The manufacturing of biotech and pharmaceutical products have traditionally taken place using stainless steel (SS) equipment for decades. Stainless steel comes in numerous grades and surface finishes that have varying degrees of chemical resistance and surface finishes. The cost of SS materials grows exponentially when dealing with the most chemcially resistant robust and high purity grades of stainless steel. And as expensive as these materials may be, the term "stainless" is misleading, as some common chemical exposures may lead to premature rouge, pitting, and other damage to the surfaces.
Single-Use systems are not a new phenomenon. However, at this time, there are more applications for single-use systems than ever before. Single-Use components are used for bags in media/buffer preparation, bioreactors, intermediate and drug substance hold bags. Single-use materials are also used in transfer tubing, sterile connectors, fittings, sensors, filters among several other uses. The benefits of using single-use materials are many: lower capital cost, no utility or validation requirements for CIP/SIP, and the ease in changing the equipment design without demolition. But there are risks as well: determining the exact material composition through full characterization, the potential impact of leachable & extractables within the process stream and sterility assurance are some examples. Process Design Solutions provides industry-leading expertise to our clients in comprehensive Single-Use systems program development and execution. This ensures our clients make Single Use decisions based on process requirements and how well the single use components capabilities meet these requirements.
Process and Utility De-bottlenecking
One of the drivers to adopt single-use solutions is faster facility/equipment delivery when compared to traditional stainless steel solutions. Single-use systems can be obtained pre-steriized, thus eliminating the requirements for CIP and SIP. As a result, the labor and time required for CIP and SIP validation is removed leading to quicker availability of the manufacturing system to be used in production. In addition to the savings in time and resources, the lack of CIP/SIP requirements also leads to a reduction in utility consumption - water purification, WFI and Clean Steam generation, chemical consumption, power utilization, etc. This reduction of processing operations can lower staffing requirements and lead to an overall cost of goods sold (COGS) reduction for the end user.
PDS has performed process and utility assessments for a number of clients. And while there are cases where single-use technology does not provide dramatic improvement in the overall cost or time-to-production, our detailed assessments provide a solid foundation in providing relevant data to our end users which ultimately are used to support business cases to either transition or not transition into Single Use technology.
Extractable & Leachable Program Development
One of the greatest benefits in using stainless steel systems is the non-reactivity of the metal with the process solution, under most conditions. One challenge with use single-use systems is that poorly defined materials may pose a risk to your process by either introducing foreign material to the product stream, or by removing a critical component of the process solution. This could result in a loss in yield, at best, or a risk to product quality and patient safety, at worst. Selecting the appropriate materials for the appropriate application is critical when deciding to use single-use materials. The right single-use material will be as inert to the process as stainless steel, but at a fraction of the cost.
Our single-use experts have been working with these materials in a wide variety of applications for over 15 years and have seen this industry develop into something very robust. As a contributing member of the ISPE Single-Use Community of Practice, PDS has helped guide this industry into a quality-compliant state by requiring vendors to supply the applicable data to perform extractable and leachable assessments.
Process Design Solutions has also provided hands-on extractable and leachable assessments for clients on thousands of components and sub-components. Unfortunately we've seen that the data provided by vendors is not all the same, and is not always complete. We've established programs to assess components for extractables and leachables in a uniform manner, providing quantifiable data that allows our clients to determine when a part is acceptable for use and to successfully defend those decisions in front of regulatory agencies.
Material Compliance Services
The relative ease in the manufacturing of plastics can lead to a high degree of variability between components of the same material, in terms of purity, strength, and reactivity. This situation is magnified when you consider a single-use system made up of a dozen or more components - even something that seems as simple as a bag. The onus is on the manufacturer of a drug product or intermediate to ensure the components being used are suitable for their intended use and pose no risk to the patients.
We've worked with our clients to establish programs to ensure the appropriate component, constructed of the appropriate material, is available on demand. We are able to provide fully characterized Material of Construction (MOC) data for most of the industry leaders down to the sub-component levels. In addition, we've helped clients establish a Supply Chain / Materials Management Quality Services Program with effective Technical Quality Agreements (TQAs), thus allowing our clients adopt strategies to ensure an uninterrupted supply of single-use components and materials.
PDS has also been responsible for physical verification of single-use components. In the past, we've provided our clients with Engineering Test Protocols for single-use biocontainers, tubing, filters, fittings/ports, elastomers/o-rings, sensors and aseptic connection devices (ACDs) to test against vendor claims, application-specific requirements and/or peer-reviewed testing methodologies (ASTM, USP, ISO, EP, etc.).
Complete Single-Use Program Development Services
In addition to all the individual services described above, PDS can also develop a comprehensive Single-Use Program for you to cover all your single-use needs. This would include the above services, as well as:
An evaluation of your current process systems for effective single-use implementation
Establishment of requirements at each process step
A Design Review and Risk Assessment for each unit operation, which would include extractable and leachable assessments
Establishment of process-specific material of construction (MOC) requirements based on the application and associated level of risk
Development of disposable component flow diagrams for full traceability of each single-use component and the process condition in which it is used
Life-cycle Design Engineering Services from Conceptual Design, through Basic and Detailed Design, and into Implementation
A comprehensive single-use program, when applied correctly, is a powerful tool in defending the use of single-use systems. It can prove you have a science and risk-base rationale for determining where these components are used, under what conditions they're used, the MOC and reactivity of the components, and traceability of the components. It can also prove you have control over your materials and are prepared for any potential changes to vendor parts or supplier capabilities