Cambridge Healthtech Institute’s 2nd Annual
Virus and Pathogen Clearance and Safety in Biologics
Adventitious Agent Contamination, Risk Mitigation, New Technologies and Case Studies
Part of CHI's 8th Annual The Bioprocessing Summit
August 18-19, 2016 | Westin Boston Waterfront | 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 the safety of biologics. The second annual Virus
and Pathogen Clearance and Safety in Biologics conference will discuss the technical and regulatory aspect of detection, risk mitigation and risk management of virus and other pathogen contamination in biopharmaceuticals that come 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 We are seeking case studies and strategies, especially unpublished and innovative work on
methods employed in understanding and handling pathogen safety in biomanufacturing.
Final Agenda
Thursday, August 18
11:30 am Registration Opens
12:15 pm Lunch Available for Purchase in the Exhibit Hall
1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing
1:55 Chairperson’s Opening Remarks
Mark Plavsic, Ph.D., Head, Process Development & Manufacturing, Torque Therapeutics Inc
2:00 Considerations for Use of New Technologies for Adventitious Virus Detection
Arifa Khan, Ph.D., Supvy Microbiologist, Viral Products, FDA CBER
Several advanced nucleic acid based technologies have emerged with capabilities of broad virus detection. High throughput sequencing (HTS) has the potential for identification of both known and novel viruses without prior knowledge of virus genome
sequences. Therefore, HTS may complement the currently recommended testing for the presence of unknown viruses, including latent and endogenous viruses that may not be detected by the conventional assays. This presentation will describe the need
for new virus detection methods, challenges of using HTS, and ongoing efforts toward filling the critical gaps for using new virus detection technologies for detection of adventitious viruses.
2:45 Design, Evaluation, and Characterization of Viral Clearance Procedures: USP Chapter <1050.1>
Mark Plavsic, Ph.D., Head, Process Development & Manufacturing, Torque Therapeutics Inc.
The new USP Chapter <1050.1> on viral clearance will be published in 2016. It is meant to supplement USP Chapter <1050> and the ICH guidance Q5A. The purpose of this talk is to provide an overview of key features of this new publication
and make the audience aware of the value it brings to those practicing the art of viral clearance.
3:15 Protein A: the Untold Story
Pete Gagnon, Vice President, Process Sciences, Avid Bioservices Inc.
This presentation will review recent discoveries about the way protein A really works: how it affects IgG, why it is generally unable to reduce host contaminants below 500 ppm, and how to enable it to reduce them below 10 ppm. New data will be
shown from case studies conducted with prospective biosimilar Humira, Herceptin, and other antibodies. Examples will demonstrate consistently better purification with 2 chromatography steps than can be achieved by the traditional 3-step platform.
3:45
Genetic Engineering of CHO Cells for Viral Resistance to Minute Virus of Mice (MVM)
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Joaquina Mascarenhas, Ph.D., Senior Research & Development Scientist, MilliporeSigma
We have engineered a host cell line resistant to MVM infection, while maintaining desired productivity and product quality profiles. This approach can be applied to different CHO host cell lines as well as therapeutic protein producing recombinant
cell lines. This is another level of “defense” to current viral risk mitigation strategies.
4:00 Refreshment Break
4:15 Panel Discussion with Session Speakers
This panel will explore from both a manufacturing and regulatory perspective the most effective way to establish pathogen removal targets. The balance between product purity and protein structural integrity will be a main focus of this
panel
Pete Gagnon, Vice President, Process Sciences, Avid Bioservices Inc.
Arifa Khan, Ph.D., Supvy Microbiologist, Viral Products, FDA CBER
Mark Plavsic, Ph.D., Head, Process Development & Manufacturing, Torque Therapeutics Inc
Joaquina Mascarenhas, Ph.D., Senior Research & Development Scientist, MilliporeSigma
5:15 End of Day
5:15 Registration for Dinner Short Course
Friday, August 19
8:00 am Registration Opens and Morning Coffee
8:25 Chairperson’s Remarks
Donald Jarvis, Ph.D., Professor, Molecular Biology, University of Wyoming & President, GlycoBac LLC
8:30 Redevelopment of a Viral Filtration Step for a Large and Complex Monoclonal Antibody Based Fusion Protein
George Enriquez, Ph.D., Senior Process Development Specialist, Bio Process Department,
Shire
A quality by design (QbD) based, late stage purification process development approach was used for a 300kD, complex monoclonal antibody (Mab) based fusion protein. A manufacturability risk assessment identified viral filter fouling as
a high risk to a robust, cost effective manufacturing operation. Through systematic filter scouting and optimization development work, the combination of a pre-filter and a viral filter was found to deliver high throughput, high recovery
& short processing time.
