Identification of Approaches to Simulated Leachable Studies
Full Title: Identification of Approaches to Simulated Leachable Studies: What are They? When to do Them?
Presented by Jason Creasey, Managing Director at Maven E&L Ltd. Followed by an Industry Perspective presentation presented by Karen Pieters, Ir. Team Leader Extractables and Leachables at Nelson Labs Europe
The term “Simulated leachable studies” is open to interpretation. I hope to provide a definition of this term and in doing so suggest when they can and should be used. The general aim of such studies is to provide an accurate qualitative and quantitative description of the substances which might be present as leachables in a pharmaceutical drug product (DP) derived from container closure system (and sometimes its manufacturing process) when the drug product is stored up to and including its shelf-life. Simulated studies provide an alternative to analysis of leachables directly in the drug product. A simulated study aims to avoid some of the downfalls of leachable analysis such as; inaccurate analysis of leachables due to interference from drug product and/or formulation elements, availability of stored DP samples, reaching required limits of detection in the DP and time / resource constraints associated with complex method development using DP.
Simulated leachable studies must be able to accurately simulate the expected leachables in a DP and should be carefully crafted to achieve this. The system used for extraction must have similar propensity to leach from materials under study a drug product and care must be taken not to use system which either leach too much (potentially masking other substance) or too little.
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Dr. Michael J. Miller, Ulrich Herber and Lori Daane
The implementation of rapid microbiological methods (RMM) has gained significant momentum over the past few years. In particular, the ATMP segment has a desire to release cell and gene therapies using rapid sterility tests to accommodate patient needs and very short drug product shelf life. Additional rapid sterility testing needs are now being fueled by companies who are developing vaccines for COVID-19 clinical trials.
In this webinar, Dr. Michael J. Miller will present an overview of past and future microbiological methods, the current regulatory landscape for rapid sterility testing including recent policy changes, applicable technologies and validation strategies.
Rajesh K. Gupta, Ph.D. Biologics Quality & Regulatory Consultants, LLC, North Potomac
Coronavirus disease (COVID-19) is a terrifying illness with high morbidity and mortality throughout the world and with devastating effects on businesses, economies, livelihood of individuals and producing depression/fear among populations due to prolonged lock downs. The only way to control the disease appears to be by developing herd immunity, either by infection or by universal vaccination. Achieving herd immunity by infection seems horrific with a significant burden on healthcare systems and sacrificing vulnerable population, including older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer. Achieving herd immunity through vaccination will take at least several months to years after development of a safe and effective vaccine. Typically, it takes a decade or more to develop a vaccine. Scientists and vaccinologists from academia, industry and Government organizations are enthusiastically working on more than 100 vaccine candidates to develop a safe and effective vaccine. There are numerous scientific, technical, manufacturing, and regulatory challenges and risks in developing vaccines in general, particularly under a fast timeline. This Webinar will go over the challenges and risks in developing Coronavirus vaccines with a view to identifying these for resolution and mitigation along with development of the vaccines.
Presented by Rajesh K. Gupta, Ph.D. Biologics Quality & Regulatory Consultants, LLC, North Potomac, USA
ROLE OF SERUM INSTITUTE OF INDIA LIMITED IN DEVELOPMENT AND MANUFACTURE OF COVID 19 VACCINE
Presented by Harish Rao, General Manager at Serum Institute of India Ltd and Amar Shrivastava, Senior Manager at Serum Institute of India Ltd
Francis Verhoeye, Global Pilot Operations Leader at Zoetis Inc. and Benjamin Asher Senior Product Manager – Bioproduction
Presented by Francis Verhoeye, Global Pilot Operations Leader at Zoetis Inc. and Benjamin Asher Senior Product Manager – Bioproduction
•Understand the implementation journey taken to accelerate veterinary biological product development
•Identify the challenges of integrating vaccine and biopharmaceutical processes
•Learn about the single use qualification and implementation process in a multi-product facility
Sara Ullsten R&D Section Manager, Cytiva and Haiyan Hong, R&D manager of Life Sciences at Saint-Gobain
This Webinar is a continuation of Final Revised Version of BioPhorum Extractable Testing Recommendation Part 1
Since the first publication of BioPhorum (previously known as BPOG) Extractable Testing Recommendation in 2014, the combined team of end-users and suppliers has collaborated to examine all improvement opportunities to the original Extractable Testing Recommendation since 2017. During this webinar, the presenters will highlight all the changes to the final revised version of BioPhorum Extractable Testing Recommendation. Specifically, the output of a data review of 26 extractable data sets spanning wide varieties of single use components, which has led to the changes to be made in the original recommendation, will be presented.
