The medical research community on BrightTALK brings together medical and research professionals. Find relevant webinars on medical research, laboratory science, continuing medical education and more presented by recognized medical researchers. Join the conversation by participating in live webinars and round table discussions on the latest in medical devices, medical research practices and trends in the healthcare industry.
The ability to visualize immune responses non-invasively would have tremendous value for basic immunology. In pre-clinical models it would be possible to track events such as the host response to infections, to look at inflammation more generally, and to follow the course of interventions such as checkpoint blocking antibodies in the treatment of tumours.
PET imaging agents require a workflow compatible with the half-life of commonly used isotopes, and must take into account the pharmacokinetic properties of these agents. The specificity of what is being imaged requires the design of compounds that can distinguish between differences in metabolic activity (18F-fluorodeoxyglucose) or that serve as ligands for specific receptors, such as antibodies that recognize surface structures. We have used nanobodies, the smallest antibody-derived fragments that retain antigen-binding capacity. These fragments are ~15 kDa in size, are rapidly cleared from the circulation and are easily modified by chemo-enzymatic means for the installation of metal chelators or click handles to enable radiolabelling. Using nanobodies, we have been able to image various populations of immune cells, and based on longitudinal immuno-PET observations we have been able to make predictions of success and failure in immunotherapy of the B16 mouse melanoma model. The use of 89Zr-labelled nanobodies for immuno-PET will be a powerful adjunct to more conventional, invasive models, and will provide resolution superior to fluorescence- and luminescence-based models.
Does western blotting give you more trouble than expected? Do you feel like your precious samples are being wasted on bad westerns? Join us and find out how you can improve your western blots! In this seminar, you will learn general guidelines for performing and troubleshooting your westerns, such as:
• Choice of different blotting membranes
• Parameters affecting blotting efficiency
• Conditions for optimizing your immunodetection
• Information on SNAP i.d.® 2.0 system: A faster way to perform immunodetection
A digital debate analysing the future for biologics in the UK and the factor affecting market access in this territory. Our expert panel will cover a number of key topics including:
•Are the savings offered by biosimilars being used to innovate and take advantage of the exciting new biologic technologies or just filling in the NHS potholes?
•Will the industry continue to invest in cutting-edge research if the UK is not prepared to fund access to it
•In a post-Brexit world how can the UK continue to be a global leader at the cutting edge of biologics research?
Understanding the movements, modifications and interactions of proteins within a cell is key to unraveling the fundamental tenets of biology. However, the low-level expression of many proteins, combined with the transient nature of their interactions and movements, makes analyzing and understanding these processes quite difficult. Duolink® PLA, which is based on the principles of the proximity ligation assay (PLA), offers a solution to overcome these hurdles and to study the actions of endogenous proteins within cells and tissues. Combining the specificity of antibodies with the sensitivity afforded by rolling circle amplification, Duolink® PLA allows you to detect, visualize, and quantitate proteins and their interactions (even single events) where they happen within cells or tissue, all without overexpression or genetic manipulation. This seminar will cover the basic assay principle and advantages of the Duolink® PLA technology, and discuss recent applications and developments of the technology that make it an excellent tool to understand the fundamental mechanisms of biology, as well as disease states. Applications of Duolink® PLA include the investigation of cellular responses to varying stimuli, receptor dimerization and signalling cascades, post-translational modifications, and regulation of protein expression. New developments include use in flow cytometry and multiplexed detection.
Market access is influencing drug development and commercial launch strategy more than ever before, with 85% of prescription drugs in the United States reimbursed through managed care plans. Biopharma companies must take into account a multitude of factors when considering physician prescribing behaviors, and need a more integrated "pull-through" strategy across their teams, from managed markets, to marketing, to field sales. Just as an engine needs a steady supply of fuel to run efficiently, prescriber-facing teams – the commercial engine of life sciences companies – need market access data and insights to accelerate brand success. Today, the challenge is optimizing this fuel supply, as market access and commercial teams often operate in a siloed way with regards to data, market changes and insights.
