BioProcess International 2020 Post-Event Report
Explore the highlights of the BioProcess International 2020 virtual conference in the post-event round-up.
Post-Event Report: BioProcess International 2020
Executive summary, panel discussions and selected sessions on-demand
Over the course of five days on 21 – 25 September 2020, over 1800 bioprocessing professionals from 38 countries around the world gathered online for the BioProcess International Virtual conference. The week featured a range of industry leading keynotes, panel discussions and sessions - as well as make your own cocktails, a cooking class, and interactive quiz networking events.
In this post-event report in association with Avantor, we have gathered together some of the highlights from the week, including analysis of the hottest discussions and biggest news stories by BioProcess International magazine editors, and full on-demand recordings of selected sessions.
Whether you joined us for the event and are looking for a summary of the week, or else want to see what you missed out on, this is a great round-up of the week and will hopefully whet your appetite for 2021 BioProcess International events.
Jump to any article using the contents on the following page, or at any time using the Contents menu in the top left. There you can also download this report as a PDF.
Cheryl Scott, Senior Technical Editor at BioProcess International, explores some of the key topics from the week, with a focus on how advancing technologies are unlocking solutions for biopharmaceutical development.
Watch the full session by Christiane Schwittay, Director, Strategic Marketing Biopharma Production, Avantor.
Watch the full session by Jungmin Oh, Manager - New Product Development, Avantor.
Event Overview: Quality is Key
Advancing technologies unlock solutions for biopharmaceutical development.
By Cheryl Scott, Senior Technical Editor at BioProcess International
Quality is Key:Advancing technologies unlock solutions for biopharmaceutical development
Quality may have been in the name of only half of a single track this year, but judging by the most-watched presentations at the first virtual BPI Conference and Exhibition, it was on top of nearly everyone’s mind. In particular, attendees were interested in how modern information and analytical technologies can help their companies deliver on the quality–safety–efficacy promise that good manufacturing practice (GMP) regulations require. Cheryl Scott, cofounder and senior technical editor of BioProcess International magazine, explores some of the takeaways from key sessions.
Keynotes
That is perhaps most evident in well-received keynote addresses by Anthony Mire-Sluis (head of global quality at AstraZeneca), Jeff Baker (deputy director of the Office of Biotechnology Products in the US FDA’s Center for Drug Evaluation and Research), and Nadine Ritter (president and analytical advisor at Global Biotech Experts, LLC).
Mire-Sluis gave a visionary presentation. In “Digitally Uplifting Quality to Advance Product Supply and Create Competitive Advantage,” he described a biopharmaceutical development “laboratory of the future” with advanced analytics and mixed-reality technology, fully digital laboratory execution and documentation systems, standardized automation and “internet of things” connections, and even simple handheld near-infrared (NIR) devices for identifying raw materials and final drug products. He envisioned the use of artificial intelligence in data mining and trending as well as standard operating procedures (SOPs) continually updated in real time and accessed by tablet rather than printed and circulated on paper.
Mire-Sluis highlighted some specific evolutions in quality/analytics, as companies have transitioned from classic approaches to faster, more accurate methods that qualify as process analytical technologies (PAT). For example, wet chemistry assays once were the norm for raw-material identification/qualification. Now companies have the option of handheld Raman spectroscopy for nearly instant results. Similarly, rapid and accurate microbial detection and identification are possible using matrix-assisted laser-desorption ionization mass spectrometry (MALDI-MS) instead of the more basic fluorescence, turbidity, and colorimetric results offered by first-generation optical systems. And slope spectroscopy instruments familiar to readers of BioProcess International 1–3 have supplanted the traditional cuvette-based means of protein-concentration measurement.
Finally, Mire-Sluis quoted the 19th-century English art critic, philosopher, and philanthropist John Ruskin: “Quality is never an accident. It is always the result of intelligent effort.” Modern information technology can enable biopharmaceutical companies to apply that tenet to the realization of their drug products and manufacturing processes.
The philosophy was reflected also in both of Baker’s well-attended presentations: “Discuss, Deploy, or Defer: New Technologies in Real-World Biopharmaceutical Manufacturing” and “Specifying the Spokes and Handicapping the Hub: Management of Residual Uncertainty in Biopharmaceutical Development and Manufacturing.” BPI Conference attendees are often eager to find out what FDA speakers have to say, and Baker made it clear early on that he wasn’t there simply to read aloud passages from regulatory documents anyone can find online. He wanted to talk about risk management and how advanced technologies can help companies do it.
