In the fall of 2020, BPI premiered its Readers’ Choice Awards program. Concentrating on articles published from September 2019 through June 2020, with rankings based on digital engagement, BPI staff identified the most popular articles within each of six categories of bioprocess coverage. You ranked those articles in terms of innovativeness, applicability, and presentation. We’re pleased with the turnout and delighted now to congratulate the winners, who were announced first online.
BPI congratulates the winner of our Readers’ Choice Award for analytical articles this year, Veeren M. Chauhan (University of Nottingham, UK). In “Fluorescent Nanosensors: Real-Time Biochemical Measurement for Cell and Gene Therapies” from our May 2020 featured report on manufacturing 4.0, Chauhan introduced tools that permit real-time analytics of subcellular biochemical processes. These could play a significant role in the optimization of CGT manufacturing and facilitate the transition of such “advanced-therapy” products to mainstream status.
Fluorescent nanosensors are emerging technologies that enable “silent” measurement of key biochemical parameters to high spatial and temporal resolution. Manufactured in a range of sizes (10–1,000 nm in diameter), nanosensors are made of inert biocompatible materials that bind to or encapsulate fluorophores. Their enhanced measurement capabilities indicate a strong potential for characterizing complex biochemical processes upstream, downstream, and in situ for CGT manufacturing. A new wave of analytical biosensors with biodegradable polymeric matrices could enrich biomanufacturing through advanced production methods coupled with innovative analytical instruments. With applications still nascent, the true potential of this technology is yet to be determined.
The second-place analytical award goes to Michael Butler and Adam Bergin (Ireland’s National Institute of Bioprocessing Research and Training) and Katrin Braasch and Elham Salimi (University of Manitoba, Canada) for “Cell Viability in Bioprocesses: Making a Case for Reevaluation,” from our November–December 2019 issue. They highlight the ideal state of cells in production culture and how developers can best determine viability and other aspects of that state using such alternative viability test methods as dielectric spectroscopy, digital holography, and biocapacitance.
The third-place analytical award goes to Abdi Ghaffari (Queen’s University, Ontario, Canada), Ian McGill, and Ali Ardakani (Novateur Ventures) for “Trends in COVID-19 Diagnostic Test Development,” from our June 2020 issue. They provide a timely and thorough update of diagnostic developments for detecting the SARS-CoV-2 virus and identifying people infected and suffering from COVID-19. Accurate and rapid results play a critical role in understanding the disease, selecting appropriate treatments, controlling pandemic spread, and developing informed back-to-work policies.
Business Strategy Award
BPI congratulates the winners of our Readers’ Choice Award for trends in business strategies, Dawn M. Ecker and Patricia Seymour (BioProcess Technology Group, BDO USA). Their article, “Mammalian Biomanufacturing Industry Overview,” appeared in BPI’s January–February 2020 issue. Biologic-based drugs are an increasingly important part of portfolio growth strategies for pharmaceutical and biopharmaceutical companies. As the number of commercial products and pipeline candidates grows, key issues facing the industry include the current and future state of biomanufacturing capacity, the availability of that capacity, and technologies influencing upstream and downstream bioprocessing. The authors provide a high-level overview of the current state of the supply of and demand for mammalian-cell–based biopharmaceuticals, forecasting where the industry is heading and how manufacturers are keeping pace.
Second-place goes to Philip Cherian (Philip Melorr Inc.). His article, “From Supplying Components to Providing Total Solutions: Overviewing Supplier Side Capabilities,” appeared in BPI’s October 2019 issue. Biopharmaceutical industry suppliers are moving toward bringing total solutions to the biopharmaceutical industry to address the race to bring products to market. Chronological examples trace how major suppliers are consolidating to become full-fledged process partners, helping to speed development and generate increased value for the industry they serve.
Third place goes to Gordon C. McCauley (adMare BioInnovations). His article, “The Next Global Life-Science Leader,” appeared in BPI’s March 2020 issue. To strengthen the global competitiveness of the Canadian life-sciences industry, his organization supports the most therapeutically and commercially promising research of leading academic and biotechnology partners, providing specialized expertise, infrastructure support, and training.
