Genetic Engineering & Biotechnology News

DEC 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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16 | DECEMBER 2018 | Genetic Engineering & Biotechnology News | GENengnews.com Investigators must take cognizance of the construction materials, design of modules and other components, effi- ciency, and overall cost factors, according to a number of speakers at the recent annual Bioprocessing International conference in Boston. Protecting Bulk Drug Substance During Cold Chain Handling Storage, preservation, and transport of bulk drug prod- ucts demand robust and resilient materials, explained Joe Cintavey, product manager and material science specialist with the PharmBIO division of Gore. Cintavey discussed the use of PTFE (polytetrafluoroethylene), a versatile polymer that has long been the core of the company's product offer- ings, and its newest application in the area of bulk transport and storage. With much of drug development moving into the area of biologics, including vaccines, monoclonal antibodies (mAbs), and antibody drug conjugates (ADCs), keeping temperature-sensitive products stable is essential, as they are often frozen at temperatures from –40°C to –86°C. At these temperatures, the choice of materials is greatly nar- rowed because of the tendency of traditional polymer-based materials to become brittle and fragile while frozen. "Break- ing and cracking is a major concern when handling a bulk drug which may be valued in the hundreds of thousands of Bioprocessing The Bristol-Myers Squibb campus in Devens, MA, used to be solely focused on large-scale biologics manufacturing. Recently, however, the campus added two buildings, a Biologics Development Building (for the early production of investigational medicines) and a Clinical Manufacturing Building (for the production of investigational medicines to support clinical trials). At the expanded facility, workers strive to accelerate development of the company's growing portfolio of biologics medicines. Single-Use Puzzles Come with Many Pieces K. John Morrow Jr., Ph.D. The bioprocessing industry today is being yanked in two directions, as single-use technologies gain the ascendant, while at the same time there is still a demand for cold, hard steel for large-scale production. In order to gauge their performance, single-use technologies are evaluated on a small scale. Thus scalability is an important consideration, since modeling strategies depend upon their applicability when developing large commercial operations. Optimization of lentiviral vector production requires a detailed analysis of upstream processing, notes Carol Knevelman, Ph.D., head of process R&D at Oxford BioMedica. She presented her team's work on the design and application of this technology for use in gene therapy protocols at the Sartorius Stedim Biotech Upstream & Downstream Technology Forum in Goettingen, Germany, earlier this year. "We have focused on understanding and improv- ing our suspension cell culture production process," Dr. Knevelman explained. "Our strategy was to employ small-scale systems in order to study the impact of process parameters on vector titer and quality. With the increased number of experiments a'orded by this strategy, we were able to employ 'design of experi- ment' approaches in a shorter time frame." The Oxford Biomedica team sought to evaluate the engineering characteristics important for successful scale-up and process robustness in order to maximize the chances for success at commercial scale. With this knowledge, the team assessed several commercially available bioreactors and selected a system that met the critical parameters required for the process. "We have been successful in developing a GMP-compliant manufacturing process at 200-L scale," Dr. Knevelman continued. "And we have recently invested in the au- tomated ambr® 250 high throughput system, which we plan to qualify for future process development and characterization activities." Oxford BioMedica's LentiVector ® platform is an advanced lentiviral-based gene delivery system designed to overcome the safety and delivery chal- lenges associated with earlier-generation vectors. The platform was designed so the vector can be modi™ed for a wide range of applications, including selective targeting for gene and cell therapies. The vector has been adapted for CAR-T cancer therapy and has been successfully employed in a long-term Parkinson's dis- ease project, recently licensed out to Axovant Sciences. Clinical trials utilizing the ™rst candidate product, ProSavin ® , have previously demonstrated encouraging clinical bene™ts in Parkinson's patients. Subsequent optimization of the vector system has led to the development of a second-generation vec- tor, AXO-Lenti-PD. The vector delivers three genes that encode key dopamine synthesis enzymes. When injected directly into the brain's striatum, AXO-Lenti- PD genetically modi™es cells to produce dopamine, replacing that which is lost during the course of the disease. If this gene therapy strategy is successful, it will provide long-term bene™t for a number of years following a single administration, unlike current drug treatments which lose ežcacy with continuous use. "When we began this program a number of years ago, we envisioned a one-shot injection protocol," noted Dr. Knevelman. "Axovant is now advancing to a trial of the second-generation product. Oxford BioMedica is also developing a LentiVector platform–based treat- ment of wet age-related macular degeneration which has completed Phase I clinical trials." Q Confronting Viral Production Challenges

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