Join a vibrant conversation with industry leaders to discuss how the industry is changing and adapting to operationalize market access pull-through for improved commercial success.
If you are interested in learning about photonics simulation using the COMSOL Multiphysics® software, then tune into this webinar.
Photonics (the generation, detection, and manipulation of light) plays a fundamental role in modern technology. It is used in a wide range of applications, such as telecommunications, medicine, computing, and manufacturing.
During this webinar, we will discuss using COMSOL Multiphysics® for photonics simulations, in particular periodic structures and crystals. We will show how modeling can provide insight into the design and characterisation of photonic devices. This includes solving for the propagation of electromagnetic waves, even in the presence of wavelength-dependent material properties, as well as multiphysics effects like heating or mechanical loading.
The webinar includes a live demonstration and a Q&A session during which you can ask questions.
In this webinar, Eloísa Urrechaga, M.D., Ph.D., will discuss the importance of iron status assessment in accurately diagnosing and treating anemia. The complexities of anemia require solutions that will help meet the daily challenges of distinguishing iron deficiency anemia (IDA) and isolating anemia of chronic diseases (ACD) from the combined state of IDA/ACD.
After this webinar, you will be able to:
• Discuss current advancements in anemia diagnosis
• More clearly understand the role of accurate iron status assessment
• Cite the latest research experience with Beckman Coulter analyzers in assessing iron status
P.A.C.E. credit is available for your participation.*
Eloísa Urrechaga, M.D., Ph.D., has more than 30 years of experience in hematology and laboratory medicine. She is a specialist in clinical analysis technology, robotics in hematology, iron and anemia, erythropoiesis and glycohemoglobin. Currently, Dr. Urrechaga is responsible for the hematology laboratory at the Hospital Galdakao-Usansolo in Spain.
Dr. Urrechaga contributes her expertise to the Spanish Science and Innovation Ministry by assessing new technologies. She also provides counsel to the Health Research Council for the validation of research projects in the Czech Republic and Argentina. In addition, she is a member of several international organizations, such as the World Health Organization Guideline Development Group and European Network for Rare and Congenital Anaemias. Dr. Urrechaga also serves as an editorial board member and scientific reviewer for a number of journals.
*Beckman Coulter Inc. is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. ® Program. These credits are recognized by the State of California. At this time, we cannot issue continuing education credits for those who provide healthcare (or work for an institution that provides healthcare) in Massachusetts or Vermont.
While innovation intelligence provides a wealth of data regarding future drug possibilities and their attachment to therapeutic areas, this information can be difficult to extract and integrate into workflows and processes. As such, it is hard for organizations to formulate a targeted strategy based on all the information available.
In this webinar, we will be investigating the ever increasing pressure to improve collaborative efficiency between R&D, IP and other divisions within pharmaceutical organizations in order to drive successful drug discovery and commercialization.
We will also be discussing:
- Approaches that can be taken to overcome these difficulties
- Steps that can be taken to align all teams during the entire phase of discovery & commercialization
- How to use innovation data systematically to drive further success and explore new opportunities
For the past two decades, Solid Phase Microextraction (SPME) has represented a convenient alternative to conventional sample prep procedures. SPME allows the simultaneous extraction and enrichment of analytes of interest from a given matrix in a single step while avoiding, or drastically minimizing, the use of organic solvents and time-consuming cleanup procedures.
Like any other analytical method, the various parameters governing the SPME process need to be carefully optimized in order to achieve robustness and sensitivity. However, certain aspects of SPME method development are often overlooked by many users, leading to unsatisfactory performance of the technique.
This webinar will shed light into several aspects of SPME method development. The presentation will include a theoretical explanation of SPME fundamentals and practical suggestions to overcome common errors and bias encountered when using SPME.