The revised extractable testing recommendation will be presented to highlight:
1) How to access the final version of the Biophorum Extractable Testing recommendation and example reporting template;
2) “Data Sharing Rules of the Road” recommendations for simplifying access to the reports
3 ) Where are the extractable data report flexibilities when using BEDS templates?
To facilitate a harmonized extractable data reporting to end users, the presenters will introduce the newly designed BioPhorum Extractable Data Summary (BEDS) template. Some levels of details with regards to what specific information or format of templates are compulsory and what are flexible for supplier to tailor to their own preferences will be detailed during the webinar. How end users can gain access to these extractable summary reports from suppliers, including subsuppliers, will be addressed.
Additionally, several FAQs questions will be presented to clarify some common questions. The webinars will end with 30 minutes of a panel discussion for participants to seek clarify of all presented information.
Dan Hill, Manufacturing Scientist at Biogen and Maryann Cuellar, Life Science Product Manager at Kaiser Optical Systems, Inc.
The use of in-line Raman spectroscopy as an in-line process analytical technology (PAT), in the biotechnology industry, has matured over the past decade from a technology with promise to a standard tool for real-time, continuous monitoring of cell culture processes. There is an ever-growing body of work demonstrating successful application from metabolite and product quality monitoring to process control in both process development and GMP manufacturing environments. This is due, in part, to advances in technology robustness, user- and integration-interfaces, improved sensitivity, and fluorescence rejection. Organizations are now faced with the difficult task of best leveraging these tools and extracting the most value from them. Thus, defining and executing Raman program strategy is critical to the technology’s long-term success and sustainability.
This presentation will describe Biogen’s past efforts and strategic direction as it relates to in-line Raman spectroscopy for cell culture operations and how we intend to leverage its capability beyond metabolite monitoring and glucose feedback control to become an essential element of our Advanced Process Control efforts.
Danny Chou, President and Founder at Compassion BioSolution, and Mark Mark Bumiller, Technology Manager at Entegris.
Presented by Danny Chou, President and Founder at Compassion BioSolution, LLC
Followed by an industry perspective presented by Mark Bumiller, Technology Manager at Entegris.
In the past decade, we have witnessed the arrival of a large number of analytical technologies that are useful for characterizing sub-visible particles in protein therapeutics. Even with the diverse tools that are available today, there are still important gaps that have not been filled but yet have a significant role in our ability to fully analyze particles for either product characterization or formulation development purpose. The goal of this presentation is to highlight some of these gaps and share the opportunities that may be captured by new tools that are on the horizon. Finally, the speaker will elaborate on how simultaneous monitoring of sub-micron and micron-sized particles can assist biopharmaceutical formulation development and help fulfill current and future regulatory requirements.”
Lawrence De Belder, Senior Principal Engineer at j&J and Bob Lenich, Director of Life Sciences Business at Emerson
Presented by Lawrence De Belder, Senior Principal Engineer Continuous Manufacturing at Johnson and Johnson
Followed by an Industry Perspective presented by Bob Lenich, Director of Life Sciences Business at Emerson
The counter is at Six today: Orkambi, Symdeko, Trikafta (Vertex); Prezista (Johnson and Johnson); Verzenio (Eli Lilly); Daurismo (Pfizer) –are all approved by the FDA – Johnson and Johnson’s Tramacet for the Japanese market not included. Several large Pharma companies have chosen the path of Continuous Manufacturing, and announced they will use this platform as their default for development and consequently – commercial manufacturing of their Oral Solid dose drug product pipeline.
During this webinar, the author will explain the consequences of this decision, and different strategies to handle a pipeline that can be highly dynamic. Different techniques will be discussed that can be used to bring products with bad flow properties into a continuous process. Impact of different equipment in development, clinical and commercial environment will be detailed out, and mitigations will be proposed to overcome these differences. All will be placed in front of a background of regulatory requirements, changing market demand, and evolving strategies of equipment vendors.
