Engineering Commons^™

Identification Of Antioxidant By-Products Based On Their Specific Chemistry And Their Potential Detection During Sus Extractable Study, Samuel Dorey, Fanny Gaston, Nathalie Dupuy, Sylvain Marque, Gerard Audran

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Single-use films in biopharmaceutical and biotechnology industries are mainly made from polymers such as PE, EVA and EVOH. Depending upon the environmental aggressiveness during various stages of the polymer lifetime, additives are added to protect them such as substituted hindered phenols acting as antioxidants, melt (processing) stabilizers, and to some extent as photo-antioxidants.

Ionizing radiation effects on polymers have been widely investigated. They consist mainly of free radicals production. These free radicals can in turn lead to degradation and or crosslinking phenomena (release of gases, discoloration, changes in mechanical properties and gas permeability, degradation and leaching of polymer additives into …

Implementation And Characterization Of Solvent Detergent Viral Inactivation In Single Use Bags, Michael Cunningham, Ven Raman, Nitin Sood, Jessica Shea, Lori Mullin, Eric Youssef, Pedro Almeida, Elizabeth Goodrich

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Biomanufacturing of recombinant products from mammalian cell culture systems and plasma derived products requires at least two orthogonal virus reduction steps to comply with regulatory pathogen safety risk mitigation guidelines. Solvent detergent viral inactivation (SD VI) has historically been effectively utilized for the inactivation of lipid-enveloped viruses from plasma derived products, yet only recently have process development activities focused on implementation of SD VI in single use systems. The adoption of single-use technologies for bioproduction continues to progress, driven predominantly by the benefits of operational flexibility, speed of implementation, lower capital investment, and elimination of cross contamination concerns. However, the …

Single-Use Capacitance Measurement Of Cell Viability, Dan Kopec, Stuart Tindal, Marcus Weise, Sven Grob, Henry Weichert, Thomas Schnitzler, Manfred Biselli, Mario Becker

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The biomanufacture of complex biologics continues to expand and develop with no end foreseen and in order to build on the industries rapid adoption of single use technology an ethos of what is measured and controlled in stainless steel can be, and should be transferable to plastic. The realization of this continues to be a challenge but one of the key critical parameters in cell cultivation; in-situ viable biomass is now quantifiable using single use capacitance measurement. A single-use sensor patch is fully integrated in a 5L Rocking Motion Bioreactor bag, gamma sterilized and applied to CHO DG44 and Hybridoma …

Material Science Enabled Quality By Design: The New Standard In Sus Development, Christian Julien

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

There is a growing interest from the end-user community in creating supply chain transparency as it pertains to critical raw materials used within their pharmaceutical manufacturing processes. Single-use systems contain mainly polymeric materials, often in diverse combinations drawing from a wide range of thermoplastic and elastomeric resins. Continued adoption of single-use assemblies into the entire spectrum of unit processing and production operations has led to increased scrutiny thereof and consequently many end-users have strengthened their technical diligence teams to include material scientists. These SME’s are tasked with enhancing the understanding of the materials of construction utilized in single-use systems. Their …

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 …

Single-Use Bioprocess Containers: Raw Material Control Strategy For Optimal Cell Growth, Susan Burke, Sara Ullsten, Eva Blanck, Eva Lindskog, Shujian Yi, Jeffrey Carter, Pokon Ganguli, Herman Parma

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

There is an upward trend in the use of disposable containers for manufacturing biopharmaceuticals. Single-use systems offer several advantages such as increased flexibility, the elimination of cleaning procedures, and reduced capital expenditure. However, due to the plastic nature of these disposable bags, the materials of construction can be more complex than traditional stainless steel vessels. They are often made of films containing multiple layers of polymers with various additives for processing. There have been scientific reports of the inhibition of biopharmaceutical cell culture growth attributed to a leachate originating from an antioxidant commonly used in the plastic films of single-use …

Electrical & Computer Engineering News, Georgia Southern University

Electrical & Computer Engineering: News & Publications (2014-2023)

• CWiNs Research Lab at GS Hosted NSF Research Experience for Undergraduates
• Are you Up2Speed? IEEE will get you there!

Skin Effect Suppression In Infrared-Laser Irradiated Planar Multi-Walled Carbon Nanotube/Cu Conductors, Kamran Keramatnejad, Yang Gao, Yunshen Zhou, Hossein Rabiee Glogir, Mengmeng Wang, Yongfeng Lu

Department of Electrical and Computer Engineering: Dissertations, Theses, and Student Research

Skin effect suppression in planar multi-walled carbon nanotube (MWCNT)/Copper (Cu) conductors was realized at the 0-10 MHz frequency range through infrared laser irradiation of MWCNTs, which were coated on the surface of the Cu substrate via the electrophoretic deposition (EPD) method. The effect of laser irradiation and its power density on electrical and structural properties of the MWCNT/Cu conductors was investigated using a wavelength-tunable CO2 laser and then comparing the performance of the samples prepared at different conditions with that of pristine Cu. The irradiation at λ=9.219 μm proved to be effective in selective delivery of energy towards depths close …

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 …

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.