9:00 Characterization of an Sf-rhabdovirus Negative Insect Cell Line
Donald Jarvis, Ph.D., Professor, Molecular Biology, University of Wyoming & President, GlycoBac
LLC
The recent discovery that insect cell lines derived from Spodoptera frugiperda (Sf) are contaminated with a rhabdovirus raised questions about their biosafety as a commercial recombinant protein production substrate. To address this problem,
we created Sf-rhabdovirus-negative (Sf-RVN) cells, which have no detectable trace of this adventitious agent. In this presentation, we will describe the features of Sf-RVN cells as an alternative host for use in the baculovirus-insect
cell system.
9:30 Use of a Non-Infectious Virus Like Particle for Viral Clearance Spiking Studies
David Cetlin, Founder & CEO, 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.
10:00 Networking Coffee Break
10:30 Retrospective Evaluation of Low pH Viral Inactivation and Viral Filtration Data from Multiple Company Collaboration
Xinfang Li, Principal Scientist, Process Science and Engineering, ImmunoGen, Inc.
Considerable resources are spent within the biopharmaceutical industry to perform viral clearance studies which are conducted for widely used unit operations that are known to have robust and effective retrovirus clearance capability.
The collaborative analysis from the members of BioPhorum Development Group Viral Clearance Working Team considers two common virus reduction steps in biopharmaceutical processes: low pH viral inactivation and viral filtration.
11:00 Viral Clearance for Commercial-Scale Norovirus
Virus-Like Particle Manufacturing Processes
Ross Taylor, Ph.D., Director, Process Development, Takeda Pharmaceuticals Inc.
Norovirus infection is the most common cause of acute gastroenteritis in the U.S., estimated to afflict 21 million people per year. For manufacturing of a vaccine candidate, the baculovirus expression system has been used for production
of two distinct norovirus virus-like particles (VLPs). Processing of VLPs employs enveloped virus inactivation and orthogonal chromatography steps. Viral clearance validation has been conducted for select unit operations of the
VLP manufacturing process.
12:00
pm Robust Virus Filter Design Space via Enhanced Macroscale Surface Geometry
Aernout Martens, Ph.D., Global Product Manager, Virus Filtration, Pall Life Sciences
Maximizing virus filter capacity while maintaining high viral safety is critical to overall bioprocess cost of goods reduction. In order to provide both high protein capacity and robust virus retention we have applied surface geometry
to a virus filter membrane at the macroscale. This enhances the available surface area relative to the frontal surface area. The improvement in capacity is demonstrated using colloidal gold, polyclonal IgG, and monoclonal antibody
solutions. Bacteriophage data confirms that keeping the downstream retentive surface of the membrane unchanged maintains the retentive characteristics of the membrane, improving the balance between critical performance parameters.
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:15 Session Break
1:25 Chairperson’s Remarks
1:30 Progress in Development of Virus-Retentive Size-Exclusion Filter Paper
Albert Mihranyan, PhD, Professor of Nanotechnology, Wallenberg Academy Fellow, Nanotechnology and Functional Materials, Department of Engineering, Uppsala University
2:00 Raw Materials as the Source of Porcine Circovirus, Porcine Hepatitis E Virus and Mycoplasmas, Strategies to Prevent and Remove from Biologics
Barbara J. Potts, Ph.D., Senior Consultant, Potts and Nelson Consulting, LLC
Strategies will be presented to prevent the contamination of biologics with porcine circovirus, porcine hepatitis E virus from contaminated porcine raw materials and from mycoplasmas found in peptones and bovine sera. Removal and
inactivation methods will be presented that have been successful including a case study of porcine circovirus in pepsin.
2:30 Panel Discussion: Determining Viral Clearance Targets and Selecting Clearance Method
This panel will discuss technology advancements available to biological drug manufacturers to meet viral clearance standards. Protein reactions to these methods will be explored
David Cetlin, Founder & CEO, MockV Solutions LLC
George Enriquez, Ph.D., Senior Process Development Specialist, Bio Process Department, Shire
Xinfang Li, Principal Scientist, Process Science and Engineering, ImmunoGen, Inc.
Albert Mihranyan, PhD, Professor of Nanotechnology, Wallenberg Academy Fellow, Nanotechnology and Functional Materials, Department of Engineering, Uppsala University
Barbara J. Potts, Ph.D., Senior Consultant, Potts and Nelson Consulting, LLC
3:30 Close of Conference