Cambridge Healthtech Institute’s Inaugural
Virus Detection, Clearance and Safety of Biologics:
Adventitious Agent Contamination, Risk Mitigation, New Technologies and Case Studies
August 6-7, 2015
Part of CHI's 7th Annual The Bioprocessing Summit
August 3-7, 2015 | Westin Copley Place Hotel | Boston, Massachusetts
Recent incidents due to adventitious agents in manufacturing processes have resulted in an increased regulatory scrutiny and the need for new technologies and better risk management strategies to ensure safety of biologics. The inaugural Virus Detection,
Clearance and Safety of Biologics conference will discuss technical and regulatory aspects of detection, risk mitigation and risk management of viral contamination coming from raw materials, cell culture processes, bioreactor contamination and downstream
processing. There will also be discussion on new technologies for detection of new pathogens. We invite you to attend to learn from, and network with, the leading experts from around the world on safety of biotherapeutics against viral and other adventitious
agents.
Thursday, August 6
1:55 pm Chairperson’s Remarks
Horst Ruppach, Ph.D., Global Manager Viral Clearance and Global Coordinator Virology, Biologics Testing Solutions, Charles River Biopharmaceutical GmbH
KEYNOTE PRESENTATIONS:
2:00 Application of Regulatory Guidance to New Molecular Detection Methods for Virology and Mycoplasmology
Barbara
J. Potts, Ph.D., Senior Consultant, Potts and Nelson Consulting LLC
Molecular detection methods both old (PCR) and new including massively parallel sequencing, chip technology, and PCR combined with MASS Spec Time of Flight are ready to replace some of the classical virology detection methods. This talk will outline
a path forward that the biotechnology industry can follow to successfully accomplish this change. An example of this path that has yielded success for mycoplasma PCR replacement of a culture method will be provided.
2:45 Mitigating Viral Contamination in Vaccines and Biologics Manufacturing
Otmane
Boussif, Ph.D., Director, Purification & Formulation Processes, Sanofi Pasteur
Contaminations of mammalian cell culture bioreactors are still being reported. In order to prevent this threat, manufacturers developed several risk mitigation strategies. Raw materials, media and solutions are the most likely source of contamination
of mammalian cell-based operations, with risk related to material source and supply chain. Therefore implementations of additional point-of-use barriers risk, as well as sensitive analytical tools are considered. This presentation will discuss
alternative technologies for media treatment through case studies.
3:15 Anion Exchange Membrane Adsorber and Viral Clearance Capacity – an Alternative to Anion Exchange Chromatography?
Horst Ruppach, Ph.D., Global Manager Viral Clearance and Global Coordinator Virology, Biologics Testing
Solutions, Charles River Biopharmaceutical GmbH
Anion Exchange Chromotography shows frequently high viral removal capacity when run under certain conditions. This presentation will summarize experiences made with different types of Anion Exchange Membrane Adsorbers. The general capacity and robustness
to remove viruses will be demonstrated and compared with the capacity of Anion Exchange Chromatography. The pros and cons of using Membrane adsorbers for viral clearance removal will be outlined and discussed based on experimental data.
3:45 Poster Highlight Presentation: Use of Virus Like Particle’s as Viral Clearance Spiking Surrogates during Downstream Process Development Studies
David A. Cetlin, Founder & C.E.O., MockV Solutions LLC
Viral clearance studies are accomplished by challenging scaled-down versions of purification steps with live viral “spikes”. These studies are typically conducted in BSL-2 facilities and are costly. A non-infectious viral surrogate would be
useful for scientists developing or characterizing downstream purification process steps. Discussed here is an attempt to use a Virus Like Particle to determine the Mouse Minute Virus removal efficacy of a chromatography column step.
4:00 Ice Cream Social in the Exhibit Hall with Poster Viewing
4:45 An Alternative Approach to Evaluation of Viral Clearance on New vs. End-of-Life Anion Exchange Chromatography Resin
William Daniels, MSc, Senior Scientist, Purification Process Development, Pfizer, Inc.
