Cambridge Healthtech Institute’s Inaugural
Detection, Characterization and Control of Impurities in Biologics
Hot Topics, Emerging Contaminants and Impurities, Case Studies and New Technologies
August 16-17, 2018
Cambridge Healthtech Institute’s Inaugural Detection, Characterization and Control of Impurities in Biologics conference will bring together leading scientists from biopharmaceutical industry, academia and government to discuss
hot topics, emerging contaminants and impurities and new characterization tools for impurities that may come from various sources and stages of product development and manufacturing. Through new presentations, informative panel discussions, high-level
poster presentations, and interactive breakout discussions, top scientists will share new insights into characterization and control of various impurities. Some of the hot topics for this year will be new and novel technologies for virus and pathogen
detection, host cell proteins, lipases and enzymatic degradation, aggregations, leachable, chemistry and manufacturing controls (CMC) strategy for regulatory filings.
Final Agenda
Thursday, August 16
11:30 am Registration Open (Grand Ballroom Foyer)
12:15 pm Enjoy Lunch on Your Own
1:15 10th Anniversary Cake Break in the Exhibit Hall with Last Chance for Poster Viewing (Grand Ballroom)
1:55 Chairperson’s Remarks
Diane Paskiet, MS, Director of Scientific Affairs, Scientific Affairs and Technical Services, West Pharmaceutical Services
2:00 Control of Impurities for Novel Biologic and Biosimilars from Regulatory Perspective
Audrey Jia, PhD, Principal Consultant, Regulatory Affairs, DataRevive LLC, Ex-FDA, Office of Biotechnology
Biological products contain product-related and process-related impurities that are derived from the expression system and the manufacturing process. This talk focuses on discussions during the clinical development of the biological products, how
impurities are evaluated for its quality and related safety and efficacy, and how the impurities are controlled for novel biologic and biosimilar products. Case studies for impact of impurities and regulatory considerations are presented.
2:45 Approaches to Monitoring Impurities Using USP Standards
Kevin Carrick, PhD, Director, Science & Standards, Global Biologics, United States Pharmacopeia (USP)
Impurities must be monitored and controlled to ensure the quality of the drug substance and drug product. Impurities range from process-related, such as host cell DNA, host cell proteins and particulates, to product-related, such as degradants,
precursors and aggregates. This presentation will outline approaches found in the USP for monitoring impurities from process-related to product-related.
3:15 Continuing Advances in Risk Mitigation in the Use of Fetal Bovine and Other Sera
Rosemary J. Versteegen, PhD, CEO, International Serum Industry Association
This presentation will focus on the mitigation of risk in the use of animal sera in cell culture. The talk will review and provide new data on programs such as traceability certification, geographic testing of origin, age determination of source
animals, and gamma irradiation of animal sera.
3:45 What Happens When
You Combine Traceability with Science
Kate Linterman, Business Development, Oritain
Forensic science can be applied to products we use every day to trace where they have come from. From the food we eat to the clothes we wear and the raw ingredients that go into our pharmaceuticals. This presentation explains the technology and
its applications through real in-market examples.
4:00 Refreshment Break (Foyer)
4:15 New Reference Standards for Monitoring Proteinaceous Particles in Biotherapeutics
Srivalli Telikepalli, PhD, Research Chemist, Biomolecular Measurement Division, National
Institute of Standards and Technology
Subvisible and visible particle standards are being developed using an ethylene tetrafluoroethylene polymer, which better mimics the morphology and optical properties of proteinaceous particles. These particles can be used to standardize subvisible
particle measurements and to better understand various instrument biases. The development and various applications of this standard, along with the current efforts to standardize the visual inspection methodology will be discussed.
4:45 Sources of Particles in Biologic Products: Considering Assessment of Packaging Materials
Diane Paskiet, MS, Director of Scientific Affairs, Scientific Affairs and Technical Services, West Pharmaceutical
Services
It is critical to understand the types and sources of particulates in biologic products and how their presence may affect product quality and patient safety. The linkage between particles, biologic formulation and packaging development involves
understanding contributions from all sources. This presentation will provide insight into measurements of particles originating from packaging components, comparison of data from various technologies and current standards.
5:15 End of Day
6:00 - 9:00 Recommended Dinner Short Course*
SC11B: Development of Innovative and Completive Biologic Formulations in Complex Patent Landscape
Instructor: Jan Jezek, PhD, CSO, Research & Development, Arecor, Ltd.
* Separate registration required.
Friday, August 17
8:00 am Registration Open and Morning Coffee (Grand Ballroom Foyer)
8:25 Chairperson’s Remarks
Richard Cavicchi, PhD, Research Physicist, Biomolecular Measurement Division, Material Measurement Laboratory, National Institute of Standards and Technology
8:30 High-Throughput and Automated Impurities Detection Methods for Accelerated Biotherapeutic Manufacturing Programs
Derek Ryan, PhD, Senior Scientist, Analytical Development, KBI Biopharma, Inc.
With increasing demands to reduce the biotherapeutic time to clinic, process development efforts have adopted increasingly accelerated platforms. To keep up with this accelerated pace, a combination of high-throughput and automated methods
have been developed to deliver insight into host cell protein and high molecular weight impurities clearance during process development.
9:00 Appearance of a Novel Basic Charge Variant during Redevelopment of a Monoclonal Antibody Production Process: The Path to Identification and Control
Jeremy Pike, MS, Development Scientist, Early Stage Process Development, Alexion Pharmaceuticals
Re-development of a monoclonal antibody production process resulted in a major change in a product-related charge variant. Multiple process development studies were executed to explore the potential source, assess potential impact to product
safety and efficacy, and identify process levers for control. Multi-functional cooperation was crucial in identifying the potential cause and product impact, as well as the most likely modification responsible for this product quality
shift.
