Engineering Commons^™

Interchangeability Of Sus - Functional Specification And Materials Of Construction, Chris Smalley

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Functionally equivalent substitution of an alternate supplier of a Single Use Component for an existing Single Use design provides a business contingency, or a process improvement, with equivalent performance and product quality. As an end-user, we are responsible for assessing the quality requirements to assure that the specifications are being met. This presentation will discuss the need for standards for designs and points to consider when implementing a Single Use Strategy that incorporates the potential for interchangeability

Large Scale Freeze-Thaw Bag System For Protein Bulk Storage: Prototypes Development, Phillippe Lam

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Freezing of large quantities of protein bulk has generally been handled using “freeze-thaw vessels”, which are essentially jacketed metal tanks with additional cooling surface provided by internal coil and fin assemblies. With the recent industry push towards using disposables, it is desirable to explore disposable technology alternatives to costly freeze-thaw vessels. In this presentation we discuss our approach at designing and testing of first and second generation prototypes for a large bag freezing system developed in-house. The system, which is compatible with our existing and commercially available freeze-thaw skids, can handle 300 L of bulk at a time. Our approach …

Particulates Reduction Efforts In Single Use Technologies: A Case Study, Klaus Wormuth, Royce Brockett, Mathieu Labedan

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Single use technologies require a close collaboration between supplier and end-user with regards to cleanliness issues, primarily focused on particulate contamination. Since a large percentage of drug recalls relate to particulate contamination, and detection of a single visible particle in a dose of injectable drug is considered a critical issue and thus causes significant time and money to remedy, reduction of risk related to particulate contamination is of highest priority. Particulate detection is challenging in single use systems due to the complexity of the devices. As this presentation will show, concerted efforts to reduce particulate generation at all steps of …

Appraisal Of The Mixing Performance Of Single-Use Shaken Bioreactors, Gregorio Rodriguez, Tibor Anderlei, Andrea Ducci, Martina Micheleti

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The pharmaceutical industry is at the forefront of the production of antibodies using mammalian cell-based cultures, with single-use technologies gaining prominence in the manufacturing process. At laboratory scale mammalian cells are usually grown in low shear devices, with disposable shaken bioreactors being largely employed in the early stages of bioprocess development. It has been a recent industry trend to use shaken bioreactors at large scale in the upstream process, performing cell culture in single-use bags which eliminate the need for cleaning in place, offer flexibility and lower production down-times. Single-use Orbitally Shaken Bioreactors (OSRs) consist of a shaker, a structural …

Integration Considerations For Replacing Stainless Steel Tanks With Single-Use Mixers, Hana Sheikh

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

There is an increased interest in single use technology in the biotechnology industry. The first integration of single use technology in traditional facilities may come with many growing pains during implementation. There are challenges in meeting the demands of end users and the changes to standard operating procedures and processes. By replacing stainless steel tanks with single use mixers, there can be a significant change to operations such as: sampling, pool hold, mixing, additions, and pool transfer. Through thoughtful design of the single-use mixers many of these changes to operations can be managed and integrated seamlessly into the processes. In …

An Approach To Evaluate New Single-Use Film Types, Katharina Blasckczok, Lidija Lisica, Regine Eibl

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

During the last decade, single-use bioreactors or storage vessels made of flexible bags have been well-established in biopharmaceutical production. However, some developers and producers of biopharmaceuticals refuse their usage because of potential interactions of the plastic material with cells and proteins. Most dreaded apart from extractables are leachables (such as bDtBPP [1]), that derive from additives and are formed during the bag manufacturing process or gamma sterilization. Leachables can migrate from the film contact layer into the process fluid under process conditions and can inhibit cell growth or impair product quality. A further reason for cell growth limitations can be …

Flexural Fatigue Behavior Of Rocking Bioreactor Films, Donald Buckley, K. Amanda Misner, Terry Saunders, Andrew Burns, Hongyi Zhou, Eugene Boden, Susan Burke, Ross Acucena, Mark Roberts

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The fields of biopharmaceutical processing and cell therapy are adopting single-use, closed systems throughout their workflows to enhance sterility, minimize waste wash effluent and enable manufacturing flexibility compared to traditional stainless steel bioreactors. One of the key single-use technologies in use is the rocking bioreactor, comprising a polymer film bag (outfitted with ports and sensors) mounted to a tray capable of mixing the contents of the bag and a control system (controlling temperature, agitation, and potentially media perfusion).

