How to Manage and Mitigate Personnel Contamination Risks in Sterile Manufacturing

Because of the high risk attached to personnel interventions, which typically include but are not limited to tasks such as conducting repairs, it is essential for pharmaceutical manufacturers to conduct detailed risk assessments for the integrity of their products and the safety of their patients. Due to the unpredictable nature of human behavior, it is critical to assess personnel interventions through Quality Risk Management (QRM), train personnel on conduct, and limit access to aseptic areas. Without proper protocols and safety procedures in place, pharmaceutical companies risk compromising product sterility, exposing critical surface areas, disrupting air flow, all of which can lead to costly shutdowns and product recalls. 

Annex 1, paragraph 8.16 in the fourth volume of the European GMP guidelines is very precise about personnel intervention and how it should be conducted inside aseptic areas to reduce the risk of contamination. In addition to using Quality Risk Management (QRM) as a tool for evaluating personnel interventions using a structured approach which we mentioned earlier, pharmaceutical companies must also test these interventions in controlled environments using Aseptic Process Simulation (APS) to see how they might affect sterility and jeopardize specific tasks. As the cornerstone of sterile pharmaceutical manufacturing, risk assessment plays a key role in identifying actions and conditions that might lead to contamination during the process as well as measures to prevent and minimize the risk. This step is critical especially when it comes to planning APS trials, as it allows pharmaceutical companies to zoom in on key areas and scenarios that could jeopardize product sterility. 

How to Conduct a Structured Risk Assessment for Personnel Interventions in Aseptic Areas In 4 Steps  

The structured approach required to manage contamination risks linked to personnel interventions in aseptic areas is made up of four major steps, which include Risk Identification, Risk Evaluation, Risk Control, and Risk Monitoring and Review. At the initial phase, risk identification, potential sources of contamination associated with the presence and activities of personnel in restricted areas are identified. Pinpointing these sources at this stage is vital, especially in situations where personnel have direct contact with sterile products or product-contact surfaces. These risks are assessed in the second step, the Risk Evaluation phase, using the appropriate methodology such as Failure Mode and Effects Analysis (FMEA), in our case. Using this approach, risks are assessed and weighed using a 1-3 scale scoring system which checks for severity, probability, and detectability. Severity evaluates five key factors including but not limited to surface types and potential airflow disruption, while probability evaluates how often the intervention occurs based on historical data, and detectability measures how effectively monitoring systems can detect contamination issues. After the three scores are calculated, they are multiplied together to find the Risk Priority Number (RPN), which helps in determining whether a risk is acceptable or not using a predefined matrix. In the event the RPN sounds the alarm, the risk control phase is implemented to mitigate the risk using various mitigation strategies and adopting support strategies like the Doctor-Nurse approach. In the Risk Monitoring and Review phase, which is the final step, the risk must be continually monitored and periodically reviewed to ensure intervention frequency and execution remain within acceptable parameters. In the event significant changes or deviations are identified during interventions, the Risk Assessment must be updated to reflect these changes. 

Is Your Sterile Pharmaceutical Manufacturing Regulatory Compliant? 

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