Frances Sexton, Carsten Worsøe, Ken Wong, and Satish Kumar Mohanvelu
Since the first publication of Biophorum (previously known as BPOG) Extractable Testing Recommendation in 2014, the combined team of end-users and suppliers has collaborated to examine all improvement opportunities to the original extractable testing recommendation since 2017. During this webinar, the presenters will highlight all the changes to the final revised version of Biophorum Extractable Testing Recommendation. Specifically, the output of a data review of 26 extractable data sets spanning wide varieties of single use components, which has led to the changes to be made in the original recommendation, will be presented.
The revised extractable testing recommendation will be presented to highlight:
1 End-users and suppliers collaboration set up;
2 Specific updates to the extraction study recommendation;
3 Specific areas of flexibility when implementing the protocol;
4 Updates to the analytical test method system suitability;
To facilitate a harmonized extractable data reporting to end users, the presenters will introduce the newly designed Biophorum Extractable Data Summary (BEDS) template. Some levels of details with regards to what specific information or format of templates are compulsory and what are flexible for supplier to tailor to their own preferences will be detailed during the webinar. How end users can gain access to these extractable summary reports from suppliers, including subsuppliers, will be addressed.
Additionally, several FAQs questions will be presented to clarify some common questions. The webinars will end with 30 minutes of a panel discussion for participants to seek clarify of all presented information.
Andrew Teasdale, Senior Principal Scientist at AstraZeneca and Piet Christieans, Phd,Scientific Director at Nelson Labs
FULL TITLE: Assessing the Risk of Interaction Between Extractables and Leachable and Therapeutic Proteins
Presented by Andrew Teasdale, Senior Principal Scientist Impurity management and External Advocacy at AstraZeneca
Biologics and Peptides often present their own challenges in respect to leachables. They are typically administered parenterally and therefore there is a high risk of interaction between dosage form and packaging / administration system. They are often low dose and sensitive to structural modifications, this can impact Safety (immunogenicity), Quality (instability, aggregation) and Efficacy (loss of potency). This webinar will examine the potential risk factors through case study examples including reactive leachables, the impact of sterilisation and adverse events and their route cause. It will conclude by looking at opportunities to look predictively at potential issues and how this can be incorporated into product design
Followed by Piet Christieans, Phd,Scientific Director at Nelson Labs
Mikkel Nissum, Vaccine R&D Quality Site Lead at GSK Vaccines
Presented by Mikkel Nissum, Vaccine R&D Quality Site Lead at GSK Vaccines
Only clean drinking water rivals vaccination in its ability to save lives. Yet, development and manufacturing of vaccines remain challenging. Vaccines comprise a heterogeneous variety of targets. Each target requires a dedicated development and manufacturing process adding to the timelines for getting new vaccines to the patient and to ensure a reliable supply. For the downstream processing part, often the process is composed of an optimized set of up to three chromatographic steps to provide the final desired quality of the target. On top of the long development time required to develop such a multi-step process, at times, the end result may not be satisfactory, in particular regarding purity of the target.
In order to overcome this downstream processing challenge, we embarked on establishing a purification platform based on affinity purification. The main advantages of such a platform for vaccine manufacturing would be:
1)By applying a positive selection principle for chromatography, the number of chromatographic steps may be reduced to just one step
2)Establishing a platform would require minimal process changes from one target to another
3)Downstream processing would become predicable in terms of development time and costs
The journey of establishing the affinity purification platform focusing on main challenges and key results will be presented in the Webinar.
Rui Portela and Klaus Mauch, CEO at Insilico Biotechnology AG
Machine Learning is believed to be a game changer for industry, especially by big Pharma as reflected by significant investments. Starting from an introduction to machine learning, this contribution outlines the current machine learning status for process development with examples, provides future directions towards more global high-value machine learning centric development, concepts to engage people in the digital evolution and ideas for machine learning centric business models.
