Bridging Polymer Science to Biotechnology Applications: A Single-Use Technology Conference Report

MeetingPic1-300x132.jpgSingle-use (SU) technology is used more every year throughout the biotechnology industry. As applications now span from cell banking to drug product, that in turn is raising interest in the interaction of extractables with proteins and cells. The second “Single-Use Technologies” conference organized through Engineering Conference International (ECI) was subtitled “Bridging Polymer Science to Biotechnology Applications” and delved into the science of plastics in bioprocessing applications. On 7–10 May 2017 at the Hotel dos Templários in Tomar, Portugal, people from many job functions gathered to share their issues, understanding, and solutions.

The conference was well attended by representatives from end-user organizations; academia; and suppliers of resin, film, single-use components, and gamma irradiation solutions. They participated in positive, scientific, collaborative discussions among different functional areas. This meeting covered a few topics in greater depth that had been addressed at the first such conference in 2015 while expanding discussions to novel technologies such as disposable sensors, bioprocess applications, scale-up issues, and cell/gene therapies. The program included six workshops and six main sessions. Discussions brought appreciation for everyone’s challenges and needs. Representatives from other industries (e.g., medical devices) attended as well. It is imperative that all groups work together collaboratively for SU technology implementation to reach its full potential.

Keynotes: A keynote presentation by Jay Kunzler (research fellow at Dentsply Sirona) demonstrated similarities between the medical device and biopharmaceutical industries and how to leverage lessons learned from use of plastics in other industries. Kunzler emphasized the value of collaborating with suppliers and ensuring that products are free of extractables/leachables to help expedite approval with health authorities.

In another keynote presentation, Manuel Carrondo (director of the Institute of Experimental Biology and Technology in Portugal) painted a picture of how industry and technology have evolved. He also discussed choosing between single-use and stainless steel equipment for applications such as antibody–drug conjugates (ADCs) and for small- or large-volume products.

Preconference Workshops
Polymers and Sterilization: Diane Hahm (technical consultant at DuPont) and Trishna Ray-Chaudhuri (senior associate II in corporate quality product supply administration at Genentech) chaired this preconference workshop. It began with an overview of polymers, common reaction types, and methods used to characterize polymers — including molecular weight and distribution, rheology, and morphology — from Karlheinz Hausmann (R&D fellow at DuPont) a recognized expert on polymers. He detailed the polymers that are most likely to come into direct contact with biopharmaceutical solutions: polyethylene and ethylene copolymers, barrier polymers, and other polymers known for toughness. Finally, he covered additives and their potential migration or interactions with bag contents.

Tiffani Burt (global process platform leader at Sealed Air Corporation) overviewed the extrusion processes used to create films that go into bioprocessing. She provided a clear explanation of extrusion and how subsequent blown or cast processing methods differ.

Susan Burke (senior R&D manager in life sciences at GE Healthcare) reviewed the physical properties to be considered for SU components. She also addressed mechanical properties of polymer films and their influence on handling.

Olivier Vrain (e-beam technical operations manager at Steris AST) gave an excellent overview of sterilization, covering basics such as radiation measurement units and comparing methods. He described three radiation sterilization methods in detail: gamma, electron beam (e-beam), and X-ray. An important consideration is dose distribution for a product in its packaging. For gamma irradiation, the package surface generally receives the maximum dose, whereas e-beam’s highest dose can be just under the surface because of secondary electrons. Determining the minimum and maximum doses is an important part of validating such processes, which also includes process parameters and temperature (both important factors that can influence sterilization). Vrain concluded by highlighting the effects of sterilization on polymers: oxidation, discoloration, crosslinking, and so on. One particularly memorable point is that three polymeric materials are apt to fail: acetal thermoplastics, polypropylene, and polytetrafluoroethylene.

