Extractable Data Mining: Common Extractables From Polymeric Manufacturing Materi
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.
RecordedMar 23 202079 mins
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Alan Kelly is a Project Engineer who has been employed within the pharma/biopharma industry in Ireland for the past 25 years and is currently in his 18th year at Sanofi Waterford. Previous employers include Leo Pharma and Elan. During his current tenure at Sanofi Alan has held several engineering roles, including Project Lead on two high speed aseptic vial-filling isolator technology lines integrated with industrial scale freeze dryers and as Process Engineering Manager during start-up of fill finish. Alan has worked in the Technical Services Department at Sanofi responsible for technical expertise input into front-end studies for new aseptic filling lines with isolator technology. In his most recent role in MSAT, Alan is responsible for next generation product transfers, identifying innovative technology including: real time microbial monitoring, drone vial studies to assess aseptic filling line set-ups and multi-purpose PAT technology for detection of trace silicone oil, leak detection and primary/secondary drying functionality for freeze dryers. Alan has successfully led cross functional teams in the qualification of high speed automatic visual inspection technology for cartridges and manual visual inspection of syringes. Alan has presented at international conferences including ISPE (Case study on VHP Cycle Development and Qualification of large scale aseptic Filling Isolator technology, European Compliance Agency (ECA) on “Case study on Manual Visual Inspection of syringes”, Alan is an active member of PDA Ireland Chapter and lead organiser for recent events including Annex 1 Conference (Revision of the EU GMP Guideline) May 2019 and Advances in Aseptic Processing with a focus on Media Fill simulations Oct 2018
Clare Blue Director of Analytical Development at Biogen
Presented by Clare Blue, Director of Analytical Development at Biogen
One of the biggest challenges for AAV gene therapy products is establishing an appropriate analytical strategy to support product manufacture, release, stability, comparability and characterization at different stages of development. This presentation will highlight some of the existing analytical challenges and provide guidance on development of an appropriate strategy to help overcome these.
Thomas O’Connor, Scientist at FDA, Mark Demesmaeker and Chris McCready at Sartorius
Full Title: Moving the Implementation of Digital Technologies in Pharmaceutical Manufacturing Forward
Presented by Thomas O’Connor, Scientist at FDA
Industry 4.0 encompasses a wide range of technologies including industrial internet of things (IIOT), artificial intelligence (AI), and digital twins that have the potential to significantly increase the efficiency and robustness of pharmaceutical manufacturing. The implementation of Industry 4.0 technologies within the context of pharmaceutical manufacturing especially for applications that impact the control of the process or quality decision making may be subject to additional uncertainty in determining how the technologies fits within existing regulatory approaches. The presentation will describe FDA’s manufacturing science research programs that aim to proactively address such regulatory uncertainties. Case studies on the application of digital twins and advanced process control will be highlighted.
Firelli Alonso, Ph.D., Senior Director, External Supply at Pfizer
Presentation by Firelli Alonso, Ph.D., Senior Director, External Supply at Pfizer
Sourcing for the manufacture and control of Antibody-Drug Conjugates (ADCs) used in clinical trials requires strategic planning, establishment of a specialized support network, and execution of several interdependent tasks. ADCs are complex molecules, a fusion of a biological, the monoclonal antibody (mAb), and of small molecules, the linker and the toxic payload. Facilities of acceptable standards for the handling of high potency materials need to be engaged, and there is a limited supply currently. This is further complicated by the fact that there is not one contract facility that has fully integrated services, a “one-stop shop” capable of mAb production, linker and/or payload synthesis, conjugation of mAb to linker-payload to make the Drug Substance, and finally, formulation of the ADC to make the Drug Product. Strategizing the best outsourcing practices for producing and testing ADCs, and establishing guiding principles for externalization to ensure the selection of the right CMOs for ADC outsourcing and technology transfer, will be further discussed.
A case study be presented describing initiatives and bioprocessing approaches to maximize capacity utilization within a new large scale (12x 15kL) drug substance biologics manufacturing facility at Samsung Biologics. Facility design, manufacturing and validation strategies utilizing two harvest and purification suites with regards to cadence and product changeover (PCO) will be discussed and an overview of Samsung’s experience with advanced technologies, including (N-1) perfusion, application of single use technologies will be presented. The webinar will also describe how activities are coordinated to ensure successful tech transfers to support clinical and commercial programs, including facility fit and gap assessments to ensure manufacturing processes are adequately transferred to support successful cGMP manufacture of biologics. The webinar will highlight initiatives and working practices at Samsung Biologics to ensure our biologic manufacturing operations are cost effective, flexible and responsive to the needs and demands of our clients and can adapt to a rapidly to accommodate a diverse pipeline of antibody biotherapeutics.
