Pharmaceutical Forensics for Safe Manufacturing and Supply
by Ravi Kalyanaraman, Director at BMS
Pharmaceutical Investigations and Technology (PIT) is a group within Global Analytical Technology (GAT) department in the commercial Quality organization within Bristol-Myers Squibb. The PIT group has been a key part in BMS for 30 + years in providing analytical support for commercial manufacturing and in pharmaceutical forensics. This include particulate and foreign matter characterization in pharmaceutical products and screening counterfeit drugs. Several analytical tools and techniques are used by PIT to support the pharmaceutical forensics.This talk will feature all the analytical techniques used by PIT and how the results are used in resolving manufacturing issues and to protect patients from counterfeit drugs.
Followed by Why Use Raman Microscopy for Pharmaceutical Forensics?
by Dr. Robert Heintz, Senior Applications Specialist at Thermo Fisher Scientific
Raman microscopy is uniquely suited for providing essential information for pharmaceutical forensic applications. The use of visible lasers allows for analysis of very small samples with spatial resolutions down to a micron or better. Materials can be analyzed in glass containers and through transparent packaging. Mapping and imaging provides information on the spatial distribution of components as well as particle sizes and shapes. Confocal operation allows for probing inside transparent materials and analyze different layers or inclusions without the need to cut or cross-section the sample. Raman microscopy is non-destructive and preserves the sample for further analysis. Raman spectra can be used not only for the conformation of expected components but also the identification of unknown contaminants or impurities. Spectral features are very sensitive to molecular structure and can be used to distinguish polymorphs and other very chemically similar materials. All of these aspects of Raman microscopy make it an indispensable tool for pharmaceutical forensics.
RecordedJun 14 201974 mins
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Fouad Atouf, Ph.D., Director at USP and Horst Ruppach, Ph.D. Scientific Director at Charles River
Qualification of raw materials used in the manufacturing of cellular therapies requires the use of risk assessment strategies to categorize the critical components of a manufacturing process. In addition to cell culture supplements, excipients and other formulation’s components must meet the required quality to ensure consistency in manufacturing and subsequently the quality and safety of finished cell therapy products. This presentation will discuss the critical challenges facing the development of cell therapies, and the type of qualification programs to help ensure consistency in the manufacturing of cell and gene therapies.
Presented by Fouad Atouf, Ph.D., Director at US Pharmacopeia
Fouad Atouf is Vice President, Science—Global Biologics, for USP. He leads all scientific activities related to the development and maintenance of documentary and reference standards for biologics and antibiotics, and oversees the biologics laboratories in USP–U.S. and USP–India. His department supports the work of the associated USP Expert Committees. Dr. Atouf has been at USP for over 10 years and served in a variety of scientific leadership roles including being the regional champion for the Middle East and North Africa Region, where he helped facilitate programs designed to enhance the understanding of the role of regulations and standards in the registration of medicinal products. Dr. Atouf has strong background and experience in the development and regulation of cellular and tissue-based products. Prior to joining USP in 2006, his research at the U.S. National Institutes of Health focused on developing methods for the in vitro generation of cell-based therapies for diabetes. Dr. Atouf is the author of numerous publications in peer-reviewed journals and a frequent speaker at national and international scientific conferences. Dr. Atouf earned his Master’s degree in Biochemistry and his Ph.D. in Cell Biology from the Pierre & Marie Curie University, Paris, France.
Narasimha Rao Nedunuri, CEO of CLONZ Biotech and José Castillo, PhD, CTo and co-founder of Univercells
Cost contribution of continuous manufacturing both in operational and capital expenditure in Monoclonal antibody production.
Evaluating cost of production per gram conventional fed batch vs continuous process.
Key considerations for adapting continuous process for the production of Biosimilar MAbs.
Presented by Narasimha Rao Nedunuri, CEO of CLONZ Biotech
Narasimha Rao Nedunuri is one of the founding members of CLONZ Biotech, a Biosimilar Monoclonal Antibody company based in Genome Valley, Hyderabad, India.
He is currently serving the company as the Managing Director & CEO .
