In the world of Advanced Therapy Medicinal Products (ATMPs), ensuring sterility is not just a regulatory requirement—it’s a fundamental necessity for patient safety. The complex nature of ATMP manufacturing, with its reliance on living cells and manual interventions, presents unique challenges that demand rigorous sterility assurance practices.
In a recent webinar hosted by Thermo Scientific, Shanshan Liu, Technical Director at No Deviation, delved into the critical role of Aseptic Process Simulation (APS) in maintaining sterility assurance for ATMPs. The webinar provided valuable insights on overcoming challenges, adopting best practices, and ensuring robust contamination control throughout the manufacturing process.
Here are the 8 key takeaways from the webinar to help you navigate the complexities of APS in ATMP manufacturing and safeguard patient health.
1.Sterility Assurance is a Matter of Patient Safety
Sterility assurance is not just a regulatory obligation — it is a critical safeguard for patient health. The tragic 2007 outbreak of bloodstream infections caused by contaminated syringes highlights the devastating consequences of lapses in sterility. For patients, especially those who are critically ill, maintaining strict sterility throughout the manufacturing process is a matter of survival. This underscores the importance of rigorous sterility practices in advanced therapy medicinal products (ATMPs) manufacturing.
2. Aseptic Process Simulation (APS) is Essential
Aseptic Process Simulation (APS), also known as media fill, is crucial for validating sterility assurance in ATMP manufacturing. APS replicates real-world manufacturing processes using growth media to identify potential contamination risks. A successful APS should closely mimic routine operations, including worst-case scenarios such as extended culture durations. It should account for manual interventions, which pose the highest contamination risks, and ensure that container closure integrity is maintained during storage and shipping. This comprehensive approach helps ensure the sterility of the final product.
3. ATMPs Manufacturing Come with Unique Challenges for APS
Manufacturing ATMPs presents several unique challenges that complicate sterility assurance. Many steps involve manual interventions, which inherently increase contamination risks. The limited and precious nature of patient-derived starting material means there is little room for error. Furthermore, the number of filled unit(s) and the batch duration are fundamentally different from the traditional filling operation.
4. Key Principles for ATMP APS
APS should mimic routine aseptic handling as closely as possible, testing worst-case parameters to ensure robustness. All steps, from solution preparation to sampling, must be included, ensuring comprehensive coverage of the manufacturing process. The number of interventions should reflect the maximum possible during manufacturing, regardless of process type, while considering both open and closed systems. Intermediate components, such as samples and used media, may require incubation to maintain quality. Additionally, material transfers must be carefully managed, whether between containers, through connection points, or via manual locking and tubing connections.
5. Adopt a Risk-Based Approach for APS
To optimize APS, it is essential to adopt a risk-based approach to identify the most critical steps and interventions. This involves recognizing worst-case scenarios that pose the highest contamination risks and ensuring these are thoroughly simulated during APS. Similar processes may be bracketed together to streamline validation without compromising effectiveness. Evaluating the level of system automation is also important; more manual processes inherently carry higher risks, so automating where possible can greatly enhance sterility assurance.
6. Media Fill Master Plan and Protocols
Developing a robust Media Fill Master Plan involves addressing several critical areas to ensure aseptic processes are validated effectively. Specific discussions should address the validation strategy, discuss the aseptic operation and identify the worst case(s).
While a well-structured protocol is essential to ensure efficient and compliant execution of processes. The critical content of APS protocol should clearly define the scope of the study and ensure the sample accountability.
7. Design for Sterility Assurance, Not Just Validation
Sterility assurance must be an integral part of the design process, not something addressed solely through validation. This means developing processes and systems that minimize contamination risks from the outset. Automated and closed systems are preferred as they reduce human intervention, which is a major contamination source. Cleanroom classifications should be appropriate for the type of operations being performed.
8. Continuous Validation and Improvement
Sterility assurance is not a one-time task but an ongoing process that requires continuous validation and improvement. Initial APS validation must be followed by periodic revalidation to ensure processes remain under control. When failures or deviations occur, thorough investigations are needed to identify root causes and implement corrective actions. Maintaining detailed traceability of process steps, interventions, and personnel involved is crucial for identifying potential risks and ensuring consistent sterility assurance. This commitment to continuous improvement helps maintain the highest standards of patient safety.
Ready to Enhance Your Sterility Assurance?
Ensuring sterility assurance in ATMP manufacturing is critical, and No deviation is here to help. Our team of experts provides comprehensive support for aseptic process validation, sterility assurance, and ATMP manufacturing solutions.
Stay ahead in pharmaceutical manufacturing by partnering with No deviation. Contact us today to learn how we can enhance your processes and safeguard patient health.
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Shanshan Liu is the current Technical Director at No deviation, responsible for the company’s technology and innovation roadmap, as well as the professional growth of employees. She also sits on the Core Team, defining the company’s international growth and business strategy.
Holding an M.Sc. in Biochemical Engineering from the University of Birmingham, Shanshan brings 18 years of global experience across consulting firms and pharmaceutical giants like Novartis, focusing on process, quality, compliance, and regulatory areas.
Shanshan is passionate about connecting people and technologies in the life science industry and is devoted to fostering international collaborations. She currently serves on the ISPE International Board, contributing to its global mission and vision.
