Cambridge Healthtech Institute’s Seventh Annual

Rapid Methods to Assess Quality & Stability of Biologics
( 生物製劑的品質與穩定性 )

Improving and Accelerating Prediction and Screening 



The seventh annual Rapid Methods to Assess Quality & Stability of Biologics conference will bring together experts in analytical and formulation development to discuss regulatory expectations, prediction, measurement and manipulation for protein stability and instabilities in early and late-stage development. The conference will feature case studies, unpublished work on new methods and tools employed in real time, and accelerated stability studies for proteins, cell and gene therapy products, high-throughput analytics, multi-attribute methods, biophysical methods, HOS, use of DOE and QbD.

Final Agenda


7:30 am Short Course Registration Open and Morning Coffee

8:30-11:00 Recommended Short Course*

SC2: A Modern Approach to Biologics Formulation Development

Instructors: Kevin Zen, PhD, Senior Director, Biologics Development, Allgenesis Biotherapeutics

Danny K. Chou, PharmD, PhD, President and Founder, Compassion BioSolution; Former Senior Research Scientist, Biologics Development, Gilead Sciences

This course offers a forum on how to develop sound formulations for biologic drugs. Case studies will be presented to demonstrate how to incorporate QbD concepts to do risk assessment, design multivariate experiments, and assess critical quality attributes including subvisible particle characterization in order to develop a robust formulation for the bulk drug substance or final drug product in the context of designated container closure systems. This course utilizes real-world examples and interactive discussion.

11:00 Main Conference Registration Open


12:30 pm Chairperson’s Opening Remarks

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

12:40 KEYNOTE PRESENTATION: Formulation Development for Biosimilar

SINGH_SATISHSatish K. Singh, PhD, Head, Sterile Product Technology, Moderna Therapeutics

Development of the formulation for biosimilars requires a combination of intellectual property, state-of-the-art technical considerations as well as strategic considerations around product development. Some of these aspects will be highlighted in this presentation using case studies.

1:10 Use of Affinity Capture - Self Interaction Nanoparticle Spectroscopy (AC-SINS) for Clone Ranking and Formulation Screen During Antibody Early Discovery

Sun_TingwanTingwan Sun, PhD, Senior Scientist, Protein Analytics, Adimab LLC

Self-association of antibodies on gold nanoparticles, including SINS and AC-SINS, has been broadly used for clone ranking and lead selection at the early stage of antibody discovery. However, it has quite a limited use in formulation screening due to incompatibility of commonly used formulation buffer excipients, such as histidine. Here, we report a modified gold nanoparticle assay with improved buffer pH, salts and detergents compatibility, enabling high throughput formulation screening.

1:40 Developing a Bio-Layer Interferometry Based Platform for Formulation Screening

Naik_SubhashSubhashchandra Naik, PhD, Senior Scientist, Reform Biologics

Formulating monoclonal antibodies (mAbs) to obtain meaningful shelf-life is an iterative process using multiple excipients and conditions. A bio-layer interferometry (BLI) platform shortens this process to improve formulation screening throughput. A proprietary chaperonin biosensor can rapidly screen mAb stability while a BLI based ELISA can be used to test the functional efficacy with mAbs biological target. The formulation conditions were further validated using traditional orthogonal and with extended stability studies.

2:10 Refreshment Break

2:30 High Throughput Approaches to Enable Robust Early Stage Formulation Development

Tanenbaum__LauraLaura Tanenbaum, PhD, Scientist, BioTherapeutics Drug Product Development, Janssen R&D

This talk presents a case study in which rapid formulation screening strategies were utilized for accelerated New Molecular Entity (NME) advancement. Under relevant bioprocessing stress conditions (temperature, freeze-thaw, agitation, and mental stress), formulations were evaluated using multiple high throughput analytical tools to progress selected formulations through additional long-term evaluation. This approach enables a detailed understanding of protein stability at an early stage and limits the need for reformulation throughout the product lifecycle.