The webinar is divided in three main sections: 1) optimization of extraction conditions 2) matrix modifications 3) optimization of desorption conditions for gas and liquid chromatography. Each section is divided in various subsections dedicated to each parameter affecting the performance of the SPME technique. The webinar attendees will be guided through comprehensive understanding of the technology and the critical parameters that influence the extraction process with practical examples from already existing methods.
The world of the field force is changing. Increased digitalisation, powerful new tools and a growing expectation that they ‘conduct’ multiple channels means new skills, ways of working, and even thinking, are needed.
This shift will radically change the structure of the traditional Pharma organization. Differences between HQ and local offices will become less pronounced as the field force gains the ability to deploy highly tailored, right-on-time content, in the best possible format for individual physicians.
Find out more about how the time of the Multichannel Rep is now, how upskilling and reskilling are the buzzwords for new engagement models, and how not to have your field force being left behind in the digital race!
•Getting the right digital tools into the hands of reps
•How to evaluate what the best channels for your situation are
•Finding out what good looks like
•How to engage your field force, manage the change, and sustain their motivation
After the first demonstration of an optical frequency comb based on a mode-locked laser in 1999, Ti:sapphire lasers with repetition rates around 1 GHz were the sources of choice for scientists around the world. Their key feature was a mode spacing 10 times higher than that of comparable 100 MHz sources (simplifying mode identification) and the ability to generate a fully coherent super-continuum with 100 times more power per mode either directly from the cavity or using an external microstructured fibre (enhancing signal-to-noise ratio). The world’s first optical atomic clock was built in 2001 using a 1 GHz Ti:sapphire laser and subsequently it has been shown that these lasers indeed support an accuracy at the 10–20 level with a 1 s stability at the 10–17 level and optical linewidths at the millihertz level, i.e. ideal candidate clockworks for a new generation of optical atomic clocks. The Ti:sapphire technology has even been taken out to as far as 10 GHz, a regime where individual modes with powers in excess of 1 mW can be separated with a grating spectrometer and used individually for direct spectroscopy, spectrograph calibration or optical arbitrary waveform generation.
To overcome some of the disadvantages of early Ti:sapphire lasers (requirement for frequent alignment, cleaning and use of AO modulators for control purposes) and to make the full advantages of GHz frequency comb technology accessible to the science community, Laser Quantum has developed the hermetically sealed and permanently aligned taccor 1 GHz Ti:sapphire laser featuring an integrated pump laser with direct pump power control. This intervention free laser forms the basis for the new taccor comb system featuring an f-2f interferometer and full comb-stabilization electronics.
This webinar reviews the benefits of gigahertz Ti:sapphire frequency combs and focuses on the recent progress using Laser Quantum‘s hermetically sealed line of taccor lasers.
The UK Quantum Technology Hubs led by the Universities of Birmingham, Glasgow, Oxford and York are offering fully funded PhD studentships in the areas of sensing and metrology, enhanced imaging, quantum computing and secure communications, Find out more about each hub’s research and their partners, and the studentship opportunities available.
The UK Quantum Technology Hubs are part of the UK government’s £270 million National Quantum Technologies Programme set up to exploit the potential of quantum science and develop a range of emerging technologies with the potential to benefit the UK.
Single-Use Process Analytical Technologies (PAT) tools have a great potential to not only increase process understanding at the seed stage but also simplify cell culture operations. By utilizing PAT, the risk from bioburden or contamination can be significantly reduced and the overall operating efficiency increased. In fact, PAT also provides a data-driven platform to integrate Process Development and Manufacturing Operations that can mitigate risks associated with technology/process transfer.
Surgical procurement of adequate tissue can be challenging. This presentation will be an in-depth look at rapid on-site evaluation of tissue biopsies from various sites. Best practices for handling, grossing and histology sectioning of tissue biopsies for companion diagnostics will be discussed. This will be followed by a brief overview of this approach applied to immunohistochemistry stains and fluorescence in situ hybridization.