Basics of Biotechnology and Bioprocessing: Gary Lye (professor at University College London) and Qasim Rafiq (senior lecturer and associate professor in bioprocessing of regenerative, cellular, and gene therapies at UCL University College London) chaired this preconference workshop. It opened with Gary Lye’s overview, “Bioprocessing 101: Cells to Proteins, Operations to Processes, Control to Quality.” He began with a primer on key biological concepts, including protein structure and function, how proteins are expressed, different expression systems available, and key analytical techniques used. This provided an essential foundation to set the context for protein therapeutics as the basis of the modern biotechnology industry.

Depending on the product of interest, different expression systems have been used. Traditionally microbes such as Escherichia coli have been used to produce insulin and growth hormones; however, such systems cannot produce more complex proteins that require posttranslational modifications and other expression systems such as mammalian cells. Each expression system offers advantages and disadvantages, and selecting an appropriate system depends on the product (protein) of interest.

Lye overviewed production processes for therapeutic proteins and identified bioreactor (fermentor) platforms for cell expansion with different modes of operation: batch, continuous, and fed-batch. Bioreactor design and engineering are important to cell and protein production, particularly in performance and scale-up considerations. Lye discussed key factors for engineering characterization: the Reynolds number for determining fluid flow (with systems ideally being in the turbulent region), power input, oxygen mass transfer, and shear. He also highlighted key bioprocess parameters such as product titer and impurities as well as environmental and operational conditions (e.g., temperature, pH, and dissolved oxygen). Finally, he reviewed downstream processes for product recovery and purification, featuring the complexity, expense, and loss of yield that come with each recovery and purification step.

Veronica Caravalhal (principal engineer and group leader at Genentech) followed with a presentation that focused on manufacturing therapeutic antibodies and how SU technologies are helping to advance the field. She overviewed cell-line engineering aspects, indicating how ~1,000 clones are investigated at the milliliter scale in microplates before larger scale suspension-adapted cultures of specific
clones of interest. Next she outlined the seed and inoculum train process and demonstrated major challenges with three case studies highlighting the impact of raw materials, equipment, and scale. Finally, she compared stainless steel and SU bioreactors, with major advantages of the latter being flexibility, fast set-up, and reduced cleaning validation requirements. Significant challenges of the technology include assessment of extractables/leachables, ensuring sustainability of supply, and standardization of components. Caravalhal concluded with examples of how Genentech has integrated SU technologies for certain applications, particularly bioreactors and disposable downstream equipment such as tangential-flow filtration (TFF) and chromatography systems.

Qasim Rafiq delivered the final presentation of this session. He began by outlining how the emerging area of cell and gene therapies (CGTs) is developing into a fully fledged industry with recent product approvals, clinical successes, and increasing commercial investment. Rafiq outlined differences between traditional bioprocessing of proteins and of living cells as therapies; namely, the challenges of maintaining cell quality throughout, the anchorage-dependent nature of many CGT candidates, and the challenge of variation (particularly for patient-specific therapies).

Next, he segued into the two main manufacturing paradigms of CGTs: autologous (patient-specific) and allogeneic (universal donor), the former requiring new manufacturing and business models. Rafiq described bioprocesses for both manufacturing paradigms before highlighting the critical role that SU technologies play in CGT manufacture with examples of systems that included the Xuri cell-expansion system (GE Healthcare), ambr microbioreactor system (Sartorius Stedim Biotech), and CliniMACS Prodigy platform (Miltenyi Biotec). Rafiq concluded that CGT production never will involve reusable platforms, especially for patient-specific therapies, and standardization of SU platforms could ensure consistency of CGT manufacturing.

Main Conference Sessions
Properties of Polymers As Applicable to Biopharmaceutical Manufacturing: Magali Barbaroux (vice president of R&D for fluid management technologies at Sartorius Stedim Biotech) and Sheryl Kane (principal engineer in materials science at Amgen) chaired this session. The final form, fit, and function of a plastic part is determined by the polymer family and formulation (including additive packages), the polymer processing equipment, and the sterilization method. All three must be considered in design and qualification of a plastic component. The most thorough validation of polymers makes sense only with the appropriate control of variability through all processing steps. That makes openness, transparency, trust, and partnerships among all stakeholders (from polymer supplier to converters, SU system manufacturers, sterilizers, and end users) mandatory for disposables adoption in biopharmaceutical applications.