Nedunuri, a Molecular Biologist turned Entrepreneur has 18 years of experience in the field of Life Sciences Research including Cancer Biology, Proteomics, and Molecular diagnostics. He also had business experience in a USA based company, with the responsibility of establishing a business division for its Indian subsidiary.
At CLONZ , a 7 year old start-up, along with the co-promoters coming from recognized leaders who launched complex Biosimilar MAbs, driving the company to emerge as a significant Global Biosimilar MAb company.
Bastiaan Leewis of MeiraGTx and Ankita Desai of Eppendorf
Full Title: Implementation Of An Affordable And Scalable Manufacturing Strategy For Gene Therapy Products
Presented by Bastiaan Leewis, MSAT Manager of Industrialization at MeiraGTx
As a start up with multiple clinical programs within an accelerated track we started designing our processes and aimed to build facilities to ensure therapeutic drug products reach patients as quickly as possible. As scientists and as people this tends to be the main goal, and although there are many challenges to commercializing a therapeutic drug product this is only the first step. To be able to continually serve patients, the company must be set up in a way to be sustainable throughout the clinical phase until revenue can be generated via commercial sales. Understanding the patient and company needs are a key cornerstone for having successful products and a successful company transition from clinical to commercial products. Within this presentation I will illustrate and explain the approach chosen by MeiraGTx for some of the platform components.
Followed by Bioprocess solutions for upstream bioprocess development and scale-up
Presented by Ankita Desai, Bioprocess Field Application Specialist at Eppendorf
Upstream bioprocess development is an integral part of gene therapy product development. Cell culture bioprocess development is usually carried out at small working volumes. This helps save time and resources, because several experiments can be conducted in parallel, costs for media are kept low, and relatively little laboratory space is required. When more material is needed for characterization, trial runs, and finally for commercialization, biopharmaceutical companies transition the process to bench scale and then up to pilot or production scale. In this presentation, we will present bioprocess solutions for parallel process development at small scale. Furthermore, we will discuss bioreactor scalability and address several scaling approaches.
Diane McCarthy, PhD, Senior Scientific Liaison, US Pharmacopeia and Kai Scheffler Product Manager at Thermo Fisher Scientific
By Diane McCarthy, PhD, Senior Scientific Liaison, Global Biologics, US Pharmacopeia
Biotherapeutic products are typically characterized by multiple orthogonal methods to evaluate product quality and purity, including assessment of aggregates, variants, and degradation products. For monoclonal antibodies and many other biotherapeutics, analysis of post-translational modifications, such as glycosylation, are also important since these modifications can impact the efficacy, stability, and safety of the final product. This presentation will provide an overview of methods and standards used during characterization, with an emphasis on monoclonal antibodies.
Followed by Charge Variant Separation Coupled to High Resolution Mass Spectrometry for Routine mAb Analysis
By Dr Kai Scheffler, Product Manager at Thermo Fisher Scientific
Biotherapeutics such as monoclonal antibodies are a heterogeneous mixture of structurally similar molecules that differ in mass and charge, referred to as charge variants. Charge variants result from sequence variations and post-translational modifications such as e.g. deamidation and sialylation resulting in species that are more basic or acidic than the main mAb monomer. The heterogeneity can be revealed by charge-sensitive separation methods, such as ion exchange chromatography. The use of MS-compatible buffers allows for online hyphenation to a mass spectrometer. This hyphenated setup provides the chromatographic resolution of ion exchange chromatography coupled to the identification of the separated variants by mass spectrometry.
In this webinar we will discuss a charge variant analysis (CVA) workflow that entails ion exchange chromatography using pH gradients for protein elution with online mass detection on a high resolution Orbitrap-based mass spectrometer. This workflow enables routine application to a wide range of antibody samples for comprehensive analysis based on a single injection without the need for sample preparation.
Jackal Tsou, Supervisor at Mycenax Biotech Inc.and Gerben Zijlstra, Global Technology Consultant at Sartorius Stedim Biotech
As the development process of monoclonal antibodies has come to a steady, it is assumed the automatic flow can be adopted and it is the beginning test ground for continuous manufacturing, to link the upstream cultivation to downstream purification in a continuous mode. We will show some preliminary results for this new era, Biomanufacturing 4.0.