3:00 Predicting Physiochemical Stability of New ADCs Modalities from Discovery to Development

Kara Huang, PhD, Senior Scientist, Drug Product Development, AbbVie

Anticipating physiochemical stability issues of ADCs is important for both assessing compound developability during discovery and setting product formulation and shelf-life during development. These potential liabilities can be discovered using a combination of forced degradation studies and rapid/sensitive assays. We present an improved approach to predict the overall ADC stability via characterization of the linker-drug component and utilization of computational models to simulate long term storage conditions.

3:30 Presentation to be Announced


3:45 Session Break

3:55 Plenary Keynote Session View details

5:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

6:30 End of Day


7:30 am Registration Open and Morning Coffee


7:55 Chairperson’s Remarks

Subhashchandra Naik, PhD, Senior Scientist, Reform Biologics

8:00 Protein Physical Stability: A Pre-Formulation Screening Based on Colloidal and Configurational Biophysical Properties

Calero-Rubio_CesarCesar Calero-Rubio, PhD, Scientist, Biologics Drug Product Development, Sanofi

Protein self-interactions and other biophysical properties are hypothesized to be one of the primary contributors to protein aggregation under long-term storage conditions. Relationship between biophysical properties and protein aggregation is yet to be generalized across a broad selection of mAbs and formulation buffers. We have revised the historical hypothesis regarding protein physical stability and biophysical properties by combining statistical analysis of the solution behavior of several mAbs mimicking a pre-formulation workflow.

8:30 Impact of Cavitation, High Shear Stress and Air/Liquid Interfaces on Protein Aggregation

Mark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU)

Shear associated protein aggregation is described since the early days of bioprocessing. However, within this work generated isolated shear rates (> 108 s-1) did not cause any of the 9 tested proteins to aggregate. On the contrary, when shear occurred together with cavitation or air/liquid interfaces protein aggregation was found. Hence, shear cannot be considered as a trigger for protein aggregation during up- and downstream processes. 

9:00 New USP General Chapter <1049.1> Design of Stability Studies for Biotechnology Product Development and Lifecycle Management

Schmidt_DaleDale R. Schmidt, MS, Senior Scientific Liaison, US Pharmacopeia

This presentation will provide an overview of the new USP General Chapter <1049.1> Design of Stability Studies for Biotechnology Product Development and Lifecycle Management. The intent of this chapter is to provide detail regarding stability studies necessary for expiry setting, product characterization, market registration, and patient/physician use. The chapter addresses the overall strategy, lifecycle management, and design of stability studies through all stages of the product lifecycle.

9:30 Presentation to be Announced


9:45 Coffee Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

10:30 N-glycan Characterization in the Development of mAbs and Fusion Proteins

Kast_ElisabethElisabeth Kast, PhD, Senior Scientist, Protein Analytics, AbbVie

N-glycans are often an important critical quality attribute for biologics and should be monitored and assessed during development. Implementation and use of robust, reliable and informative methods for monitoring glycosylation in biologics development will be discussed.

11:00 Use of 2D NMR based HOS Fingerprinting to Probe Molecular Basis of Viscosity of Monoclonal Antibodies

Majumder_SubhabrataSubhabrata Majumder, PhD, Postdoctoral Fellow, Pharmaceutical Research and Development, Biotherapeutics, Pfizer, Inc.

2D NMR based higher order structure fingerprinting of therapeutic monoclonal antibodies (mAbs) provides a direct readout of its solution behavior at an atomic resolution. In this presentation, HOS fingerprints of few mAbs of varying viscosity under a set of solution conditions will be discussed. Such fingerprinting at dilute concentrations can be adopted at early stages of formulation development to predict high concentration solution behavior and to screen for viscosity-reducing excipients.

11:30 Relationship Between Physicochemical and Biological Properties with Higher Order Structure of Monoclonal Antibodies

Maity_HaripadaHaripada Maity, PhD, Director/Principal Investigator, Bioverativ, A Sanofi Company

A strong correlation among higher order structure (HOS), conformational stability, and functional properties is generally observed for proteins. Characterization of HOS is primarily performed by different biophysical techniques. The selection and sensitivity of these techniques is very important, and may depend on protein to protein.