A viral clearance study for new and used (end-of-life) anion exchange chromatography (AEX) resin evaluated the effect of extensive resin cycling on the capacity to bind virus in flow-through mode. A single column of new resin was tested alongside a single
column of used resin, with both columns showing consistent capacity to clear two virus types in duplicate as well as demonstrating no viral particles in carryover (“mock”) pools produced after each viral clearance run.
5:15 Panel Discussion: Advances in Viral Clearance and QbD Approach to Viral Safety
Moderator: 
Horst Ruppach, Ph.D., Global Manager Viral Clearance and Global
Coordinator Virology, Biologics Testing Solutions, Charles River Biopharmaceutical GmbH
Panelists:
Paul W. Barone, Ph.D., Associate Director, Consortium on Adventitious Agent Contamination in Biomanufacturing,
MIT Center for Biomedical Innovation
Otmane Boussif, Ph.D., Director, Purification & Formulation Processes, Sanofi Pasteur
Siemon Ng, Ph.D., Scientist, Microbiology & Virology Platform, Department of Analytical Research & Development
North America, Sanofi Pasteur
Barbara J. Potts, Ph.D., Senior Consultant, Potts and Nelson Consulting LLC
5:45 End of Day
6:30-9:00 Recommended Dinner Short Course
ABC: Anything But Chromatography – Precipitation, Crystallization and Flocculation
Friday, August 7
8:00 am Registration and Morning Coffee
8:55 Chairperson’s Remarks
Kathryn Martin Remington, Ph.D., Principal Scientist, Development Services, BioReliance
9:00 FEATURED PRESENTATION: A Survey of Industry Data on HTST, UV-C and Nanofiltration for Media Treatment and Their Efficacy of Removal and Inactivation of Virus
Paul
W. Barone, Ph.D., Associate Director, Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB), MIT Center for Biomedical Innovation
To reduce the risk of virus contamination in cell culture based biomanufacturing operations many manufacturers have implemented or begun to consider implementing large scale media treatment to remove or inactivate virus. Typical technologies that
have been considered for this task are HTST treatment, UV-C irradiation and nanofiltration. CAACB consortium has collected member data and surveyed the literature to begin to assess the efficacy of each of these three media treatment technologies.
A preliminary assessment of the results will be presented.
9:30 Successful Implementation of Modular Viral Clearance Claims for Early Phase Clinical Filings
Shilpa Ananthakrishnan, MSc, Scientist I, Process Sciences, Purification, AbbVie Bioresearch Center
Demonstration of viral clearance capability is integral to developing downstream process. Dedicated viral clearance steps are incorporated into the process to ensure patient safety by providing robust and predictable capacity for virus removal and
inactivation. In order to minimize viral clearance testing for early phase clinical programs, we have established modular claims for dedicated clearance steps within our platform manufacturing process. The claims have been successfully submitted
in IND filings and have enabled greater efficiency in early and phase trials.
10:00 Coffee Break
10:45 Viral Risk Mitigation Strategies for Cell Culture Media and Other Raw Materials
Kathryn
Martin Remington, Ph.D., Principal Scientist, Development Services, BioReliance
Contamination prevention strategies should involve a multi-faceted approach, including cell line screening, raw material testing and implementation of viral inactivation and removal steps in the downstream process. Other measures, such as viral reduction
procedures for culture media and raw materials complement the strategy and may reduce the potential for viral contaminants to enter the downstream process. Data will be presented to demonstrate the efficacy of procedures such as UVC treatment
and virus reduction filtration to reduce viruses in cell culture media.
11:15 Process Strategies to Improve Virus Clearance in Early Downstream Processing
Deqiang Yu, Ph.D., Senior Scientist, Process Development, Bristol-Myers Squibb Co.
This talk will focus on virus clearance in early steps of downstream processing. Protein A step is used for virus clearance but not very effective. The strategies to improve virus clearance in Protein A will be discussed. Harvest treatment will be also discussed as a potential virus clearance step to increase process capability.