Presented by Jackal Tsou, Team Supervisor of Downstream Process Development at Mycenax Biotech Inc.
Pearl has worked over 15 years in the biotechnology industries to serve both operating and consulting roles for more than 30 biomedical projects. As Director of Project development, she operates in CMC, project management, project oversight, regulatory consulting and business development fields. Pearl’s educational credentials include a Bachelor of Nutrition and Health Science and a Master in Molecular Biology and Biotechnology. She has brought the very first biological medicinal product from preclinical to NDA approval in Taiwan.
Followed by Gerben Zijlstra, Global Technology Consultant at Sartorius Stedim Biotech
Gerben is a regular speaker on process intensification and continuous biomanufacturing. He received his Ph.D. from the University of Wageningen, NL, in the field of process integration in cell culture.
He has worked for more than 20 years at CMO DSM Biologics and has been involved in the development of several Bio-therapeutics. He was one of the early adopters of single-use bioreactors and is the first inventor of the Concentrated Fed-Batch – XD® technology. Gerben was deeply involved in the tech transfer of XD® technology to the Brisbane, AU site, which received the 2014 ISPE facility of the year award for process innovations. As a consultant at Xendo, Gerben has been working on Continuous BioManufacturing and Gene Therapy projects. Since 2016 he has joined the Sartorius Team, where he currently holds a position as Global Tech Expert for Intensified BioManufacturing.
Jeremy Springall PhD, Scientist II, Analytical Sciences, R&D Biopharmaceutical Development, AstraZeneca
Full Title: How to Utilize Design of Experiments (DoE) Principles for the Development of High Throughput, Robust Methods for the Assessment of Product Quality
Being able to generate accurate and precise analytical data to provide information on product quality in a timely manner is a great challenge facing analytical groups. By adopting a Design of Experiments (DoE) approach, we can overcome many hurdles facing the implementation and adoption of these high-throughput chromatography methods with the data generated being of comparable quality to that from longer lot release methods.
Presented by Jeremy Springall PhD, Scientist II, Analytical Sciences, R&D Biopharmaceutical Development, AstraZeneca
Jeremy Springall has worked in the Analytical Sciences group, part of R&D Biopharmaceutical Development, at AstraZeneca for the past five years. His responsibilities include assess new technologies and work processes to support early and late stage development assets as well as being a CMC analytical team lead on several non-mAb projects currently in the AstraZeneca development pipeline. Previous roles include In-process analytical development scientist at UCB and analytical development scientist at Patheon, both in the UK. He holds a Ph.D. in bioorganic and medicinal chemistry and a BSc in chemistry from the University of Bath, UK.
Jincai Li, Vice President of WuXi Biologics Kevin Mullen, Sr. Product Manager, Single-Use Systems at Thermo Fisher Scientific
Presented by Dr. Jincai Li, Vice President of WuXi Biologics
With the rapid growth of the biotherapeutics industry, the need and challenge for high quality, cost efficient production has been increasing as well. At the same time, the number of approved biologics products are also steadily increasing, and more and more products are being developed by small to mid-size biotech companies, with product market size that vary greatly and therefore leading to varying production scale needs. The presentation will talk about the paradigm shifts in today’s facility design and operations, with multi-purpose facility and smaller, modular facility being favored by many companies. In addition, rapid adoption of disposable technology has enabled faster and lower cost facility design & start-up. With the modular, disposable technologies, the unique “scale-out” approach has the advantage of providing highest flexibility to customers while simultaneously lowering tech transfer and scale-up risks. The presentation will also cover the somewhat unique challenge of transitioning from clinical manufacturing to commercial manufacturing and maintaining both clinical and commercial manufacturing in the same facility.