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 …

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 …

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.

Multiple Detector Wireless Fnirs Sensor To Detect Hemodynamic Activity, Sivaram Karra

Theses and Dissertations

An established, non-invasive and flexible technique, "functional Near Infra-Red Spectroscopy" (fNIRS), has opened new opportunities for the study of brain functionality. This powerful method uses the optical properties of a tissue at multiple near infra-red wavelengths to dynamically determine the levels of both oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (Hbr). Traditional techniques such as functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), Electroencephalography (EEG) and Event Related brain Potentials (ERP) have increased our understanding of brain functionality, however, the basic limitations of these technologies such as high cost of equipment, difficulty of operation and levels of radiation make access …

Mathematical Problems In Petri Nets Theory And Applications, Zhiwu Li, Murat Uzam, Guanjun Liu, Georg Frey, Ying Tang

Henry M. Rowan College of Engineering Departmental Research

(Editorial)

Evaluation Of First Order Error Induced By Conservative-Tracer Temperature Approximation For Mixing In Karstic Flow, Philippe Machetel, David A. Yuen

Sinkhole Conference 2015

Fluid dynamics in karst systems is complex due to the heterogeneity of hydraulic networks that combine the Porous Fractured Matrix (PFM) and the interconnected drains (CS). These complex dynamic systems often need to be treated as “black boxes” in which only input and output properties are known. In this work, we propose to assess the first-order error induced by considering the temperature as a conservative tracer for flows mixing in karst (fluvio-karst). The fluvio-karstic system is treated as an open thermodynamic system (OTS), which exchanges water and heat with its surrounding. We propose to use a cylindrical PFM drained by …

Study On The Critical Velocity Of Groundwater To Form Subsidence Sinkholes In Karst Area, Fuwei Jiang

Sinkhole Conference 2015

Subsidence sinkholes in karst area are a common geological hazard causing disaster accidents. However, the critical hydraulic conditions of forming subsidence sinkholes have not been well understood. Based on the theories of pipe flow, this paper derives expressions of a critical hydraulic condition for assessing whether it leads to subsidence sinkholes. A case study with samples of the cohesive soils taken from the Wuxuan county, Guangxi province, China, was conducted to evaluate the derived critical value. Combining the derived critical value and the monitoring data of hydraulic conditions in the study field, our results indicate that subsidence sinkholes are not …

Numerical Simulation Of Karst Soil Cave Evolution, Long Jia, Yan Meng, Zhende Guan, Lipeng Liu

Sinkhole Conference 2015

This study is focused on numerical simulation of the formation and development of karst soil caves related to cover-collapse sinkholes. The so-called ‘karst soil cave’ refers to the caves formed in the soil layers above bedrock of sinkhole regions. Because the soil caves are formed and developed under groundwater seepage, studying groundwater level changes can help understand soil cave development and collapse. Based on the improved Terzaghi loosening pressure theory and using excess pore water pressure, two kinds of critical groundwater level decline are discussed. The first, denoted as ∆H0, is the critical groundwater level decline related to soil cave …

Building Codes To Minimize Cover Collapses In Sinkhole-Prone Areas, George Veni, Connie Campbell Brashear, Andrew Glasbrenner

Sinkhole Conference 2015

Cover- collapse sinkholes are forming with increasing frequency under buildings. Analyses of sinkhole distribution in Beacon Woods, Florida, preliminarily indicate their occurrence is an order of magnitude greater in urban versus undeveloped areas, suggesting the structures themselves are enhancing the collapse process. The most likely causes are induced recharge via at least one of two sources. First, runoff and drainage from roads, structures, and impoundments that is not adequately dispersed will promote sinkhole development. Second, leaking water, sewer, and septic systems beneath or adjacent to a structure will also promote collapse. The process of cover-collapse from induced recharge is well …

Hazard Of Sinkhole Flooding To A Cave Hominin Site And Its Control Countermeasures In A Tower Karst Area, South China, Fang Guo, Guanghui Jiang, Kwong Fai Andrew Lo, Qingjia Tang, Yongli Guo, Shaohua Liu

Sinkhole Conference 2015

Zengpiyan Cave, one of the most important cave hominin sites of the Neolithic in the South of China, was listed on the national register of cultural preservation sites in 2001. Large quantities of precious material in the Zengpiyan site were unearthed since the beginning of the trial excavation in 1973. These materials include hominin skeletal remains, fire pits, human burials, stone implements, tools fashioned from mollusk shells and animal or plant fossils. According to the historical record, ancient people lived in caves in the karst plain of Guilin. They moved out of the caves approximately 7000 years ago. These cave …