Cell and Gene Therapies Award
BPI congratulates the winners of its Readers’ Choice Award in cell and gene therapies (CGTs). Readers granted first place to the June 2020 article by Sue Washer and David R. Knop (Applied Genetic Technologies), “Viral-Vectored Gene Therapies: Harnessing Their Potential Through Scalable, Reproducible Manufacturing Processes.” A growing pipeline of late-stage gene-therapy clinical trials for diverse indications is expected to yield additional product approvals over the next several years. The authors review current manufacturing challenges of adenoassociated virus (AAV)–vectored gene therapies, including the need for adherent-cell systems to scale out (requiring additional vessels and personnel) rather than scale up. Adherent processes also might not be robust enough for late-stage clinical or commercial manufacturing.
The authors highlight the advantages of a herpes-assisted vector expansion (HAVE) approach as a vector-expansion system. The method includes coinfection of baby hamster kidney (BHK) cells in suspension culture with two recombinant herpes simplex virus (HSV) vectors. The approach can tailor selection of the cap gene sequence for optimum cell targeting and transduction, and it can be used with different AAV serotypes. The authors also describe several clinical and regulatory advantages of the HAVE method over other AAV-production platforms.
Second-place is awarded to Joseph Rininger, Ashley Fennell, Lauren Schoukroun-Barnes, Christopher Peterson, and Joshua Speidel (Latham Biopharm Group) for their November–December 2019 article, “Capacity Analysis for Viral Vector Manufacturing: Is There Enough?” Focusing on AAV and lentiviral/retroviral vectors, the authors project current and future manufacturing demands by considering product yield, potential batch sizes, number of trials, and other parameters.
Third place goes to Kim Bure (AveriCELL), Yonatan Lipsitz (Sana Biotechnology), Mark Lowdell (INmuneBio), Ivan Wall (Aston University), and Peter Zandstra (Notch Therapeutics) for their May 2020 article, “Quality By Design for Advanced Therapies: An Informed Route to Enhanced Late-Stage Clinical Success and Empowered Process Flexibility.” The authors review the challenges of adopting QbD in advanced therapies. They suggest that “aggregating parameters and outcomes from multiple patients” could provide an understanding of process design space.
Downstream Processing Award
BPI congratulates the winners of its Readers’ Choice Award in downstream processing. First place goes to the October 2019 article by Helge Abrecht, Geoffrey Pressac, Amélie Boulais, and Philippe Permanne (GlaxoSmithKline and Sartorius Stedim France SAS) on “Adenovirus Downstream Process Intensification: Implementation of a Membrane Adsorber.” The manufacturing of adenoviruses includes a series of purification steps traditionally based on well-established chromatographies. The authors replaced an anion-exchange capture step with a single-use membrane adsorber in an adenovirus downstream process. The goal was to show that this replacement enabled process intensification.
The authors first assessed three membrane adsorbers at small scale and selected one for additional studies. They compared the resin and membrane adsorber directly using an existing protocol developed for the resin. After several optimization runs to test different pH levels and NaCl concentrations, the authors determined maximum dynamic binding capacity and other parameters. A pilot-scale trial showed that conditions used for the resin could be applied to the membrane adsorber. The authors assessed the impact of loading conditions and scaled up the membrane chromatography process. Results showed that the membrane adsorber process could increase capacity of the chromatography step.
Second-place goes to Jeffrey D. Goby, Joelle N. Khouri, Anoushka Durve, and Kenji Furuya (Boehringer Ingelheim), and Eike Zimmermann (Allogene Therapeutics) for their September 2019 article, “Control of Protein A Column Loading During Continuous Antibody Production: A Technology Overview of Real-Time Titer Measurement Methods.” The authors compared the benefits and challenges of using traditional off-line high-performance liquid chromatography (HPLC) measurement methods with those of an off-line ultraperformance liquid chromatography (UPLC) instrument.
The third-place downstream processing award goes to Steven M. Chamow and Angela L. Linderholm (Chamow and Associates); Katherine E. Harris, Ute Schellenberger, and Brett Jorgensen (TeneBio); and Payal P. Pratap (Scripps Research) for their May 2020 article, “Capture of CH1-Containing Bispecific Antibodies: Evaluating an Alternative to Protein A.” The authors used a commercially available affinity resin with selectivity for human antibodies and derivatives containing a CH1 domain to purify a bispecific antibody, achieving higher product purity than obtained using protein A.