Dejan Arzenšek, Principal Scientist at Novartis and Maryann Cuellar, Life Science Product Manager at Kaiser Optical Systems,
Presented by Dejan Arzenšek, Principal Scientist at Novartis
Followed by an industry perspective presented by Maryann Cuellar, Life Science Product Manager at Kaiser Optical Systems, Inc.
The discussion will be focused around the exploration of multiple techniques and their possibilities to secure tight control of the major critical quality attributes (CQA) and different PAT tools for measuring different attributes in (near) real-time. A feasibility study of PAT tools covered in this talk demonstrates the technology for in-line measurements in fed-batch process steps and potential of their use in a continuous process.
Full title: CONSIDERATIONS ON IMPACT OF RAW MATERIAL VARIABILITY IN GENE THERAPY MANUFACTURING: APPLYING LESSONS LEARNED FROM BIOLOGIC'S MANUFACTURING
As the number of cell and gene therapy products grow it is important to consider aspects of gene therapy production process robustness, and one key characteristic is the variability of incoming raw materials. Understanding and controlling raw material variability is an important aspect of process development, characterization and commercialization. In the recent history of therapeutic protein production with cell cultures, many problems caused by raw material variability were only discovered post-commercialization, and failure to understand and address key raw material variability during process development led to costly underperformance and batch failure. In this article, we consider some known sources of raw material variability and specifically, those that have been known to impact cell culture production processes. Trace element impurity variation, particularly iron, copper, manganese and zinc, are candidates for high process impact risk. Compositional variation of undefined material (i.e., fetal bovine serum [FBS]) is another important potential failure mode. This includes known nutrient components, such as amino acids and cholesterol, as well as unidentified components, such as growth factors. Cell and gene therapy processes also include relatively new materials for cell culture, such as plasmid DNA and the transfection agent polyethyleneimine, the understanding of the variability of which must be considered.
Thorsten Lorenz,and Sorina Morar-Mitrica of Novartis, and Renee Tobias, Halo Labs
Presented by Thorsten Lorenz, Head Early Drug Substance Development and Sorina Morar-Mitrica, Principal Fellow Sr Drug Product Lead Early Phase Biologics at Novartis
Thorsten Lorenz studied Biochemistry at the University of Bochum in Germany. He performed his PhD work at the Max Planck Institute for Medical Research in Heidelberg and afterwards joined Novartis as postdoctoral fellow. In 2011, he took the lead for the buildup of a laboratory for protein characterization and pre-formulation assessment. After taking roles of increasing responsibility in the unit, Thorsten was appointed Team Head Developability Assessment in 2017, responsible for the assessment of molecular properties, downstream process and stability characteristics as well as immunogenicity and in vivo stability risks for the Novartis Biologics pipeline at the transition from Research to Development.
Since April 2019, Thorsten has been leading the Early Drug Substance Development group in Novartis Technical Development New Biologics Entities.
Follolwed by an Industry perspective presented by Renee Tobias, Director of Marketing, Halo Labs
Michael Butler, PhD, CSO, Cell Technology, National Institute for Bioprocessing Research and Training (NIBRT)
Presented by Michael Butler, PhD, CSO, Cell Technology, National Institute for Bioprocessing Research and Training (NIBRT)
The metabolic state of mammalian cells in a bioprocess can be monitored by high-resolution optical systems or by changes in dielectric properties. Each method can determine a metabolic inflection points just prior to loss of cell viability. Such changes can be observed up to 20h before cells stain with trypan blue. We have established a threshold of cytoplasmic conductivity below which cells cannot be recovered from apoptosis. This point occurs at a time when there are observable changes in the cell membrane that can be detected by high-resolution optics. This early detection of metabolic changes allows dielectrics and high-resolution optics to be offered as a means of monitoring a bioprocess and maintaining cell viability over prolonged time periods.
Mark Plavsic, Chief Technology Officer at Lysogene
Presented by Mark Plavsic, Chief Technology Officer at Lysogene
Together with product efficacy, product safety is an essential characteristic of any medicinal product including cell and gene therapy (C>) biologics. Adventitious agents (viruses, bacteria, mycoplasma, prions, etc) pose constant risk to these biologics, and, as such they may impact directly product and patient safety. It is therefore of supreme importance to intentionally (by design) employ effective measures across the whole C> product manufacturing process to mitigate risk of adventitious agents. This presentation will review various interconnected steps throughout the manufacturing process, from the raw materials to the fill and finish, that would, in concert, help mitigate the risk while providing a high degree of product safety by design.