One of the challenges encountered in rocking bioreactor bags is the fact that upon inflation/filling with media, the originally flat bioreactor bags …

Preventing Leaks In A Single Use System, Trishna Ray-Chaudhuri

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Assurance of the integrity of a single use system is important to ensure process fluids are contained and to limit the potential for a sterility breach. This discussion will describe an approach for the technical assessment of single use systems (SUS) for a specific biopharmaceutical process step. The presentation considers the key properties that need to be evaluated to ensure the integral components of a single use assembly are able to meet the performance attributes for the process step.

Understanding the polymer properties associated with the plastic materials used in single use system (SUS) ensures that the system will be …

An Investigational Study On The Impact Of An Incopatible Filtration Of Benzyl Alcohol Using A Polyethersulfone Membrane, Michael Difiore

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Chemical compatibility of a process stream with a disposable component is a critical element of determining the suitability of the single-use system. Chemical compatibility is often a collection of data on the physical interactions of a disposable with a solution, including but not limited to filter integrity, membrane swelling, and hardware deformations. Compatibility conditions recommended by the disposable manufacturer such as solvent concentration, temperature, and contact time should be compared to actual process use conditions. An incompatible filtration operation can impact the integrity of the filter, in addition to introducing material-derived impurities to a process stream that may not be …

Monitoring Clearance Of Extractables And Leachables From Single-Use Technologies By Nmr, Nicholas Margarian, Kate Lee, Kunal Nagpal, Ken Skidmore

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Process validation at Genentech requires NMR methods capable of detecting and reliably quantifying trace levels of process impurities and leachables. Measurements must be done in solutions which are far from ideal for NMR. Depending on the application, high protein and buffer concentrations, along with the presence of water, necessitate an approach to NMR measurements and data interpretation which differs greatly from traditional NMR methods. Here, we show how we deal with these complications, and how our methods may be applied to measuring the concentrations of leachables from single-use products.

Hazard And Risk Assessments For Impurities, Residual Solvents, Extractables, And Leachables., Jan Oberdoerster

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

During their life-cycle (i.e., manufacture to end-use), single-use products in the biotechnology industry come in contact with processing equipment, packaging components, and delivery systems. Small amounts of chemicals that may transfer to the single-use product at any step in the life-cycle may subsequently leach into the pharmaceutical drug product and be delivered to the patient along with the dose. It is important that this chemical transfer does not occur in quantities that alter the safety, identity, strength or quality of the drug product. The assessment of potential leachable chemicals begins with a detailed analysis of compounds released from the single-use …

Container Closure Integrity (Cci) For Single-Use Systems (Sus): Regulatory Trends, Challenges And Technology Transfer Of Test Methods, Carole Langlois, Marc Horeve

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Single-use fluid management solutions are being applied in critical downstream and final filling applications including applications requiring container closure integrity testing. Single-use bags are increasingly used for the storage, mixing, shipping, freezing of drug substances and drug products. Since single use bags are migrating towards more critical process steps and applications, there is a growing regulatory scrutiny and industry requirement for testing the containers in order to guarantee their integrity and their sterility before their use in commercial production processes.

This presentation will consider the regulatory trends for Container Closure Integrity of single-use systems with a focus on the proposed …

Single Use Sensors: Sensing A Need For Change, David Pollard

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Single use sensors are vital for the advancement of bioprocess monitoring and control. The application of process analytical technology is gaining momentum to drive process control and improve process consistency. The data is being combined into MVDA parametric models to apply real time release strategies with the intent to reduce the QC burden. Progress has been hindered by inadequate sensing tools that struggle to meet the user requirements. End users have resorted to using conventional probes via insertion ports with separate steam sterilization. Some of the existing single use sensor offerings have been plagued with inaccuracy , drift and reliability …

Silicone Tubing Extractables And Their Relationship To Particulates, Csilla Kollar

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Extractables and particulates information of single-use components including tubing is one of the primary considerations for their selection for pharmaceutical applications. The information is used to assess risk to patient safety, product compatibility, process performance and demonstrate due diligence to regulatory agencies. Many factors need to be considered in the extractables study design such as solvent choice, testing conditions including time, temperature and agitation, surface area to volume ratio, wall thickness, selection of analytical techniques, detection/quantitation limits, and expression of results. Studies must be performed under similar conditions that reflect those that can be encountered during use.