Lung cancer is the most commonly diagnosed non-skin cancer in the United States. Each year, over 222,000 people are diagnosed with lung cancer, and over 150,000 succumb each year to the illness, making it also the deadliest cancer in the country. With constant advancement of treatment options, the importance of accurate diagnosis and detection of lung cancer becomes more and more relevant to the survival of the patient. Immunohistochemistry has served as the catalyst for these advancements in lung cancer diagnosis. This presentation covers many of the basic science, facts, and statistics of lung cancer, as well as the utility of immunohistochemical testing with markers such as TTF-1, napsin A, desmoglein-3, and p40 in the accurate diagnosis and survival rates of lung cancer.
Do you find the process of writing a scientific paper unfamiliar and stressful, and wish that there is an expert to guide you through it?
In this webinar/publishing clinic session, you will learn about top challenges that researchers face when publishing scientific papers, followed by solutions and recommendations by experts in the field.
Topics covered include:
- Most-encountered challenges to publishing and how to tackle them
- Success story: Journey as an early career researcher
- Success story: Practical tips that worked
Presented by: Dr. José Oliveira, Editor-in-Chief, Small, Wiley and
Dr. Patchanita Thamyongkit, Associate Professor, Department of Chemistry, Faculty of Science, Chulalongkorn University
Growing patient influence combined with new technologies and the requirements of new reimbursement models means clinical research is undergoing rapid transformation. Industry is being compelled to move towards more patient centric solutions to keep up with these changes. With healthcare stakeholders in agreement that patient engagement is key to realising the value of clinical trials, regulators, sponsors, CROs, research funders and publishers are all moving towards more patient-focused models.
With the advent of new methodologies, such as electronic data sources and medical records, recruiting patients for trials now demands extensive collaboration between patients and trial centers to effectively and efficiently run trials. The patient has never been more important.
To mark Clinical Trials Awareness Week, pharmaphorum, in partnership with INC, will present a live webinar exploring the challenges and solutions of the current environment and how collaboration can benefit research participation, as well as the vital role the patient advocate plays in these matters.
If you are interested in modelling smart materials and MEMS using COMSOL Multiphysics®, then tune into this webinar.
Smart materials are materials whose properties or shape respond dynamically to stimuli in their environment. For example, piezoelectric materials experience strain under an applied electric field, while magnetostrictive materials deform in the presence of a magnetic field.
In this live webinar, you will learn how to model MEMS sensors and actuators based on smart materials for a wide range of applications, including vibration and active shape control as well as structural health monitoring and energy harvesting. We will also demonstrate the applicability of the COMSOL Multiphysics® simulation environment for coupling mechanical, electrical and thermal models of smart materials.
At the end of this webinar, you can ask questions during the Q&A session.
In typical analytical workflows, sample preparation accounts for over 60% of the time taken to generate results and 30% of any errors generated. To help analytical chemists maintain the cornerstones of all analytical processes, namely; speed, specificity, sensitivity, and reproducibility, considerable resources have been devoted to the development of new and unique technologies in the sample preparation field. With specific reference to solid phase extraction and solid phase microextraction, this presentation will outline new technologies and techniques developed in sample preparation for food analysis.
The life sciences landscape is moving at a rapid pace, which in turn is increasing the demands on marketers to create innovative, digital content faster while maintaining industry compliance.
Veeva Systems recently conducted an annual industry study, focused on content and digital asset management within life sciences. Gleaned from the experiences and opinions of leaders across the life sciences industry, the research uncovers current practices and the industry’s need for more advanced approaches for global marketing and regulatory compliance.
Join this webinar to hear the key insights from the survey results, and discuss key highlights with host David Bennett, VP Commercial Content Strategy Europe, Veeva.
From this webinar you will:
– Learn the current state of commercial content and digital asset management in life sciences promotions
– Garner an understanding of how your organization compares to the industry
– Understand how to accelerate your content across the digital supply chain
Nearly 50% of business leaders fear they will become obsolete over the next several years, and nearly 80% feel threatened by digital startups. Why? New technologies and digital strategies are challenging existing business models and forcing companies of all sizes to reimagine patient care, product innovation and distribution models to remain competitive.