Christian Airiau,Global Head Data Sciences at Sanofi and Chris McCready, Lead Data Scientist at Sartorius
Full Title: Hybrid Models: The Best of Both (Mechanistic & Empirical) Worlds to Accelerate and De-Risk Process Development
Presented by Christian Airiau, PhD, Global Head Data Sciences, Biologics Development at Sanofi and Chris McCready, Lead Data Scientist at Sartorius Stedim Biotech
Process optimization through the use of modeling is a key objective to accelerate and de-risk process development. A critical step to improve our process development, process monitoring and process control is to understand the strength and limitations of each types of modeling approaches. Using the most relevant empirical approaches - from DoE to Multivariate Analysis - and the mechanistic understanding we have about our processes – Kinetics, thermodynamics – we are rethinking the way we conduct process development.
Dr Joe X Zhou CEO Walvax Bio Group & Sarah Wang Head of Segment Marketing Biosimilars and Bioconjugations at Sarotrius China
Presented by Dr Joe X Zhou, CEO at Genor Biopharma, Walvax Bio Group
Following patent cliffs for Erbitux, Rituxan, Sandosta_n and several big blockbusters, Herceptin, Avastin are now among the next biosimilar targets. This is creating huge potential for biosimilars, prompting innovators to shift their focus to target more emerging markets which remain untapped for many companies. In this presentation, Joe will be sharing with you his vision of the biosimilars market with a focus on China. He will also discuss key considerations for mAb and biologics therapeutic development, providing a broad overview of challenges and opportunities presenting in the market.
1. Landscape changes of mAb therapeutics
2. New targets and process/manufacturing innovation
3. Key consideration of mAb industry in China
4. Case study: Development strategies of PD-1 mAb as anti-tumor therapeutics in China for global market
Followed by Biosimilar development—how to deal with the similarity challenge
Presented by Sarah (Xuyu) Wang, Head of Segment Marketing, Biosimilars and Bioconjugations at Sartorius Stedim Biotech
Globally we have more than 1000 biosimilars in the pipeline till the beginning of 2019, Sales of mAb biosimilars is also taking up as popular targets being approved both in Europe and US. With the 3rd wave of the biosimilar coming the challenges is still ahead---how to keep the similarity from the beginning of the development to the manufacturing stage and cover the whole lifecycle? With the evolving cell line development platform, good analytical strategy and QbD implementation better similarity will be achieved step by step.
Full Title: MES –Integrating Technology, Quality and Compliance – Opportunities, Challenges and Strategies.
Defining the role of MES in using technology to achieve compliance.
Addressing challenges in implementation of MES in current scenario with focus on Indian companies.
Technology taking the compliance and quality framework to the next level.
Organizational strategies to leverage the Power of technology by implementing MES.
Michelle Raikes, M.S., Scientist IV and Dr. Fredrik Nordstrom, Sr Research Fellow at Boehringer Ingelheim
Full Title: Quantification and Control of Amorphous contents by Raman, Application and Case Studies in Pharmaceutical Processing
Presented by Michelle Raikes, M.S., Scientist IV and Dr. Fredrik Nordstrom, Sr Research Fellow at Boehringer Ingelheim
Amorphous regions in crystalline material can have significant impact on bioavailability, processability and stability. Conversely, crystalline material can act as nuclei for recrystallization and resulting in instability of amorphous systems. Raman spectroscopy is sensitive to polymorphic differences and amorphous content in pharmaceutical materials. This make Raman spectroscopy a powerful process analytical technology (PAT), when combined with multivariate modelling, to control the amorphous content in a pharmaceutical process. We will present pharmaceutical case studies showing process-induced amorphization of crystalline drugs across the DS and DP processing steps. In addition, we will compare the kinetics of crystallization of amorphous material when stored at various relative humidity and temperature conditions. The results clearly demonstrate that Raman spectroscopic techniques combined with multivariate methods is a powerful and effective tool for quantitation of amorphous content in crystalline material with applications ranging from API isolation, milling and to multiple unit operations in DP manufacturing. The information generated was critical to determine the root-causes and outline appropriate mitigation measures
Robert Dimitri, Associate Director, Digital and Data Sciences Lead at Takeda and Pep Gubau, CTO and co-founder, Bigfinite
A walkthrough of the journey towards Digital Transformation for Takeda's Massachusetts Biologics Operations Site. This presentation shares the journey towards enhancing the site's digital and analytics capabilities and bringing it closer to a digital world and the progress and processes taken thus far.
Presented by Robert Dimitri
Robert Dimitri is a Director in Takeda’s Business Excellence group for the Biologics Operating Unit as the Digital Transformation and Innovation Lead. Previously he led the Digital and Data Sciences group in Manufacturing Sciences at Takeda’s Massachusetts Biologics Site leading a team for the implementation of digital tools used for the analysis of internal manufacturing operations data, used to support the production of biologic drugs to treat rare diseases. He has over 15 years of experience in this field, having worked previously as a process engineer and developing software to perform process data analytics. Robert has a B.S. degree in Chemistry and Computer Science, an M.S. in Computer Science, and an M.B.A.