Continuing to share knowledge about polymers, processing, and sterilization methods, this session integrated an example of practices in other industries. Talks, posters, and open discussions confirmed the willingness of all key players to collaborate, and some of their key learnings follow.

The needs of a bioprocess bag can’t be met by a single polymer. The multiple polymers in a single film often are adhered in a melted state using tie layers typically made of a matrix resin that has been functionalized to optimize bonding at the interfaces of noncompatible materials. Tie layers often are miscible with one film layer and can form chemical bonds with the adjacent layer. As critical film components, tie-layer materials must be considered along with other polymers that constitute multilayer films when designing and testing the film structure.

A knowledge gap exists between supplier and end-user specifications and standards regarding gels in films for SU systems. Attendees discussed the mechanisms of gel formation and black specks, focusing on how to minimize their presence in films. Before specifications are set, the impact of gels and other film imperfections must be assessed — especially because a trade-off has to be made between additives content and gel formation. Specifications should take into account the risks that gels and other imperfections impose on a process (the possibility of leaks) and product (potential introduction of impurities).

Recent experimental data obtained using different techniques and scrutinized by chemometrics have showed that within the dose range of 30–50 kGy, gamma irradiation has almost no impact on the structural, surface, and core properties of a commercially available film (S80). Formation of radicals does yield discoloring molecular species and acid release, sometimes observed in gamma-irradiated SU systems, but that can’t explain oxidation of proteins. Interaction between gamma irradiation and plastic materials remains a topic of interest for further investigation.

Rapid prototyping technology (widely used in the plastic industry) can be applied to SU bioreactors for faster time to market and reduced cost. This technology is perfectly adapted to process development, but implementation is limited by the availability of materials suitable for bioprocess applications (for regulatory compliance and stability after gamma irradiation).

Designers need to make their products fit for their anticipated use, especially with regulatory status of bioprocess plastics focused on a “risk-based” approach rather than a pure “quality” focus. Overengineering this new approach provides a false sense of advanced understanding. The most thorough validation of polymers makes sense only with appropriate variability control in formulation and processing conditions.

Although this session focused on common SU system applications (e.g., bags and bioreactors), emerging technologies such as sensors and applications such as regenerative medicine may require new polymers and/or different processing techniques for commercial acceptance and success. Collaborative partnerships and lessons learned by makers of SU systems can help to overcome these future challenges.

The Infamous Extractables and Leachables (E&L): Xueyuan Wang (principal project specialist at Bayer Healthcare) and Isabelle Uettwiller (regulatory affairs director and head of the validation laboratory at Sartorius Stedim Biotech) chaired this session. It focused on knowledge gained over time with new procedures, resin manufacturer perspectives on E&L, and modeling extractables throughout a bioprocess. Presentations showed results and challenges of suppliers implementing new standard testing methods, how resin manufacturers develop better understanding to meet customer needs, and how new E&L studies/results can be used to facilitate implementation.

Armin Hauk (lead R&D scientist at Sartorius Stedim Biotech) focused on the fate of leachables and ways to predict their concentration by modeling extractables throughout dynamic bioprocess steps. Hauk’s model takes process conditions, diffusion-controlled leachables, adsorption and desorption processes, filtration/purification steps, and other process parameters into account.

James Hathcock (senior director of regulatory and validation consulting at Pall) compared test protocols of the US Pharmacopeia and the BioPhorum Operations Group (BPOG). He focused on testing results of filter capsules and lessons learned when adopting the BPOG protocol. Those results could improve end-users’ understanding of extractable profiles under different testing conditions.

Jérôme Vachon (lead scientist at SABIC) shared the experience of a polymer producer in supporting customer E&L needs. He presented extractables study results of three different resins and how their profiles change according to test parameters and sterilization methods. Collaboration among resin manufacturers, tubing/film manufacturers, and integrators could help end users to implement SUT and relieve the concerns of regulatory agencies.