“FDA has encouraged deployment of advanced manufacturing tech for 20 years,” he reminded us, highlighting a number of programs and partnerships involving organizations such as the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL). It’s all part of the agency’s 21st-century focus on management of residual uncertainty through probabilized outcomes and totality of evidence in drug development.
There’s a difference, Baker pointed out, between avoiding uncertainty and managing it. We must accept that uncertainty is neither good nor bad, but just an attribute of biological systems to be understood the best we can. He encouraged attendees to differentiate between mere data analysis and real knowledge management, between mere statistical calculation and statistical thinking. “Make clinical relevance central to risk assessment. Optimize value rather than minimizing cost. Prioritize value understanding over specification.”
When companies consider a new technology and whether it should be discussed, deployed, or deferred, Baker said, “it depends on what risks you’re managing.”
As to what regulators are looking for in their inspections and reviews, he emphasized the totality of evidence approach. “There is no simple checklist. It’s not simply red–yellow–green, score these things, and if they add up to less than 27 then you’re good.” Managing residual uncertainty requires true risk assessment. Developers must identify relevant risks, assess their likelihood of occurring, and identify necessary activities for mitigation — all based on multiple sources of information. “You need to make a sound scientific argument based on effective engineering practices that (a) you know what you’re doing and (b) the outcomes you want are very likely.”
Baker brought up fingerprint analysis, often imagined in TV crime dramas as an exact overlay of identical images. In reality, however, forensic analysts compare a number of unique points on different marks, and if all those align, then the prints are deemed to be from the same person. “This is what we do in biotech,” he explained. Specifications, stability testing, qualification, failure modes and effects analysis (FMEA), comparability, and continuous improvement all measure a number of aspects and compare them using risk management to determine whether or not results match. “Fingerprint-like biosimilarity” is better for saying something is not the same than for saying it is so, Baker emphasized. He hammered his points home using quotes from sources as far-ranging as Bruce Springsteen and Lao Tzu — all in support of the holistic approach to both risk and quality based on solid science.
BPI editorial advisor Nadine Ritter got into the nuts and bolts of it in “CMC Data Integrity and Quality Practices in Process and Analytical R&D Lab: Risk and Benefits.” She explained how data system design and controls should enable easy detection of errors, omissions, and aberrant results throughout a product lifecycle. Ritter spoke of the “sliding scale” of phase-appropriate GMP compliance — and what kinds of studies can and can’t be performed in non-GMP laboratories during drug development. And she helped attendees differentiate between GMPs and good laboratory practices (GLPs), which apply specifically to all nonclinical studies related to product safety — not merely a “subset of GMP.” That applies to manufacturing, control, and testing of materials that will be used in humans, and 21CFR11 applies to data generated in all laboratories supporting drug development.
Ritter highlighted three pillars of “good R&D quality practices” for information technology: quality (ensuring that data generated are technically appropriate and scientifically meaningful), integrity (ensuring that documentation is clear and complete, and that it represents adequately the activities that were conducted) and safety (ensuring that all documentation is traceable to its source, retrievable on demand, and secure against loss or damage).
Upstream and Downstream Case Studies
Many other speakers presented results from their own experiences using new and emerging technologies. Here, too, product quality was often the focus. For example, Yelena Ilin (Sanofi) detailed a “Mechanistic Investigation and Characterization of Product Quality Variability in a Cell Culture Process,” in which her team used a cell-free system to investigate the formation of low–molecular-weight product variants in a production culture. Using that tool to mimic those aberrant results, Sanofi researchers could study the specific factors without confounding impacts on cell growth or productivity.
In “High-Resolution Optical and Dielectric Methods for Monitoring Cells in Bioprocesses,” Michael Butler (principal investigator in cell technology at NIBRT in Ireland) highlighted new PAT technologies for upstream process monitoring and control. “Optical and capacitance methods are robust, inline measurements of cell viability and growth,” he said. Cell deviations of different types occur during loss of viability, from early apoptosis often detected by an enzyme-linked immunosorbent assay (ELISA) to late stages involving membrane damage identified by trypan blue dye exclusion. Upstream process engineers know that early detection is always best, and the new instruments measure early stage apoptosis. Butler finally touted dielectrophoresis (DEP) cytometry as a markerless, electronic single-cell detector that can identify subpopulations of cells during apoptosis events.
