The impact of human biological samples (HBS) across the end-to-end research and development process is huge. Having access to the right sample at the right time can unlock new science to enable the development of new treatments for patients. To secure rapid access to samples, AstraZeneca’s biobanks are closely situated at its global research sites. Samples come not only from AstraZeneca (AZ) sponsored clinical trials, but also from academic collaborations or sourced from approved vendors.

The AZ biobanks currently hold four million samples globally, to support ongoing and future science. Our ‘One Biobank’ strategy includes a single sample catalogue where all samples are visible to our scientists as well as the governance oversight of all sample use globally. The biobanks are part of the Biosamples function which provides expertise across the HBS lifecycle, covering sampling needs and logistics on every clinical program within AZ, the registration and storage of samples in the biobanks, and the compliance and governance to make sure that every human sample is treated in the right way.

The sample catalogue in AZ also includes primary cells and cell lines classified as HBS, depending on local legislation. We have defined processes to provide biobank and governance oversight of these cells, but rely on the AZ cell banks to provide the storage conditions and additional oversight required for the cells.

Karin Gedda has during her many years in AstraZeneca (AZ) been working in all phases of early drug discovery, from identification of targets through lead optimization to successful selection of candidate drugs and submission of drugs for clinical testing. Being a cell biologist/biochemist by training, her focus has been on supporting projects with high-quality screening data using a variety of assays in different formats. Over the last four years she has moved on to leading the sample management teams and now holds the role as Head of AZ Gothenburg Biobank within Precision Medicine and Biosamples. The AZ biobanks hold clinical trial samples as well as samples from academic collaborations and commercially sourced material. Lately, with the formation of the new Biosamples function, Karin’s focus has been on defining AZ biobanks’ strategy moving forward.

Understanding the criticality of raw material attributes to our products and processes allows us to define appropriate specifications and variability, a crucial part of a robust end-to-end control strategy for our products and processes. This talk will focus on Roche's journey to a proactive and predictive state of raw material variability understanding and control, specifically through the lens of visible particles.

Dr. Yohe is a Principal Materials Science Engineer in the Pharma Technical Innovation team at Roche-Genentech, where his focus is on advancing Roche's understanding and control of raw materials. Stefan has been with Genentech since 2013, and has held a number of diverse roles in the areas of medical devices, advanced drug delivery technologies, formulation, MSAT, and purification. He holds PhD in Biomedical Engineering from Boston University, and a BS degree in Materials Science and Engineering from The Pennsylvania State University.

The testing and approved release of raw materials for use in GMP manufacturing can be a process that takes weeks to accomplish, requiring companies to keep extensive inventories. To expedite the release of critical raw materials the Biogen RapidID platform was developed and implemented. The Biogen RapidID program describes an integrated IT and laboratory analytical instrumentation system, allowing incoming materials to be received, tested, and released in just a few hours. Two technologies make up the RapidID analytical platform: Raman and x-ray fluorescence to positively identify over 75 raw materials. To ensure compliance with the relevant agencies, a robust method validation and transfer strategy was implemented for the methods for both respective analytical instruments. The RapidID platform has been successfully implemented at Biogen since 2019.

Christie is a senior associate at Biogen, located in Research Triangle Park, North Carolina. As a member of the Analytical Technology department for the Quality Control organization she is responsible for the validation, implementation, and global transfer of new methods and programs in the raw material space. Christie joined in 2015 and has been in the pharmaceutical industry since receiving her bachelor’s degree in Biology from North Carolina State University in 2006.

This presentation will focus on the regulatory guidelines around transmissible spongiform encephalopathy (TSE) risk and how TSE clearance studies can be used as a strategy for controlling such risk. European guidelines on investigation of manufacturing processes for plasma-derived medicinal products with regards to variant Creutzfeldt-Jakob disease (vCJD) risk, as well as FDA discussions, provide guidance on how manufacturers can design TSE clearance studies to ensure the highest probability of regulatory acceptance. The presentation will focus on the advantages and disadvantages of each system for controlling TSE risk, and how these impact the interpretation of TSE clearance studies. In addition, options for steps that manufacturers should consider including and that could provide effective clearance of TSE agents will be presented.

Andy is a virologist who served for nine years at the MRC Virology Unit in Glasgow. In 1995, he moved to the industry sector, initially as Director of Virus Validation services with Q-One Biotech Ltd, and later at the Pathogen Safety group of Baxter Healthcare in Vienna, Austria. Over the last 25 years, Andy has been actively involved in the virus and prion safety field, presenting at numerous regulatory agencies either in support of products or as an invited speaker at expert workshops. This has included presentations at the UK Medicines and Healthcare products Regulatory Agency (MHRA), German Paul-Ehrlich-Institut (PEI), French Health Products Safety Agency (AFFSAPS), US FDA, European Medicines Agency (EMEA), and Japanese Ministry of Health, Labour and Welfare (MHLW) supporting regulatory submissions for various products. He has extensive experience in regulatory affairs and virus/prion safety issues. In 2005, Andy founded ViruSure with the goal of providing a high-quality testing service in the field of virus and TSE safety testing to the biopharmaceutical industry.

As distributors of human pluripotent stem cells (hPSCs) working to serve the greater scientific community, quality is everything. Poor quality cells can impact reproducibility, jeopardize results, waste time, and drain resources. While consensus guidance for the characterization of hPSCs was established by the International Stem Cell Banking Initiative more than ten years ago, many research groups use them inconsistently, or have failed to adopt them altogether. In screening materials submitted to the WiCell Stem Cell Bank for distribution, we have identified a substantial and concerning variability in cell quality, highlighting the need for improved testing strategies and standards.

