Commercial Manufacturing Facility Research Articles

Thinking big: the need for innovation in the production of lentivirus-based cell and gene therapies

<b>Elisa Manzotti</b>, Founder, BioInsights, speaks to <b>Hanna Leinonen, John Moscariello, Lee DaviesScott Cross </b>and <b>Will Junker</b> <div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/H Leinonen copy.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name">Hanna Leinonen</h3><h5 class="author-title">Senior Scientist, Kuopio Center for Gene and Cell Therapy</h5> Hanna M. Leinonen holds a PhD in Molecular Medicine from the University of Eastern Finland (2014). She has 15 years’ experience on lentiviral vectors and 6 years’ experience on bioprocessing. She is currently working as a Senior Scientist in Kuopio Center for Gene and Cell Therapy (Finland) focusing on development of upstream processing for viral vectors (lentivirus, adenovirus, AAV). </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/26118d9d52f34a12859025a3d5f4aabc.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name">John Moscariello</h3><h5 class="author-title">Executive Director, Viral Vector and Gene Editing Process Development, Bristol Myers Squibb</h5> John Moscariello currently serves as Executive Director of Viral Vector and Gene Editing Process Development at Bristol-Myers Squib (BMS). At BMS, John’s group develops viral vector processes that enable rapid timelines to generate clinical viral vectors as well as the development and characterization of commercial viral vector processes. Prior to his work at BMS, John was the Vice President of Process Development at AGC Biologics where his team was responsible cell line development, upstream and downstream process development, analytical and formulation development, and technical support for AGC Biologic’s commercial manufacturing facility and supported development activities from generating processes for Toxicology/Phase 1 supply up to and including commercialization and post-approval process support. John is very active in the biotechnology community. He is on the Scientific Advisory Board for various conferences, including the BioProcess International conference series, and the CBI conference series on achieving efficient facilities and the next frontier of single-use technologies. John obtained his Ph.D. in Chemical and Biological Engineering from the University of Wisconsin-Madison, and his B.Eng. in Chemical Engineering from the University of Delaware. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Lee Davies 1.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name">Lee Davies</h3><h5 class="author-title">Director, Process Research &amp; Development, Oxford Biomedica</h5><p class="oneComWebmail-MsoNormal"><i>As Director of Process Research and Development, Lee helps drive development, innovation and improvements in&nbsp;</i><i>world-class lentiviral vector manufacturing processes,&nbsp;</i><i>applying scientific and engineering principles to all aspects of upstream and downstream process development, including process optimisation and scale-up, technology transfer to GMP manufacturing and process characterisation to support chemistry, manufacturing and controls (CMC) regulatory submissions.&nbsp;</i><i>As part of&nbsp;the</i><i>&nbsp;Process Research and Development team, Lee works</i><i>&nbsp;at the&nbsp;cutting edge of gene therapy, ensuring its applicability to the needs of the wider gene and cell therapy community. The team’s mission covers the&nbsp;</i><i>life cycle of gene therapies, taking</i><i>&nbsp;processes from the early phase development work through to&nbsp;fully optimised large scale, GMP-ready processes, manufacturing and commercialisation.&nbsp;</i><i>Prior to joining Oxford Biomedica 6 years ago, Lee worked at the University of Oxford as a postdoctoral researcher and obtained a D.Phil in Gene Therapy for Cystic Fibrosis.</i> </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Scott_122321_WebReady copy.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name">Scott Cross</h3><h5 class="author-title">Senior Principal, Dark Horse Consulting</h5> Scott has over 20 years experience working with viral vectors, vaccines, and biologics in GMP environments. He has been responsible for cleanroom design, build out and commissioning of vector facilities, as well as the oversight of viral vector, cell therapy, fill finish and manufacturing support departments. Scott started his career at Merck and Co. where he worked on the development of an Adenovirus-based HIV vaccine and later, the development, optimization, and validation of release assays for live virus vaccines. He then moved to Indiana University (IU) where he managed the IU Vector Production Facility (IUVPF), overseeing GMP production and testing of Lentiviral and Retroviral vectors for the IUVPF and the National Gene Vector Laboratories (NGVL). While at the IUVPF he also managed the design, build and commissioning of a new viral vector GMP production and testing facility. After leaving the IUVPF, Scott joined Cincinnati Children’s Hospital Medical Center (CCHMC) managing the GMP Vector Production Facility, Viral Vector Core, and the Aseptic Processing Labs. Scott then moved to the University of Florida where he was the Director of Cell Therapy, Fill Finish and Manufacturing Support Operations for Florida Biologix and Brammer Bio. He was also responsible for the design of two new fill finish suites. Most recently, Scott served as Vice President of Vector Operations at Orchard Therapeutics where he was one of the original ten members and responsible for viral vector development, GMP vector production, plasmid production, oversight of 10 CDMOs, due diligence, and facility design. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/Will Junker headshot copy.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name">Will Junker</h3><h5 class="author-title">Head of Vector Manufacturing Quality, Kite Pharma</h5> Will Junker is Head of Vector Quality and oversees the operation of QC, QA and QE to bring Kite’s vector manufacturing facility on line through licensure. Before this role, Will built Kite’s Quality Engineering function globally. His 35 year career in BioPharma includes 13 years at AstraZeneca and 15 years at Aventis/Sanofi as well as a few years at Baxter BioScience in technical/quality roles of increasing responsibility. </div></div></div>

