Cambridge Healthtech Institute's 14th Annual

Characterizing Protein Aggregates and Impurities

Strategies and Tools for Detection and Characterization of Aggregates and Impurities in Biologics

January 17 - 18, 2023 ALL TIMES PST

Cambridge Healthtech Institute’s 14th Annual Characterizing Protein Aggregates and Impurities conference covers the latest trends, challenges, and solutions in understanding the characterization and mitigation of problems generated by protein aggregation, impurities, and contaminants in biopharmaceuticals. This conference features case studies, new and unpublished data, and interactive discussions on how to carry out risk assessment and mitigation for aggregates and impurities arising from products, excipients, processes, and packaging, immunogenicity concerns, prediction and modeling, and new tools for detection, and quantitation. This conference is part of the Characterization of Biotherapeutics & Vaccines Pipeline which also features the 9th Annual Characterization of Biotherapeutics conference and the inaugural Characterization and Development of Vaccines.

Tuesday, January 17

Registration (Indigo Foyer)12:45 pm

Refreshment Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)1:00 pm

Organizer's Welcome Remarks1:30 pm

ROOM LOCATION: Aqua Salon E

IMPORTANT CONSIDERATION FOR DEVELOPMENT OF NOVEL BIOTHERAPEUTICS

1:35 pm

Chairperson's Opening Remarks

Susumu Uchiyama, PhD, Professor, Biotechnology, Osaka University

1:40 pm KEYNOTE PRESENTATION:

Optimizing Drug Product Presentation and Manufacturing Processes for Gene Therapy Products

Sandeep Yadav, PhD, Senior Director, Drug Product Formulation & Fill/Finish, Sangamo Therapeutics

Biotechnology companies are extensively leveraging adeno-associated viruses (AAVs) to deliver therapeutic DNA for genomic medicine applications. The field however is still in early stages of gaining experience with stability, analytics, drug substance (DS) and drug product (DP) manufacturing processes. Some of the notable challenges are extremely low titers, limited manufacturing lots to develop process knowledge, and complex analytical methodologies required to characterize AAV systems. Collectively, these challenges lead to higher cost of goods (COGs) while catering to the rare/orphan disease space. This talk focuses on developing and optimizing DP formulation/presentations and manufacturing strategies to support patient safety, healthcare provider convenience, and reducing COGs to enable patient accessibility.

2:20 pm

Latest Developments in Particulate Impurity Characterization Technologies for Biologics

Bruce A. Kerwin, PhD, Principal, Kerwin Biopharma Consulting LLC

Within the talk novel approaches for the characterization of particulate impurities in biologics will be presented, and compared to state-of-the-art technologies for submicron and subvisible particle analysis. Besides new analytical technologies, the integration of machine learning for data analysis will be presented.

2:50 pm Trehalose and Sucrose: Essential Components of Platform Biopharma Formulations and COVID 19 applications

Sudhakar Voruganti, Dr., Director, Business Development, Pfanstiehl

  • Introduction of Pfanstiehl and its high quality/purity GMP components
  • Commercial Biotherapeutics Stabilized with Trehalose and Sucrose
  • Examples for utilizations and functionalities of Sucrose and Trehalose in Covid 19 related formulations and applications
  • Essential components of a “Platform Biopharma Formulation”
  • Understanding important physicochemical properties of Trehalose and Sucrose
  • Purity, Quality, Consistency in Pfanstiehl’s Trehalose and Sucrose

Refreshment Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)3:20 pm

GUIDANCE, STANDARDS, AND TOOLS FOR AGGREGATES AND IMPURITIES

4:00 pm

USP Standards and Tools for Impurities Analysis in Biotherapeutics

Kevin L. Carrick, Director, Global Biologics, USP

The monitoring and control of process-related impurities is an important element in process development and product manufacturing. USP has developed standards and tools to assist in the quantitation of host cell DNA and host cell proteins.  This presentation will cover USP standards, documentary and reference standards, for host cell DNA quantitation, and new reference materials in development to support quantitation of host cell proteins.

4:30 pm

Advances in Methods for Detection, Characterization, and Enumeration of Process and Product-Related Particles

Richard Cavicchi, PhD, Research Physicist, Biomolecular Measurement Division, Material Measurement Laboratory, National Institute of Standards and Technology

Identification, counting, and minimization of particles continue to be important for the safety and efficacy of biotherapeutics. Protein aggregates, which can arise as pure protein or nucleated on other particle types, present unique measurement challenges. While the standard methods used for lot release are still based on light obscuration methods from the 1990s, significant advances have resulted in improved capabilities over a wide size range. Recent developments will be discussed.

