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Controlling the Microbiological Quality of Non-sterile Drugs.

Updated: Nov 17, 2021

Applying risk assessment tools to determine the adequate Microbial testing for non-sterile finished drug products.

A few days back, FDA published the draft guidance for Industry - Microbiological Quality - Considerations in Non-Sterile Drug Manufacturing. The draft document provides further insight as to the agency’s expectations with regards to microbial testing for non-sterile drug products (NSD) that includes solid dosage forms as well as aqueous and non-aqueous based drug product formulations.

The guidance was drafted as a result of numerous FDA Adverse Event Reports (FAERs) and Drug Recalls involving microbial contamination of non-sterile dosage forms. The agency acknowledges that the number of microbial contamination incidents are likely to be significant higher that those that are reported as FAERs. Additionally, a review of inspectional observations (483s and Warning letter citations) highlights the agency’s expectation for drug manufacturers to implement adequate microbial specifications considering the formulation water activity, preservative system and microbial control of components, specifically those that are naturally derived. Other factors include (1) the controls over the manufacturing process with focus on the design, monitoring, cleaning and maintenance of water systems and (2) route of administration and target patient population. The totality of such factors must be considered when implementing microbial specifications and while investigating microbial contamination events. Based on the draft guidance, Drug Manufacturers should evaluate their current microbial testing scheme via a comprehensive risk assessment and if required augment their current microbial specifications to not only meet the agency’s expectations but to ensure patient safety. As an added bonus, the documented risk assessment serves as the foundation while investigating microbial contamination events and ultimately support the quality unit’s decision with regards to product disposition or market action, if applicable. In future blogs, I will provide further insights regarding Microbial Testing for Non-sterile drug products including the consideration for expanding the microbial specifications to microorganisms in addition to the specified microorganism per drug monographs (USP General Chapters) which are discussed in the referenced draft FDA guidance.


Ernesto Alfonso

V&C Valence GMP Consultant

Quality Professional and Principal GMP Consultant with more than 30 years of hands-on experience developing and implementing compliant quality management systems for the global medical device and pharmaceutical industry. - Technical Expert in the areas of pharmaceutical microbiology, analytical chemistry, aseptic manufacturing, failure investigations, corrective and preventative actions, internal and external audits, process validation and design / process controls. - Competency building and managing global quality units with a solid record developing and implementing global quality management systems in accordance with appropriate good manufacturing practices and requirements (cGMP) with special focus on the subsystems and processes detecting, correcting and preventing quality issues. - Excellent working knowledge of global regulatory compliance regulations with direct experience communicating with US, EU and other regulatory authorities through inspections, submission, responses and other contacts. - Persuasive communicator with well developed negotiation skills. Excellent record developing positive relationships with internal and external customers. Specialties: CGMP Quality Management and Regulatory Compliance. Sterile Manufacturing & Sterilization Processes. Compliance Remediation. Audit. Training. Six Sigma and Lean principles.

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