Why single-use isolators are a game changer for drug product manufacturing?
Aseptic filling is a critical step in the production of biological drugs and other APIs, demanding absolute precision and sterility to ensure patient safety. The advent of single-use isolators is transforming the way CDMOs can manage their aseptic production lines, bringing about a revolution in efficiency and safety.
Single-use isolators, while functionally similar to fixed filling isolators, are designed for one-time use only. As such, they must adhere to all NF ISO 14644 standards, undergoing rigorous testing and qualification processes to meet these stringent requirements. These isolators serve as essential manufacturing tools, necessitating that single-use isolator suppliers possess comprehensive expertise in sterile industry protocols to ensure they meet all necessary prerequisites for qualification.
Since 2019, GTP Bioways has been at the forefront of this revolution, offering comprehensive drug substance manufacturing, formulation & aseptic filling services powered by a state-of-the-art single-use isolator technology. Our 700-square-metre cGMP manufacturing unit, built in compliance with European and global drug manufacturing requirements, underscores our commitment to excellence.
Seamless integration of the filling isolator and efficiency
Based on the prerequisites outlined in a previous blog post, we selected a French supplier to implement our optimal solution based on a single-use isolator for filling/stoppering isolator in the filling line. We requested the establishment of a flexible system that utilises two types of pumps: a positive displacement pump for viscous liquids and the second pump designed for conventional liquids requiring single-use equipment. This single-use system integrates seamlessly into a continuum of isolators, each fulfilling a specific function (container and stoppering system sterilisation, equipment loading, pre-filling preparation/feeding, filling/stoppering, capping). Rather than an open line, it is a closed filling line that addresses the constraints of continuous yet sequential filling. This design enables operators to manage the filling line with minimal manpower, allowing them to focus exclusively on feeding the aseptic filling and stoppering tool. Meanwhile, high-risk tasks are handled by the fully automated system, which manages the entire hazardous area.
Navigating regulatory challenges for aseptic filling
The qualification of this single-use isolator combined with a 6-axis robot requires comprehensive knowledge of aseptic filling activities to model and simulate operations accurately, thereby validating the entire process. Implementing an MFT (Media Fill Test) strategy that satisfies regulatory requirements is essential while introducing this innovative and unprecedented technology. Predicting the reaction of the pharmaceutical industry and regulatory bodies to such technological advancements is challenging, particularly as there is no equivalent within large pharmaceutical companies. Innovation in this field does not stem from the routine large-batch production of molecules seen in global laboratories.
Advanced Aseptic Filling for Personalised Medicine
Innovation lies in the capabilities we must develop in the near future to serve patients with targeted therapies for increasingly precise diagnoses that require treatments tailored to each individual. Consequently, the era of high cadences and production tools designed for a single product is coming to an end. Production units will need to balance cost-effectiveness in producing small runs with the manufacturing of small batches, avoiding the prolonged storage of products that can result in losses for pharmaceutical laboratories due to overproduction.
The fact that this isolator is single-use does not reduce the scope of qualification and validation activities. Despite its one-time use, filters, connection systems, isolator walls, and design elements must adhere to the same stringent standards as those of a fixed isolator.
In conclusion, the isolator we have developed together with our supplier represents a significant technological advancement in aseptic filling. Having undergone comprehensive validation and filled tens of thousands of MFT vials under various conditions, this robust tool ensures operational safety and reliable sterility. The sterility of the single-use isolator post-irradiation can be reliably guaranteed for several days, and the assurance of system sterility facilitates the filling of sterile products under optimal conditions.
The flexibility of the filling system, capable of handling a wide range of fluid viscosities by utilising different types of pumps, further underscores its advanced design and maturity. Meeting the high standards expected by industrial sterile equipment users, this single-use isolator stands as a testament to innovation in an industry that values continuity.
For CDMOs, incorporating single-use isolators into aseptic filling processes presents an opportunity to significantly improve production efficiency, align with stringent regulatory standards, and adapt to the ever-changing demands of the pharmaceutical industry. This innovative approach is a key step forward in ensuring high-quality, safe, and efficient pharmaceutical production.
