Bioprocess Alert

Continuous culture is best explained by discussing the basic components of the process. The theory is well known and simple to understand: Medium is both added and removed throughout much of the fermentation in order to keep cell numbers in balance. Actual execution can be difficult for starters, as there are more pumps, tubes and considerations than a simple batch fermentation.

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Driven by epidemic events and by governmental vaccination programs, there is a rising demand for development of new vaccines and the industry is growing at a double-digit rate. The vaccine industry is facing the challenge of developing new products to serve so far unmet needs and fulfilling the demands on dose numbers, both in an economically viable way. Upstream bioprocessing is an important piece of the puzzle. High titer, robustness of the process, constant product quality, fast turn-around times, and scalability are some of the success factors.  

With this ebook we would like to share expert views and case studies on some of the hot topics in vaccine bioprocess development. We hope the information on viral vector production, continuous bioprocessing, and process scale-up will prove useful for your development projects.

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Sensors are essential devices that can be used for most, if not all, typical biopharmaceutical development and manufacturing processes to monitor fundamental process parameters such as flow, temperature, pH, and dissolved oxygen throughout all process stages. As the bioindustry progresses toward automation, digitalization, and other "Manufacturing 4.0" concepts, robust single-use and smart sensors for bioprocess monitoring will be needed. Read this BPI eBook to garner valuable perspectives on both of these types of sensors. Discussions herein focus on smart sensor capabilities, applications, and validation. Learn More

The technology used in the continuous process can pose a challenge. With this white paper a comparison of the peristaltic performance of three TPE tubing materials provides powerful insights into the effectiveness of different products. Drug manufacturers are increasingly adopting continuous bioprocessing to manufacture biologics as efficiently as possible. A key consequence of continuous bioprocessing is that single-use components and assemblies must maintain integrity for process cycle times of up to 90 days. Learn More

Changes to bioprocessing in the biopharmaceutical industry are driven by the need for increased speed, lower cost of goods (CoG), and greater flexibility. To meet these challenges, the industry is adopting strategies that include intensified processing. That requires screening large numbers of clones and then further testing the most promising ones in benchtop bioreactors. The need to perform large numbers of time-consuming, resource-intensive experiments has led to development of micro- and mini-scale bioreactor systems that offer a small-scale, high-throughput (HT) solution for accelerating clone/media selection and process development. Learn More

Andrew Hessel is a futurist and catalyst in biological technologies, helping industry, academics, and authorities better understand the changes ahead in life science. He is a Distinguished Researcher with Autodesk Inc. Bio/Nano Programmable Matter group, based out of San Francisco. He is also the co-founder of the Pink Army Cooperative, the world first cooperative biotechnology company, which is aiming to make open source viral therapies for cancer.

In this Ebook Single Use Support discusses the role their BULK.STREAM® solution plays in closing the gap between Downstream and Fill & Finish by offering biopharma companies access to a new and almost 100% secure management process for liquids on the basis of single use bags. The technologies increase patient safety and minimize the risk of bio contamination and product loss towards 0%. The process enables the storage and shipment of high-quality substances in a faster and more secure manner, and at a lower loading volume than to date.
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In this white paper, Watson-Marlow Fluid Technology Group (WMFTG), fluid path solutions provider of peristaltic pumps and single-use components, outlines the results of a study which makes comparisons between the semi volatiles extractables pro­file of post-cured and non post-cured samples of its Pumpsil platinum-cured silicone tubing. The study concludes that drug manufacturers must embrace the arguments for post-cured silicone tubing which can significantly reduce the amount of cyclosiloxanes that are present after tubing manufacturing. 

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An ever-decreasing sample volume required for analysis is allowing more and more cell and microbial cultures to be downscaled from Erlenmeyer flasks to microwell plates. Due to the standardized SBS-format of microwell plates automation solutions can be implemented, greatly expanding the possibilities of fast screening and optimization studies. Learn More

This video, produced by AdvantaPure, explains the features and benefits of their highly validated AdvantaFlex TPE Tubing.

This video, produced by G-Con, tells the story of how prefabricated PODs were delivered in 8 months to Rubius Therapeutics' cGMP facility in Smithfield, Rhode Island. Meeting their aggressive timeline and providing speed to market for clinical manufacturing.