Christian Julien (director of pharma process solutions at Meissner Filtration Products) presented extractables results from a biocontainer film based on BPOG protocols and compared them with previous results. The outcomes of this study could promote understanding of extractable profiles and different testing protocols.

Sensors and Their Integrations and Use with Single-Use Technology: Martina Micheletti (senior lecturer at University College London) and Torsten Mayr (associate professor of analytical chemistry at Graz University of Technology) chaired this session. They sought discussion of the potential for traditional sensor technologies to be converted into reliable and robust SU versions. Can recent developments in accuracy of small-scale sensors and microfluidics be adapted to work with SU bags, and for which operations would they be suitable?

The session started with Martin Smolka (materials scientist at the Joanneum Research Institute for Surface Technologies and Photonics) presenting on roll-to-roll manufacturing methods of large-scale sheets of polymer film with precise characteristics. He presented two applications of the technology: an in vitro diagnostic chip for chemiluminescence detection and a high-throughput drug screening plate for neuron imaging.

Torsten Mayr offered an example of optical chemical sensors and described how they can be developed to measure oxygen concentration and pH. He showed results from cell culture applications and ended with a snapshot of a new luminescent-nanobead technology for rapid pH measurements.

Thomas Nacke (of the Institute for Bioprocessing and Analytical Measurement Techniques in Germany) presented sensor technology based on the change of dielectric properties such as conductivity at microwave frequencies. Such sensors can be integrated into SU bags by clamping them to tubing or installing them on the outer surface of a bag. Used to measure conductivity during E. coli bacterial growth, this type of sensor helped users correctly predict growth profiles.

John Carvell (director of Aber Instruments) presented an impedance probe for online detection of viable biomass concentration. He also discussed challenges encountered in integrating the probe within stirred and rocked SU bioreactors and described the journey to commercialization.

Interaction of Plastic with Cells/Proteins: Susan Burke (senior manager of life-sciences R&D at GE Healthcare) and Weibing Ding (principal scientist in process development at Amgen) chaired this session, touching on protein interactions with plastic surfaces and the impact of extractables on proteins and cells.

Dan Nicolau (professor and chair of the bioengineering department at McGill University) described factors affecting the compatibility of proteins with plastic surfaces. His team has established a database of biomolecular adsorption information that can be used to assess potential interactions. To understand the potential for changes in the solution concentration of proteins, it is important to evaluate how they interact with plastic components in SU systems. Nicolau also discussed the impact of extractable compounds on protein structure and the health of cell cultures. As SU adoption grows, we continue to learn about the impact of such materials on biopharmaceutical systems.

Matthew Hammond (principal materials and polymer scientist at Amgen) presented a case study on protein degradation found to occur with storage in a SU bioprocess container. Studies led to the conclusion that hyperperoxide extractables from the plastic film were responsible for protein cleavage. Those compounds are formed by gamma irradiation of the container. So concerns regarding extractables are not limited to SU bags and assemblies.

Zara Melkoumian (senior bioprocess technology manager at Corning Life Sciences) continued discussion from her 2015 presentation about the root cause for low cell growth in polycarbonate shaker flasks with certain sensitive Chinese hamster ovary (CHO) cell lines. Growth was hindered by an extractable compound 3,5-dinitro bisphenol A formed during a high-temperature molding process in combination with gamma irradiation. The takeaway from Melkoumian’s work is the need for further understanding of how plastic processing and gamma irradiation affect the chemistry of plastics and how that in turn affects proteins and cell cultures.

Challenges of Scale-Up of Single-Use Systems: Andre Pastor (senior expert at Bayer) and Simone Biel (field marketer for single-use technology at Merck) chaired this session focused on challenges encountered during scale-up of SU systems. Case studies presented here investigated the rheology of different types of SU bioreactors. Key questions were addressed: What is the best mixing type to ensure the best supply of nutrients (including oxygen) in a homogenous cell culture without creating detrimental shear or other stress factors? Once established at small scale, how do we best translate a process to manufacturing scale?