As of this abstract, of the cell lines submitted to WiCell for banking and characterization more than 1000 from 31 providing investigators more than 1000 have been tested by WiCell for thaw viability, genetic stability (karyotype), identity via short tandem repeat (STR) analysis, sterility (bacteria and fungus), and mycoplasma. More than one-third of these lines failed this routine quality testing. While there were failures across all tests, the majority of cell lines failed due to unexpected abnormal karyotype. Retrospective analysis of more than 1500 cultures submitted to WiCell for karyotype illuminated striking shifts in relative frequencies of abnormalities, and identified previously unrecognized recurrent abnormalities in human PSCs.

These results show that current ad hoc screening strategies are variable and largely insufficient. Furthermore, it highlights the need for, and value of, centralized repositories with established quality standards that ensure distribution materials are routinely and appropriately screened.

Tenneille Ludwig currently serves as the Director of the WiCell Stem Cell Bank overseeing the banking, distribution, and core services operations at WiCell. Dr. Ludwig obtained her bachelor's and master’s degrees from Washington State University prior to completing a PhD in embryology and developmental biology with a minor in bioethics from the University of Wisconsin-Madison in 2001. Her subsequent work in the laboratory of Dr. James Thomson (2001–2007) focused primarily on the optimization of cell culture conditions and resulted in the development of the first defined, feeder-independent culture system for human embryonic stem cells (TeSR/mTeSR). Currently, she is a member of the Stem Cell and Regenerative Medicine Center and the Embryonic Stem Cell Research Oversight (ESCRO) committee at UW-Madison, and serves as a steering committee member for the International Stem Cell Banking Forum (ISCBF), the International Stem Cell Initiative Genetics and Epigenetics Study Group, and the International Society for Stem Cell Research industry committee. Her primary focus remains collaborating within these groups to refine consensus standards for banking, characterization, and distribution of research and cGMP grade materials, and working with investigators to support the advancement of stem cell technologies through clinical trial.

Although often operating in the background, biobanking plays a critical role in the diagnosis and development of treatments for a variety of diseases. However, as we witness the urgent international efforts to develop vaccines and other therapies for the current COVID-19 pandemic, patient sample collection, processing, and analyses are at the forefront of this emergency. Biospecimen issues have long been important factors in handling the response to emerging infectious diseases. The US CDC has maintained a biobank for decades, and has found through analysis of its samples that infectious agents responsible for outbreaks such as the hantavirus and Legionnaires' disease were present years prior to the epidemic. Tissue samples from the 1918 Spanish influenza pandemic were used to determine that the origin of the virus was related to strains that commonly infected pigs and humans, and was not of avian origin as had been previously thought. Studies of the 1918 pandemic and subsequent influenza outbreaks have been instrumental in vaccine research as well. The Ebola outbreak in Africa in 2014–2016 presented some unique challenges, due to the high infectivity of patient blood samples. There were also security concerns, i.e. that Ebola patient samples could be used for bioterrorism purposes.

COVID-19 presents some unique issues in the biobanking world. The vast scope of the pandemic, with over 11 million patients globally as of early July, means that laboratories and biobanks are handling many samples involved in developing diagnostics and vaccines. The US CDC has published guidelines for handling COVID-19 samples. Some biobanks have developed their own guidelines, usually based on those of the CDC. Generally, these guidelines mandate the use of biosafety level 2 (BSL-2) rules for laboratories, including the use of protective equipment, use of class II biological safety cabinets, proper disinfection routines, etc. Also, a new US NIH COVID-19 Scientific Interest Group (SIG) has also been organized, where interested parties can join in an online discussion and exchange information about research and resources. At this time, we can expect that this pandemic will continue to be our most critical international concern for months to come, from a public health perspective, as well as from the resulting economic impact. As the number of cases continues to mount, as well as the unfortunate loss of life, biobanks will continue to work in the background to handle their roles in the response. This presentation will provide an update on biobanking activities during the pandemic.

Dr. Jim Vaught spent 14 years at the US National Cancer Institute, most recently as the Chief of the Biorepositories and Biospecimen Research Branch. He has been working in the field of biobanking and biospecimen science for over 20 years. In 1999, he was one of the founding members of the International Society for Biological and Environmental Repositories (ISBER) and served two terms as its president. In 2018 he was the recipient of ISBER’s Founder’s Award. His current work includes providing biobanking consulting services and serving on a number of advisory boards. He is a Senior Research Fellow at the International Prevention Research Institute in Lyon. He is the author of over 80 peer-reviewed articles and book chapters in chemical carcinogenesis and drug metabolism, biobanking, and biospecimen science. From 2006 to 2012 he was Senior Editor for Biospecimens and Biorepositories for the journal Cancer Epidemiology, Biomarkers and Prevention. He is the current Editor-in-Chief of Biopreservation and Biobanking, the official journal of ISBER. In 2017 he was appointed as a Guest Professor at Central South University in Changsha, China, where he is a lecturer for a post-graduate biobanking course. In 2018 he was appointed as a Guest Professor at the Children’s Hospital of Shanghai.

It has been long recognized that raw materials can be a challenging source of input variation in pharmaceutical process performance and product quality. To further enhance raw material understanding and control we have added a data analytics initiative to our attribute-based raw material control strategy. This initiative focuses on assessing the trends in attribute data to monitor the performance of raw materials. Our vision is to predict and prevent raw material related issues by understanding material variation, mitigating supply risk, and preventing any impact to process performance and product quality. In this talk, we will present the digital infrastructure that enables streamlined data review, and business framework that formulates effective and timely actions to mitigate the risk. Case studies and lessons learned throughout the development of this initiative will also be presented.