In a recent typical experiment, eight bioreactors were sampled three times per day with feedback control for multiple separate nutrient feed solutions per vessel, based upon independent metabolite triggers. Over the course of the run each vessel was triggered feeds 35-40 times with feed volumes ranging from 2 to 40 mL for over 300 automated feeds across the eight vessels. Refined data extraction templates streamlined data imports and the electronic notebook system, and PI integration can enable remote monitoring. The enhanced system capabilities are being increasingly leveraged to support ongoing process development efforts.

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Althea, an industry leading CMO specialized in cGMP manufacturing, analytical development, aseptic filling and protein delivery technologies was looking to evaluate flow systems for multiple applications throughout their facilities. One of the main issues looking to be addressed was the replacement of weigh scales for volume measurement with flow sensors. To that end, three competing flow sensor set-ups were configured and tested for both their measuring performance and suitability as a viable solution for the application.

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Microbial contamination monitoring for process control in the pharmaceutical industry in water for injection (WFI) or pure water (PW) has relied on laboratory-based methods developed a hundred years ago. This laboratory-based approach has a number of potential sources of contamination, even when handled by highly skilled personnel, including the sample port, sampling container and testing procedure.

In this case study we discuss how a leading biopharma company in France observed positive results on its laboratory-based testing method for microbial monitoring, leading to suspicion of microbial contamination in the water system. As a root cause analysis was being conducted, the company suspected that biofilm was forming in the system, leading to positive test results. The plant turned to the Mettler Toledo Thornton 7000RMS Microbial Detection Analyzer to provide real-time analysis of their water system for process control and to immediately identify any out of specification events.

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How Does PAT Apply to the Bioreactor

This 20-page white paper provides a comprehensive, but accessible, overview of requirements and recommendations related to the FDA's Process Analytical Technology (PAT) initiative for the biopharmaceutical industry.

  • Understand critical process parameters (CPPs), critical quality attributes (CQAs), and key performance indicators (KPIs) for fermentation control in the bioreactor.

  • Know which CPPs and KPIs are the most reliable to efficiently monitor your process.

  • See the most recent examples of PAT applied in the biopharma industry and R&D.

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This video, produced by Hamilton Process Analytics, illustrates how traditional pH sensor management in a production process is costly and labor intensive - the cost of the sensor only accounts for 20 percent of total operational cost.

The Bio-Process Systems Alliance (BPSA) has published a 20-page Market Data Report - A Data-Driven Assessment of Single-Use System Reliability: 2016-2018. The report, funded and overseen by members of BPSA, used a confidential third-party to undertake this priority project that now allows SUS end-users to quantitatively assess the overall performance of SUS in order to make comprehensive business decisions. Additionally, this initiative allows each SUS supplier to benchmark their own performance against industry averages. Both end-users and suppliers can then target improvement initiatives toward complaint rate categories that align with their specific business or quality goals. Learn More

This video, produced by IDEX Health & Science, discusses real-time antibody titer monitoring for bioprocessing using their Tridex protein analyzer.

In today's state-of-the-art bioprocessing systems, one of the most essential subsystems provides gas management for the gases necessary for cellular metabolism. At the heart of the gas management subsystem is the thermal mass flow controller (MFC), advanced digital technology that precisely measures and controls process gas delivery. This new white paper describes the inner workings of digital MFCs with an emphasis on their robust ability to gather, generate and communicate a broad range of process data. The white paper focuses on practical ways to utilize MFC device data to improve process control, system uptime, diagnostics, preventive maintenance and, ultimately, bioprocessing yields. Learn More

G-CON Manufacturing and Vanrx Pharmasystems have collaborated on the development of the Microcell POD. A fully integrated, pre-qualified, pre-installed aseptic filling facility comprised of Vanrx's Microcell Vial Filler installed inside G-CON's prefabricated cleanroom POD. The first of its kind offering requires a lead time of just 3 months and is able to be shipped globally. The Microcell POD is seen as ideal for drug development, and the manufacturing of personalized medicines and clinical trial supplies. Learn More

This technical note, authored by IDEX Health & Science, describes a novel, compact device, the Tridex Protein Analyzer, capable of rapid, automated at-line measurement of antibody titers from stirred bioreactors using an aseptic sampling device. Assay linearity and accuracy were evaluated over a measurement range of 0.1 to 6.5 g/L using a simulated cell culture titer curve spiked with bovine serum albumin (BSA) and human IgG. Manual and automated aseptic sampling measurements using the Tridex analyzer compared very favorably with a commercial Protein A HPLC system. Excellent intra-assay precision (CV < 3%) was demonstrated for both off-line and at-line measurements with the Tridex analyzer. Learn More

This video, produced by Hamilton Process Analytics, utilizes narration and animation to provide insights into the basics of pH measurement.

