What are single-use systems?
Single-use systems (SUS) commonly refer to bio-manufacturing equipment designed to be used once for a single process and then discarded. They are generally composed of plastic components that have been sealed and irradiated with gamma irradiation to ensure sterility. The need for flexibility and faster production are the major driving forces propelling towards the current choice; and, single-use systems are the growth drivers of bio-manufacturing.
The key advantages of SUS include eliminating the risk of cross-contamination across different batches of the same/other product(s). Therefore, assisting in maintaining regulatory compliance for bio-pharmaceutical production. Additionally, SUS is relatively cheap with less complicated validation requirements, compared to large stainless steel/glass components. Large stainless steel/glass components need to be cleaned and sterilised (if needed) prior to every use. This reduces the need for water and chemicals for cleaning and related infrastructural requirements. SUS is essentially a plug-play system enabling rapid installation and implementation, which reduces downtime in productivity. These advantages often offset the need to purchase SUS equipment after every use in bioprocessing.
Implementing single-use systems
The basic strategy involves:
- Assessment of the appropriate design and assembly, along with compatibility of the SUS materials with the process involved in the bio-production.
- A look-out for the availability of adequate data on extractable components from the vendor.
This would ensure that the final product is in accordance with the extractable and leachable limits set out by the regulatory authorities. Proper installation and validation requirements are some of the key areas to be considered prior to implementing single-use systems for bioprocessing.
From filter membranes, pipette tips and silicone tubing, SUS has expanded to Benchtop Bioreactor Systems; Flow Sensors; Pressure, UV, and Conductivity Sensors; Tube Sets and diverse closure-container systems used in bioprocessing. The basic tips for implementing single-use technology for a specific need are outlined below:
- SUS provides a cost-friendly alternative to multiple use systems. Thus a financial check with the supplier is a crucial step of planning to use SUS in bio-manufacturing.
- Evaluate the space required for installing and implementing the use of SUS. You should consider the design of the equipment in terms of both size and the shape; thus, ergonomics as a part of wider consideration.
- Prior to the procurement of SUS equipment, adequate risk assessment is essential to identify the quantities of extractable and leachable compounds from the SUS material that might impact the composition of the finished and packaged biopharmaceutical. It is important to consider the compatibility of the processing fluids and product components with the SUS material.
- Regulatory agencies have strict mandates on extractables and leachables that might be present in the finished bio-pharmaceutical, for toxicological concerns. In turn, this implies that the vendor is responsible for adhering to strict quality control norms. The supplier thus needs to provide quality assurance, qualification packages and an audit of the manufacturing area, if required.
- It is always advisable to use dual sourcing practices to secure the supply chain of SUS equipment. This practice lowers the risk of dependence on a single supplier, as in single sourcing.
- Cross-contamination is one of the key GMP deficiencies reported from biopharmaceutical plant audits, and SUS equipment/consumables being sterile easily assist in overriding the problem. However, they need to be properly installed, preserving their sterile condition; the disposable headplate of BIOne Single Use Benchtop Bioreactor System is an example. It is essential to prevent external or operator contamination, thus ensuring that the final product is sterile. Using an aseptically cleaned room for installation and implementation can help in eliminating the risks of microbial contamination.
- After securing the supply of SUS equipment, it is important to assign the task of system integration to trained and experienced personnel. The person should be aware of the cGMP guidelines, and familiar with the validation requirements of the bio-manufacturing processes and troubleshooting. Often, the time taken to implement SUS is linked to the validation requirements. Validation requirements include assessment of the contact time of SUS material with the biopharmaceutical, the point of contact and the stage of the product manufacturing where the contact takes place. These are likely to impact the product stability and the extractable and leachable content in the final product.
- Often the plastic components used in SUS are not compatible with conventional sterilization techniques. Such attempts are likely to make the plastic parts brittle owing to a change in the polymer properties, thus increasing concerns of leachables and extractables from them into the final biopharmaceutical. For example, the wetted material of disposable PVDF Turbine Flow Meter is resistant to gamma irradiation up to 50 kGy, or to a temperature of 140°C. Strict adherence to sterilization guidelines needs to be followed. Due to the same reason, one needs to properly ensure that the SUS equipment does not have cuts or broken marks in any place which comes into contact with the product at any stage of manufacturing.
- Growing awareness and need for environment protection warrants the need for suitable disposal methods after the use of SUS equipment. This also ensures long-term industrial sustainability. SUS materials mainly contribute to solid waste generation. Thus, the materials need to be biodegradable or recyclable, without chemically or biologically toxic components. In cases where such hazardous materials are present, an appropriate disposal route needs to be identified in accordance with the local legislation.
- It is important to consider the cost-effectiveness of the use of SUS when a bio-manufacturing process transitions from a small-scale to scaled-up commercial batch. The technological adaptability and availability should also be considered.
Single-use manufacturing systems, owing to the simplicity of their use, have found applications in clinical batch manufacturing and even in larger-scale manufacturing. Such systems are likely to witness their increasing use in manufacturing of new and already approved drugs and other bio-products, replacing the conventional multiple-use facilities.