BPSA

1. What makes up a “typical” Single-Use System? (SUS)

Single-Use systems consist of fluid path components to replace reusable stainless steel components. The most typical systems are made up of bag chambers, connectors, tubing and filter capsules. For more complex unit operations such as cross flow filtration or cell culture, the Single-Use systems will include other functional components such as agitation systems, and Single-Use sensors.

2. What are the primary benefits of Single-Use Systems?

Single-Use systems boast improved productivity, cost structure, and a reduced environmental footprint compared to traditional stainless steel facilities. This is driven by the demanding cleanliness and sanitization standards in the biopharmaceutical industry. Productivity: Workers spend much less time changing out disposable systems then they do cleaning and sanitizing a traditional stainless steel system. Cost: Without reusable parts to clean, there are no chemicals, water, steam, or other utilities used in the cleaning/sanitizing process. Also, a facility engineered for disposables is simplified, using less space, so the total energy consumption is reduced. Environmental Footprint: While the plastics in the Single-Use systems are usually incinerated, the footprint contributed by this is less than then that contributed by waste water, chemicals and energy used for cleaning traditional stainless steel systems. Cost Effectiveness: Single-Use bioprocessing can reduce capital cost for building and retrofitting biopharmaceutical manufacturing facilities. Manufacturing Efficiencies: Single-Use systems can achieve significant reductions in labor, faster batch-turn around and product change-over; Single-Use system modularity facilitates scale-up, speeds of integration and accelerates batch changeovers and retrofits. Quality and Safety: Single-Use offers reduced risks of cross-contamination, reduced risk of bioburden contamination, reduction of cleaning (and cleaning validation) issues and other benefits that can help satisfy the requirements of regulatory agencies. Sustainability: Single-Use bioprocesses systems can provide a range of environmental benefits beyond those of stainless steel systems. Although Single Use system may generate additional solid waste, benefits include reduction in the amount of water, chemicals and energy required for cleaning and sanitizing as well as avoiding the labor-intensive cleaning processes required with stainless steel systems

3. Are Single-Use systems limited to specific stages of the manufacturing process?

Currently Single-Use technology can be utilized in a variety of stages as well as unit operations in bio-processing manufacturing. However, some unit operations and process scales currently have limitations due to existing capital installed and lack of technologies available in SUS formats. Historically, media and buffer preparation were some of the first unit operations to utilize Single-Use technologies. As technologies have evolved, there are now larger scales and more unit operations such as Cell Culture, Mixing, Purification, Formulation and Filling. As the Single-Use industry continues to evolve and the bio-processing industry realizes the benefits, further investments will be required from the supply base to develop even larger scales as well as newer technologies.

4. Do manufactures need to replace all stainless technology to take advantage of the benefits of Single-Use systems?

Not necessarily — the benefits of integrating Single-Use systems into unit operations can be achieved by making either a full conversion to plastic based solutions or an appropriate combination of Single-Use and stainless technologies. Manufacturers can increase process flexibility and improve efficiencies even with partial conversion to Single-Use technologies. Examples include cell culture operations integrating Single-Use bioreactor technology with traditional stainless reactors and final fill operations combining Single-Use systems with traditional vial filling equipment.

5. Are Single-Use systems limited to specific stages of the manufacturing process?

6. What are the factors to consider when implementing a Single-Use technology?

There are four basic questions/areas to ask when thinking about implementing Single-Use technologies: Application, Capital for Investment, Data Available and Risk Tolerance.

What is my application (product and process)? Will I be performing upstream and/or downstream processing of cell therapy, drug product or other bio-pharma process? What part or stage of the process will I be working? Is my process/product scope and overview well understood and documented? Is my application mixing and buffer preparation? Is my application fermentation or other bioreactor cell growth process? Will I require significant filtration and refinement? Will I be making final drug product? What environmental control and handling procedures do I have in place and how to they differ with Single-Use?
How much capital do I have available to invest in initial start-up and/or technology conversion costs?
What data is available from the suppliers to help answer the questions I will get from the FDA when validating my product and process? Do the suppliers have a DMF? Have the suppliers performed extensive testing on extractables/leachables, USP Class VI, etc.
How can I reduce the amount of risk associated with my product/process? Am I the first to market with this process/product? Do others have a roadmap or platform that can be followed instead of reinventing the wheel? What data do I have or is available that can help reduce the amount of risk? Have I implemented QbD to eliminate future problems and issues? There are many case studies available on how companies have addressed the four topics mentioned above. Refer to other specific FAQ questions links or BPSA’s landing page: www.bpsalliance.org. For specific inquiries and a referral to an industry expert or liaison, contact ottk@socma.com

7. What effect can Single-Use technology have on capital and start up costs associated with designing and commissioning a new manufacturing facility?

Single-Use systems typically have lower capital and start up costs. The capital equipment associated with supporting a Single-Use unit operation is far less expensive than for multi-use stainless systems. One example is that the materials used to build support systems for Single-Use operations need not be electro polished and passivated, like the product contact surfaces of a multi-use system. Commissioning a Single-Use system is often faster and simpler than a multi-use system. The product contact surfaces or Single-Use systems can be qualified well in advance of the actual installation, compressing start up commissioning time lines.