Ting Wang, PhD joined Amgen in 2014 and is currently Principal Engineer in Process Development. Her academic and industrial experiences have been focusing on understanding, predicting, and preventing raw material variability and its impact on pharmaceutical process performance and product quality for both biologics and small molecules. In her current role, she leads a cross-functional program to understand the variability of material attributes and identify control strategies to minimize the impact of material variation. She provides technical input into pharmaceutical excipient assessments and guideline development to support marketing applications and lifecycle management. She co-led the development of the ASTM (E3077-17) standard and implementation across Amgen's network. She also partners with suppliers to enable new functionality and improve efficiency in material data management. Ting earned her PhD in Pharmaceutical Sciences from the University of Maryland, Baltimore. She serves on the 2020–2025 USP Expert Committee for Excipient Monographs. Ting is also a member of the American Association of Pharmaceutical Scientists (AAPS) and the International Society for Pharmaceutical Engineering (ISPE).

Human and other mammalian cell lines and xenograft tissues, including patient-derived xenografts (PDXs) and patient-derived organoids (PDOs), are essential tools as pre-clinical biomedical research model systems. They are used to study different aspects of biological processes (infection, enzymes, gene structure, and expression control), behavior of different types of human tissues and cells, diseases such as cancers and infection by microbes (e.g., viruses, bacteria), and effects of drugs on normal and abnormal biological processes.

A major concern in using cell lines and patient tissue samples as preclinical research models is that on average 22.5% (range 0–100%) of these samples are misidentified. This can compromise the validity and reproducibility of the research based on these model systems, waste valuable research funds and effort, and damage the reputations of research groups. This presentation will describe the enormity of the problem with examples from the literature and my own work that show how the scientific literature has been contaminated with inadequately authenticated cell lines. Current and new tools that can address this problem will be described.

Christopher Korch received his PhD at the University of California at Davis in Genetics and studied in France, Norway, Sweden, and the USA. In 2000, his University of Colorado Cancer Center core facility was one of the first to implement techniques for characterizing and authenticating human cell lines. In the last 19 years, he has published together with several groups on the identification and confirmation of the identity of authentic and over 80 imposter cell lines and clinical samples by DNA sequencing and STR genotyping. Some of the more salient findings include work with the following groups:
• Prostate Group showing about 30% of the prostate cell lines were misidentified and not suitable models of prostate cancer.
• Thyroid Group showing about 50% of the thyroid cell lines were misidentified and many were not suitable models of thyroid cancer. These finding shocked the endocrine field and have been seminal in the re-evaluation of earlier research. It initiated major efforts to establish authentic thyroid cell lines.
• Ovarian, Endometrial, and Breast Cancer Groups, which in 2012 published a major study on the identity of endometrial and ovarian cancer cell lines, showing extensive contamination, redundancy, and misidentification among these cell lines, raising questions about the validity of many publications using these cell lines.
• The International Cell Line Authentication (ICLAC) which has established that over 500 cell lines are misidentified, i.e., imposter cell lines.
• The ANSI/ATCC Standards group which is revising the Standard for Cell Line Authentication by STR profiling, which is due out in 2020.

Furthermore, Dr. Korch has been interviewed for a book, the Canadian Broadcasting Corporation, magazine articles including Science and Discover Magazine, and several documentaries (such as https://www.biocompare.com/Reproducibility/Cell-Line-Authentication/) and webinars about this problem.

The biopharmaceutical industry has rapidly grown over the past four decades, and mammalian cells now produce the majority of the top drugs by sales. Common cell lines such as Chinese hamster ovarian cells have been selected, somewhat by accident or convenience, and now we rely upon these cells for producing hopefully large quantities of high quality product. However, the random nature of the selection of our top production clones means that alongside the excellent traits they present, each cell line has limitations that pose challenges to optimal biopharmaceutical production, ranging from inefficient metabolism to clonal variation and secretion of contaminating host cell and viral proteins. Can we take a rational approach to engineer each trait and obtain substantially improved cell lines?

We have taken a rational approach to engineering CHO cells to address each of the aforementioned challenges. Specifically, we sequenced the genome of the Chinese hamster and several leading CHO cell lines to obtain a "parts-list" of the cells. We subsequently mapped out all of the molecular pathways involved in CHO cell growth and protein production. Using novel systems biology and AI algorithms, we have predicted how to engineer these cells to obtain cells with limited secretion of bioproducts such as lactic acid and host cell proteins. We have further developed cell lines with more predictable bioprocess behavior, and that provides well controlled and more homogeneous glycosylation. Thus, by rationally engineering the cells, major challenges in cell line development, bioprocessing, and purification can be addressed.

Dr. Nathan Lewis is an Associate Professor of Pediatrics and Bioengineering at the University of California, San Diego. He received his training in biochemistry at Brigham Young University, bioengineering at UC San Diego, and genome editing at the Wyss Institute at Harvard Medical School, where he focused on omics and big data analysis using systems biology modeling techniques. Currently Dr. Lewis serves as the Co-Director of the Center for CHO Systems Biology at the University of California, San Diego, and heads scientific strategy for the CHO cell program at the Center for Biosustainability at the Technical University of Denmark. In these capacities, Dr. Lewis' lab has led substantial efforts to rationally engineer CHO cells to improve production cell phenotypes, and control the quantity and quality of recombinant protein drugs. These efforts were enabled by their work on sequencing and annotating the genomes of the Chinese hamster and a variety of CHO cell lines. His team has also mapped out the molecular pathways controlling CHO cell growth and protein production, and developed novel systems biology and AI algorithms to diagnose the molecular bases of cell and production traits and control process and product quality. Finally, his team has helped lead the development and deployment of novel genome editing strategies to enable high-throughput screening of genetic modifications and implementation of multiplex editing to obtain enhanced CHO cells. Through these many efforts, his team has developed a powerful toolbox for the rational engineering of mammalian cells for the bioproduction of valuable biotherapeutics.

