Cambridge Healthtech Institute’s 4th Annual
Rapid Methods to Assess Quality & Stability of Biologics
Improving Prediction and Screening
Part of CHI's 8th Annual The Bioprocessing Summit

August 15-16, 2016 | Westin Boston Waterfront | Boston, Massachusetts

Assurance of quality and stability of biologic formulations over the course of intended usage is critical in developing safe and efficacious biopharmaceutical products. Increasing regulatory expectations and aggressive development timelines calls for rapid methodologies to predict and assess the quality and stability of biologics. The fourth annual Rapid Methods to Assess Quality & Stability of Biologics conference will bring together experts in analytical and formulation development to discuss regulatory expectations, prediction and manipulation for protein stability and instabilities cause by particles and impurities. Conference will feature case studies and strategies, especially unpublished and innovative work, on methods employed in real time and accelerated stability studies, protein aggregates and effective use of DoE for assessment and data comparability from early to late stage development.

Final Agenda

Monday, August 15

8:00 am Short Course Registration

9:00 – 11:30 Recommended Morning Short Course*
SC2: Accelerated Stability Testing of Biologics

* Separate registration required

11:30 Main Conference Registration Opens


1:00 pm Chairperson’s Opening Remarks

Peter Tessier, Ph.D., Department of Chemical & Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute

Methods for Selecting and Engineering Monoclonal Antibodies with Improved Biophysical Properties

Peter_TessierPeter Tessier, Ph.D., Department of Chemical & Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute

It is critical to optimize the biophysical properties of monoclonal antibodies in addition to their bioactivities due to the increasing demands for processing and formulating antibodies at high concentration. I will discuss our work on developing novel methods for identifying, engineering and characterizing antibodies with reduced propensity to self-associate and increased developability (high solubility, low viscosity, low non-specific interactions).

1:45 A Fast Method for Monitoring Multiple Attributes of Therapeutic Proteins

Wei Xu, Ph.D., Principal Scientist, Analytical Method Development, Merck

Therapeutic proteins such as mAbs have become the top choice in treating many life threatening disease conditions. An increased demand for new therapeutic mAbs and higher regulatory expectations require the biopharmaceutical industry to increase efficacy in the research and manufacturing process. High speed analytical methods are highly desirable to speed up the bioprocess of therapeutic proteins. Discussion will focus on development of a fast peptide mapping method with very short sample preparation and analysis time using design of experiments.

2:15 Thermodynamics of Liquid-Liquid Phase Separation in Monoclonal Antibody (mAb) Solutions

Prasad_SarangapaniPrasad Sarangapani, Ph.D., Scientist, Regeneron, Inc.

2:45 Refreshment Break

3:15 Rapid Peptide Mapping for Monitoring Multiple mAb Attributes

Nisana_AndersenNisana Andersen, Ph.D., Associate Scientist, Protein Analytical Chemistry, Genentech, a Member of the Roche Group

Characterization of mAbs and their attributes is an important aspect in identification of critical quality attributes. LC-MS/MS peptide mapping, intended for in-depth analysis of mAb attributes, is employed during characterization. Once attributes have been identified and characterized, fast MS-only methods capable of monitoring these attributes can be more suitable. Here, application of a rapid peptide map method used to monitor relative amounts of previously characterized mAb attributes is discussed.

Reese_Eric3:45 For the First Time, Simultaneous Detection of Protein Aggregation and Affinity Measurements in a Single SPR Experiment

Eric Reese, Ph.D., VP, Sales & Marketing, SensiQ Technologies Inc

No SPR-biosensor has been capable of delivering information on drug affinity and detect protein aggregates simultaneously in the same experiment. SensiQ Technologies presents data from a current collaboration describing how this limitation can be eliminated via simultaneous detection of both protein aggregation and affinity determination in a single experiment as enabled by Pioneer FE SPR.

4:00 Preclinical Tools in Formulation Optimization to Improve Biological Performance of Antibodies

Sabine_EichlingSabine Eichling, Ph.D. Candidate, NBE Formulation Development, AbbVie

Formulation development for biologics has focused on the refinement of physical and chemical stability during shelf-live. Effects of formulation composition following s.c. injection were usually not considered. The addition of biological read out parameters, such as bioavailability and ultimately efficacy, enables further improvement in the antibody transport to the target tissue. The aim of this work is to develop translatable models to understand the transport of antibodies following s.c. injection and predict the effect of the formulation.

4:30 Breakout Discussions

Analytical Challenges For Low Concentration/Low Dose Drug Products

Dominick DeGrazio, Associate Scientist, Drug Product Development, Janssen R&D

  • Are there potential solutions to the analytical obstacles being seen often with increasingly potent molecules?
  • For low dose IV or subQ administration, how can pharmacy manual requirements for certain characterization attributes be fulfilled if there is no practical analytical solution available?
  • What are new, upcoming technologies that could provide analytical alternatives, but are currently not commercially viable options yet?
  • What is necessary to develop these technologies as quickly as possible so that they may be implemented as a qualified, routine analytical tool?