Followed by an Industry Perspective by Pep Gubau, CTO and co-founder, Bigfinite
Ruth Daniels, Senior Scientist, Microbiology Expert, Janssen and Kevin Williams Microbiological Test Development, bioMérieux
Presented by Dr. Ruth Daniels, Senior Scientist - Microbiology Expert at Janssen
This webinar presentation will discuss:
• Endotoxin hold time studies to identify LER
• In silico assessment of interfering factors and associated LER mitigation strategies
• Case study: optimization of product-specific LAL assay to overcome LER
Followed By A Presentation From Kevin L. Williams, Microbiological Test Development at bioMérieux
Karen Zink McCullough, Owner, Principal Consultant at MMI Associates and Veronika Wills, Manager, Technical Services
Presented by Karen Zink McCullough, Owner, Principal Consultant at MMI Associates and Veronika Wills, Manager, Technical Services
The Bacterial Endotoxins Test is not a test for pyrogens (fever causing agents). It is not a test for the presence of Gram negative bacteria. Based on extensive comparisons of endotoxins activity in the BET and fever rabbits executed in the 1970s and 1980s, we may say that the BET is a test for levels of Gram negative bacterial endotoxins activity that may be predictive of a fever in mammals.
The various methodologies that are described in the harmonized in the harmonized chapter use the primary Reference Endotoxin Standard (RSE) or secondary Control Standard Endotoxin (CSE) to prepare assay standards, perform suitability testing as instructed in the chapter and inoculate positive product controls. These standards are relatively pure preparations of lipopolysaccharide. However, the utility of the compendial assay for non-compendial applications is limited. Our discussion will focus on the compendial uses of these BET assays.
Dr Friedrich von Wintzingerode, QC Lead iNeST Project at Roche and Shabnam Solati, CEO & Co-Founder at CTL-MAT
FULL TITLE: A Comprehensive Approach to Assess the Impact of Microbial Impurities on Patient Safety and Product Quality of Biologics
Presented by Dr Friedrich von Wintzingerode, QC Lead iNeST Project (individualized Neoantigen Specific Therapy) at Roche
Large-scale Production of Biologics is susceptible to microbial contamination because many manufacturing steps occur under non-sterile conditions in aqueous systems at ambient temperature or 2-8 °C under substantially neutral pH conditions. Regardless of where in the Drug Substance (DS) manufacture (manufacture of the Active Pharmaceutical Ingredient), or Drug Product (DP) manufacture (manufacture of the Final Drug, e.g. formulated mAbs filled in vials or syringes) they occur, microbial contaminations can have a significant impact on product quality and patient safety. Even after bioburden removal by 0.2 µm filtration subcellular microbial components like toxins, lipopeptide/lipoproteins, flagellin, bacterial and fungal DNA, cell wall polysaccharides, extracellular proteases or endoglycosidases remain in the product. Those microbial components potentially lead to toxic, allergic or inflammatory responses in humans or product degradation or modification. The Case-by-Case Assessment of Bioburden (CCAB) approach described here enables a comprehensive assessment of these risks.
Dr Christine P. Chan, Director in Global Manufacturing Science & Technology at Sanofi
Bioprocess changes can impact quality attributes of biologics and may affect efficacy and safety of the product. During development and throughout the product lifecycle, when process improvements are implemented, it is essential to gather sufficient data to support the conclusion that product safety and efficacy has not been adversely affected. This demonstration exercise requires careful planning of the comparability studies and is based on the background knowledge of protein structure, biological function, and clinical attribute profiles of the product accumulated during development.
In this webinar, I will discuss the key concepts of establishing product quality profiles, and the hierarchical assessment approach to demonstrating comparability of biopharmaceuticals in support of process changes.
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.
The Journal for Asia's Pharmaceutical and Biopharmaceutical Industry
BioPharma Asia aims to keep its 30,000 readers abreast of all developments in the areas of Drug Development, Drug Delivery, Manufacturing, Quality Assurance, Outsourcing and Regulatory Affairs, with only the highest quality articles, written by the most respected authors, associated with only end-user companies. This ensures that the information will always be guaranteed to remain timely, informative and above all totally unbiased.
Extractable Data Mining: Common Extractables From Polymeric Manufacturing MateriPing Wang, Director at Johnson & Johnson and Donald DeCou, E&L Technology Manager at West Pharmaceutical Services[[ webcastStartDate * 1000 | amDateFormat: 'MMM D YYYY h:mm a' ]]78 mins