FDA 483 - AbbVie Ltd - April 18, 2024

During an inspection by the U.S. Food and Drug Administration (FDA) at AbbVie Ltd's drug product manufacturing facility in Barceloneta, PR, from April 10 to April 18, 2024, several significant observations were documented on a Form FDA 483. The inspection highlighted a lack of thorough review for unexplained discrepancies, specifically regarding microbial contamination. The company failed to consistently initiate investigations or identify the source of objectionable microorganisms found in raw materials, such as powdered sugar and acacia peroxide, and in finished pharmaceutical products like Synthroid tablets. Instances were noted where contamination in materials used for Synthroid production or in the final drug product itself (e.g., Synthroid 125mcg and 75mcg lots) did not trigger proper investigations into their origin and extent, often despite reporting growth during selective microbial testing. Additionally, deficiencies were noted in cleaning validation samples from manufacturing equipment and water systems, where atypical microbial growth and potentially objectionable organisms like Ralstonia Mannitolilytica and Burkholderia cepacia were identified, but without subsequent investigation. A second key observation concerned inadequate laboratory controls. The microbiology laboratory lacked established scientifically sound standards and sampling plans to assure product quality. Specifically, controls were missing to document and track recurring microorganisms that contribute to the overall microbial presence at the site. Insufficient data also prevented the establishment of trends from environmental monitoring samples, even when known objectionable organisms were periodically identified in the water system. These observations indicate a need for AbbVie Ltd to implement robust corrective actions to enhance their quality systems, investigative processes, and laboratory controls to ensure drug product quality and regulatory compliance.