This article explores some of the advantages a QbD approach can bring to drug development programs and how it can ensure more robust commercial manufacturing methods for consistent production of quality medications. Quality by Design (QbD) brings a systematic approach to drug development that aims to ensure quality by applying analytical and risk-management methodologies to the design, development and manufacturing of new medications. At its core, the approach looks to design quality into workflows up front. Learn More

This video, produced by Sartorius, provides practical advice for those trying to develop and implement continuous processes. It explains the tools and techniques that can be used during process development and describe how process-scale equipment can be configured to allow effective and predictable scale-up.

This video, which has 120,000+ views, describes the process by which a biological product-in this case, a pure, concentrated solution of Green Fluorescent Protein (GFP)-is derived from clarified lysate.  This is accomplished through multiple variations of two basic procedures: chromatography and filtration.

This video, which has 100,000+ views, describes the process by which a biological product-in this case, molecules of Green Fluorescent Protein (GFP)-is recovered from host e coli cells.  The steps of this process are, in very basic terms: (1) separation of cell solids from the broth, (2) disruption of those host cells to release the product contained in them, and (3) isolation of the product through removal of cell debris and other impurities.  Tools used to perform these steps include centrifuges, cell disrupters and microfilters.

This video, which has 300,000+ views, describes the role of the fermentation process in the creation of biological products and illustrates commercial-scale fermentation at a cellular level.  Included are descriptions of types of fermentation; intracellular, extracellular, types of cells (aerobic, anaerobic), and cell nutrition/media.

In this video, produced by OSIsoft, Poul Waagner Nielsen, Project Manager, Manufacturing Intelligence, at LEO Pharma describes using the PI System as a central warehouse of production data for the people and manufacturing systems in their six factories spread across Europe. Learn More

This 20-page white paper provides a comprehensive,
but accessible, overview of requirements and recommendations related to the U.S. FDA's Process Analytical Technology (PAT) initiative for the biopharmaceutical industry.

  • Understand critical process parameters (CPPs), critical quality attributes (CQAs), and key performance indicators (KPIs) for fermentation control in the bioreactor.
  • Know which CPPs and KPIs are the most reliable to efficiently monitor your process.
  • See the most recent examples of PAT applied in the biopharma industry and R&D.

Learn More

This video, produced by OSIsoft, features a brief discussion with Patrick T. O' Sullivan, Data Science Lead at Janssen in Cork, Ireland. During which he shares how Janssen is using the PI System to reduce the amount of time they spend doing data prep for their multi-million data point systems.

This video, which has 170,000+ views, utilizes a combination of animation and narration to explain the basics of Raman spectroscopy and the principles associated with application of the technology.

The titer of an antibody being expressed in a stirred bioreactor is usually measured offline using a process that involves removing an aliquot aseptically from the bioreactor, centrifuging the aliquot, and analyzing the resulting supernatant. The supernatant is analyzed either by bio-layer interferometry (BLI), Protein A HPLC, or ELISA. Such an approach may limit throughput, workflow, and efficiency. Aragen evaluated a prototype chromatography-based device that is directly connected to a bioreactor. Learn More

This video, produced by Saint-Gobain, explains the three steps commonly associated with the validation process; Installation Qualification (IQ), Operation Qualification (OQ) and Performance Qualification (PQ). These processes, when combined, usually make up the foundation of a validation package.

This video, produced by Saint-Gobain, provides a concise definition of the practice of validation accompanied by a well-informed explanation that expands on the definition to provide an improved understanding to the associated principles and practices.

This video, which has 345,000+ views, explains the measurement principles behind the four most common approaches to the measurement of liquid flow; Mechanical, Magnetic, Vortex and Ultrasonic.

This video, which has 40,000+ views, uses a combination of illustration and narration to explains the principles and practices associated with gel electrophoresis.