Stepping back from that microscopic view, David Lee (upstream cell culture process research associate at Seattle Genetics) described an “Evolving Cell Culture Platform to Address Amino-Acid Misincorporations for Fed-Batch Processes.” His team observed amino-acid misincorporation in the data from new products made using an established platform. The group discovered that was attributable to increases in growth and product titer that caused cells to “starve” as nutrients depleted too quickly in culture. So SeaGen modified its platform process to maintain acceptable product quality. Development of a platform based on chemically defined media provided a long-term solution: “We are using continuous improvement of the cell culture process to ensure that the platform is robust for different phenotypes.”
On the downstream side, Brian Murray (biologics purification development scientist at Sanofi) presented a “Fully Automated Platform Approach to First-in-Human Purification Development: MAbs and Beyond.” His company used automation to intensify its platform purification development approach with minimal hands-on time of under a day. The group plans to work on creating flexible tools for platform experiment execution with integrated analytics to measure, for example, host-cell proteins through surface-plasmon resonance and product variants through size-exclusion chromatography.
The Bigger Picture
David Kahn (vice president of biopharmaceutical development at Macrogenics, Inc.) encouraged attendees to consider following the example of the “Use of Developability Assessments at a Midsize Biotechnology Company.” He described this product-focused work as “a critical activity occurring at the interface of research and development,” although R&D often are spoken of in the same breath. “These assessments minimize the risks of poor performance in the clinic and increased costs and complexity in the production of viable clinical/commercial drugs,” Kahn explained. “Macrogenics has prioritized those assessments of highest value and continues to consider adding new technologies/capabilities to our toolbox.”
Such assessments are important when it comes to processes as well as products, as Andrew Sinclair (managing director of Biopharm Services) showed in “Maximizing the Impact of Process Intensification: Assessing Implications of Scale and Technologies.” To illustrate his message, he focused on a continuous downstream processing operation. Using proprietary analysis software, he showed how reducing the number of batches run per week will save on cost of goods (CoG). Those benefits increase with scale: maximizing chromatography resin capacity while minimizing consumables use (and number of changeovers) and reducing process complexity while simplifying and integrating technologies. But he cautioned viewers that there is “no single simple solution.” Continuous processes must be optimized like any other operations.
“Economic analysis provides insights to help you find the best technology options and configurations and rationale in support of decisions you make,” Sinclair concluded. “This helps you focus limited researches to maximize value by setting baselines and providing a way to measure progress.”
A Digital Reality
The pandemic has forced people in many industries to jump quickly into using new technologies. As travel was restricted, virtual meetings and events have become the new norm around the world. Many of us have discovered the value of on-demand review capabilities after events like the BPI Conference for brushing up on topics and checking details we may have missed. And even though we all miss the fun of live events, we are making the most of what modern information technology offers to help us do our work — not to mention, visit with family and friends we otherwise might never have seen at all this year!
Meanwhile, emerging options in PAT, automation, and data management are changing how work is done in bioprocess development and biotherapeutics manufacturing. Interest in information technologies and other advances ran high among those in attendance this year, with the increasing focus on speeding products through development providing the impetus — whether those candidates are intended to address the pandemic or not. We know what regulators want: quality, safety, and efficacy of all biopharmaceuticals for market. The details of how best to achieve those goals as quickly as possible — and without compromise — are increasingly digital. But biological principles still reign.
ABOUT THE AUTHOR
Cheryl Scott (cheryl.scott@informa.com) is cofounder and senior technical editor of BioProcess International magazine, part of Informa Connect.