Upstream Production Award
BPI congratulates the winners of our Readers’ Choice Award for upstream-production articles, Alessandro Mora (now with Kadmon Holdings) and Yassine Ezzyat (Jounce Therapeutics). In “Anticipating Cell-Line Challenges to Drive CMC Readiness,” from our June 2020 issue, Mora and Ezzyat explore strategies that drug developers and manufacturers consider when seeking to accelerate mammalian cell-line development (CLD) programs. They focus especially on exploiting early stage pools of Chinese hamster ovary (CHO) cells to shorten timelines.
Early identification of a stable pool is critical to chemistry, manufacturing, and controls (CMC), Mora and Ezzyat write. Increasingly, companies are establishing CHO cell pools within two to three weeks, not only to facilitate clone selection and establishment of cell banks, but also to expedite process and assay development. Performing some of those activities concurrently helps to accelerate CMC timelines, the authors point out. Companies also are using platform approaches for development processes, then tightening controls for clinical trials. Mora and Ezzyat observe that the bioprocessing industry is likely to invest significantly in high-resolution analytical technologies that can illuminate key cell-line attributes, enhancing pooling studies further.
The second-place upstream production award goes to Noemi Moroni, Annarita Di Nunzio, Adele Perli, Roca Puca, and Leonardo Sibilio (Menarini Biotech) and Kimesha Hammett, Graziella Piras, and James Brooks (Thermo Fisher) for “Streamlined Serum-Free Adaptation of CHO-DG44 Cells Using a Novel Chemically Defined Medium,” from BPI’s September 2019 issue. The writers describe their collaboration to optimize adaptation of CHO cells from serum-supplemented to chemically defined media. Their partnership yielded a five-week adaptation protocol based on contemporaneous replacement of (rather than conventional stepwise reduction of) serum-supplemented media.
The third-place upstream award goes to Yongxue Ding, Bill Zeck, and Steven P. Allen (Abbott Diagnostics) for “Comparative Study of Single-Use and Reusable Fermentors: Production of Recombinant Proteins Through Bacterial Fermentation” in BPI’s October 2019 issue. Noting a critical need for single-use (SU) fermentors, the authors compared protein-production performance in two newly available SU systems with that of a standard steam-in-place (SIP) unit. The team found that both SU systems could substitute for a SIP unit in cases requiring larger quantities of proteins than a SIP unit could produce.
BPI congratulates the winners of our Readers’ Choice Award for manufacturing-themed articles: Gene Tung and Chung Lai (Merck), Keith Morris (PM Group), Pietro Perrone (Cytiva), and Rene Reinbigler and Steven Miller (Millipore Sigma), all members of a BioPhorum working group. In “The Value of Plug-and-Play Automation in Single-Use Technology” from our November–December 2019 issue, they present the findings of their team of automation experts. “Our group’s vision is to move from the current state of unique and custom software development to a reusable, standardized approach that enables rapid integration of intelligent process skids.”
Applying a plug-and-play (P&P) structure to biopharmaceutical manufacturing could decrease manufacturing costs, shorten manufacturing timelines, and improve product quality. The authors suggest how companies could transition from existing equipment assets to P&P-enabled equipment. The benefits of flexible and standardized automation based on modular methods derive primarily from having intelligent equipment integration preconfigured rather than developed for each device.
The second-place manufacturing award goes to Anne Richelle and Moritz von Stosch (GlaxoSmithKline, Belgium) for “From Big Data to Precise Understanding: The Quest for Meaningful Information,” from our January–February 2020 issue. They highlight the potential of machine learning and systems biology tools to extract meaning and develop models for gaining insight and testing hypotheses in silico before committing expensive resources to laboratory experiments.
The third-place manufacturing award goes to Tony D’Amore and Yan-ping Yang (Sanofi Pasteur R&D, Canada) for “Advances and Challenges in Vaccine Development and Manufacture,” from our September 2019 issue. D’Amore and Yang suggest how the industry could overcome obstacles in vaccine development using closed-system processing in SU technologies, high-throughput process development, continuous manufacturing, and advanced analytical instrumentation.
Once again, we congratulate all the winners. BPI is grateful to the product and service suppliers that sponsored our eBook announcements: BioPharm Services, Horizon Discovery, Novasep, Richter-Helm, Thermo Fisher Scientific, and Tosoh Bioscience. And we thank YOU, our judges, for making this program a success. We’re looking forward to the 2021 program this fall, when together we’ll consider articles from September 2020 through June of 2021.