9:30 Evaluation of the Simple Plex Ella Platform For Accelerating Process Development and Supporting Next-Generation Manufacturing
Caitlin Kramer, MSc., Associate Scientist, Process Development Analytics, Bristol-Myers Squibb
The ProteinSimple Ella instrument was evaluated for its potential application in substituting for traditional ELISA impurities assays. In-process samples for multiple BMS mAbs were examined for dilutional linearity and spike recovery. Ella
was evaluated from both a high throughput process development perspective and a process analytical technology perspective, for future use in next-generation manufacturing scenarios.
10:00 Networking Coffee Break (Foyer)
10:30 Optimization of Capping Parameters for Maintaining Container Closure Integrity for Ultra- Low Storage Temperature
Pooja Sane, PhD, Scientist, Formulation, BioMarin Pharmaceuticals
Loss of elasticity of rubber stoppers below the glass transition temperature, Tg, can lead to development of micro-leaks causing a potential container closure integrity (CCI) issue. During cold shipping on dry ice for temperature sensitive
products, this can lead to ingress of carbon di-oxide (CO2) gas in to the vial. On returning the vial to room temperature, the rubber stopper would regain its elasticity trapping the CO2 gas inside the vial which could dissolve in
the drug product solution and lead to a drop in its pH. This is concerning especially in case of pH sensitive biologics where their stability could be compromised. In this work, we present a systematic approach to optimize the crimping
parameters for a plastic vial with a rubber stopper.
11:00 Development of High-Throughput Assays to Track Lipase-Induced PS80 Degradation in Support of Commercial Process Development
Jay West, PhD, Scientist II, Process Development Analytics, Bristol-Myers Squibb
Lipase-induced degradation of sorbate-based excipients/surfactants poses a critical risk for long term stability of therapeutic proteins and monoclonal antibodies. Our discovery of rapid PS80 loss required timely analytic method development.
Here we share two novel methods: LC/MS measurement of PS80 mono-oleate species, and a fluorescence method to measure total lipase activity. These were implemented in a high-throughput complimentary format to develop commercial processes
for multiple therapeutic proteins.
11:30 Relating Measurements Made by Orthogonal Methods for Subvisible Particle Characterization
Richard Cavicchi, PhD, Research Physicist, Biomolecular Measurement Division, Material Measurement
Laboratory, National Institute of Standards and Technology
Orthogonal measurements are often used with the goal of verifying an assessment of particle count and size distribution. While such methods usually agree when calibration beads are used, significant discrepancies have been noted when characterizing
protein aggregates. To determine the causes of the differences, we present case study experiments that perform simultaneous orthogonal measurements on a per particle basis. We also estimate an important parameter, the spatially averaged
protein aggregate density, which plays an important role in measurements such as the resonance mass technique. The results may lead to calibration parameters for relating measurements.
12:00pm Enjoy Lunch on Your Own
1:25 Chairperson’s Remarks
Anne Stokes, PhD, GSK Fellow and Director, TSE and Virus Control, GMP Operations, Biopharmaceutical Development and Supply, GlaxoSmithKline
1:30 FEATURED PRESENTATION: TSE and Virus Control Framework for the Development and Manufacture of Biopharmaceuticals
Anne Stokes, PhD, GSK Fellow and Director, TSE and Virus Control, GMP Operations, Biopharmaceutical Development
and Supply, GlaxoSmithKline
Biopharmaceutical products are inherently at risk of contamination from adventitious or endogenous viruses, novel microbial agents and transmissible spongiform encephalopathies (TSE, or prion diseases), which can be introduced into manufacturing
processes. These agents pose a risk to the manufacturing facility and patient safety. This presentation will outline the control framework to prevent these agents in the manufacturing process and will discuss the tools and strategies
for detection, characterization and control.
2:00 Second Generation Reference Materials for Adventitious Virus Detection by Metagenomics
Edward Mee, DPhil, Senior Scientist, Live Viral Vaccines, Virology, National Institute for Biological Standards and Control
Metagenomics offers great potential for improved adventitious virus screening; however, many practical challenges exist, including cost, complexity and the difficulty in defining limits of detection for unknown viruses. Well-characterized
reference materials containing representative virus genome, capsid and envelope structures will enable meaningful inter-laboratory comparisons, support method development and act as process run controls.
2:30 Next-Generation Sequencing: A New Approach to Adventitious Virus Detection
Cassandra Braxton, PhD, Senior Manager, Global QC Virology, Biogen
Cell culture-based methods are limited in their detection capabilities in that they are only able to detect viruses that cause cytopathic effect, hemadsorption, or hemagglutination. Biogen is exploring next-generation sequencing (NGS)
as a new approach to adventitious virus detection. This presentation will provide an overview of NGS, considerations for implementation in a GMP environment, and evaluation against current adventitious virus detection methods.
3:00 Predicting MVM Clearance by Nanofiltration and Anion Exchange Chromatography Using a Non-Infectious “Mock Virus Particle”
David Cetlin, Founder & CEO, MockV Solutions LLC
Viral clearance is an expensive and logistically challenging aspect of bioprocess development. A non-infectious “Mock Virus Particle”, engineered to physicochemically resemble MVM, was used as a spiking surrogate during
small scale Virus Filtration and Anion Exchange Chromatography experiments. The results demonstrate the validity of utilizing this surrogate as a cost-effective way to predict or optimize for MVM clearance as part of process development
and characterization studies.
3:30 Close of Conference