References
- https://bioprocessintl.com/manufacturing/monoclonal-antibodies/uv-vis-based-determination-protein-concentration-validating-implementing-slope-measurements-using-variable-pathlength-technology/
- https://bioprocessintl.com/analytical/downstream-validation/evaluation-of-a-variable-pathlength-spectrophotometer-a-comparable-instrument-for-determining-protein-concentration/
- https://bioprocessintl.com/analytical/laboratory-equipment/using-slope-spectroscopy-methods-risk-assessment-and-cost-savings/
Key challenges and potential solutions for eliminating bottlenecks and optimizing biopharma downstream processes
Watch the full session by Christiane Schwittay, Director, Strategic Marketing Biopharma Production, Avantor
Key challenges & potential solutions for eliminating bottlenecks & optimizing biopharma downstream processes
On Day 2 of the conference, Christiane Schwittay, Director, Strategic Marketing Biopharma Production at Avantor, presented a session on the key challenges and potential solutions for eliminating bottlenecks and optimizing biopharma downstream processes. Here you can watch the full on-demand presentation, or read the overview on the following page.
Significant investments have been made in upstream technologies and processes, with the goal of increasing upstream yields – including efforts to improve raw material characterisation, add single-use systems, perfusion systems and more precisely controlled bioreactors.
On the downstream side, improvements in throughput have not kept a similar pace to those for upstream, leading to potential bottlenecks in the end-to-end process.
Finding efficiencies across downstream processing steps and cost-effectively aligning the productivity of downstream production with upstream yields requires complex analysis and optimisation.
This presentation elaborates on the key aspects of downstream processing, looking at different areas where improvements by new techniques and new technologies could be made, from current process chromatography technologies, new powder and liquid handling strategies to raw material data analysis.
The presentation will be immediately followed by a live panel discussion with additional Avantor subject matter experts on the topic of optimizing downstream processes.
Christiane Schwittay, Director, Strategic
Marketing Biopharma Production, Avantor
Single-use tech “unstoppable” if suppliers can meet soaring demand, says GSK
Single-use tech “unstoppable” if suppliers can meet soaring demand, says GSK
BioProcess Insider contributor Gareth Macdonald explores one of the stories that came out of the event.
COVID-19 has further increased already soaring demand for single-use tech according to a GSK expert who says boosting supply is key.
Most biopharmaceuticals are made in stainless steel systems. But the past decade has seen interest in using disposable single-use systems increase. Initially the focus was in clinical supply.
However, as Weibing Ding, director of GSK Pharma in King of Prussia, Pennsylvania told BPI East virtual conference delegates, a growing number of companies are trialing single-use systems for commercial-scale production.
“Single-use technology is the factor in transitioning the biopharmaceutical industry from traditional facilities to flexible plants,” Ding said, adding “single-use technology is ubiquitous in all unit operations in commercial drug substance and drug product manufacturing. Over 95% of BOM [bill of materials] can be single-use systems, or have single use components.”
But despite this potential, there are challenges involved in using single-use systems with – according to Ding – availability being the difficulty at present.
“By now we all know there are many, many benefits of using single-use technology. However, as expected, there are challenges. Technical quality and regulatory based challenges are being addresses fairly effectively,” he said.
“Supply constraint has become the top constraint for the industry. The main contributing factors to the supply constraints include short of certain materials; inaccurate demand forecasts; and the COVID-19 situation.
“We need to be very careful here that elongated supply constraints to not turn the tide of single use system implementation. As the old saying goes, forewarned is forearmed.”
Aside from increased demand, another issue is the lack of standardization. According to Ding validation processes take longer than they need to because the systems are different for each project.
“The qualification and validation work that includes product comparability assessment typically takes months to complete. The current situation is that the assemblies are custom designed by end users and suppliers. They are not interchangeable.
“To help expedite the delivery of drug products, including COVID-19 related vaccines and mAb products, there is a need to harmonize the design so that single-use systems from different suppliers – while meeting user’s functional specifications – can be used interchangeably.
He added, “To achieve that we need a diligent cross industry collaboration.”
Nevertheless, Ding predicted single-use technology has a bright future, explaining “standardization is progressing well. Second, new technologies such as such as sensors and films are being developed.
“Third emerging modalities such as cell and gene therapies, ADCs and COVID-19 vaccine adjuvants and mAbs are all increasing the use of single-use technology.
He added, “Therefore, provided we resolve the supply constraint situation, single-use technology is the future of biomanufacturing and it is unstoppable.”
Tech used for new Ebola drug key to COVID-19 fight, Regeneron
Tech used for new Ebola drug key to COVID-19 fight, Regeneron
BioProcess Insider contributor Gareth Macdonald explores one of the stories that came out of the event.