View this on-demand webinar hosted by PharmaVOICE to learn from Andrea Bradbury, Co-Founder and Chief Quality Officer, Suvoda Software, a leader operating at the intersection of life sciences and technology as she shares how she built her business on a digital platform to accelerate her organization’s global expansion while meeting the needs of mobile, digital customers and employees.
Topics covered include:
- Streamlining clinical research, sales and HR processes with digital tools
- Elevating the digital agenda at your organization
- Scaling technologies globally
- Applying nimble design models for life science operations
- Implementing top life sciences trends in 2017
To successfully develop and launch an asset it’s crucial to identify and define the commercial value early in the process.
On the 19th April Cello Health, in association with PMGroup, will host a free webinar which will discuss the background and context of early asset development and how to achieve a successful market assessment strategy.
It will look at how marketers can understand the competitive market landscape as early as possible.
TeVido BioDevices uses the innovative process of 3D bioprinting living human cells for use as implants or grafts for use in reconstructive surgery and wound care, for example in post-surgery care for cancer patients.
TeVido uses a simple yet sophisticated approach to produce living tissue products - inkjet printers modified to print cells instead of ink.
In this live webinar, Dr. Scott Collins, CTO and VP of Research and Development at TeVido, will explain TeVido’s innovation journey, from concept, through research and prototying, to funding, patenting, and testing the company’s highly innovative offering in the field of biotechnology.
Immunotherapy is changing the cancer care paradigm: for a small but significant group of patients, cancer has become a chronic disease and immunotherapy biomarkers like PD-L1 play an important role. In this presentation, Professor Kerr will provide a summary of the immunotherapy treatment landscape, address what makes immunotherapy biomarkers unique compared to biomarkers like HER-2 and ALK, describe the function (physiologic and as a biomarker) of PD-L1 and other biomarkers relevant to the PD-1/PD-L1 pathway. He will also address the role of emerging immunotherapy biomarkers that are independent of the PD-1/PD-L1 pathway.
With a wealth of market and regulatory changes impacting the medtech sector, it’s time for digital technology to steer the direction of your future business. This expert webinar will evaluate how to strategically embed digital within your own organisation and explore the challenges and the opportunities for transforming customer relationships, driving commercial outcomes.
– Respond to the changing regulatory environment: how technology empowers your business
– Build a business case for digital transformation and gain organisational support
– Strengthen your customer relationships and improve engagement in a diverse payer landscape
– Learn from pharma (and other industries) to find opportunities and avoid pitfalls
– Measure impact and return on investment from digital engagement
The benefits of three dimensional (3D) cell culture are widely appreciated. More cell-based technologies are now becoming available that enable researchers to preserve the native 3D structure of cells in vitro. These can be broadly divided into three areas: aggregate-based methods; hydrogels and extra-cellular matrices; and inert scaffold-based technologies. Each has strengths and weaknesses and there is no one technology that satisfies all applications. Tissues in the body are mostly composed of different cell types that are often highly organized in relation to each other. Often cells are arranged in distinct layers that enable signalling and cell-to-cell interactions. Alternatively in tumours, cancer cells form aggregates and tissue masses composed of different cell types. Recreation of these types of architecture will significantly evolve 3D cell culture to a new level where real tissue-like structures can be generated in vitro.
This webinar will review the alternative approaches available to researchers and provide an overview of their capabilities and example applications. More sophisticated models are developing as 3D cell culture technology becomes established and accepted as a means of creating more physiologically relevant cell-based assays. Methods that are relatively straightforward to use and that recreate the organized structure of real tissues will become valuable research tools for use in discovery, validation studies, and modelling disease.
