Water Activity and Microbial Risk Assessment of Non-sterile Drug Products
Oct 1, 2024
By Myriam Gueye – Segment Marketing Manager at Sartorius
Controlling water activity (aw) is crucial for maintaining the stability of non-sterile drug (NSD) products against microbial contamination. Unlike sterile products, NSDs are not free from microorganisms, making it essential to prevent microbial growth to protect patient health.
Water activity measures the amount of free water in a product that can support microbial growth, ranging from 1.00 in pure water to 0.00 in completely dry materials. This measurement is vital for formulation development, setting microbiological specifications, planning microbial testing strategies, and assessing microbial risk. International pharmacopeias provide methods for measuring aw and connect aw values with recommendations for microbial testing, as detailed in USP <1112>, USP <922>, EP 2.9.39, and JP 3.05.
Products with high aw, such as oral liquids, nasal sprays, or shampoos (>0.95), can become breeding grounds for Gram-negative bacteria, including the notorious Burkholderia cepacia complex, if not properly preserved. In contrast, dosage forms like tablets, capsules, or chewable gels with low aw (<0.60) are more resistant to microbial growth and, when stored in moisture-resistant packaging, may remain free from contamination throughout their shelf life.
The relationship between water activity and microbial stability is complex. While some non-sterile products require routine microbial testing, others with low aw or effective preservatives and packaging may not. The FDA provides guidance on when microbial limit testing can be reduced based on a product’s formulation, manufacturing process, and risk management. The FDA Draft Guidance “Microbiological Quality Considerations in Non-sterile Drug Manufacturing” emphasizes that cGMP regulations require a stability assessment program, focusing on microbiological control, even for components with low water activity.
In conclusion, water activity is a key factor in the pharmaceutical industry, aiding in microbial risk assessment and guiding decisions on product release and stability testing. By effectively managing water activity, manufacturers can ensure the safety and efficacy of NSDs.