Followed by a presentation by Kevin Mullen, Sr. Product Manager, Single-Use Systems at Thermo Fisher Scientific
Scott R. Burger, MD, Principal of Advanced Cell & Gene Therapy, LLC and Heidi Hagen, Co-founder and CSO for Vineti Inc
The quest to retrieve, analyze, and leverage that data has become the new gold rush in life sciences. This presentation will discuss the role of big data in cell therapy process development, real time analytics and commercial scale manufacturing.
Kumar Gaurav, AGM (Regulatory Affairs) at Panacea Biotec Ltd
Current trends and regulation affecting Biopharmaceutical Industry
Journey from Lab scale to Commercial –Overcoming Scalability design hurdles
QbD-Bringing Improvements in Biologics development and Manufacturing Space
Dr Benoit Ramond, Head of Microbiology & Sterile Technology, Sanofi and Dr David Jones, Director at Rapid Micro Biosystems
Today Pharmaceutical industry remains conservative for microbiology testing methods and has reluctance to develop and to use Alternative and Rapid Microbiological Methods (RMM) supported by a number of misunderstandings and prejudgments based on the following myths:
- RMM are not accepted by regulation authorities,
- RMM will never replace classical microbial methods,
- RMM will not offer return on investment (ROI),
- Data generated from RMMs will exceed current specifications and limits involving increase in batch rejections.
Nevertheless a movement is in progress for the use of new technologies and systems because classical microbial methods, in spite of their long return of experiences and their confidence for the regulatory point of view, have a number of disadvantages such as:
- Time to results in days to weeks,
- Results vary with microbial population, media, culture conditions,
- Lack of reactivity in case of exceeding limit results,
- Sensitivity could be insufficient giving underestimations in the contamination risk,
- Existence of confluent growth.
This webinar provides an overview of the current situation about RMM technologies, regulatory expectations, it proposes some initiatives facilitating the implementation of RMM including a strategy for validation and it gives a projection for the perspectives of the RMMs for the future.
Ken Wong, Deputy Director at Sanofi Pasteur and Dujuan Lu, Manager/Global Lead of Extractables & Leachables at SGS
Full Title: Case Study and Experience on Sanofi's and SGS's Implementation of BPOG's Leachable Risk Assessment Model and Extractable Testing Protocol
Presented by Ken Wong, Deputy Director at Sanofi Pasteur
Brief review of the BPOG's Leachable Risk Ranking model. A case study of the leachable risk model implementation into Sanofi will be presented. All changes to specific risk factors and weights changes will be discussed. Finally, the lesson learns and experiences of the risk model performances on several projects will be shared.
Followed by Case Study and Experience in Extractables and Leachable Studies of Plastic Process Materials – a CRO perspective
Presented by Dujuan Lu, Manager/Global Lead Extractables & Leachables at SGS Life Sciences
Extractables and leachables (E&L) from the plastic process materials used during pharmaceutical and biopharmaceutical manufacturing can potentially pose risks to the safety, efficacy, and stability of pharmaceutical and biopharmaceutical products.
The USP risk assessment model will be briefly reviewed. Challenges regarding design of extractions and analytical evaluation threshold (AET) calculation for process materials will be discussed. A few case studies regarding the E&L studies of process materials will be shared.
Uwe Voelker, Site Head, Sterile Drug Product Manufacturing at Roche
Adoption of strategic and systematic use of lean principles to improve operational efficiencies and cost competitiveness
Systematic reduction of waste, complexity and variability,
Reduction of order lead time,
Higher employee satisfaction and engagement tackling the cultural challenges
Achieving speed and reliability in the manufacturing value chain.
Presented by Uwe Voelker, Site Head, Sterile Drug Product Manufacturing at Roche
Uwe Voelker is currently the Site Head (GM) at Roche in Mannheim, leading Pharma Operations (Biologics DP site). He was previously in VP-roles in both Quality and Techn. Operations, local and global roles, a.o. Head of Global Quality Small Molecules, Site Head in a Biologics DP site in Switzerland.
Uwe is well versed in all aspects of Quality Management; Lean, Operational Excellence and Change management.