Presented by Rui Portela, Senior Data Scientist, GlaxoSmithKline Vaccines
Rui Portela works as Senior Data Scientist at Global Data Analytics and Innovation group in Technical R&D of GSK Biologicals, Belgium. He is a molecular and cell biologist, with a MSc in biotechnology from the New University of Lisbon (UNL) and PhD in Bioengineering Systems (MIT-Portugal program – UNL). Previously, Rui worked on model based bioprocess optimization at GSK and IBET as research scientist, applying metabolic network analysis, PAT, simulation of molecular processes and hybrid modeling methods to enable more efficient process operation/design.
And Klaus Mauch, CEO at Insilico Biotechnology AG
Klaus Mauch is one of Insilico’s co-founders and became managing director in 2004 and CEO in 2006. In his previous role as CTO, he was responsible for the design and development of Insilico’s modelling and simulation platform where he established novel methods for the computer-aided construction of cellular networks. Before that, he gained extensive experience in metabolic engineering and applied systems biology as a group leader at the Institute of Biochemical Engineering, University of Stuttgart. Klaus is a member of the Advisory Board of the Division Systems Biology and Synthetic Biology of DECHEMA, board member of the Industrial Association White Biotechnology (IWBio), and board member of the Association of German Biotechnology Companies (VBU).
Sune Klint Andersenand Principal Scientist at Janssen Pharmaceutical and Lars Markwort, co-founder and CEO of Bioinicia SL
Presented by Sune Klint Andersen, Principal Scientist at Janssen Pharmaceutical Companies of Johnson & Johnson
Sune Klint Andersen is Principal Scientist for Spray Drying at the Janssen Pharmaceutical Companies of Johnson & Johnson. He has a Ph.D. in Chemical Engineering. He has worked with pharmaceutical spray drying for 17 years within process development for R&D and commercial scale, application of Quality-by-Design and PAT, particle engineering, drying kinetics, aseptic spray drying and advantages and disadvantages of spray vs freeze drying processes. He previously worked at Novo Nordisk for 7 years.
and followed by Lars Markwort, co-founder and CEO of Bioinicia SL
Lars Markwort is co-founder and CEO of Bioinicia SL. He holds a Ph.D. in Chemistry and worked for 20 years in the analytical and process equipment industry, supplying mainly the semiconductor and pharmaceutical industries. At Bioinicia he is guiding the scaling up of electrohydrodynamic processes to industrial production with a focus on drying, micronization and encapsulating of labile bioactives for applications in pharmaceuticals and nutraceuticals.
Kim Li, PhD, DABT, MPH, Amgen Inc and Dries Cardoen, Team Leader of Study Directors at Nelson Laboratories, LLC
Presented by Kim Li, PhD, DABT, MPH, Amgen Inc.
Followed by an industry perspective presented by Dries Cardoen, Team Leader of Study Directors - Inhalation/topical/transdermal products at Nelson Laboratories, LLC
Permitted Daily Exposure (PDE) has origin in ICH Q3C: Impurities – Guideline for Residual Solvents. This webinar will discuss the principles and methods of applying PDEs to extractactables and leachables (E&L) impurities in pharmaceutical products. We will review the regulatory advice on the DO’s and DON’Ts. Then we will review the current toxicology risk assessment practice on data gathering, literature synthesis and selection of the critical studies with robust toxicity endpoints. We will show how the toxicity endpoints are transformed into chemical-specific PDE values with modifying factors. We will highlight the importance of clinical relevance to further refine the PDE values. For a case study, we will share an extraction study of a polyolefin bag for use with a lyophilized product. We will examine the risk matrix per USP Assessment of drug product leachables associated with pharmaceutical packaging/delivery systems. The toxicology assessment of the extractables profile of the bag will illustrate the derivation of chemical-specific PDEs, as well as the refinement by taking clinical relevance into consideration.
Niki Wong, Principal Research Scientist at AbbVie Operations Singapore Pte Ltd
Full Title: New Technologies for Improving and Controlling Product Quality, Expression, Timelines and Yield in Upstream Process Development
Presented by Niki Wong, Principal Research Scientist at AbbVie Operations Singapore Pte Ltd
Increasing product demands at competitive pricing drive the need for accelerated product approval timelines, with reduced manufacturing risks and costs. New technologies which can debottleneck upstream process development or improve manufacturability success in early phase process development, translate into cell culture processes with high yield and desired product quality. An overview of different strategies and recent perspectives in upstream process development will be presented.
