PDA will soon release a Technical Report on single-use disposable biopharmaceutical processing equipment. Robert Repetto, director of technology and innovation at Pfizer and a key member of the committee that drafted the consensus document, shares information on what to expect.
PhM: There's been a lot written about single-use systems, of course, but what knowledge gaps will the technical report fill in for the industry?
R.R.: While there are hundreds of articles published every year regarding Single Use Systems the vast majority of these have some commercial basis and typically represent one supplier’s or organization’s viewpoint and experiences. The PDA Technical Report is a consensus document and the concepts and points of interest have been vetted and discussed among the task force members, which consists of Suppliers, Regulators and End Users. The PDA Technical Report is very comprehensive, presenting strategies that tie together Technical, Quality, Business and Implementation factors for Single Use Systems, in a coherent fashion rather than addressing one or two of these aspects as is seen in many existing articles.
PhM: The focus of the TR is on implementation—from this standpoint, what are end users still finding the most challenging? What's hindering implementation?
R.R.: One area that is frequently over looked when considering SUS is a well thought out implementation plan. In order to achieve improvement over traditional multi use systems and have a successful implementation an organization must evaluate how SUS fit into their existing quality systems, material logistics, and work flows. Each organization has to evaluate if a particular SUS application will be effective individually. Several factors come into play which might make SUS successful for one organization and not another. The organization’s business model, existing facilities, need for flexibility, stage of development, experience, and number of runs per year, all become factors which impact a successful implementation. Overall the biggest challenge facing End Users is fear of the unknown, stemming from an inadequate understanding of regulatory expectations for Single Use Systems as well as the Single Use Technology itself, which publication of this Technical Report will help resolve.
PhM: The report is also written with an eye towards "making sure regulators accept your process." What are some of the key best practices for end users to remember in this regard?
R.R.: The best advice is that your process must comply with the same regulations and quality systems requirements, regardless of whether your process uses traditional or single use technology; the cGMP’s apply to the end users.
PhM: You're encouraging "transparent partnerships" between solution providers and end users. It sounds obvious and easy, but what makes it difficult in practice?
R.R.: SUS can eliminate equipment assembly, cleaning and sterilization and much of the value from single use systems comes from this “ready to use” status. However, to be successful end users must ensure that these value added activities were done effectively and that can only happen by developing quality systems which can monitor and control SUS quality throughout the SUS Supply chain. Only a partnership with a SUS supplier can ensure that quality is as good as, or better than what is achieved with traditional systems. A purchase order doesn’t make a partnership! SUS suppliers provide equipment that includes the outsourced value added activities that make a SUS ready to us and these value added activities are important for the success of both organizations. A winning control strategy for SUS has elements in both the supplier’s and end user’s quality systems. Because of this, strong communication is essential.
PhM: The task force was comprised of end users, suppliers, regulators, and other experts. Can you give an example of one part of the report that clearly illustrates the input from these diverse groups? What sections or topics were the most contentious and hard to hammer out?
R.R.: Early on it became clear we should not call a SUS supplier a vendor. Vendors sell things that don’t require a long term commitment to be successful. The Task Force came to the realizations that to be successful suppliers and end users had to be able to share information to build successful control strategies. Developing a relationship focused on success requires good communication and understanding expectations, so the task force focused on way to improve these areas between a supplier and end user. We all learned a great deal from the different perspectives that drive SUS success and the technical report is a much better document because of these long discussions.
PhM: Extractables and leachables are always an issue—what will the technical report present on the topic that's new or uniquely useful?
R.R.: Extractables and leachables can be a make or break issue for SUS implementation and this is one area where the SUS supplier can provide a great deal of information and value. E and L profiles are dependent on the consistency of the materials utilized in your process and collecting this information from suppliers is a logical starting point, but the end user must understand any specific product and process risks. Plastic resin suppliers are a potential source of variability. The SUS supplier can build control strategies to address this issue underscoring the essential need for a strong relationship with your SUS supplier.
PhM: Finally, a general question: The quality of single-use systems is always under scrutiny. Where are we now, in 2012, in terms of the quality of single-use components and systems?
R.R.: The general feeling among the task force is that SUS’s can be very reliable and may be used successfully to make either clinical or commercial material, but only when an organization has the necessary controls and quality systems in place. The industry’s experience with traditional multi use systems helps set baseline expectations for SUS in terms of reliability, but to truly be successful an organization may need to develop control strategies specific for SUS and not just apply methods used with traditional multi use systems.
As an example, a pressure hold is often used with traditional systems to verify integrity and before a tank or bioreactor is charged with processing fluids. This pressure hold strategy will not work however for a SUS Bioreactor since the vessel walls are flexible and typically cannot withstand significant pressures. SUS Bioreactors can however accomplish the same integrity goals as is verified in a traditional pressure hold test, but it will be accomplished with different control strategies than what was used with traditional stainless steel Bioreactors. In the case of a SUS Bioreactor, this might actually begin with bag and component pressure testing performed during assembly when the system was in a state where proper measurements could be obtained. The End User’s Quality systems must ensure that control strategies for SUSs comply with Global Regulations and cGMP requirements. In 2012 the SUS supplier will have a more integral role in executing these strategies.
Please see the PDA Website for news regarding publication of the PDA Technical Report and Workshop on Single Uses Systems. www.pda.org