In 2021, the FDA released new draft guidance for microbiological considerations in non-sterile drug manufacturing highlighting product development, risk assessments, and CGMPs relevant to non-sterile drug (NSD) manufacturing quality. Notably, it provides recommendations to help manufacturers assess the risk of contamination of their products with objectionable microorganisms with the goal of establishing controls to mitigate such contaminations and enhance safety and product quality.
This new draft guidance applies to a wide variety of non-sterile drugs including solid and liquid products (e.g., topical creams, lotions, swabs, and oral solutions). Non-sterile drugs include non-prescription drugs, often referred to as over-the-counter (OTC) drugs, and prescription drugs.
Product safety and quality is not limited to the presence or absence of objectionable microorganisms. The amount and type of microorganism must be monitored and controlled during manufacturing to ensure safety throughout product shelf life. However, high levels of non-pathogenic microorganisms in NSDs can be harmful as well.
With this draft, the FDA has gone a step further to help guide product quality. It provides clarity to the term “objectionable microorganism” and explicitly defines it as an organism that can be objectionable due to detrimental effects on the product of potentially cause harm to the user or can be objectionable due to the total number of organisms present. Having a clear definition is key, since many regulations are vague, and this is an area where most companies struggle to understand the impact.
We must understand what makes a microorganism objectionable. There is no exhaustive list and recalls show us that there are always emerging and new microorganisms.
Microorganisms are fast and they adapt quickly, so we need to consider routine product and environmental testing to keep them under control.