Moritz von Stosch of GlaxoSmithKline Vaccines Followed by Klaus Mauch and Shilpa Nargund of Insilico Biotechnology AG
Title: Beyond Purely Data-Driven Approaches for Efficient Knowledge Management in Process Development
Knowledge from first principles is freely available and generally valid, and when integrated along with Artificial Intelligence (data-driven) methods, it can greatly improve the understanding and applicability. The applications of such an approach, referred to as hybrid modelling, to a fermentation and controlled drug release case are presented and the learnings from the development of these models are shared.
Vivek Halan Zumutor Biologics Pvt Ltd, Bangalore, India
This Webinar will discuss MMC in purifying biologics which includes monoclonal antibodies (mAbs), Bispecific antibodies (BsAbs), antibody fragments (Scfv,Fab) and other recombinant proåteins. My discussion is intended for audience from biopharmaceutical industry as well as active collaborators from academic institutes.
Dr Udayanath Aich, Associate Director at Bristol-Myers Squibb
Real time monitoring and in-time release of products create a demand to move testing from QC release (off-line) analysis to the manufacturing shop floor (in-line, on-line or at-line monitoring), in order to address Biopharmaceutical manufacturing goals of reducing speed, cost and maximizing quality of product. BioPhorum Operations Group (BPOG) published a Biomanufacturing Technology Roadmap in July 2017 with the active collaboration of Biopharma industry representatives and supply partners. As part of implementation of roadmap strategy, BPOG’s ILM-RTR technical forum team is developing User Requirement Specifications (URS) for prioritized CQA’s and CPP focusing on the critical control points and future requirements of real time release (RTR). The URS documents will promote effective development of desired Short, Mid and Long term technologies by the innovators and supply partners.
Presented by Dr. Udayanath Aich Associate Director at Bristol-Myers Squibb
Dr. Udayanath Aich has an extensive experience and management skills in analytical chemistry, and CMC analytical strategies for early, late and commercial biologics products. He then decided to move to M.I.T to gain extensive skills in the area of Biopharmaceutical characterization and drug development. Dr. Aich joined at Thermo Fisher Scientific in the chromatographic and mass spectrometric division to broaden his extensive analytical skills. Then Dr. Aich worked as Investigator at GlaxoSmithKline in the area of protein and glycans characterization, process analytics, CMC analytical strategies as ATL and structure-function study. Finally, before joining at Bristol Myers Squibb, Uday was working at Sanofi related to high throughput technologies, process analytical technologies (PAT), Analytical method harmonization, multi-attribute method Dev, analytical method dev, robustness, qualification and transfer for early and late stage product including 2nd generation commercial product as part of life-cycle analytics.
Britta Manser, Manager EU SLS Continuous Bioprocessing for Pall Corporation
Bioburden control within continuous manufacturing
Bioburden control within continuous manufacturing is a key area of concern in the biotech industry. In this short video from Pall Biotech, Britta Manser outlines how existing technologies can help mitigate potential risks linked to bioburden control among new technologies.
Do you like the idea of producing 100 g of your mAb product every day? This is now possible using a continuous processing platform. Download a brochure to discover how.
Geoffrey Hodge, Chief Technical Officer at Unum Therapeutics and Gary Pigeau, Ph.D., Director at GE Healthcare
Engineered autologous T cell products have proven to be an extremely promising new therapeutic modality, but they are currently time-consuming and costly to manufacture. This presentation will review the history of biotherapeutics development to look for lessons we can learn that may accelerate advances in autologous cell therapy manufacturing. It will also highlight the differences between traditional biotherapeutics manufacture and autologous cell manufacture to identify areas which may require us to look to other industries for inspiration. Finally, it will present an integrated vision for an autologous cell therapy manufacturing facility of the future which incorporates current initiatives, lessons from the past, and ideas from other industries to improve the robustness, cost, and time of autologous cell therapy manufacture.
Followed by Enterprise solutions for cell and gene therapy
The cell and gene therapy industry is growing at a rapid pace, with more and more attention on manufacturing rigor and scalability. Solutions are needed to achieve these outcomes while providing the speed and agility to succeed in this dynamic space. To tackle these issues and make life-saving therapies more accessible, the industry needs a new way of thinking. This presentation will discuss approaches that can be applied in modular fashion to create a customized production facility with the flexibility to evolve over time.
