liquid Chromatography (HPLC) systems, specifically HPLC-(b)(4) and HPLC-(b)(4), which had not undergone routine operational qualification (OQ) since their initial qualification in 2014. These systems are critical for the analytical testing of glycan mapping for Velaglucerase Alfa Drug Substance and Idursulfase Drug Substance and Drug Product. The FDA highlighted that vendor assessments in October 2021 revealed this lapse. Furthermore, the limited OQs conducted for these HPLCs in 2020 and 2021 did not include an evaluation of the Fluorescence Detector (FLD), which is integral to validating and routinely testing several critical methods from 2019 to March 2022. This observation indicates a failure to ensure equipment suitability and data integrity for product release, aligning with general good manufacturing practices under the Federal Food, Drug, and Cosmetic Act. Shire Human Genetic Therapies, Inc. is expected to respond to these observations by detailing their corrective and preventive actions to ensure proper equipment calibration, validation, and quality oversight.