The logistics of decoupling drug substance manufacturing from final drug product formulation is now possible using integrated single-use freeze-thaw assemblies which incorporate reliable components. In this white paper we will explore how freezing the biological material in single-use assemblies has been enabling technology for managing the logistics. Learn More

This video features an interview with Erik Klijn, Senior Data Analytics Lead, at Janssen. During which he discusses the deployment of an OSIsoft PI system to conduct advanced analytics in biopharma manufacturing. This includes an application where the PI system is used to analyze the impact of raw materials on bioreactor performance.

This video, which has 8,000+ views, reviews the 3 pillars for maintaining a validated state. Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ).

This video, which has 5,000+ views, was produced by the U.S. FDA to explain the concept of interchangeability. The video features an interview with Leah Christl, Ph.D., former Associate Director for Therapeutic Biologics and lead of the Office of New Drugs (OND) Therapeutic Biologics and Biosimilars staff at FDA CDER.

This video, which has 10,000+ views, was produced by the U.S. FDA to address the question of "What are biosimilar products?" The video features an interview with Leah Christl, Ph.D., former Associate Director for Therapeutic Biologics and lead of the Office of New Drugs (OND) Therapeutic Biologics and Biosimilars staff at FDA CDER.

This video, which has 50,000+ views, was produced by the US FDA and uses animation supported by narration to provide an introduction to the practice of gene therapy.

In this white paper, Colder shares how t he logistics of decoupling drug substance manufacturing from final drug product formulation is now possible using integrated single-use freeze-thaw assemblies which incorporate reliable components. They explore how freezing the biological material in single-use assemblies has been enabling technology for managing the logistics. Learn More

This video, which has 5,000+ views, explains the functionality of a rotary pump by utilizing a narrated animation to demonstrate its operation.

This video discusses the basic principles for selecting an appropriate impeller for blending fluids in a stirred tank is an excerpt from the AIChE Academy eLearning Course "Fluid Mixing Technology for Operators".

This video, produced by Applikon, identifies the various bioprocessing challenges able to be addressed through the utilization of their DeltaV based V-Control solution. With an emphasis upon the suitability for seamless scalability from benchtop to production.

This video, which has 18,000+ views, demonstrates how to prepare an ultralight foam from cross linked gelatin, which can be used to keep cells alive for up to a week at room temperature. No incubator, CO2, dry ice or liquid nitrogen required.  The material is easy to make and prepare and the method works for both adherent and suspension cells.

This video, which has 100,000+ views, is hosted by UCSF Professor Wallace Marshall. It features his "Top 10 List" of unexpected and amazing things that individual cells can do. These include growing to be huge, navigating mazes, and performing feats that seem to belong in science fiction.

This video, which has 25,000+ views, uses animation and narration to  explain the measuring principle of Pt100 thin-film sensors. It also provides hints for installation in the process and describes the evaluation of the signals using temperature transmitters and displays.

This video explains the differences between the two most common  curing methods of silicone tubing; platinum curing and peroxide curing. In so it provides the viewer with an improved understanding of the advantages and challenges to be found with each.

This video, which has 18,000 views, describes the various pressure relief solutions available to protect operators and process equipment alike.

This video by Mettler Toledo, which has 9,500+ views, shares the  three things you really should know about the recommendations  made in USP 41 for achieving good weighing practices.

This video, which as 12,000+ views, utilizes a series of highly informative slides to explain the principles and practices associated with upstream bioprocessing aspects of fermentation.

This video, which has 10,000+ views, explains the role of cell therapy and that which differentiates it from the other therapeutics.

This video, which has 40,000+ views, explains through a narrated illustration the principle of measuring level with vibration.

This video, which has 35,000+ views, explains how the oxygen concentration in a liquid can be measured using the amperometric or optical measurement principles.

This video, which has 80,000+ views, uses narration and illustration to explain how a pH electrode and meter work together to measure pH.

This video, which documents a Gene Therapy site build, provides insight into the role modular/prefabricated facilities are playing in the advancement of our industry.

This video, which has 40,000+ views, provides a helpful introduction to the principles and practices associated with measuring flow with a Coriolis meter.

This video, which has 165,000+ views, provides a narrated demonstration of proper procedure for cleanroom gowning in bioprocessing.

This video, which has 80,000+ views, explains the role of clinical trials in drug discovery.

This video, part 2 of 6, provides an introduction to the principles and practices associated with viral safety.

This video, part 1 of 6, provides an introduction to the principles and practices associated with viral safety.