We have been …

Polyolefins And Their Influence On Single Use Technology For Bioprocessing, Amy Plancon, Marnik Vaes

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The presentation will focus on polyolefins and their use in single use systems for bioprocessing and the manufacture of biologic drugs. The nature of polyethylene and polypropylene will be explored, as well as material properties and how those properties can be influenced by the polymer manufacturer to meet specific needs in the market. This influence might include the introduction of additives, the substitution of specific ingredients, and the promotion/development of particular processing conditions. The impact of antioxidants will be presented, along with an overview of extractables and leachables protocol as they relate to the polyolefin family.

Approach To Biomaterials Selection Using A Risk-Based Approach, Patricia Rafidison

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Global source of materials for Healthcare applications continues to attract industry attention and regulators’ scrutiny, mainly due to the nature of the supply chain and its complexity, calling for more traceability, security, and reliability. Therefore, it becomes critical, when choosing a biomaterial, to use a risk based approach when assessing its function and intended use prior to its qualification. Key risk elements are to be identified, assessed and documented to obtain a reliable product performance and safety profile. A rigorous material qualification plan, based on science, a controlled quality system as well as a change control mechanism are to be …

Headache Be Gone: Clearance Of Extractables And Leachables In Single-Use Technologies Through Ultrafiltration/Diafiltration, Kate Lee, Nicholas Magarian, Kunal Nagpal, Ekta Mahajan, Kenneth Skidmore

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Application of single-use technologies in biopharmaceutical manufacturing can be driven by several factors such as reduced capital costs, reduced risk of cross-contamination, increased process flexibility, and reduced cleaning validation. However, implementation of single-use technologies have been restricted due to a number of concerns, with the most commonly cited being the presence of extractables and leachables (E/L) from single-use technologies. In general, overly conservative estimates of E/L are used in the risk assessment due to lack of data on clearance, resulting in a time-consuming, costly, and extensive E/L assessment for single-use technologies.

A proof-of-concept study is presented here to simplify these …

Overview Of The Links Between Material Properties And Film Extrusion Process, Ralf Reiser, Stefan Jendrosch, Ingo Schnellenbach

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Ensuring a good product requires specifically a combination of selected parameters covering materials, processes & controls / testing. This presentation will show how these concerted activities lead to deliver a good film matching the application needs in Biotechnology applications

Material properties: Bags are formed out of a plastic film by different sealing technologies, using heat, ultrasonic sound or electric fields. Key critical parameters vary from sealability, mechanical & barrier properties, leachables & extractables, surface specification, melt flow properties, gel count, transparency …

Process + Machine: Extrusion or lamination processes have some technical limitations and machines most relevant topics …

Case Study: Identification, Characterization And Mitigation Of Growth Inhibitory Leachable Compound From Disposable Plastic Vessels, Zara Melkounian

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The inhibition of CHO cell growth was observed in culture medium incubated in disposable plastic vessel, but not in a control glass vessel. Gamma irradiation of vessels during terminal sterilization step was required to produce the growth inhibitory leachable, as unsterilized vessels showed no inhibition of cell growth. Also, the growth inhibition was cell line specific in that some CHO cells were more sensitive than others, and some were not sensitive at all.

Using chromatographic and spectroscopic methods we were able to identify and characterize a single leachable responsible for this growth inhibition in some CHO cells. By understanding the …

Wakey Wakey Sleepyhead- A Case Study In Adapting Single Use Bioreactors To A Sensitive Cell Line, Ganesh Prasadh Vissvesvaran

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Single Use Bioreactors have been in vogue for almost a decade. Characterization of films and adaptation of bioreactor preparation to accommodate sensitive cell lines is still a challenge and our Industry continues to invest in analytical technology for root cause analysis. This effort, in turn, can result in more stringent requirements that can be levied as part of new film/bioreactor qualification. The case study presented here details the challenges posed by a sensitive cell line, root cause assessment, interim and long term solutions.

Final Program, Ekta Mahajan, Gary Lye

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

No abstract provided.