Valentin Jossen (research associate at the Zürich University of Applied Sciences) investigated the expansion of human adipose-tissue–derived stromal/stem cells (hASCs) on microcarriers in a wave-mixed SU bioreactor with one-dimensional motion. Computational fluid dynamics (CFD) modeling was verified by particle image velocimetry (PIV) measurements. The results help standardize microcarrier-based production processes with improved understanding of parameter-dependent hydrodynamic stress and optimal rocking angle and rate combinations that won’t change stem cell characteristics.

Marco Rotondi (development engineer/scientist in biotechnology applications at Aston University, UK) presented a similar approach using a cylindrical container and stirring–mixing technology (the automated ambr250 platform). CFD prediction of microcarrier-based processes for the culture of adherent cells were comparable to these experimental results, enabling optimization of cell growth performance and scalability with improvement of bioreactor geometry. “Which type of bioreactor is now best applicable for which cell culture fermentation,” Rotondi asked, “rocked, stirred, or orbital shaken?”

Martina Micheletti (senior lecturer at University College London) compared mixing and fluid dynamics characteristics of a 2-L cylindrical, orbitally shaken CultiBag bioreactor (Sartorius Stedim Biotech) with conical bottoms of different heights and a 3-L Cell Ready stirred-tank reactor (Millipore Sigma). Phase-resolved PIV and high-frequency visual fluid tracking were used to investigate mixing characteristics. Cell culture performance effects were investigated using a GS-CHO cell line and measurement of recombinant protein productivity. Micheletti discussed how the results could be used to improve scaling methodologies.

Many SU container shapes and mixing technologies have been developed. However, all CFD and experimental data presented showed that more flexibility in the geometry of SU bioreactors is needed to optimize cell culture performance. SU system suppliers should investigate further using such data to develop new bioreactors best fit for their intended purpose.

Advances in Application of Single-Use Technology: Peter Neubauer (professor of bioprocess technology at Technische Universität Berlin) and Sara Ullsten (R&D section manager at GE Healthcare) chaired this session showing how disposables have been implemented in new areas and how technological advances can advance them further. Dana Olson (purification development engineer II at Genentech) discussed how disposables have been implemented in antibody-conjugation processes, particularly offering advantages in operator safety with highly toxic small molecules. Gary Lye highlighted the advantages of SU technologies for very small batch sizes (e.g., with patient-specific therapies).

Technical  advancements were presented in two talks: Stefan Junne (scientific assistant and chair of bioprocess engineering at Technical University of Berlin) presented on improved rocking motion of bioreactors, and Alexander Groβ (principal investigator of microreaction technologies at Technical University Ilmenau) gave a futuristic presentation of droplet-based microfluidics.

GMP Requirements for Single Use: Ganesh Vissvesvaran (senior manager at Genentech) chaired this workshop on standardization of good manufacturing process (GMP) requirements, flexibility in SU components, and selection and specification of equipment. Participants divided into three rotating groups to discuss three questions for 20 minutes each: current gaps in standardization, a quality approach to GMP implementation of SU technology, and a GMP inspector’s view of SU systems.

Key technology gaps were identified in implementation of disposables for harvest and purification processes, primarily driven by financial and timeline perspectives. The impact of gamma sterilization also is emerging as a significant topic for study. Adoption of SU systems would be facilitated further by development of scale-down models and better control of manufacturing processes for SU components through clear definition of critical quality attributes (CQAs).

There was broad consensus that comparability between single-use and stainless steel systems must be driven by risk assessment and functional specifications. Traditional validation requirements for stainless steel equipment may not apply directly to disposable systems. On the regulatory front, a major concern was the ability to question certificate of analysis (CofA) results provided by suppliers. The final accountability for SU components rests with end users. The concept put forth of a “global regulator” could lead to standardization of requirements and fewer audits.

Enabling Needs to Support Single-Use Adoption: Hana Sheikh (MSAT engineer II at Genentech) chaired this workshop, which covered a number of topics, including training needs, integrity testing, particulates, and shipping drug-substance bags.