Raw materials can wreak havoc on processes and facilities in a myriad of ways, seemingly with surprises at every turn. At the Merck Raw Material Center of Excellence, our goal is to achieve deep understanding of each raw material in a fit-for-use context to get ahead of unexpected plot twists. The fit-for-use paradigm applies to both commercial qualification as well as technical risk assessments that facilitate the transition from clinical to commercial. As our fit-for-use raw material knowledge management grows, we are also looking ahead to obtain digital, trend-able data in the form of electronic certificates of analysis (CoAs) from suppliers.

Ewelina Flamm, Associate Director at Merck, is passionate about raw materials (RM) and industry collaboration. She is a subject matter expert (SME) in Merck's Raw Material Center of Excellence Group supporting large molecules with 13 years of experience. She focuses on advancing raw material knowledge and expectations within Merck as well as industry standards via external partnerships, with a key focus on clinical and commercial raw material technical risk assessments (fit for function alignment), origin of materials, raw material lifecycle management strategy, and improving electronic access to RM data. Don't make her choose a favorite raw material!

Adventitious viruses are a major safety concern in biologics, especially for live viral vaccines and gene therapy products where manufacturing does not generally include rigorous viral clearance steps (inactivation and removal). Detection of known and unknown adventitious viruses is particularly important when new cell substrates or production platforms are used for development of vaccines or to accelerate manufacturing and increase vaccine yield. Next-generation sequencing (NGS), also called high-throughput sequencing (HTS), has capabilities for broad and sensitive virus detection. Recent progress in developing NGS technologies for adventitious virus detection in biologics has focused on method standardization and assay validation. NGS is a rapid assay that could potentially substitute the currently recommended in vivo assays and perhaps even the in vitro assays for adventitious virus detection in vaccines and other biologics. This can aid in reducing animal use and address some of the limitations of in vitro assays for broad detection of both known and unknown viruses. This presentation will include the current general thinking for using NGS for adventitious virus detection to supplement, substitute, or replace the currently recommended tests and highlight the rapid progress for NGS implementation as a rapid adventitious virus detection assay to accelerate SARS-CoV-2 vaccine development in Office of Vaccines Research and Review (OVRR) submissions.

Dr. Arifa S. Khan received her PhD in Microbiology from the George Washington University, Washington, DC. She is currently a Supervisory Microbiologist and Principal Investigator in the Division of Viral Products, Office of Vaccines Research and Review in the Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA). Dr. Khan joined the FDA in 1991 after working in Dr. Malcolm Martin’s laboratory at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) since 1979, where she contributed significantly to the field of murine leukemia retroviruses, endogenous retroviruses, and simian immunodeficiency virus (SIV). In CBER, Dr. Khan established and maintains a rigorous research program on the development of sensitive, state-of-the art assays for adventitious virus detection, with a focus on safety of novel cell substrates and vaccines. Dr. Khan’s current research efforts include standards and standardization of next-generation sequencing for adventitious virus detection in biologics. Her regulatory responsibilities include review of candidate viral vaccines for HIV and emerging viruses such as SARS-CoV-2, and to provide expert consultation on novel cell substrates and adventitious viruses in CBER and CDER. Dr. Khan has been involved in licensure of several viral vaccines and development of FDA, International Conference on Harmonisation (ICH), Public Health Service (PHS), United States Pharmacopeia (USP), and World Health Organization (WHO) guidance documents related to cell substrates and viral safety. She is the FDA lead on adventitious viruses and next-generation sequencing for cell substrates and product safety.

The field of cell and gene therapy (CGT) continues to grow at a fast pace. These unique biologics pose both regulatory and testing challenges. Manufacturing process consistency is mainly controlled by (1) raw material and reagent qualification programs, (2) in-process monitoring, (3) in-process control testing, (4) lot release tests, (5) traceability, and (6) validation of the manufacturing process. The viral vectors used for CGT, as well as the raw materials used to manufacture these advanced therapies, are all subject to testing for characterization and safety to ensure product quality and performance. Testing of viral banks ensures identity, potency, purity, and safety prior to the use of these vectors in and throughout production. Biosafety testing of viral vectors ensures that the drug substance and drug product are free of adventitious agents and impurities before administration to patients. In this talk, we will review some of the challenges and solutions in viral vector testing.

Dr. Marian McKee is Vice President of Biosafety at Eurofins Lancaster Laboratories Inc. (ELLI) where she leads the Viral Clearance, Cell Banking, and Viral Safety departments. She has more than 20 years of experience driving research, design, and execution of services for biologics safety and characterization testing. In her current role, she provides guidance and the long range planning for biosafety, including development and strategic insight into the company’s gene and cell therapy offering.