8. How does Single-Use technology affect ongoing manufacturing efficiencies and production costs?

9. Are there established standards or guides for Single-Use systems?

While there are no industry standards specifically for Single-Use process systems, there are several standards and technical guides that can be applied. Some specific examples are the ASTM Standard F838-05 on Sterilizing Filtration, the ANSI/AAMI/ISO Standard 11137 on Sterilization of Healthcare Products – Radiation and the ANSI/AAMI/ISO Standard 13408 ovn Aseptic Processing of Healthcare Products. These and other industry standards and technical, as well as government regulations and regulatory agency guidelines, that can be applied to Single-Use systems, are further described in the BPSA Component Quality Reference Matrix. BPSA is also a leader in developing new best practice guides for Single-Use systems that are simulating the development of standards or guides by other organizations (e.g. ASTM-BPE, PDA, ISPE). BPSA guides also cover Irradiation and Sterilization Validation, Determination of Extractables and Leachables and Disposal of Single-Use Systems. See these at www.bpsalliance.org

10. Is there information available on irradiation and sterilization/validation?

The American National Standards Institute (ANSI), American Association of Medical Instrumentation (AAMI) and the International Organization for Standardization (ISO) have jointly issued a standard on Sterilization of Healthcare Products (ANSI/AMI/ISO 11137) that is recognized by regulative authorities around the globe. To help biopharmaceutical manufacturers and Single-Use equipment suppliers better understand the application of this standard and its’ various options to Single-Use systems, BPSA has published a Guide to Irradiation and Sterilization of Single-Use Systems. This BPSA guide explains the basic principles of sterilization validation under ANSI/AAMI/ISO 11137, discusses considerations in choosing among alternate approach options, and suggests where microbial control by irradiation without validation may be applicable and beneficial in terms of development time and cost without compromising safety or quality. See the references at www.bpsalliance.org

11. What are extractables and leachables and how should they be considered during validation?

Drug developers and regulators are concerned about potentially adverse impact on drug product quality or safety by chemicals that may migrate into the drug product from fluid contact process equipment (including Single-Use systems), final drug product containers or secondary packaging. Extractables are chemicals that migrate from fluid contact materials under exaggerated conditions (e.g. solvent, time, temperature) and represent a “worst case” library of chemicals that could potentially contaminate or interact with drug product. Leachables are chemicals that can be found in final drug product and typically include some extractables from process equipment as well as from the final container/closures or packaging along with any reaction or degradation products of those extractables and the active drug. The BPSA Guide – Recommendations for Extractables and Leachables Testing, provides a risk-based approach for determination of extractables and leachables from Single-Use process systems that has been recognized by US FDA CBER reviewers and applied successfully by several biopharmaceutical manufacturers. See the guide at www.bpsalliance.org

12. What are the options for disposing of Single-Use systems and components?

There are a range of disposal options for Single-Use systems; the best solution will be dependent on the composite and volume of plastics, local regulations and available waste treatment facilities. Although recycling is viewed as environmentally appealing it is not amenable to most Single-Use systems due to low volumes and mixed plastic content. Landfill options for typical systems include treated, untreated as well as grind and autoclave. Incineration is a widely accepted treatment option in both the US and Europe that reduces the volume of waste. Cogeneration is an attractive alternative which converts the plastic waste is into energy that produces heat or electricity for consumption by individual facilities or entire communities. Pyrolysis is relatively new technology that converts plastic waste into oil that can be used as fuel. To learn more about the advantages and disadvantages of each option please reference BPSA’s Guide to Disposal of Single-Use Bioprocess Systems at www.bpsalliance.org

13. How does the environmental impact of Single-Use manufacturing compare to traditional stainless manufacturing?

14. Who can be contacted to learn more about implementing Single-Use technology into my operation?

BPSA is comprised of 40 member organizations within which reside a variety of experts who are willing to assist you in the implementation of Single-Use systems. The first stop to gathering the knowledge to educate on Single-Use manufacturing is to contact BPSA Executive Director Kevin Ott, ottk@socma.com who can direct you to the proper resources contained within the membership of both the BPSA and the additional standard-setting and technical organizations that deal all aspects of Single-Use systems. 15. What is the Value of BPSA and the Benefits of Membership? BPSA’s mission is to advance the adoption of Single-Use systems, worldwide. BPSA promotes this purpose by conducting networking activities, monitoring legislative and regulatory initiatives involving SUS, publishing industry guides on specific topics relevant to the industry, and being the information clearinghouse for education on all aspects of Single-Use. Suppliers of Single-Use components, End Users of Single-Use systems, ancillary service providers and contract manufacturers are all eligible for BPSA membership as dues-paying organizations. Membership information and applications for membership can be seen at www.bpsalliance.org. Finally, BPSA is the only national organization that represents industry-interests in Single-Use and that serves as the focal point for education on matters related to this industry and its customer base.

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