Environmental monitoring, Microbial control -Nonsterile formulations, APIs
What should be frequency of Microbial monitoring -Settle Plate and Air Sample monitoring for non sterile areas for Environmental Monitoring. What are the limits for microbial counts. Whether action and alert limits should be defined for Environmental monitoring for non sterile areas for OSDs, Liquid dosage forms, other formulations, APIs
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Regulations governing non-sterile manufacturing for microbial controls and environmental monitoring are not as clear as for steriles. No specific frequency of Environmental monitoring or limits for Microbial controls defined for non sterile manufacturing. USP 1116 also mention that impact of risk of microbial contamination is negligible in non sterile products. However USFDA 21CFR 211.113 require appropriate procedures to prevent objectionable microorganisms in non sterile products. Also non sterile drug products require to comply to microbial specifications in the range of for 1000-100 cfu/g or ml for different product categories. Given this, a microbial control and environmental monitoring programme for non-sterile manufacturing area (Cleanrooms – ISO 8 / Grade D / Class 100,000) helps to prevent potential microbial contamination, comply with microbial specifications for products and meet regulatory and auditor expectations. In the absence of specific guidance for microbial monitoring of non sterile areas, concepts applied to sterile manufacturing can be useful references. But the limits, frequency of monitoring, alert & action limits all may be defined more flexibly, supported by a risk assessment with appropriate reference to guidances like USP 1116. For e.g. one can start with a target acceptance criteria of 200cfu/m3 for air sample and 100cfu/plate for settle plates. ( Grade D area requirement for Sterile Manufacture as per Eudralex Annexure 1). When starting a microbial (environmental) monitoring programme of cleanrooms after initial qualification or requalification of a facility, one can start with monitoring every week and generate 10-12 data points. From this data prepare trend chart, define alert and action limits (say Alert limit – Mean+/-2 Sigma, Action Limit: Mean+/- 3 sigma). The setting of alert and action limits help to investigate excursions and take corrective measures in advance (e.g increasing frequency of sanitation, disinfectants, fumigation of the area, review practices .. so on and so forth). Once Alert and action limits are set, the frequency of monitoring can be brought down to once a month.
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