Regeneron says rapid response technologies pioneered to combat Ebola are helping accelerate efforts to create COVID-19 countermeasures.
Last week Regeneron won US FDA approval for Inmazeb (atoltivimab, maftivimab and odesivimab-), its treatment for Zaire Ebola.
The product is made from three monoclonal antibodies that target the Ebola glycoprotein, preventing the virus binding and infecting cells.
Regeneron created Inmazeb using the same rapid response manufacturing platform it is currently using for RGEN-COV2, its COVID-19 treatment candidate.
Shawn Lawrence, senior director, cell culture, preclinical manufacturing and process development, told the Bioprocess International (BPI) virtual conference last month that Regeneron’s VelociSuite technologies helped accelerate the Inmazeb.
“VelociSuite allows generation of fully human monoclonal antibodies on timeline compatible with fighting infectious disease outbreaks.”
From immunization of the target Ebola glycoprotein into Velocimmune mice through antibody selection to the creation of cell lines expressing the Inmazeb antibodies took 76 days Lawrence said.
He likened the project to Regeneron’s work on the pandemic, explaining “The rapid response paradigm was critical for developing an Ebola treatment, but the obvious infectious disease concern currently is COVID-19.”
Regeneron released the first data from a descriptive analysis of a Phase I/II/III trial of RGEN-COV2 in September.
According to the firm the data show the mAb cocktail reduces viral load and shortens the time to alleviate symptoms in non-hospitalized patients with COVID-19.
Regeneron has been gearing up to make commercial quantities of RGEN-COV2 for months and has earmarked capacity at its 130-acre site in Rensselaer, New York.
In May, the firm said it had cleared capacity at the plant to allow it to begin making the product as soon as possible.
At the time CEO Leonard Schleifer said, “We have been working to clear manufacturing capacity in our New York plant so that we can make it at large scale.
“We hope to be able to have a couple hundred thousand doses by the end of the summer and then continue to manufacture from there. In terms of pricing, donations, and fair values and all that sort of stuff that’s just got to come down the road a little bit.”
Optimization of Downstream Processing: A Case Study for Enhanced Monoclonal Antibody Purification
Jungmin Oh, Manager - New Product Development, Avantor
Optimization of Downstream Processing: A Case Study for Enhanced Monoclonal Antibody Purification
Jungmin Oh, Manager - New Product Development at Avantor, presented a case study for enhanced monoclonal antibody purification to help optimization of downstream processing. Here you can watch the full on-demand presentation, or read the overview on the following page.
An optimized downstream process is needed to efficiently manufacture and support the more than one thousand antibody therapeutics currently in clinical development. Although technological advancements such as chromatography resins with higher binding capacities, in-line process monitoring, and digitization has improved antibody manufacturing, downstream processing is still a major bottleneck. Herein, we will present an optimized downstream purification process that utilizes a novel approach to connect unit operations such as affinity chromatography resin, viral inactivation and cation exchange polishing steps.
Additionally, we demonstrate the use of novel buffers and additives for column washing and generation to increase impurity clearance in a single step to meet quality requirements while simultaneously reducing overall process time. We have screened various buffer additives and identified few for use in affinity chromatography step that can remove at least 50% more host cell protein impurities and antibody aggregates in a single step as compared to traditional approaches. In totality, these additives utilized in conjunction with optimized purification process represents a highly efficient and advantageous approach to obtaining purified monoclonal antibodies.ter experts on the topic of optimizing downstream processes.
Jungmin Oh, Manager - New Product Development, Avantor
Competition for CMOs drove inhouse investment, says Regenxbio
Competition for CMOs drove inhouse investment, says Regenxbio
BioProcess Insider contributor Gareth Macdonald explores one of the stories that came out of the event.
Regenxbio says increasing competition for capacity in the CMO space prompted the adoption of a hybrid gene therapy manufacturing strategy.
Industry demand for contract manufacturing organizations (CMOs) with the technical skills required to manufacture gene therapies has increased in recent years.
According to the Alliance for Regenerative Medicine, as of Q3 last year, 370 trials involving gene therapies were ongoing, which is an increase on the 351 underway in the equivalent period in 2018.