5:00 pm

Standards for Particle Detection: From Nanometers to Visible

Dean C. Ripple, PhD, Group Leader, Bioprocess Measurements Group, NIST

I present strategies for the use of particle reference materials, discussing their strengths and limitations. Both the properties of interest in reference material and its use vary substantially from the size range of nanometers to visible, depending on user expectations, the state of the art in instrumentation, and what is measured. Reference materials developed for size and count are also now finding use for new technologies and methods, such as AI analysis of particle images.

Close of Day5:30 pm

Wednesday, January 18

Registration and Morning Coffee (Indigo and Aqua Foyer)8:30 am

ROOM LOCATION: Aqua Salon CDE

9:00 am

Organizer's Remarks

Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute

9:10 am Plenary Fireside Chat:

Supporting and Driving Biotech: Past, Present, and Future

PANEL MODERATOR:

Julie Ames, Vice President, Corporate Communications, Biocom California

Innovation can refer to something new, such as an invention, or the development and introduction of new practices. The end result is often a new product, but it can also be a new practice, procedure, or way of thinking. Change and challenges are often what inspire innovation and propel us forward into new ways of thinking and doing. This Fireside Chat convenes long-term supporters of PepTalk: The Protein Science and Production Week who will be exploring the following:

  • Innovations and technology development in the last 5 years ​
  • Takeaways from the post-pandemic world – what lessons did we learn?
  • Collaborations and strategic partnerships – advice to early-stage/small companies ​
  • Is there a trend toward diversification of scientists’ roles, skill sets and responsibilities? Why?
  • What is an unexpected market trend you are seeing?
  • What excites you/what keeps you working in this industry?
PANELISTS:

Amy K. Butler, PhD, President, Biosciences, Thermo Fisher Scientific

Taegen Clary, Vice President, Marketing, Unchained Labs

Jonathan Haigh, PhD, MBA, Vice President, Process Development, Fujifilm Diosynth Biotechnologies

Craig R. Monell, PhD, Senior Vice President, Business Operations, BioLegend (a PerkinElmer company)

Coffee Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)10:15 am

ROOM LOCATION: Aqua Salon E

SURFACTANTS AND AGGREGATION

11:00 am

Chairperson's Remarks

Bruce A. Kerwin, PhD, Principal, Kerwin Biopharma Consulting LLC

11:05 am

A Mechanistic Understanding of Monoclonal Antibody Interfacial Protection by Hydrolytically Degraded Polysorbate 20 and 80 under IV Bag Conditions

Aadithya Kannan,PhD, Technical Development Principal Scientist, Genentech

Polysorbates (PS) are used to reduce monoclonal antibody (mAb) aggregation at hydrophobic interfaces. PS can hydrolyze over time to generate free fatty acid (FFA) degradants, primarily lauric acid for PS20 and oleic acid for PS80. This talk discusses key differences in the effect on aggregation of a surface-active mAb by degraded PS20 and PS80, using surface tension studies, static storage behavior, colloidal, and conformational stability of mAbs with degraded PS.

11:35 am

Photolytic and Oxidative Degradation of Polysorbates in Common Buffers

Christian Schoeneich, PhD, Takeru Higuchi Distinguished Professor & Chair, Pharmaceutical Chemistry, University of Kansas Lawrence

The chemical degradation of polysorbate continues to present a challenge for the development of stable protein formulations. Free radical-mediated mechanisms play a central role in oxidative polysorbate degradation. Polysorbate oxidation can target polysorbate monomers or polysorbate micelles. Here, we show that intra-micellar oxidation reactions dominate polysorbate oxidation even when initiated with hydrophilic oxidants. We further show that specific buffer-derived radicals can play a critical role in polysorbate oxidation.

12:05 pm Manufacturing physically stable proteins starting from cell line development

Dikran Khachadourian, Field Application Scientist, Halo Labs

Cell line development (CLD) is a critical aspect of drug development. However, data supporting the stability of secreted proteins during CLD is scarce. Bridging the gap between CLD and developability allows biomanufacturers to pre-screen samples for immunogenic subvisible protein aggregates. In this talk, we present Aura PTx, an instrument that enables low volume, high-throughput subvisible particle imaging, counting, sizing, and identification to generate stable biologic candidates from CLD through product release. 

 

Session Break and Transition to Luncheon Presentation12:35 pm

12:45 pm LUNCHEON PRESENTATION:Tackle Stability and Viscosity of Your Biologic with Unchained Labs Solutions

Andre Mueller, PhD, Marketing Manager, Biologics Solutions, Unchained Labs

Unchained Labs is all about unleashing solutions to tackle the increasing complexity of screening biologics and the ever-growing challenge to select the best candidate or formulation.

Join my talk to see examples of how Uncle monitors protein stability in thermal ramps or during storage, and how Honeybun rapidly measures viscosity of multiple samples in mere minutes.