Training in industry focuses on bringing in new technologies and determining how end users can collaborate with suppliers and academia to develop good training guides. It was discussed whether industry needs “new biotechnologists” who are familiar with fabrication methods, selection, and implementation of SU systems. “Should we redesign our bachelor studies in the long run?” academics asked. “How do we train users with the materials without inflating costs?”

Regarding integrity testing — Which unit operations and assembly types require preuse/postuse testing? — groups discussed what it included and whether it was application, risk, or occurrence driven. Participants considered different methods such as pressure decay and helium along with the impact of testing on SU components (especially films).

Particulates continues to be an area for concern. Discussion focused on how to set limits, quality requirements driving those, and whether requirements differ according to application. Was there correlation between protein aggregation and particulates?

Interest is increasing for use of disposable bags in shipping. Considerations include enabling use of flexible or rigid containers at low temperatures and demonstration of shipping processes.

Discussion Questions: “What is preventing your site from implementing end-to-end SU processing?” Discussion focused on gaps in unit operations, dependency on scale for implementation, business cases, and perceptions and realities of risk.

“What are challenges or advantages of implementing the ballroom concept?” Some challenges include definition of the concept to achieve closed processing, influencing the regulatory mindset (future-state room classification and process segregation), reliability of aseptic connections (risk of contamination, errors, and so on). Some advantages include distributed manufacturing, flexibility, reduced costs and footprint, and multiproduct facility flexibility.

“What hurdles do people see for implementing new technologies?” Participants focused on costs (investment, validation, approval risks) of implementing commercial products, concerns for emerging markets (e.g., local support, regulators, and so on), and implementing disposables for legacy products (reapproval risks, batch-size concerns, change reports, and so on).

Emerging Application in Single Use: Michael Goodwin (R&D director at Thermo Fisher Scientific) chaired this workshop, which touched on cell/gene therapies, continuous processing, process analytical technology (PAT), and antibody conjugation.

The personalized medicine pipeline (cell/gene therapies) is growing rapidly, with an estimated >300 products in development today defining a US$2 billion market over the next 7–10 years. Significant process work will be required to develop a simple, closed, automated SU workflow. Patient variability and quality-release testing, system standardization, and training programs will need to be considered by therapeutic companies and their respective supply chains.

Continuous processing (CP) is used in many industries; however, biomanufacturing processes typically run in batch or fed-batch mode. Some benefits of CP are smaller manufacturing footprints, continuous product quality, reduced validation (fewer steps), and lowered environmental impact. Suitability across product platforms could be in question, however. Challenges include lot definition and control, E&L questions with longer processing times, sterility assurance throughout processes, increased media costs, and the forensics of failure analysis. Workshop participants said that improved in-situ sensors, truly sterile connectors for interoperational connectivity, and improved regulatory guidance would facilitate adoption of CP.

Regulators encourage PAT implementation to help industry characterize and control processes to improve quality, drug efficacy, and productivity. Participants pointed to a great need for standardized sensors/controls in the following areas: workflow design integration, software and user interfaces, signal types, calibration, and validation protocols. Sensor development is needed to address gaps in monitoring metabolites (e.g., glucose, lactate, and glutamine) over a broad pH range (2–11), contamination effects, widened flow ranges, plug-and-play operations, shorter response times, and scaling from benchtop to production.

Finally, the benefits of implementing SU technologies into antibodyconjugation processes are similar to those for other bioprocess workflows: lowered risk of contamination and capital expenditures, shortened time to market, and reduced cleaning requirements and manufacturing footprints. Key challenges include hazardous organic solvent chemical materials compatibility and handling, process scalability, packaging/shipment validation considerations, and a lack of regulatory standards specific to this application.

Environmental Impact of Single Use Technologies: Ross Acucena (ReadyToProcess product strategy manager at GE Healthcare) chaired this workshop, which acknowledged the current state of affairs while hosting open discussion of how to continue minimizing the environmental impact of bioprocessing with disposable systems. The forum included a cross section of participants from academia, end users, and suppliers. They discussed best-practice considerations for minimizing the environmental impact from use and disposal of SU systems. The forum aligned on several approaches and efforts that tip the needle toward improved sustainability.