Katie Masterson, director of manufacturing operations at Regenxbio, told the audience at the BPI US virtual conference finding gene therapy contractors has become more difficult.
“CMO network availability today is constrained…for gene therapy it is limited as the industry is experiencing constraints because of the growing demand for these products as clinical trials and INDs have increased over the years.”
The COVID-19 pandemic has exacerbated the issue Masterson said, explaining many contractors are now prioritizing capacity for SARS-CoV-2 vaccine development and production.
This view is supported by WHO data which show there are 38 vaccines for SAR-CoV-2 in clinical development and a further 149 in preclinical trials.
In response, Regenxbio plans to use both inhouse capacity and a network of CMOs to manufacture its gene therapies.
Masterson said, “The organization decided that our strategy would consist of a combination of CMO capacity as well as the establishment of an internal manufacturing capability for both BDS [bulk drug substance] and FDP [finished drug product].”
The firm’s CMO network includes Fujifilm Diosynth Biotechnologies, under a strategic partnership established in 2018, and Advanced Bioscience Labs, which it teamed up with in 2016.
Plans for Regenxbio’s in-house capacity were unveiled in 2019 when the firm said it would set up a GMP grade vector production facility at its Rockville, Maryland headquarters.
According to Masterson “The new corporate, research and manufacturing headquarters will be ready in late 2021 with cGMP operations ready to perform early engineering runs at scales above 1,000 L in 2022.
She cited the housing of production capacity and quality control functions in the same space as a major advantage, explaining “It really will be 100% in our control, compared to the CMO only model.”
Single-use tech helps give emerging biotechs flexibility says Macrogenics
Single-use tech helps give emerging biotechs flexibility says Macrogenics
BioProcess Insider contributor Gareth Macdonald explores one of the stories that came out of the event.
Flexibility is vital for growing biopharmaceutical companies says Macrogenics, which used single-use tech to accelerate development of its Phase III manufacturing plant.
Like many younger biotechnology companies, Macrogenics initially focused on product development rather than investing in production capacity. The Maryland firm was incorporated in 2000, however, it did not set up its first manufacturing facility until 2005.
The plant was designed to manufacture candidates for Phase I/II trials and had limited capacity. Initially it could only carry out four production runs a year, but this was increased to five runs following an expansion in 2013.
In 2015, Macrogenics further expanded capacity, installing bioreactors and other technologies that allowed it to complete as many as 16 runs per year. The firm also teamed with contractors for late stage trials.
In 2018 the firm decided to set up a facility to support Phase III trials in a move prompted by the maturation of the pipeline, according to Craig Curless, senior director of manufacturing.
“We really didn’t know what our pipeline was going to be,” Curless said during his presentation at the BPI East conference – part of a virtual Biotech Week Boston in September – explaining Macrogenics opted for single-use technologies for flexibility and to keep costs down.
“We decided to use single-use equipment wherever it was possible, so that was basically everywhere in the plant except for the high-flow chromatography system, chromatography columns and the resin slurry tank.”
Flexibility was also key to Macrogenics’ technology sourcing strategy. Curless said “We tried to select the best piece of equipment for each application. We didn’t go for one vendor to supply all the equipment.”
Curless cited the range of technologies used in the plant’s downstream operations as an example.
“For filtration we use a Millipore skid. We have a Thermo Fisher harvest collection tank. We have GE [now Cytiva] chromatography columns and control systems. We have a Millipore ultrafiltration system. And we store our drug substances in Sartorius Celsius bags.”
He added that, “Another consideration for our equipment, no floor scales in the plant. So we have load cells on all of our SUMs and we also have portable stairs for the bioreactors.
“We decided that it was more space efficient to use portable stairs than building platforms…and we’re happy with that. It keeps the area more open.”
Macrogenics continued to operate its original manufacturing plant while bringing the new facility online. This required flexibility from a workforce perspective according to Curless.
“One of our challenges was how to staff a new plant while still running the old plant. So what we did is let our managers apply for positions in the new plant if they chose to or they could just keep their old position in the old plant.
“And then the manufacturing associates, we let them choose which plant they wanted to go to… and it’s worked really well. Everybody ended up in the place they wanted to be, so they were quite motivated. We had a very successful start-up of our new plant while maintaining very successful operations in our existing plant,” he said.