Session Break1:45 pm

CONSIDERATION DURING PRODUCT DEVELOPMENT & MANUFACTURING

2:00 pm

Chairperson's Remarks

Danny K. Chou, PharmD, PhD, President, Biopharmaceutical Characterization and Formulation Development, Compassion BioSolution, LLC

2:05 pm

Rescuing Catastrophic Aggregation – Formulation and Delivery Considerations to Enable Pulmonary Administration of IgM Drug Product in Early Development

Christopher Mensch, Director, Drug Product, IGM Biosciences, Inc.

The degree of protein purity and aggregation are well-established critical quality attributes requiring careful monitoring during the development of monoclonal antibody Drug Products. A strategic approach was utilized to rapidly rescue soluble and insoluble aggregation and enable pulmonary delivery of IgM mAb Drug Product.  Key formulation and delivery considerations to enable Early Development activities will be described.

2:35 pm

Characterization and Disruption of Ultra-Low Affinity HCP-mAb Interactions

Shrenik Mehta, PhD, Technical Development Scientist, Pharmaceutical Development Department, Genentech, Inc.

Mechanistic characterization as to how HCPs persist in drug products is important to refining downstream processing. Weak esterase–mAb interactions potentially enable HCP esterases to evade drug purification processes. Here, we apply state-of-the-art methods such as HRF-MS, native-MS, and ion mobility to establish esterase-mAb binding mechanisms. 

3:05 pm

Real-Time Detection of Protein Aggregation – Practical Strategies for Implementation during Product Development and Manufacturing

Danny K. Chou, PharmD, PhD, President, Biopharmaceutical Characterization and Formulation Development, Compassion BioSolution, LLC

The goal of this presentation is to provide an update on the most recent developments in real-time detection and monitoring of protein aggregation. The focus is on emerging orthogonal methods that may be implemented during product development as well as during large-scale manufacturing.

PepTalk Plaza: Speed Networking

IN-PERSON ONLY:

Speed Networking

Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute

Bring yourself, your phone, or your business cards (if you still have them) and be prepared to share and summarize the key elements of your research in a minute. PepTalk will provide a location, timer, and fellow attendees to facilitate the introductions.

Refreshment Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)3:35 pm

4:15 pm

Biophysical Characterization of mAb-Excipient Interactions

Subhashchandra Naik, PhD, Senior Research Scientist, Comera Life Sciences

Monoclonal antibodies at high concentrations interact with each other and with excipients by a variety of mechanisms. We can modulate these interactions by using excipients to change the properties of drug products. Here we look at a few excipients and how they affect mAb formulations.

4:45 pm

Strategies for Addressing Challenges of High Concentration Formulation Development: A 150 mg/mL mAb Case Study

Benjamin R. Clarkson, PhD, Scientist II, Formulation Development, NIH/NIAID/VRC Vaccine Production Program

Development of formulations for high concentration (100+ mg/mL) biotherapeutics poses numerous technical and logistical challenges during formulation and process development. As illustrated in a case study of the development of a 150 mg/mL monoclonal antibody formulation, strategic use of data generated at lower concentrations, utilization of certain predictive assays for stability at high concentrations, and careful molecule selection can enable rapid development of stable high concentration formulations.

5:15 pm

Succinate Buffer in Biologics Products: Real-World Formulation Considerations, Processing Risks, and Mitigation Strategies

Anvay Ukidve, PhD, Scientist, Formulation and Process Development, Sanofi

Succinate acid/succinate system has an excellent buffering capacity at acidic pH values (4.5-6.0). However, its use in formulating drug products is largely limited due to risk of its components crystallizing and the consequent pH shifts. Physicochemical behavior of succinate system was characterized under pharmaceutically representative conditions. mAbs formulated in de-risked succinate buffer maintained a good stability profile during typical pharmaceutical processing and upon storage, bolstering their wider use in drug products.

Networking Reception in the Exhibit Hall with Poster Viewing (Indigo Ballroom)5:45 pm

WOMEN IN SCIENCE MEET UP AT PEPTALK PLAZA

6:50 pm

Women in Science Meet Up at PepTalk Plaza

Christa Cortesio, PhD, Senior Scientist and Group Lead, Protein Science, Protein Biochemistry & Analytics Core, Kite Pharma

Michelle R. Gaylord, MS, Principal Scientist, Protein Expression Lead, Velia, Inc.

The Women in Science Meet Up at the PepTalk is a networking and inspiring event tailored for female attendees. We invite the entire scientific community to discuss these barriers, as we believe that all voices are necessary and welcome. Please join fellow scientists and discuss your personal and professional journey.​

  • What do you struggle with most as a woman in science?
  • What are you proudest of?
  • As we return to a post-pandemic work-life environment, have there been any challenges or improvements that have impacted you?
  • Do you feel that we as a society have made good progress towards equal treatment of women and men in the workplace?
  • What can each of us do to improve things further?​

Close of Characterizing Protein Aggregates and Impurities7:00 pm