12:00 pm Presentation to be Announced


12:30 Luncheon Presentation to be Announced



1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing


1:55 Chairperson’s Remarks

Haripada Maity, PhD, Director/Principal Investigator, Bioverativ, A Sanofi Company

2:00 Qualification and Validation Methods for New Particle Counting Instruments

Ripple_DeanDean Ripple, PhD, Leader, Bioprocess Measurements Group, NIST

The increased use of new types of particle counting instruments, such as flow imaging, has raised questions on how these instruments may be qualified and measurement methods validated. I will discuss the use of standards and a variety of independent measurements and data analysis methods that can address these needs, over a size range from 100 nm to visible.

2:30 Lights-Out Manufacturing? What Do We Know About Light Spectrum and its Impact on Drug Product Manufacturing

Austin Gallegos, BS, R&D Associate, Dosage Form Design and Development, AstraZeneca

This presentation will discuss our understanding of cool white light (CWL) spectrum, our current approach on accessing CWL impact on protein degradation, and the correlation between lab light stress studies and actual DP manufacturing.

3:00 Understanding and Mitigating Risk Due to Naturally Occurring Aggregates in Protein Based Formulations

Swanson_MichaelMichael Swanson, Senior Scientist, Merck

Aggregated therapeutic antibodies have the potential to induce an immune response. Elucidation of the mechanism of responses to aggregated antibodies could mitigate the immunogenic risk. In this presentation, we will discuss understanding and mitigating risk due to naturally occurring aggregates in protein formulations.

3:30 Backgrounded Membrane Imaging (BMI) for High-Throughput Subvisible Particle Characterization During Biopharmaceutical Drug Product Development

Helbig_ConstanzeConstanze Helbig, PhD, Postdoctoral Scientist, Coriolis Pharma Research GmbH

We scientifically evaluated BMI (sizing and counting accuracy, working range, impact of refractive index, interferences by silicone oil droplets), and compared BMI to state-of-the-art dynamic image analysis (DIA). For both techniques, similar upper concentration limits were found. For non-silicone oil particles, total particle concentrations (ECD≥2 µm) agreed well but size distributions differed. For BMI, removal of silicone oil droplets throughout sample processing and robustness against refractive index changes were demonstrated.

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

4:45 Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges.

5:45 End of Conference

6:00-830 Recommended Dinner Short Course*

SC7: Protein Aggregation: Mechanism, Characterization and Consequences


Thomas Laue, PhD, Professor Emeritus, Molecular, Cellular and Biomedical Sciences, University of New Hampshire

Matthew Brown, PhD, Applications Manager, Bioscience, Malvern PANalytical

Protein aggregation is recognized by regulatory agencies and the biopharmaceutical industry as a key quality attribute of biotherapeutics. Various aggregates hold the potential for adversely impacting production and patients in a variety of ways. This in-depth course reviews the origins and consequences of aggregation in biotherapeutics, and then examines strategies for predicting and quantifying aggregation in biopharmaceuticals. It benefits scientists engaged in the development, production, analytical characterization and approval of biotherapeutics and who require a good working knowledge of protein aggregation.

SC9: Impact of Impurities on Stability of Biologics


Diane Paskiet, MS, Director of Scientific Affairs, West Pharmaceutical Services, Inc.

Katherine E. Bowers, PhD, Principal Scientist, Group Leader, Fujifilm Diosynth Biotechnologies

Impurities in protein therapeutics can originate from a variety of unexpected sources. As the protein molecule is taken through the upstream/downstream processes, final product manufacturing (fill/finish) and even during patient delivery, there is a myriad of potential “hidden” impurities that can have an impact to the safety and efficacy of the bio-therapeutic. This course aims to answer the questions of what and where are the greatest risks for biologic impurities and how can we study the impact of these impurities on the protein molecule. Our mission is to collectively discuss how to identify, evaluate and mitigate impurity risks from early development and throughout the product life cycle.

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