Development of CuFeMnAlO4+δ oxygen carrier with high attrition resistance and 50-kWth methane/air chemical looping combustion tests

A Copper-Ferri-Manganese-Aluminate spinel (CuFeMnAlO4+δ) oxygen carrier, developed at the US Department of Energy’s (DOE) National Energy Technology Laboratory (NETL), shows promising results for chemical looping combustion with methane. Attrition resistance of the spinel oxygen carrier (160–600 µm) produced by a wet agglomeration method was significantly higher than that observed previously with a Copper-Ferri-Aluminate (CuFeAlO4) oxygen carrier. Improved attrition resistance of the novel carrier can be attributed to minimal alumina phase segregation and minimal carbon formation. Heats of reaction measured by differential scanning calorimetry indicated exothermicity during reduction with methane. The total oxygen transfer capacity of the material was about 10.5 wt% at 850 °C. The attrition resistance and the oxygen transfer capacity of the carrier prepared at a commercial manufacturing facility (180 kg) were very similar to observed values during the development phase with the lab scale preparations. The material displays satisfactory methane conversion and significantly high particle durability during a 54 h test campaign conducted in NETL’s 50-kWth chemical looping dual fluid bed reactor unit at temperatures ranging from 700 to 900 °C. Low oxygen carrier make-up cost, due to the use of natural ore and pigment grade raw materials during synthesis and very low attrition rates, exceeded the performance goals determined by systems studies.

Fabrication of carbon nanotube field-effect transistors in commercial silicon manufacturing facilities

Carbon nanotube field-effect transistors (CNFETs) are a promising nanotechnology for the development of energy-efficient computing. Despite rapid progress, CNFETs have only been fabricated in academic or research laboratories. A critical challenge in transferring this technology to commercial manufacturing facilities is developing a suitable method for depositing nanotubes uniformly over industry-standard large-area substrates. Such a deposition method needs to be manufacturable, compatible with today’s silicon-based technologies, and provide a path to achieving systems with energy efficiency benefits over silicon. Here, we show that a deposition technique in which the substrate is submerged within a nanotube solution can address these challenges and can allow CNFETs to be fabricated within industrial facilities. By elucidating the mechanisms driving nanotube deposition, we develop process modifications to standard solution-based methods that significantly improve throughput, accelerating the deposition process by more than 1,100 times, while simultaneously reducing cost. This allows us to fabricate CNFETs in a commercial silicon manufacturing facility and high-volume semiconductor foundry. We demonstrate uniform and reproducible CNFET fabrication across industry-standard 200 mm wafers, employing the same equipment currently being used to fabricate silicon product wafers. Using a solution-based deposition technique, carbon nanotube field-effect transistors can be fabricated in a commercial silicon manufacturing facility and a high-volume commercial foundry, demonstrating uniform and reproducible transistor fabrication across industry-standard 200 mm wafers.

Establishment of a commercial manufacturing facility for CAR-T product with small IT system in an academic organization

Background & Aim The cellular and gene therapy (CGT) is at the cutting edge of innovation and offer a major hope for unmet medical needs. At 2019 more than 1000 clinical trials are ongoing in the world and approximately 900 companies, ventures, medical institute and research organizations are committed to the cellular and gene therapy field. But the commercialization of the CGT with large scale manufacturing is still challenging because of many difficulties caused by the nature of the cellular product. To accelelate the introduction of cell therapy, we analyzed the obstacles for commercialization and propose the introduction of the small IT system for the scale up of the cell prduct manufacturing site. Methods, Results & Conclusion High manufacturing cost caused by expensive materials, high FTE, low productivity high and construction / maintenance cost of manufacturing facilities. To overcome these difficulties we have introduced IT system in chain of identities, materials control and manufacturing scheduling without the introduction of large PAS system which is usually used in a big pharma but requires very high cost. We present the results of our experience of introduction of small IT system in establishment of large scale manufacturing on a cell therapy product. The cellular and gene therapy (CGT) is at the cutting edge of innovation and offer a major hope for unmet medical needs. At 2019 more than 1000 clinical trials are ongoing in the world and approximately 900 companies, ventures, medical institute and research organizations are committed to the cellular and gene therapy field. But the commercialization of the CGT with large scale manufacturing is still challenging because of many difficulties caused by the nature of the cellular product. To accelelate the introduction of cell therapy, we analyzed the obstacles for commercialization and propose the introduction of the small IT system for the scale up of the cell prduct manufacturing site. High manufacturing cost caused by expensive materials, high FTE, low productivity high and construction / maintenance cost of manufacturing facilities. To overcome these difficulties we have introduced IT system in chain of identities, materials control and manufacturing scheduling without the introduction of large PAS system which is usually used in a big pharma but requires very high cost.