Key areas covered:
• 2D vs 3D cell culture debate
• Review of alternative approaches and the development of new technologies
• Challenges facing 3D culture methods, in terms of technologies available and methods used
• Showcase applications where 3D technology makes a difference
• Future perspective for 3D cell culture technology and further development
When new products approach the market the level of demand for them is often exaggerated.
However, in the real-world we know healthcare professionals may be less comfortable switching from a familiar product, even when clinical trial data suggests a newer product is superior. So what are we missing?
On the 11th July Cello Health Insight, in association with PMGroup, will host a free webinar where we will explore whether ‘regret minimisation’ - an alternative approach that focusses on minimising potential losses - has the potential to offer us new ways to understand the customer behaviour.
Solid phase microexatraction or SPME is a green method for extraction of analytes out of a sample. Since SPME is a non-exhaustive extraction technique, some analysts believe that SPME is not quantifiable. This presentation will provide basic information for developing a method to extract and quantify analytes using SPME. Examples will be given on the extraction and quantification of analytes out of various matrices, and SPME will be compared to other extraction techniques such as QuEChERS and SPE. In this webinar, we will discuss some new SPME technologies such as SPME-OC (over-coated) fibers and BioSPME that help to isolate and quantify analytes from interfering compounds in the matrix. Guidelines will be provided for enhancement of precision using SPME.
Next-generation sequencing (NGS) has emerged as a key technology to deliver the next level of healthcare solutions. While the $1,000 genome was achieved in 2015, Frost & Sullivan predicts the $100 genome to be possible by 2024. The significant dip in cost of extracting genetic data has led to the creation of massive genomic data volumes that are expected to be some of the largest data sets globally by 2025, exceeding data generated by YouTube and Twitter.
The importance and value of continuous bioprocessing, both upstream and downstream has economic and sustainability advantages and due to the modular nature of continuous bioprocesses means that industry is able to adapt more rapidly to changing market demands. Continuous biopharmaceutical manufacturing in the context of other industries that have already successfully adopted continuous processing. Factor other than scientific ones, are the barriers to change from batch to continuous production. an excellent example of the manufacturing strategies of the steel industry in the 20th century, when this industrial sector incrementally switched from batch to continuous operations. biopharmaceutical industry has reached a stage that requires a change in the production paradigm. For a certain class of biopharmaceutical products upstream continuous manufacturing has always been applied: for example, unstable proteins that rapidly degrade in the culture broth. In order to obtain a high quality product, the residence time in the reactor must be minimized. This can only be achieved with continuous cultivation and preferably with perfusion reactors. a brief overview on the types of cell retention devices currently used in biopharmaceutical industry.
Furthermore, this is a universal production platform that can be extended to other classes of products, such as antibodies, which are relatively stable molecules. continuous manufacturing is as productive and with a much smaller footprint of the manufacturing plant, avoiding multiple non-value added unit operations. In essence, the investment for a continuous plant is much smaller compared to a batch-operated one.
Join us to find out about the results of the 2017 Multichannel Maturometer. The ninth version of this industry-renowned survey illuminates some of the big changes sweeping through the Pharma industry, as well as highlighting some trends which are still lagging.
Questions which will be answered include:
• Is senior leadership still on the fence for digital?
• Marketing budgets – how are they changing?
• How satisfactory are those in the industry finding digital offerings?
1. The kidney proximal tubule is the primary site of drug-induced nephrotoxicity. I will describe the development of a 3-dimensional flow-directed proximal tubule microphysiological system (MPS). The kidney MPS recapitulates the synthetic, metabolic and transport activities of kidney proximal tubule cells. This MPS is as an ideal platform for ex vivo modeling of nephrotoxicity. Towards this goal, we have evaluated nephrotoxicity in response to challenge with multiple toxicants, including the heavy metal pollutant cadmium, antisense oligonucleotides, the antibiotic polymyxin B and the Chinese herbal product aristolochic acid. We believe that MPS technologies will have major impacts on predictive toxicity testing and human risk assessment. Animal and in vitro systems do not always faithfully recapitulate drug and xenobiotic responses in the clinic or occupational/environmental exposures, respectively. MPS technologies will refine safety assessment and reduce our need for surrogate animal testing. An ultimate goal is to create integrated human MPS organ systems that could replace animal models.