Modern facilities include integrated technologies that close and automate processing, delivering the scalability and control lacking in typical manual workflows. An integrated platform can be housed inside a prefabricated structure – a cleanroom or a larger manufacturing facility. Both options allow for quick addition of GMP manufacturing capacity without interrupting existing work. A manufacturing execution system can be added to bring facilities together with cloud-based oversight of what is happening in real time.
Thomas O'Connor, Scientist at FDA and Sean Bermingham, Head of Formulated Products at PSE Ltd
Full Title: Use of Computational Modelling in Specification Setting and Establishing Control Strategy
The proportion of scientific evidence supporting medical product regulatory applications derived from modeling and simulation studies is expected to continue to grow into the future. In the Quality by Design framework, mathematical models can and have be utilized at every stage of product development and manufacturing. Thus, the regulatory assessment of product quality models is not unprecedented but the frequency, types of models, and applications are evolving. This evolution is being driven in part by the adoption of advanced manufacturing such as continuous pharmaceutical manufacturing.
The ICH Quality Implementation Working Group points to consider document categorizes models based on the model’s contribution in assuring the quality of the product. Models utilized as part of the control strategy are typically categorized as either high or medium impact depending on the role of the model. Minimal guidance though is provided on model validation. A recent standard (ASME V&V 40) outlines a process for making risk-informed determinations as to whether a model is credible for decision-making for a specified context of use. The presentation will discuss how the framework could be used to develop model validation plans and support regulatory assessment using case studies from both drug substance and drug product manufacturing.
John Wasylyk, Sr Principal Scientist at BMS and Karen Esmonde-White, Senior Marcom Specialist at Kaiser Optical Systems Inc
During the lengthy process of pharmaceutical development, an Active Pharmaceutical Ingredient (API) or its intermediates can go through many physical and chemical changes. These changes are needed to produce the API with the correct chemical structure and physical property. Monitoring the progress of these transformations is important for the process understanding as well as serving as a tool for in-process control (IPC) to ensure the completeness of the transformation. IR and Raman Spectroscopies are sensitive to both chemical and physical changes of a compound and have evolved into useful tools in our lab for monitoring both chemical and physical transformations. They can be used to monitor the progress of the chemical reaction leading to the desired product, the slurry-to-slurry form transformation leading to the desired crystalline form, and the instability of API leading to undesired degradant. When used in-line, they can also be used to study the kinetics of a chemical reaction as well as the rate of crystalline form conversion...
Followed by Utility of Raman spectroscopy in continuous processing of liquids and solids
An important consideration in successful continuous manufacturing is integrating analytical tools into the flow. In batch reaction monitoring, on-line and at-line analyses enable Quality by Design (QbD) and ensure stable operations. Intense reaction conditions, non-traditional chemistries, high throughput and speeds, and miniaturized reactors are challenging environments for analytical tools originally developed for batch reaction monitoring. We present process Raman technologies adapted for continuous manufacturing processes in liquids and solids. Over the last 20 years, Raman spectroscopy has become an established technique for process monitoring and control, with applications in continuous manufacturing of liquids and solids...
Chris Chen PhD, CEO of WuXi Biologics and Dr. Sébastien Ribault, Senior Director for Global Delivery and Sales at Merck
Biopharmaceutical plants will look different in the future. Agility and flexibility for rapidly changing product portfolios, single-use technologies, continuous manufacturing, small batch manufacturing, personalised medicine manufacturing will not only change the face of a plant but will also require other logistics models. Chris will explain WuXi Biologics' approach to biological facilities of the future.
The Journal for Asia's Pharmaceutical and Biopharmaceutical Industry
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Pharmaceutical Forensics for Safe Manufacturing and SupplyRavi Kalyanaraman and Jeremy Peters of BMS and Robert Heintz of Thermo Fisher Scientific[[ webcastStartDate * 1000 | amDateFormat: 'MMM D YYYY h:mm a' ]]73 mins