Prior to joining ELLI, Dr. McKee was at MilliporeSigma (BioReliance) most recently as Head of Global Testing R&D Services. She also worked at ATCC and as a Staff Scientist at the National Cancer Institute (NCI) after completing her postdoctoral training as a Cancer Research Training Award (CRTA) fellow at NCI. Dr. McKee earned her PhD in Microbiology and Immunology at the Uniformed Services University of the Health Sciences, Bethesda, Maryland and holds a BS in Zoology from Duke University.

Raw material variability presents a high risk to successful manufacturing of consistent media products. With a recent focus on trace elements (TE) impurities, raw materials are tested and analyzed for their impact on final product performance. Over time, this results in huge data sets and the challenge is to store, manage, and share the information effectively. This presentation shows our approach to trace element testing and our efforts in using modern tools to archive, organize, and successfully utilize this data for different applications. The platform helps us to proactively track historical trends, alert supplier-to-supplier variability, and to create predictive media formulations, all with a goal to reduce lot-to-lot variability. Further, with biomanufacturer collaboration and understanding of desirable TE ranges, collectively, we can minimize and control the raw material risk to better manage impurities and variability.

Harika Vemula is currently working as a Staff Scientist in the BioProduction division at Thermo Fisher Scientific (TFS). She is a part of the TFS Raw Material Program driving the raw material characterization, risk mitigation, and data management between global cell culture network sites. She is also a member of industry consortiums and supports external collaborations to understand customer needs. Dr. Vemula has a PhD in Pharmaceutical Sciences and previous experience in upstream bioprocessing, leading process improvements and product performance investigations.

Bacterial, mycoplasma, or viral contamination in cell culture manufacturing processes is a very low probability event, but one with tremendous impact on the manufacturing process and facility if it occurs. Risk mitigation strategies, including intensive characterization of cell banks and seed material, use of animal origin-free and terminally sterilized media and media components, single use bioreactors, and thoughtful engineering of manufacturing spaces have reduced the risk. Despite all these efforts, there is still a requirement to assess manufacturing cell culture harvests for contamination.

Because the traditional adventitious agent or mycoplasma tests take considerable time, contaminant testing is generally only conducted during cell banking and following production bioreactor harvest. To mitigate risk, real-time, quantitative PCR based assays that allow for rapid, highly sensitive detection of mycoplasma, and specific risk virus, mouse minute virus (MMV) and vesivirus 2117 for CHO cultures, can be applied. Additionally, newer technologies utilizing PCR and next-generation sequencing (NGS) can enable rapid, sensitive, accurate detection and identification of bacterial contaminations. Rapid and reliable assays can enable testing for the presence of these agents at multiple points during the cell culture manufacturing process, allowing for the earliest possible detection of a contamination event and identification of the causative agent. These technologies can be implemented for either routine testing or for investigations when bioreactor parameters deviate from typical operating ranges or control limits. This presentation will review the performance and implementation of these methods and include example results from case studies.

Michael Brewer is the Director, Global Principal Consultant, Regulatory for the BioProduction Division (BPD) at Thermo Fisher Scientific. In this role, Michael is responsible for providing global support to BPD customers and serving as the regulatory thought leader and expert across all technology areas within BPD. Prior to moving to this role, he led the team responsible for product applications including microbiology, analytical sciences, and quality control. The products are fully integrated solutions for glycan profiling, bacterial and fungal identification, mycoplasma and viral detection, and host cell DNA and protein quantitation. Michael has over 30 years’ experience in the biopharma industry, including Scios, Synergen, and Amgen in a variety of roles including discovery research, analytical sciences, and quality control. Prior to joining Thermo Fisher Scientific, he led a group at Amgen that developed qualified, validated, and implemented molecular methods for host cell DNA quantitation, contaminant (mycoplasma, virus, and bacteria) detection, contaminant identification, strain typing, and genotypic verification of production cell lines.

Cell and gene therapy is a quickly growing field within the pharmaceutical industry, with a unique set of challenges in terms of the complex raw materials used in the manufacturing processes. Inherent variability of critical raw materials, which are not used in biologics manufacturing, requires close monitoring to fully understand how they impact the manufacturing process performance. As a result, characterizing the raw materials used in the manufacturing of cell and gene therapy products must be performed, in an iterative process, throughout the products' lifecycle. Due to the complex nature of these raw materials, establishing and maintaining a close working relationship with key suppliers will be a valuable tool in characterizing and understanding the impact of raw materials on the manufacturing process and subsequent product quality.

Nathaniel Golden is a Senior Associate Scientist II at bluebird bio in the Cellular Process Development department. He obtained his bachelor’s degree in Biology from the College of the Holy Cross in Worcester, Massachusetts in 2013. With over seven years of experience in the pharmaceutical industry, Nathaniel started his career at Regeneron Pharmaceuticals as a Process Sciences Associate in the Upstream Cell Culture Group, characterizing how critical raw materials impacted the upstream manufacturing process. Since joining bluebird bio in early 2019, Nathaniel has worked to leverage his knowledge of raw material variability and control strategies into the cell and gene therapy space to ensure the robustness of the drug product manufacturing process.

The regenerative medicine field is rapidly advancing, with many pivotal trials underway. As the field moves into large-scale commercial manufacturing, cryopreservation becomes an ever more critical component for ensuring maximum efficacy and long shelf-life during end-to-end production. However, the potency and yield of fragile cell types, such as induced pluripotent stem cells and genetically modified cell-based immunotherapies, are significantly reduced post-cryopreservation due to ice damage and genomic and in vivo toxicity associated with current cryoprotectants (e.g. DMSO). These issues further limit the realization of off-the-shelf advanced regenerative medicine products, such as those being developed in allogeneic cell therapy and tissue engineering.