Characterizing Changes In Protein Quality Attributes To Assess Leachable Risks From Single-Use Bioprocess Containers, Nina Xiao, Colin Medley, Ian Shieh, Gregory Downing, Ankit Patel, Shelly Pizarro, Jun Liu

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Leachables from bioprocess containers (BPCs) are a source of process-related impurities that have the potential to alter product quality and impact patient health. The leachables often exist at low concentrations that are difficult to detect and assess their impact on quality attributes (QA) of biotherapeutics stored in the BPCs. This study examines two monoclonal antibodies in a small-scale stressed model to detect and assess the presence of relevant BPC leachables by monitoring protein QA. The results from this study demonstrate that the stress model can inform a risk assessment of leachables on protein QA during routine manufacturing and assist in …

Limitation And Detection Of Bis(2,4-Di-Tert-Butylphenyl)Phosphate (Bdtbpp) From Bioprocess Container Materials, Samuel Dorey, Ina Pahl, Isabelle Uettwiller, Sebastien Janvier, Elke Jurkiewicz

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The identification of the bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP) by Hammond et al was a key to understand the detrimental effect on cell growth that may occur in single use systems composed of polyethylene. The growth inhibition depends on the concentration and cell line, while known standard cytotoxicity assays (i.e. USP<87>) are insensitive to the levels shown to have detrimental effects. There is therefore no universal standardized cell growth testing allowing determining an absolute quantitative concentration detrimental to all specific cell lines. The most sensitive cells lines tested showed a dose response that challenges the limit of detection of …

Thermodynamics Of Migration In Polymers: Can Contamination From Materials In Contact Be Predicted, Controlled And Possibly Avoided?, Olivier Vitrac, Phuong Nguyen

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The contamination from materials is coined as “migration” and refers to a combination of various mass transfer mechanisms under thermodynamic control: molecular or mutual diffusion, sorption and desorption phenomena linear with concentration or not. The contamination pathways are particularly complicated when they involve several components or steps and strong interactions between materials and the medium in contact. They have been studied and mathematically described with two possible purposes: i) simplified approaches with a goal of overestimating the real contamination and ii) more sophisticated approaches to optimize the design of polymer materials, packaging materials or to redesign plastic additives with lower …

Impact Of A Toxic Single-Use Bio-Process Container Film Leachable On Chinese Hamster Ovary Cells, Heather Nunn, Matthew Hammond

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

A high-throughput cell-based assay (HT-CBA) was developed to investigate the impacts of the polymer films used to construct single-use bio-processing equipment such as bio-process containers (BPCs) and single-use bioreactors (SUBs) on the growth and health of Chinese hamster ovary (CHO) cells. Cell growth media were incubated in BPCs constructed from several different films, and the media thus treated was used to culture CHO cells in 24 deep-well plates. Multiple films negatively impacted culture growth and viability. The compound bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP) which leaches at low levels from these films was shown to be highly detrimental to cell growth. The toxic compound …

The Effects Of Irradiation Technologies On Some Polymers Commonly Used In Suds, Olivier Vrain

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Both gamma ray and electron beam irradiation are widely used as a means of medical device sterilisation. However, it is known that the radiation produced by both processes can lead to undesirable changes within biomedical polymers.

This presentation will aim to explain the collaboration between a steriliser contractor and a university to carry out some comparative study on the two key radio-sterilisation methods (gamma ray and electron beam) in order to identify the more detrimental process in terms of the mechanical, structural, chemical and thermal properties of a common biomedical grade polymer, Poly (ether-block-amide) (PEBA).

Therefore, this presentation will have …

Application Of Bpog Standardized Extractables Protocol To Container Films: The Impact Of Different Sample Conditions And Analytical Procedures On E&L Profile, Mohamad Awada

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The E&L profile of Single-Use-Systems (SUS) include base polymers, additives, processing aids, and degradants that could potentially migrate from the container materials to contact solvents. Different conditions (such as temperature, surface area to volume ratio, dynamic/static incubation, and solvents) could produce different E&L profiles. In order to mitigate this problem, the BPOG Extractables Work Group has recently published a standardized extractables protocol recommendation in the form of a white paper (1) that defines sample conditions and analytical procedures for extractable testing.

This presentation will discuss the E&L container film results of an undergoing study preformed following BPOG guidelines compared to …