The final fill stage in biopharmaceutical manufacturing is critical as it has a direct impact on product quality, sterility, and patient safety. As the industry increasingly moves toward single-use systems (SUS) and isolator fill finish due to their operational efficiencies, increasing regulatory requirements, and compliance benefits, selecting the appropriate SUS for final filling is of paramount importance.
This blog post describes the key factors to be considered when selecting a single-use system for final fill operations.
1. Compatibility with product and process
SUS materials must not interact with the product because the resulting extractables and leachables (E&Ls) could compromise the quality and/or safety of the product. Therefore, the chemical compatibility of the SUS materials with the product is crucial. In addition, the SUS should integrate seamlessly with existing processes to ensure that it does not disrupt production workflow or efficiency.
2. System sterility
Sterility is one of the most important factors for final filling. The selected SUS should ensure robust sterility throughout its lifecycle – from manufacturing and packaging to implementation in the process. The design of the SUS should support the objective of mitigating the contamination risk by reducing the number of connections as potential points of contamination and incorporating aseptic connectors and transfer systems. For pre-sterilized systems, validated methods must be used to ensure that each step has been proven to effectively minimize the risk of contamination.
3. Flexibility and scalability
The ability to adapt to varying production volumes without compromising quality or efficiency is critical. An ideal SUS for final filling should be scalable, enabling easy adjustment to different batch sizes and fill volumes, and facilitating seamless scale-up or scale-down. Flexibility in design using various materials such as TPE and silicone to accommodate different product types and fill volumes is also essential.
4. Regulatory compliance
The selection of an SUS for final filling of biopharmaceuticals requires thorough understanding of and compliance with the regulatory framework including compliance with FDA and EMA standards and the specific requirements of Annex 1 relating to the manufacture of sterile medicinal products. The selected SUS must comply with current regulations and be flexible enough to accommodate future regulatory changes, particularly those that emphasize risk management and quality assurance. In addition, suppliers must provide detailed validation documentation to demonstrate that the system complies with these regulations. This documentation, covering sterilization methods, system integrity, and compatibility assessments, is critical for regulatory submissions and ensures that the SUS supports both compliance and the highest standards of product quality and patient safety.
5. Assembly and closed system design
The move toward closed single-use systems significantly improves sterility and process efficiency. SUS should be designed to ensure a completely closed system from the container to the filling needle. The integration of overmolding technology is a key innovation in achieving a truly closed SUS. It replaces traditional barbed connections and reduces the number of connections required. Overmolding not only creates a more reliable, leak-proof connection but also plays a critical role in maintaining the integrity of the closed system in line with Annex 1 requirements emphasizing the importance of closed systems in the manufacture of sterile products. This technology significantly reduces potential points of contamination, ensuring a higher level of sterility.
6. Supplier reliability, support and customization capacity It is important to work with a supplier that understands that every final fill process is unique and that can offer flexible solutions tailored to specific operational requirements. This ensures that the implemented single-use system is of high quality and perfectly aligned with the customer’s process requirements, improving both efficiency and compliance. A supplier’s ability to provide comprehensive support throughout the lifecycle of the single-use system – from initial design to final implementation – can have a significant impact on the success of the customer’s final fill operations.
Bottom line
Selecting the right single-use system design for final filling is a critical choice that can have a significant impact on product quality, regulatory compliance, and manufacturing efficiency. Prioritizing considerations such as compatibility, sterility assurance, flexibility, regulatory compliance, and supplier reliability can improve final fill operations and ensure product safety. It is important to partner with a supplier who understands the various requirements and challenges. In this context, Parker has demonstrated its reliability with its PureTain® final fill single-use solution. Get in touch with us. Our team of process specialists will be happy to discuss your requirements and work with you to find the best single-use solution for your final fill application.