X-Therma applies convergent biomimetic nanoscience to solve this unmet need in biopreservation, pioneering a novel chemistry that is inspired by natural antifreeze protein, developed with modern drug discovery methods. Our fully synthetic molecules are non-toxic, chemically stable, and exhibit surprising dual ice control function. The resulting product, XT-Thrive^TM, is a DMSO-, serum-, and protein-free and a completely chemically-defined cryopreservation solution.

Dr. Wei is an entrepreneur and chemistry professional in the area of supramolecular assembly and biomimetic nanoscience. She is the inventor of X-Therma’s core technology based on hyper-effective ice prevention materials. Her PhD work demonstrated the success of developing synthetic transmembrane nanopores with distinguished selectivity applying biomimetic and supramolecular chemistry principles. She founded X-Therma Inc. in 2014 to develop a state-of-the-art biopreservation formulation that incorporates a first-in-class hyper-effective (500x) and non-toxic proprietary antifreeze polymer. She led the X-Therma team as an industrial user at the Molecular Foundry, Lawrence Berkeley National Laboratory from 2015 to 2018 and gained multiple recognitions internationally and nationwide. She is the principle investigator of multiple SBIR awards to develop breakthrough cryoprotectants enabling complex tissue/organ cryopreservation with national initiatives. She is experienced in business development and fundraising and managed $7.5M in procurement projects while completing her PhD studies. She was a major author of eight peer-reviewed research papers before founding X-Therma.

While the ultimate end use may vary significantly, the overall objective of cryopreservation (CP) remains the same: obtain the highest quality cell product (survival and function) following thawing. While serving a critical role, protocols, approaches, and technologies have evolved little over the last several decades. This has resulted in a bottleneck impacting numerous areas including cell therapy, tissue engineering, and tissue banking. Recently, numerous studies have described the impact, mechanisms, and points of control of cryopreservation-induced delayed-onset cell death (CIDOCD). Despite this now well-accepted phenomena, today most researchers still rely on traditional methodologies, survival assessment within a few hours post-thaw, and fail to account for the impact of CIDOCD from hours to days post-thaw. To address this the development of new CP agents, freeze media formulations, devices, etc. are providing a path to improve survival over traditional media+DMSO. This presentation will give an overview of our current understanding of the impact of molecular stress response of cells to CP and the interrelated role of the apoptotic and necrotic cell death continuum on outcome. Discussion will cover the "do’s and don’t’s" of cryopreservation today, with a focus on how molecular control, buffering of cell stress response during and following CP, cryopreservation media, cryoprotective agents, storage conditions, warming/thawing (protocols and devices), recovery media, and viability assessment timing all impact outcome. Data will include cell viability and molecular stress results from cell systems including cell lines as well as hHSCs and hMSCs. The data will illustrate how the utilization of new approaches at each stage enables more efficient and reliable cryopreservation thereby yielding increased sample viability and functionality.

John M. Baust, PhD is the founder of CPSI Biotech. Dr. Baust has over 20 years’ experience in research and medical device development. Dr. Baust is a recognized innovator and entrepreneur in cryomedicine, and a pioneer in the area of molecular mechanisms of cell death and low temperature stress. Dr. Baust has published over 100 papers, reviews, book chapters, abstracts, and over 75 patents in the area of low temperature biology. He has been instrumental in the advancement of the field into the molecular biological era, focusing on signal transduction and apoptosis. Dr. Baust is credited with the discovery of cryopreservation-induced delayed-onset cell death (CIDOCD). He has led the development of numerous medical devices, including cryoablation devices for the treatment of cancer and cardiac arrhythmias, as well as spearheading the development of the SmartThaw device for improved cell and tissue cryopreservation. Dr. Baust also remains highly active in the study of the cell-molecular actions of cryoablation. These efforts have resulted in the identification of a significant molecular stress response component to freezing injury which is responsible for the differential sensitivity of various cancers to ablation. As an entrepreneur, Dr. Baust has founded four biotech and medtech companies. He was also on the founding team of BioLife Solutions, Inc, invented CryoStor, and was involved with the commercialization of CryoStor and HTS-FRS. Dr. Baust serves on the editorial board of Biopreservation and Biobanking as well as a reviewer for other scientific journals. He co-edited the book Advances in Biopreservation, and is a board member for the Society for Cryobiology. Dr. Baust completed his studies at Cornell University, Binghamton University, and Harvard Medical School.

Human-induced pluripotent stem cells (hiPSCs) possess tremendous potential for tissue regeneration and banking hiPSCs by cryopreservation. Their ready availability is crucial to their widespread use. However, contemporary methods for hiPSC cryopreservation are associated with limited cell survival, and the use of a high concentration of toxic cryoprotectants and/or serum. The latter may cause spontaneous differentiation and introduce xenogeneic factors, which may compromise the quality of hiPSCs. We developed a new approach inspired by nature to cryopreserve hiPSCs with no serum, minimized cryoprotectant, and high cell survival. Furthermore, the cryopreserved hiPSCs retain high pluripotency and functions judged by pluripotency marker expression, cell cycle, and capability of differentiation into the three germ layers. This novel serum-free low-cryoprotectant cryopreservation method may greatly facilitate the convenient and ready availability of high-quality iPSCs and possibly many other types of cells/tissues for emerging cell-based medicine.

