TY - JOUR T1 - A QRM Discussion of Microbial Contamination of Non-Sterile Drug Products, using FDA's and EMA's Warning-Letters between 2008 and 2016. JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol DO - 10.5731/pdajpst.2016.007252 SP - pdajpst.2016.007252 AU - Ana M.C. Santos AU - Mara S. Doria AU - Luis Soares AU - António J. Almeida AU - José C. Menezes Y1 - 2017/01/01 UR - http://journal.pda.org/content/early/2017/12/13/pdajpst.2016.007252.abstract N2 - Microbial quality control of non-sterile drug products is a concern to regulatory agencies and the pharmaceutical industry since the 1960's. Despite being an old challenge to companies, microbial contamination still affects a high number of manufacturers of non-sterile products. Consequences go well beyond the obvious direct costs related to batch rejections or product recalls, as human lives and a company's reputation are significantly impacted as well if such event occurs. To better manage this type of events and establish effective mitigation strategies, it is necessary to understand the microbial hazards involved in the manufacturing processes of non-sterile drug products, be able to evaluate their potential impact on final product quality and apply mitigation actions . Herein we discuss the most likely root causes involved in microbial contaminations referenced in Warning letters (WLs) issued by the US Health Authorities and Non-compliance reports issued by European Health Authorities, over a period of several years. The QRM tools proposed were applied to the data gathered from those databases and a generic risk ranking is provided based on a panel of non-sterile drug product manufacturers that was assembled and given the opportunity to perform the risk assessments. That panel identified gaps and defined potential mitigation actions, based on their own experience of potential risks expected for their processes. Major findings clearly indicate that the manufacturers affected by the WLs considered, should focus their attention on the improvement of processes and controls, specially raw materials and primary packaging quality control (QC). A stronger enforcement by health authorities, of better in-process contamination controls, would be beneficial. ER -