11:45 Poster Highlight Presentation: Prefiltration and Process Improvements: Enhancing Virus Filter Performance with Use of Surface Modified Membrane Prefilter
Benjamin Cacace, R&D Engineer, EMD Millipore
12:15 Extended Q&A with Session Speakers
12:30 Luncheon Presentation: Preventing Virus Contamination of Bioreactors with a Virus Barrier Filter
Christina Carbrello, Ph.D., Senior Scientist, Process Solutions, EMD
Millipore
Cell culture media is typically sterile filtered to remove bacteria and mycoplasma, however many bioreactors remain unprotected from viral contamination. Ideally, a filter could be used to remove viruses, but filtration is traditionally
perceived as being unsuitable for the upstream processes. A new virus filter has been evaluated and demonstrated high levels of virus, bacteria and mycoplasma removal while providing high flow and capacity in chemically defined media
with little to no impact on cell culture performance.
1:15 Session Break
1:25 Chairperson’s Remarks
Yoshifumi Hashimoto, Ph.D., Senior Scientist, Process Development, Protein Sciences Corporation
1:30 Implementation of an Adventitious Detection Assay Using High Throughput Sequencing within a Vaccine Manufacturer
Siemon Ng, Ph.D., Scientist, Microbiology & Virology Platform, Department of Analytical Research
& Development North America, Sanofi Pasteur
NGS has great potential for testing cell substrates, raw materials, viral seed lots and crude harvests for adventitious agents. This technology has exquisite sensitivity and broad specificity. Implementing NGS can potentially streamline
the adventitious testing package and replace animal testing. Data will be presented comparing the performance of NGS against qPCR and in vitro assay as well as the detecting adventitious agent in viral seed lots and other biological
samples.
2:00 Next-Generation Sequencing Detection of Adventitious Agents
Brenda Richards, Staff Scientist, Functional Genomics, Genzyme, a Sanofi Company
Next-generation sequencing (NGS) is an emerging technology for pathogen detection in biopharmaceutical manufacturing allowing for the identification of both known and novel microorganisms. We have used this approach to confirm the identity
of a causative agent in a bioreactor contamination and to establish the limits of detection for DNA and RNA viruses and bacteria in a background of Chinese hamster ovary cells. The presentation will include strategies, data, and conclusions
from these experiments.
2:30 Incomplete Novel Sf9 Rhabdovirus is Detected in a Sf9 Cell Line
Yoshifumi Hashimoto, Ph.D., Senior Scientist, Process Development, Protein Sciences Corporation
A novel Sf9 rhabdovirus has been identified by next generation sequencing (NGS). We performed an analysis to verify Sf9 rhabdovirus RNA and searched for virus structures in cell culture supernatant. Our results showed an incomplete Sf
rhabodovirus RNA containing a deletion of 320 nt of and absence of rhabodovirus-like particles in 1.14 g/ml fraction of the culture supernatant. We discuss discrepancy of data between NGS and conventional methods.
3:00 Networking Refreshment Break
3:15 Scaled-Down Model Qualification and Use for Process Improvement
Adam J. Meizinger, Ph.D., BS, Process Engineer II, Manufacturing
Science and Technology Laboratory, Genzyme - a Sanofi Company
3:45 Challenges in Developing Predictive Downstream Scaled-Down Models
Omkar Joshi, Ph.D., Head, Downstream Development, Global Biologics, Bayer Healthcare
Scale-down models as appropriate representation of the manufacturing process are indispensable tools in characterization of biopharmaceutical manufacturing processes. During process development, such models enable evaluation of variability
in input materials and parameters on a process and its impact on product quality to an extent that simply is not feasible at manufacturing scale. The key is to keep it simple and appropriate to needs. The presentation shows a pragmatic
and systematic approach how to increase understanding of an antibody purification process by elements like scale-down modelling and qualification, cross-functional risk assessments, and process characterization studies.
4:15 Close of Conference