Xiaoming “Shawn” He is a Professor of Bioengineering at the University of Maryland (UMD), College Park. He received his PhD in Mechanical Engineering in 2004 from the University of Minnesota Twin Cities and conducted postdoctoral training from 2004 to 2007 at Harvard Medical School and Massachusetts General Hospital. He was an Assistant Professor at the University of South Carolina from 2007 to 2011, and Associate Professor and Full Professor at Ohio State University from 2011 to 2017. His current research is focused on developing micro and nanoscale biomaterials and devices to engineer totipotent, pluripotent, and multipotent stem cells for cancer theranostics and tissue regeneration. His research has been funded with him as the PI by various private foundations and government agencies including the American Cancer Society (ACS), National Science Foundation (NSF), and National Institutes of Health (NIH). He has published more than 110 peer-reviewed articles in high-ranking journals such as Nature Nanotechnology, Nature Communications, Advanced Materials, ACS Nano, ACS Central Science, and Advanced Functional Materials, in addition to one book and four book chapters. He is serving as the Chair of the American Society of Mechanical Engineers (ASME) Biotransport Committee and as an associate editor of the Journal of Medical Devices. He is a fellow of the ASME and the American Institute of Medical and Biological Engineering (AIMBE).

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan City, China late in December 2019 is an example of an emerging zoonotic virus that threatens public health and international travel and commerce. When such a virus emerges, there is often insufficient specific information available on mechanisms of virus dissemination from animal-to-human or from person-to-person, on the level or route of infection transmissibility or of viral release in body secretions/excretions, and on the survival of virus in aerosols or on surfaces. The effectiveness of available virucidal agents and hygiene practices as interventions for disrupting the spread of infection and the associated diseases may not be clear for the emerging virus. Approaches for infection prevention and control (IPAC) for SARS-CoV-2 and future emerging/re-emerging viruses are discussed.

Raymond Nims is a consultant employed by RMC Pharmaceutical Solutions. From 2006 to 2009, Ray was a subject matter expert (SME) at Amgen, directing viral and mycoplasma testing of raw materials and products, and was business process owner for Amgen’s global contract analytical testing lab outsourcing program. From 1994 to 2006, Ray was employed by BioReliance, directing viral safety, endotoxin, and cell line identity studies for biologics cell line characterization, raw material testing, and product lot release testing.

Kelvin GM Brockbank, PhD is the President of KGB Associates, Inc., and Chief Executive Officer of Tissue Testing Technologies LLC. He is also a Research Professor of Bioengineering at Clemson University and Adjunct Professor of Regenerative Medicine and Cell Biology at the Medical University of South Carolina. His research interests include cell, tissue, and organ preservation for test systems and transplantation and automated manufacturing methods for cell-based tissue engineered products. His work has led to the establishment of two successful publicly traded low temperature technology platform companies, CryoLife, Inc. and Lifeline Scientific. Dr. Brockbank’s last company, Cell and Tissue Systems, Inc., was acquired in December 2014 for its intellectual property portfolio. He has published over 500 patents, book chapters, journal articles, and presentations at national and international conferences. He was the recipient of the “George W. Hyatt Memorial Award” for superior service in the fields of tissue banking and human transplantation in 2009 and is currently funded by several agencies of the National Institutes of Health and the Department of Defense.

Glyn Stacey’s background is in microbiology (Public Health Service, UK) and cancer research (University of Southampton) and he later progressed to work on the development of cell-derived products and cell-based assays at the Centre for Microbiology and Research, Porton Down, UK, where he established the Cell Development Group developing cell culture scale-up systems and cell-based assays. In 1998 he moved to the National Institute for Biological Standards and Control (NIBSC-MHRA, UK) where he set up a new cell biology division working on safety of cell substrates used for vaccine manufacture and establishment of genetic reference materials. In 2002, he won a UK national grant award to initiate the UK Stem Cell Bank to provide a source of ethically suitable and quality controlled human embryonic stem cell lines for research and clinical use. In 2007 he also initiated the International Stem Cell Banking Initiative which brings together pluripotent cell banks from around the world to discuss best practices. Glyn has been a principal investigator in numerous European Commission funded research programmes, scientific advisory boards, national health advisory committees, and was a member of the Horizon Scanning and Research Programme boards of the UK regulatory body Medicines and Healthcare products Regulatory Agency (MHRA). Glyn has also been involved in writing standards for cell culture applications in laboratory testing for the Organisation for Economic Co-operation and Development (OECD, 2018), cell-based manufacture of biotherapeutics and vaccines for the World Health Organization (WHO, 2010), and regenerative medicines for the UK Department of Health (2014). Glyn is currently the Director for the International Stem Cell Bank in Beijing, which is developing hESC lines for clinical trials and has seven registered clinical studies.

Dr. Afshin Sohrabi is the Head of the Near Real-Time Testing Lab with the Development Services Department, MilliporeSigma BioReliance® services leading a team developing rapid testing methodologies for biosafety testing. He joined the organization in 2014 bringing over 20 years of biotechnology experience in assay development and bioengineering. His 20 years of experience also spans R&D, operations, manufacturing, GMP, and quality.

Allen Burgenson was recently named the Global Subject Matter Expert for Testing Solutions at Lonza Walkersville Inc. in Walkersville, Maryland. Prior to this position he was the Regulatory Affairs Manager at that site for over 14 years. Allen has over 35 years of experience in endotoxin detection, both as an end-user and as a manufacturer of LAL assays, including 13 years as a Steering Committee Member for the LAL Users Group. He is currently the President of the Capital Area Chapter of the Parenteral Drug Association (PDA), and has served on several task forces to publish industry standard technical reports for that organization.

