How is contamination controlled during aseptic filling of sterile liquids?
Controlling contamination during the aseptic filling of drugs is a multi-faceted process that involves several key strategies. It is important to consider many factors and potential areas.
The filling process occurs in a highly controlled environment, often within isolators, specialized filling equipment, or cleanrooms that maintain strict sterility standards. These environments have specialized cleaning procedures and use High-Efficiency Particulate Air (HEPA) filters to remove airborne particles.
All equipment and components that come in contact with the drug product must be sterilized before each use. This includes the filling machines, containers, and closures. Ensuring that equipment has been properly sterilized in the aseptic filling process involves several critical steps:
- Selection of Sterilization Method: The appropriate sterilization method is chosen based on the type of equipment and materials. Common methods include steam sterilization (autoclaving), dry heat sterilization, ethylene oxide gas, gamma irradiation, and X-ray sterilization.
- Validation of the Sterilization Process: The sterilization process is validated to ensure it consistently achieves the desired level of sterility. This involves conducting biological indicator tests, where resistant microorganisms are used to confirm their effectiveness.
- Routine Monitoring and Maintenance: The sterilization process must be monitored regularly. This includes checking parameters such as temperature, pressure, and exposure time to ensure they meet the required specifications.
- Use of Sterile Barriers: Equipment is often stored in sterile barriers or packaging after sterilization to maintain sterility until use. This prevents recontamination during storage and handling. This includes using cleanrooms with HEPA filtration and maintaining strict hygiene protocols
- Environmental Controls: The environment where sterilized equipment is stored and used is controlled to maintain sterility.
In addition to equipment and components, personnel working in aseptic areas undergo rigorous training and must follow strict protocols to minimize contamination risks. This includes wearing sterile gowns, gloves, and masks and adhering to proper hand hygiene practices.
Another key component to ensure contamination control is continuous monitoring of the environment, which is essential. This includes regular testing for microbial contamination and particulate matter to ensure the environment remains within acceptable limits. Environmental monitoring (EM) in a pharmaceutical plant is a comprehensive process designed to ensure that the manufacturing environment meets stringent cleanliness and safety standards. There are several parts to EM. First is air quality monitoring. This involves sampling the air for microbial and particulate contamination using settle plates, active air samplers, and laser particle counters to detect and quantify airborne contaminants.
Surfaces in cleanrooms and other controlled environments are regularly tested for microbial contamination using contact plates or incubated swabs to check for microbial growth. Since humans are a significant source of contamination, personnel working in aseptic areas must also be monitored. Continuous monitoring of environmental parameters such as temperature, humidity, and differential pressure is crucial to maintain optimal conditions for sterile manufacturing.
Monitoring the quality of water and other utilities (e.g., compressed air, process gases) used in the manufacturing process is essential. This ensures that these systems do not introduce contaminants into the production environment.
As part of CGMP, regulatory compliance is a crucial aspect of EM. The US FDA and the EU EMA have guidelines that they set to ensure that the manufacturing processes meet the required safety and quality standards. Often, they will look at collected data to analyze and identify trends and potential issues. Additionally, this helps take proactive measures to prevent contamination and maintain a controlled environment.
Conclusion
By implementing these processes and controls, pharmaceutical plants can effectively monitor and control their equipment, environments, and personnel, ensuring safe and effective injectable drug products are produced.
Citations:
- Guidance for Industry Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice - https://www.fda.gov/media/71026/download
- The current state of aseptic processing & fill-finish manufacturing - https://www.crbgroup.com/insights/pharmaceuticals/aseptic-processing
- What is aseptic manufacturing? - https://www.pharm-int.com/aseptic-manufacturing-and-sterile-fill-finish/
- Aseptic Pharmaceutical Manufacturing: How It Works - https://ascendiapharma.com/newsroom/2021/11/17/aseptic-pharmaceutical-manufacturing
- Aseptic filling & processing of biologics - https://www.susupport.com/knowledge/fill-filtration/aseptic-filling
About Selkirk Pharma
Selkirk Pharma (www.selkirkpharma.com) is a world-class sterile fill/finish CMO in Spokane, Washington, USA. We are a key partner for companies that need a partner with a reliable, high-yield, US-based contract manufacturing organization (CMO). Selkirk Pharma was purpose-built by fill/finish industry veterans for on-time, in-full, sterile fill/finish GMP manufacturing of injectable drug products. You can count on our industry-leading processes, technologies, and support that reduce production bottlenecks, address product shortages, and onshore pharmaceutical manufacturing. Selkirk’s promise is the reliable delivery of your high-quality products. We offer best-in-class liquid vial filling in our Bausch + Ströbel VarioSys® fill line. We offer full Analytical and microbial services.
Want to learn more, visit our website at www.selkirkpharma.com, tour our facility, or reach out to our BD team at bd@selkirkpharma.com
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