2. Nortis has developed a technology that is used to recapitulate functional units of human organs in microfluidic devices (chips). Such organ models include vasculature, kidney, and liver models for toxicology studies, blood-brain barrier models for drug transport studies, and vascularized tumor microenvironment models for drug efficacy studies.
Hospital information technology (Hospital IT) spending in Asia-Pacific (APAC) will grow at a compound annual growth rate of 9.7% between 2016 and 2021 to reach an estimated end-stage market size of more than $15 billion. Key growth opportunities in the region include solutions for Healthcare Data Continuity, Patient Engagement & Experience, Healthcare Cloud, Big Data & Analytics, and Healthcare Cybersecurity. However, the identification of these growth opportunities is only the first step toward succeeding as an ICT vendor in this market. The real demystification lies in understanding very specific target customer needs and then building a value proposition and business model that addresses those needs.
Historically, quality of biological products has been ensured through testing representative samples. Shift in quality paradigm started with implementation of Good Manufacturing Practice (GMP) regulations with current focus on building quality during manufacture. Inherent variability and complexity of biological products pose challenges in implementing Quality by design (QbD) concept. This presentation discusses ways to build quality during manufacture of biological products.
ADCs are complex compounds resulting from the coupling of cytotoxic small molecules to a monoclonal antibody. Their characterization as well as their bioanalysis (quantification in biological fluids) remains challenging. Mass spectrometry at different levels (intact, middle, peptide) can be a valuable tool, and can now be used in a regulated environment thanks to advances in both hardware and software.
Following a decade (or more) of concerted effort by industry, regulator, and academic groups, recent technology investments are now beginning to shape how medicines are being developed and manufactured for the global marketplace. While significant focus has highlighted the emergence of continuous manufacturing processes, three additional trends have also influenced and served as underlying drivers for these technology investments. First, the emergence of scientific advances in targeted biology has created high-value personalized medicines with smaller manufacturing volumes (doses/annum). Second, new regulatory pathways, such as the FDA’s Breakthrough Therapy designation, have accelerated the development and commercialization timelines for these new medicines. Finally, manufacturing localization has extended supply chain networks to serve globally-distributed patient populations throughout the world. Together, these drivers have served to shape the future of pharmaceutical development, manufacturing, and distribution of a variety of different dosage forms. The increasing need for product development speed and commercial supply flexibility through small-footprint, modular equipment trains will be highlighted within this paper, using an immediate-release solid oral dosage form example.
Common mammalian cell lines used for biopharmaceutical production include Chinese Hamster Ovary (CHO), NS0 and Human Embryonic Kidney (HEK) cells. Each of these cell lines has been found with over 20,000 genes coded in their genome, which can result in over 10,000 proteins expressed at the same time in these cells. These proteins can be secreted from the living host cells or released to the cell culture supernatant upon lysis of the host cells during the cell culture. Biopharmaceuticals produced using these cell lines can be co-purified with a subset of the host-cell proteins (HCPs) in the cell culture supernatant.
These co-purified HCPs are considered process-related impurities for biopharmaceuticals. The HCPs can cause potential safety risks by introducing anti-HCP response in the patients. Depending on the biological functions of the residual HCPs, other potential impacts reported include lowering the biopharmaceutical protein stability and affecting the efficacy of the biopharmaceutical protein by exacerbating the symptoms.
Since the introduction of disposables and gaining popularity of Single-use Technology (SUT) for biopharmaceutical manufacturing there is nevertheless an ongoing controversial discussion on the advantages and disadvantages versus a conventional stainless steel environment.