Philip J. Cross is President of Philip J. Cross & Associates, Inc., a quality assurance (QA) and regulatory consulting company specializing in biologics, biopharmaceuticals, and biotechnology, with a particular emphasis on cell and gene therapy products. He has assisted dozens of companies in developing products, processes, quality systems, and regulatory documents to take novel products from benchtop to bedside through approval. Phil has written and acted as contact on over 50 Investigational New Drug Applications (INDs) and master files, and has performed product release for hundreds of lots of cell and gene therapy products, including many virus vectors and cell types.

Mr. Cross received a BA in Biological Sciences and an MS degree in Cellular and Molecular Biology, specializing in Virology, from the University of Delaware. He started his career at Wyeth Laboratories, where he was Head of Clinical Manufacturing and Testing for novel virus vaccines, including one of the earliest gene therapy vectors. He was also Manager and Study Director for in vitro and in vivo quality control testing of clinical supplies, including good laboratory practice (GLP) toxicology studies. Following Wyeth, Phil then became a Regulatory Compliance Manager at Centocor, where he coordinated and performed internal and external audits of drug/device manufacturing, testing, product development, clinical studies, suppliers, and regulatory documentation.

Phil returned to academia as Senior Director of QA and Compliance at the University of Pennsylvania, Perelman School of Medicine for the Gene Therapy and Translational Research Programs. This included establishing QA programs, preparing INDs and master files, and releasing cell and gene therapy products for GLP studies and clinical trials. Phil was then Deputy Director of the Harvard Gene Therapy Initiative at Harvard Medical School where he ran a good manufacturing practice (GMP) cell and gene therapy manufacturing and testing facility. He now consults full time.

Alissa M. Resch, PhD is Director of Biobanking Operations at Coriell Institute and a member of the Coriell Board of Trustees. Alissa provides oversight for all repository contracts and grants and supervises the project management teams to ensure project deliverables are met or exceeded. Alissa is also Principal Investigator of the National Human Genome Research Institute (NHGRI) Sample Repository, a diverse collection of cell lines and DNA that have contributed to several landmark initiatives, including the 1000 Genomes and International HapMap Projects.

Prior to joining Coriell, Alissa was an Assistant Professor of Genetics and Developmental Biology at the University of Connecticut, where she conducted research in the field of genomics and RNA biology. Alissa earned her doctorate in biochemistry at the University of California at Los Angeles. Upon completion of her graduate degree, she was awarded an NIH postdoctoral fellowship in bioinformatics at the National Center for Biotechnology Information (NCBI). She conducted a fellowship at the University of Connecticut before accepting a faculty position in the Department of Genetics and Developmental Biology.

Marcin Łoś was born in Olsztyn, Poland. He began his studies at the Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk in Poland. He completed experiments for his MSc at University of Bradford (UK) and defended the MSc degree at University of Gdansk in August 1999. In September 1999 he started his PhD studies in molecular biology at University of Gdansk. He spent one year at the Fraunhofer Institute for Silicon Technology in Itzehoe, Germany (2002–2003) as a researcher involved in the construction of novel virus detection methods. He obtained his PhD degree in June 2004. In 2011 he also obtained a DSc degree. In 2007 he founded the company Phage Consultants, in which he holds the position of CEO. The company specializes in prevention and eradication of various contaminants from fermentation facilities and research laboratories and contract research in the field of phage biology, pharmacology, and biotechnology. His main scientific interests are bacteriophage biology and rapid detection methods. In 2017 Marcin became CEO of Acteryon, a company devoted to phage production and phage technology development.

Dr. Troy Bigelow began working for the USDA in 2003. Troy received his DVM from Iowa State University in 2001. After graduation, Troy entered mixed animal practice including swine, dairy, and cow calf in Iowa and Wisconsin. Troy left private practice to start his government career with the USDA Food Safety and Inspection Service (FSIS). After working in a slaughter plant, Troy accepted a position in FSIS as the District Veterinary Medical Specialist. Troy oversaw humane handling activities and trained veterinarians in pre- and post-mortem inspection procedures.

In 2007 Troy moved to APHIS swine health programs where he focused on program management and development of swine program policies. He also managed the bovine spongiform encephalopathy (BSE) and equine infectious anemia (EIA) programs as interim staff. During the 2015 highly pathogenic avian influenza (HPAI) outbreak, Troy acquired a liking for emergency management. Even today Troy spends time performing his role of Deputy Incident Commander for the Veterinary Services (VS) National Incident Management Team “Indigo.”

Dr. Bigelow, who prefers to be called “Troy” came to Organisms and Vectors, now under Animal Products Import Export, in 2017 where he has been doing permitting activities. Troy who lives in Ames, Iowa, and has two children; a boy in fifth grade and a girl in third. Outside of work hours, Troy is either busy working out at the local CrossFit gym, riding a bike, managing rental properties, or remolding/construction (Troy does start to finish construction including framing, concrete, electrical, plumbing, drywall/finish carpentry). Troy also enjoys working on trucks (semi-trucks) and is often known to be in the cab of an 18-wheeler hauling livestock around the Midwest.

Snehal Parikh is a Supplier Collaboration Manager in the Global Supplier Quality team at Roche-Genentech, where he works with raw material suppliers to continuously improve the quality of incoming raw materials. Snehal has been with Roche-Genentech since 2008, and has held a number of diverse roles in the areas of statistical and quality engineering, risk management, technology transfers, make access release (MAR), annual product quality review, and external manufacturing quality site management. He is a mechanical engineer and has post-graduation experience in plastics engineering. He is also a Certified Quality Engineer (CQE) and Certified Six Sigma Black Belt (CSSBB).