The production of aseptic products is a complex process that necessitates the manufacturing of products with consistent efficacy while ensuring that the final product remains sterile. Several factors contribute to achieving sterility assurance, including high-quality operational cleanrooms, advanced barrier technology, and well-trained personnel. An additional critical aspect is the utilization of sterile equipment. Much of this equipment, ranging from connectors to storage tanks, has traditionally been sterilized using heat. Most of this equipment is recyclable and can be reused after undergoing thorough cleaning and resterilization processes.

These processes are time-consuming, expensive, energy-intensive, require a significant footprint, and are susceptible to occasional control failures. Such failures pose risks in various areas, including product sterility, cross-contamination, and the inability to achieve sterility, particularly in cases like wet autoclave loads of stainless steel tanks or the introduction of contaminants during tank connections. In recent years, there have been significant advancements in single-use aseptic technology, including bags, connectors, tubing, and filters, both as standalone units and as complete systems. These single-use systems are challenging the traditional reliance on reused stainless steel equipment and are gradually establishing themselves as the new standard in pharmaceutical production. This shift reduces concerns related to time, cost, and sterility by adopting single-use technology, enabling manufacturers to mitigate the risks associated with disinfecting or sterilizing equipment, recycling consumables, or transferring them to clean rooms.

The single-use technology currently utilized in the biopharmaceutical industry encompasses nearly all aspects of the production workflow. This includes tubing, capsule filters, mixing equipment, bioreactors, sterile liquid sealing bags for product storage, connection devices, and sampling containers used by biomanufacturers. One notable example is sterile connectors for aseptic processing, which are designed to connect containers, filters, and other functional manifolds for product transfer. Single-use aseptic connectors are essential for achieving complete closure and automation of the process. Another significant advancement is single-use bag technology, which plays a crucial role in transitioning from fixed stainless steel equipment operations. This category not only includes bags but also features disposable mixing systems, as well as 2D and 3D storage bags.

Most of these products are sterilized using gamma irradiation. This method has sufficient energy to eliminate bacteria at the molecular level by disrupting bacterial DNA and inhibiting their division. Another alternative sterilization process is ethylene oxide gas; however, it is less commonly employed by manufacturers of single-use products.

The advantages of single-use technology include: no need for cleaning; elimination of the requirement for in-house sterilization of all components, such as autoclaving; reduced use of cleaning chemicals; decreased storage requirements; minimized process downtime; enhanced process flexibility; and a reduced risk of cross-contamination.

However, several factors must be considered when implementing single-use technologies, including product efficacy and sterilization methods. Specific implementation and validation techniques are necessary to assess various key factors. The integration of this technology does not have to be comprehensive; a hybrid approach that incorporates some traditional technologies may be suitable. Hybrid systems can optimize existing technologies and reduce the costs associated with purchasing single-use supplies, depending on the volume of products intended for production and the required flexibility.

It is essential to consider ergonomic factors, such as space requirements, regarding product storage and handling. The adoption of single-use technologies enables manufacturers to reevaluate and redesign product processes, making adjustments aimed at enhancing efficiency. Depending on the nature and objectives of the operation, manufacturers can relocate certain products to flexible, smaller-footprint facilities. In other facilities, existing products can be "modernized" by incorporating quality-by-design principles. This technology update and iteration also offers opportunities for enhanced real-time monitoring, particularly through the integration of Process Analytical Technology (PAT). This includes bioprocess equipment fitted with single-use sensors that enable online monitoring of pH, conductivity, and temperature, as well as advanced in-line monitoring of product quality attributes.

Validation issues are central to a manufacturer’s strategy for adopting single-use technologies. Several validation steps must be undertaken before implementing these technologies. These steps include assessing the potential for leachables and extractables from single-use technology products that come into contact with the product. The risk associated with these substances varies based on the product, the duration of contact, and the stage of production during which the contact occurs. Furthermore, there must be adequate confidence in the reliability and consistency of the polymers used to manufacture the films, modules, and tubing.

The sterilization method and its potential deleterious effects on the product are important considerations. For instance, certain sterilization processes, such as gamma irradiation, can render some plastics brittle. Another area of concern is the leachables and extractables, which may pose a risk if the sterilization process alters the plastic. As part of the validation process, it is essential to review the extent to which the sterilization method affects the polymer's properties, including tensile strength, color, shape, and molecular weight.

Availability and development costs are critical factors influencing the implementation of single-use technologies. Not all required sizes or types have commercially available products, and if the technology is customized, close collaboration between the manufacturer and the technology provider is essential. Before making substantial progress with a specific supplier, it is necessary to conduct a thorough audit, which should include financial assessments, guarantees of supply continuity, and evaluations of production capabilities. Additionally, the supplier must provide a comprehensive qualification package.

Once all necessary validation steps have been completed, stability studies may be required to assess the long-term effects of the technology on the manufactured product. The necessity of such studies will depend on the type of technology, its maturity, and the supporting data available. Additionally, for established processes utilizing traditional technologies, change controls for single-use technologies will be required after implementation is confirmed. Changes in approval may also be necessary before use in commercial batches, depending on the requirements set forth by applicable regulatory agencies. Furthermore, for small-scale and pre-GMP processes, it is essential to consider whether the technology will be employed in scaled-up commercial batches. This necessitates an evaluation of cost-effectiveness and technical feasibility. Ideally, further work will be conducted once these questions have been satisfactorily addressed.

In summary, single-use technology offers several advantages for pharmaceutical manufacturers, including enhanced automation feasibility, compactness, and enhanced reliability. However, numerous factors must be taken into account during implementation, such as scalability, product compatibility, ergonomic space considerations, cost, sterilization methods, and their impact on product approval. Drawing from numerous successful case studies, the overall adoption of single-use technology can help manufacturers reduce product costs while strengthening sterility assurance.

Duoning is committed to the development and innovation of disposable technology products within the biopharmaceutical sector. We have established a comprehensive single-use bioprocess supply platform that includes 2D and 3D liquid storage systems, liquid preparation systems, pipelines, flow kits, freeze-thaw systems, single-use bioreactors, and supporting hardware systems. Additionally, we provide customized services tailored to meet the specific needs of various applications. With a robust supply chain and a rigorous quality management system, we can respond to customer needs quickly, efficiently, and with high quality. This approach ensures the continuity of our customers' businesses and accelerates the transition from development to clinical trials and ultimately to market.