In a “classical” facility design any validation cost effort can easily be distributed to a considerable number of production runs thus contributing only to a non-decisive amount to the overall production costs. The scale for such plant is nearly unlimited as is the scale of operation. The “flexible” approach using disposables and single-use equipment offers significant advantages regarding changeover work and time thus a high throughput of different processes will definitely take profit as any cleaning and related validation and costly analytics doesn’t apply to a larger extent.
Despite the potential benefits loudly advertised by the respective industry, these potential advantages derived from single-use equipment and disposables can be significantly diminished by lack of detailed process cost analysis, missing economic analysis and cost comparison between conventional and SU technologies as well as underestimating the cost of long term dependency on consumables. Due to missing appropriate standards, there is a widely non-compatibility between the equipment and consumables of the various suppliers, resulting in a strong dependence on the consumables of a single supplier once a single-use equipment has been purchased, curiously leaving some customers with surprise that they hardly have any room for price negotiations on the required consumables.
This paper’s focus is on the very different arguments for the application of SU equipment and consumables, including advantages and limitations of SUT, understanding improvement of process robustness, contribution to lean production as well as environmental impact of disposables.
Single-use (SU) systems are now in common use in pharmaceutical bioprocessing, as well as in other related technologies such as the manufacture of diagnostics and other biological products, and their popularity is increasing. Some types of SU systems have been in use for many decades now. The earliest SU systems being disposable filter cartridges that do not require a stainless steel (SS) filter housing. This present article seeks to focus in particular on SU bioreactors for cell culture and bacterial fermentation for the purpose of producing therapeutic proteins, monoclonal antibodies and vaccines. SU bioreactors are of particular value in early phase (Clinical Phases 1 and 2) GMP manufacturing. In some cases their use has now stretched through into commercial processing, albeit that the scale of operation is currently limited and in general the largest commercially available SU bioreactors are around 2000L working volume (WV). However, the small footprint that they require, and the reduction in investment needed for support services and utilities, means that the scale limitations can be overcome to a significant degree by having multiple SU bioreactors operating in parallel within a facility. The harvest from multiple bioreactors can be pooled for downstream processing, or each harvest can be processed as a separate batch, based upon considerations of the risks versus the economies of pooling.
Recently, there has been a renewed interest in the field of continuous processing. Some key factors driving this interest are – availability of better cell retention devices, improved cell lines and culture medium capable of supporting high cell densities.
These factors have contributed mainly in reducing the batch duration for making the required quantity of product, thus reducing the medium requirement and chances of batch failures significantly. With the continuous processing being considered as ‘back-in-the-game’, the question remains: Can the current perfusion technology compete or replace the conventional and widely preferred fed-batch technology?
Two cases are discussed to compare the performance features of fed-batch and perfusion processes. In both the cases, the product output from perfusion process is significantly higher (2 to 5 folds) than that from fed-batch, due to combination of factors like higher cell density, higher cell specific productivity, lower accumulation of toxic metabolites etc. These cases demonstrate the potential of perfusion process in significantly increasing the product output. However, there are certain challenges and points to be considered before a company decides to switch to a perfusion platform. Some of these are highlighted in the article.
The development and application of continuous manufacturing processes for vaccines presents both great opportunity as well as significant challenges, both technical and cultural, for the global industry. The key drivers are manufacturing capacity and flexibility, speed to market, and improved quality through the application of Quality-by-Design and Process Analytical Technology (QbD/PAT). Given the diversity of immunogens (toxoids, conjugate and subunit vaccines, live-attenuated and inactivated viruses, VLPs, etc.), and the variety of unique processes currently utilized to produce either single- or multi-component vaccines, it is unlikely that the transition to continuous processing will happen overnight. Additionally, cultural challenges are faced whenever a new mode of operation appears to some as “too different”, especially in a traditionally conservative sector like the developed-world vaccine industry. That said, market forces, global climate change, and Nature’s propensity to fill unoccupied niches with emerging infectious diseases will undoubtedly induce a first round of pioneers to explore this exciting new design space, ultimately leading to a more nimble industry and more and better opportunities for protection for the global population.