Tom Van Den Kerkhof Scientist at Johnson & Johnson and Sebastian Sowinski at Sentronic
Full title: Control Strategy and a Real Time Release Testing From a Development Line to Commercial Manufacturing
Presented by Tom Van Den Kerkhof Scientist at Johnson & Johnson
Followed by Sebastian Sowinski, Key Account Manager in the Spectroscopy business unit at Sentronic in Dresden
Johnson & Johnson has invested in three different continuous manufacturing lines, where PAT applications are applied to determine the uniformity of the final blend and the core tablets. Two CM lines have been implemented to accomplish the high-volume demand of two commercial products, while a third CM multi-purpose line, allowing to perform wet-granulation, roller compaction or direct compression, has been implemented in the R&D facility for the development of new drug products. In this presentation, the PAT control strategy currently applied for the commercial products as well as the one applied for new products is presented. Furthermore, the use of the generated PAT data to release the final batch is presented for a direct compression commercial product. For this commercial product, the PAT analysis performed on the core tablets by NIR spectroscopy are used to replace the final product testing in the laboratory for the release testing of assay, content uniformity and dissolution.
Ping Wang, Director at Johnson & Johnson and Donald DeCou, E&L Technology Manager at West Pharmaceutical Services
Full Title: Extractable Data Mining: Common Extractables From Polymeric Manufacturing Materials Used in Biologics Production
Presented by Ping Wang, Director at Johnson & Johnson
• Safety assessment of extractables and leachables is often based on assumption that E&L are highly toxic
• Most common extractables from about 40 sets of study data indicates that none of them is part of “cohort of concern” per ICH M7 guideline.
• Safety profiles of common extractables from common single use systems can be used to design a risk-based approach for future materials.
Followed by Current Trends in Extractables and Leachables Testing from Manufacturing Equipment to Single Use Manufacturing Components
Presented by Donald F. DeCou, Ph.D, Extractables and Leachables Technology Manager at West Pharmaceutical Services
There are many types of components that a drug formulation may contact during a typical manufacturing process. This can range from large volume mixing vessels to filters, tubing and other smaller components. More recently the use of Single Use Systems (SUS) have been steadily increasing during the manufacture, handling and storage of biologics. Each contact component has the potential to introduce leachable compounds to the drug formulation. The BioPhorum Operations Group (BPOG) has developed standardized extractables testing protocol for SUS. This talk will review some of the central concepts of the BPOG protocol as well as current trends in performing extractable, leachable and simulation studies on manufacturing components and single use systems.
Jun Huang, Director/Team Leader, Automation&Control at Pfizer and Amos Dor, Pharma General Manager & CTO at Applied Materials
Full Title: IIoT and AI for Digitalizing Pharmaceutical Manufacturing Operations: From Hype to Reality
Presented by Jun Huang, Director/Team Leader, Process Monitoring, Automation & Control at Pfizer
Driven by increased connectivity enabled by Industrial Internet of Things (IIoT) and more sophisticated data gathering and analytics/AI capabilities, manufacturing is ushering in a new era of production, where information technology (IT) and operation technology (OT) are converging to form so-called cyber-physical systems. IIoT and analytics are key complementary driving forces behind digitalization, enabling a securely connected plant and a streamlined flow of data and information between physical production and digital worlds, as well as prescription of data-driven actions pervasively across manufacturing and quality operations. Use case examples will be given to demonstrate how IIoT and analytics are implemented in practice to drive continual improvement in manufacturing visibility, quality and productivity.
Followed by an Industry Perspective Presented by Amos Dor, Pharma General Manager & CTO at Applied Materials Automation Product Group
Olav Lyngberg, Sr Scientific Fellow at Janssen Pharma and Mark Demesmaeker Head of Data Analytics at Sartorius Stedim Biotech
Full Title: The Journey Of Implementing Advanced Process Control In the Pharmaceutical Industry
Presented by Olav Lyngberg, PhD, Sr. Scientific Fellow, Advanced Technology, Technical Operations at Janssen Pharmaceuticals and
The presentation will share the journey that Janssen is taking as it progresses its strategy on Advanced Process Control (APC). Within Janssen we aspire to improve our Manufacturing Technology Organization’s performance on key metrics such as cost of goods, on time and in full product delivery, production cycle time, and right first-time process performance. Improving these metrics require a comprehensive technology strategy that can address not just one but all the key metrics together. The strategy that Janssen is pursuing has three pillars. 1: process intensification, 2: modular and flexible designs, and 3: process digitalization and advanced process control. Each pillar contributes differently to the key metrics and in aggregate and when achieved together they make it possible to reach all the goals.
