Non-Sterile Drug Products–Microbiologically Related Recalls and Compliance Issues

Non-sterile drug products represent approximately 30% of annual drug sales. Non-sterile drug products offer therapeutic advantages, manufacturing costs that permit wide patient access, and versatility of dosage form and routes of administration, which facilitate patient compliance. These advantages have resulted in an increase in the number and nature of non-sterile finished dosage forms. Regulations and standards require the provision of non-sterile drugs to controlled levels of bioburden, the absence of specified microorganisms, and the absence of objectionable microorganisms. Thoroughly understanding the microbiological risks and control performance in non-sterile manufacturing is vitally important in the improvement of the quality and compliance of non-sterile manufacturing. Prior publications have reported the magnitude and characteristics for non-sterile product recalls and regulatory compliance shortfalls from 2004 to 2011 and from 2012 to 2019. The purpose of this review is to similarly provide a valuable contemporary update of the microbiologically related quality and compliance issues specifically associated with non-sterile drug products by reviewing drug recalls and Form FDA 483s. This includes evaluation of incidences of microbiological quality and regulatory compliance issues through more detailed abundance analysis. These data and information should assist in the risk assessment and risk management necessary in the manufacture of non-sterile products and be beneficial to the pharmaceutical microbiologist.