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)

Back Bay C

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.

Oritain 3:45 What Happens When You Combine Traceability with Science 

Kate_LintermanKate 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_TelikepalliSrivalli 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_PaskietDiane 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)

Back Bay C

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_RyanDerek 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_PikeJeremy 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_KramerCaitlin 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_SanePooja 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_WestJay 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_CavicchiRichard 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

Back Bay C

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_StokesAnne 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_BraxtonCassandra 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_CetlinDavid 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


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