  • Increasing titers and downstream efficiencies can reduce processing volumes and allow for smaller SU vessels and systems (and therefore less waste per therapeutic dose).

  • Design of SU packaging in monomaterials would support easier and more efficient recycling. Because packaging does not come into contactwith biomanufacturing processes, such materials are easier to recycle.

  • Increased packaging density will improve environmental impacts for distribution of SU systems from suppliers to end users.

  • Reduction of landfill volume through compression/palletization are favorable if landfill is the end-of-life destination of these materials.

  • Opportunistic (GMP-compliant) reuse could apply to some SU systems. For example, an emptied fluid-storage container could serve as a waste vessel from another process, thereby reducing waste.

  • Improvements in material management would reduce material scrap resulting from expiry of shelf life.

  • Recycling programs could enable second uses, such as the industrial example of drums and totes being repurposed for playground material (benches and synthetic cushioning mulch).

  • Outreach and education of best practices can come from consortia and industry organizations such as the Bio-Process Systems Alliance (BPSA) and BPOG.

  • Truly closed systems could enable operation of processes in “grey space” (the ballroom approach) for favorable trade-offs in air handling, facility cleaning, water use, and so on.

  • Biodegradable materials that could maintain compatibility and low extraction profiles for end users would shift the end-of-life impact of SU systems in a more favorable direction.

  • Additive manufacturing could progress to the point at which materials such as membranes cast in solvents could be printed without generating waste for a net-zero mass balance.

  • Lower gamma-radiation dose materials — for not sterile, but “bioburden controlled” operations — could tilt the impact of sterilization in a more favorable direction.

Workshop participants discussed where in the decision-making process the factors above could be considered for the best outcomes. Some salient points captured were cost savings and lean initiatives and system-design considerations such as balancing flexibility and sustainability (e.g., having a second filter line that might never be used or having additional footage of unneeded tubing or numbers of bags). Driving toward future improvements will require more emphasis from industry placing value on sustainability aspects of SU technology; today, price and quality are paramount, with sustainability a tertiary consideration. During the workshop, end-user participants voiced their opinions that the supplier community should be more active in this space with better plans, systems, procedures, recommendations, and consultation to ensure optimal end-of-life decisions are made for their products and systems.

Looking Ahead
Subtitled “Scientific and Technological Advancements,” the third ECI conference on plastic properties (in Snowbird, UT, 23–26 September 2018) focuses on informing the community about polymer opportunities and limitations. Other topics include recent studies of polymer interactions with biopharmaceutical fluids and information on emerging technologies that enable continuous processing, improved sensing/process control, and additional applications. As always, benchmarking against best practices coming from other industries remains a critical activity and a highlight of this meeting. The fourth installment in this series will take place in Europe during the spring of 2020.

Further Reading
Here are some resources for discussion about the environmental impact of SU technologies:

Farrell M. Partner Spotlight: Millipore Sigma and Biopharma Recycling. Environmental Health and Safety Blog. 10 July 2017;

Flanagan B. Single-Use Technology and Sustainability: GE Quantifies the Environmental Impact. BioProcess Online 2017:

Sustainability Reporting Database. Global Reporting Initiative, 2016:

Whitford W, Petrich MA. SUStainability — Concerning Single-Use Systems and the Environment. BioProcess Int. eBook June 2018;

Corresponding author Ekta Mahajan is director of the technical regulatory program in process development engineering at Genentech (a member of the Roche group) in South San Francisco, CA; [email protected]. Gary Lye is head of the department of biochemical engineering at University College London in the United Kingdom. Regine Eibl-Schindler is a lecturer for biotechnology and cell cultivation techniques and head PBT of the Institute of Molecular Life Sciences at the Zürich University of Applied Sciences in Switzerland.

Find more details about the conference program in the online-archived version of this article at

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