Followed by Obtaining Increased Observability & Control of the Bioprocess
Presented by Mark Demesmaeker, Head of Data Analytics at Sartorius Stedim Biotech
As the biopharmaceutical industry is undergoing the digital transformation, a number of disruptive technology evolutions and market shifts are happening in parallel: Novel approaches in bioprocessing (e.g., intensified and continuous processing) are pushing cells and expression systems to their limits. New process analytical technologies are introduced, including online spectroscopy, advanced single-use sensors, and advanced modeling and simulations. Adding to that a trend towards increased miniaturization and throughput of cell culture processes puts an enormous burden on data streaming, management, and preparation. Recent progress in cellular and gene therapies also contributes to the evolution of bioprocessing.
Robert Gronke, Ph.D., Senior Principal Scientist, Biogen and Thomas Müller-Späth, Ph.D, CTO at YMC ChromaCon
Full Title: Antisense Oligonucleotide Purification Process: Successes and Challenges During Scale-up
Presented by Robert Gronke, Ph.D., Senior Principal Scientist, Technical Development, Biogen
Recently, our first full scale GMP batch for an antisense oligonucleotide was manufactured in the newly built synthesis suite at Biogen. A four-step purification process was then carried out in the existing flexible volume manufacturing facility that, up until this point, has been used for manufacturing Biogen’s protein-based parenterals. This was our first test case to demonstrate that Biogen can manufacture ASOs safely, at scale, and achieve high purity and yield. Results are presented on the scalability of the ASO process from bench to GMP scale, highlighting successes and challenges faced with scale-up of the downstream ASO process.
Followed by an industry perspective presented by Thomas Müller-Späth, Ph.D, CTO at YMC ChromaCon
Patrick Wray, Senior Research Investigator, BMS and Miriam Böhmler, Senior Applications Scientist at WITec GmbH
Full Title: In Situ High Speed NIR Imaging to Monitor Form Change and Drug Release from Rapidly Disintegrating Tablets
Presented by Patrick Wray, Senior Research Investigator at Bristol-Myers Squibb
Spectroscopic imaging is a powerful chemically specific and spatially resolved approach which can be used to effectively monitor tablet dissolution. This work employs Raman mapping and Near Infrared (NIR) chemical imaging to examine drug release from model tablet formulations as complementary technologies. Modern pushbroom type NIR imaging systems allow extremely fast acquisition of chemical images. Consequently this allows us to study the chemical and physical changes which occur during drug release from rapidly disintegrating formulations.
A custom designed flow through cell is used to carry out the tablet dissolutions in such a way that the sample is presented to the optics of the chemical imaging system being used. The cell is compatible for use with NIR, Raman and Mid IR spectrometers.
Two types or formulations will be presented: Rapidly disintegrating formulations with varying amounts of super disintegrant and tablets containing a model drug exhibiting fast onset of disproportionation in pH neutral conditions.
Followed by Cutting-edge Raman Imaging for New Advances in Pharmaceutics
Presented by Dr. Miriam Böhmler, Senior Applications Scientist at WITec GmbH
Confocal Raman imaging microscopy is a non-destructive chemical characterization method based on an energy shift in excitation light scattered by molecules or crystal lattices. This is known as the Raman effect and it can be detected by a spectrometer as a Raman peak within a Raman spectrum, which can serve as a “fingerprint” for individual materials in the sample.
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Identification of Approaches to Simulated Leachable StudiesJason Creasey, Managing Director at Maven E&L and Karen Pieters, Ir. Team Leader E&L at Nelson Labs Europe[[ webcastStartDate * 1000 | amDateFormat: 'MMM D YYYY h:mm a' ]]80 mins