Polymeric Hollow-Fiber Heat Exchangers for Thermal Desalination Processes

Metallic shell-and-tube heat exchangers used in thermal desalination require huge capital investments, suffer from corrosion/erosion, create heavy metal pollution, and display a large footprint. This paper has explored their potential replacement by polymeric solid hollow fiber-based heat exchangers. Using solid hollow-fibers of polypropylene (PP) (wall thickness 75 μm, outside diameter 575 μm) a number of heat exchangers were fabricated in the laboratory (heat exchange area, 195−960 cm2) and at a commercial manufacturing facility (heat exchange area, 0.15−0.44 m2). The heat transfer performances of these devices were studied for a hot brine (4% NaCl, ca. 80−98 °C)−cold water (8−25 °C) system as well as for a steam (101−113 °C)−cold water (8−25 °C) system; these systems are typically encountered in thermal desalination plants. Overall heat transfer coefficient values of as much as 2000 W/(m2 K) were achieved. This is close to the limiting value imposed by the PP wall thickness, namely, 2660 W/(m2 K). Heat...

Company Profile: Tengion

Founded in 2005, Tengion is a clinical-stage organ regeneration company with products in urologic, vascular and renal regeneration based on its proprietary Autologous Organ Regeneration Platform. Tengion uses biocompatible materials and a patient's own (autologous) cells to assemble neo-organs or neo-tissues that are designed to catalyze the body's innate ability to regenerate. Tengion is a fully-integrated organization, with scalable US and European manufacturing and distribution capabilities, experienced research, development, clinical and commercial teams, and significant intellectual property. The company's corporate headquarters and commercial manufacturing facility are in East Norriton, PA, USA, and its research offices, a development laboratory and a pilot manufacturing facility are located in Winston-Salem, NC, USA. Tengion's product candidates may ultimately address the most critical problems facing organ and tissue failure patients, enabling people to lead healthier lives without donor transplants or the side effects of related therapies.

Laboratory set-up to pilot plant investigations on vapour phase ammoxidation of 2,6-dichlorotoluene

The scaling-up of the gas phase catalytic ammoxidation of 2,6-dichlorotoluene (DCT) to 2,6-dichlorobenzonitrile (DCBN) over VPO catalysts in a pilot plant was investigated. The focus was led on the process variables that might be critical to the design of a commercial manufacturing facility. Furthermore, catalyst scale-up, catalyst stability and a development of a product separation section particularly for the solid reaction products was studied. The scaling-up of the gas phase catalytic ammoxidation of 2,6-dichlorotoluene (DCT) to 2,6-dichlorobenzonitrile (DCBN) over vanadium phosphate catalyst in a pilot plant was investigated. The focus was led on the process variables that might be critical for designing a commercial manufacturing unit, in particular on evaluation of reaction temperature that may cause hot spots, temperature gradients, etc. Furthermore, catalyst scale-up, catalyst stability and a development of a product separation section particularly for the solid reaction products was studied. The up-scaling of the process using 100 ml of catalyst was investigated both by reactor simulations and catalytic experiments. For reactor simulations, a pseudo-homogeneous model of a fixed bed tubular reactor with negligible axial and radial diffusion operating in the steady-state was applied. The kinetic model based upon the Langmuir–Hinshelwood mechanism was used. The results showed that the temperature control will be crucial in scaling-up of the process. The influence of the reactor geometry, reactor operating conditions and catalyst stability on the reactor performance is discussed. The possibility of an appearance of hot spots in the reactor is addressed. High selectivity of DCBN (85%) can be achieved for an extended period of time. A good agreement between experimental and simulation results is observed.

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Bell Model 230 Makes First Flight

THE Model 230 helicopter, produced by Bell Helicopter Textron, made its first flight (August 12, 1991) at the company's commercial manufacturing facility in Quebec, Canada. The new intermediate twin‐engined helicopter was developed at the Bell plant in Mirabel. Co‐test pilots for the first flight of the Model 230 were Leo Meslin and Dwayne Williams. Also on board for the first flight was Bell engineer Steve Schmidt. Certification of the Model 230 is scheduled for the first quarter of 1992.