System Suitability for Analysis Using Mass Spectrometry

Nisana Andersen, Ph.D., Associate Scientist, Protein Analytical Chemistry, Genentech, a Member of the Roche Group

  • Importance of system suitability for MS analysis
  • Key points for system suitability for MS analysis
  • Regulatory requirements for system suitability for MS analysis: ICH, FDA, EMA, and Health Canada Guidance


New Tools for Characterization of Protein Aggregation and Stability

Sanket Patke, Ph.D., Research Investigator, Drug Product Science and Technology, Pharmaceutical Development, Bristol-Myers Squibb

  • What are the available high-throughput tools?
  • Strategies to detect and manage chemical degradation
  • PAT for in process/ in line detection


5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

Tuesday, August 16

7:30 am Registration Opens and Morning Coffee


7:55 Chairperson’s Remarks

Richard Cavicchi, Ph.D., Physicist, Bioprocess Measurements Group, National Institute of Standards and Technology

8:00 Current Technologies for Subvisible Particle Analysis for Biologics

Andrea_HaweAndrea Hawe, Ph.D., CSO, Coriolis Pharma

An overview on analytical methods for sub-micrometer and micrometer particles in biopharmaceutical products will be given, with respect to measurement principle, capabilities for sizing, quantification and identification, typical applications, and limitations. Methods covered include: field flow fractionation, analytical ultracentrifugation, flow cytometry, laser diffraction, dynamic light scattering, nanoparticle tracking analysis, resonant mass measurement, electrical sensing zone analysis, light obscuration, flow imaging and Raman microscopy.

8:30 Dimers and Aggregates – Criticality and Specifications - Are We Barking up the Wrong Tree?

Volker_SchnaibleVolker Schnaible, Ph.D., Senior Principal Scientist, Pharma Technical Development Europe (Biologics) Analytics, F. Hoffmann-La Roche AG

Theoretical concerns about the role of aggregates/particles as a contributing factor to immunogenicity events (e.g. ADA) and the lack of a solid database translate into specific requirements from health authorities. We performed extensive biophysical characterization of different dimer species of monoclonal antibodies. The immunogenicity of these species was evaluated in transgenic mice that are tolerant against human IgG1 but immunocompetent. The outcome of these studies is presented.

9:00 Particulate Characterization for Biotherapeutics – Overcoming Technique Challenges and New Learnings

Ankit Patel, Ph.D., Scientist, Genentech

In this presentation, we will discuss the inherent instability of a conjugate type vaccine, various reasons for such instability and appropriate mitigation strategy that can be employed.

9:30 Selected Poster Presentation: Forced Degradation Study of Biopharmaceutical Antibodies Using Electrochemistry

Beijing Huang, Post Doc Researcher, Bioanalytical Science Group, National Institute of Standards and Technology (NIST)

Forced degradation, the intentional application of stress conditions to artificially induce changes in product attribute, is a critical step in the evaluation of pharmaceutical antibodies. Information about changes that may occur to the antibody after exposure to stress conditions can be used to design production, processing and formulation. In this work we demonstrate the use of electrochemistry for controlled and quantitative forced degradation of NISTmAb IgG1κ reference material via oxidation.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Effect of Particle Density on the Sizing and Counting of Subvisible Protein Aggregates by Orthogonal Methods

Richard_CavicchiRichard Cavicchi, Ph.D., Physicist, Bioprocess Measurements Group, National Institute of Standards and Technology

Measurements of protein aggregates using different techniques often result in discrepancies arising from the differences in measured properties, e.g. flow imaging: area, electrical sensing zone: volume, resonance mass: mass, etc. A key parameter that relates the results reported by orthogonal methods is the particle density. We attempt to estimate this parameter by performing two measurements on individual aggregates, and will discuss how this result can be used to relate measurements by orthogonal methods.

11:00 Detection and Quantitation of Residuals in Vaccine Components Using NMR

Marina_KirkitadzeMarina Kirkitadze, Ph.D., MBA, Deputy Director, Analytical R&D Biochemistry, Sanofi Pasteur

The focus of the presentation is the NMR method development to determine the limit of quantitation (LOQ) and limit of detection (LOD) of the process-related residuals in the vaccine product candidates. The results demonstrated that NMR method can successfully identify and quantify a residual in protein component of vaccine and in viral vaccine samples.

11:00 Applied Analytical Techniques to Monitor IsoAsp in Biologics Formulation Development

Dominick_DeGrazioDominick DeGrazio, Associate Scientist, Drug Product Development, Janssen R&D

The development of a suitable biologic formulation occurs often before analytical methods are validated. Certain chemical modifications are critical to monitor during the development process as they may cause protein instability and reduce biologic efficacy. Aspartic acid isomerization is one such modification, but is arguably the most difficult to detect. Analytical tools to track IsoAsp are discussed that can aid in making formulation decisions before the availability of qualified methods.

12:00 pm Prometheus NT.48: Biologics Stability Screening has Never Been Faster, Easier & More Fun

Breitspecher_DennisDennis Breitspecher, Ph.D., Head, Research & Development, Biochemistry Research & Development, NanoTemper Technologies, GmbH

Prometheus NT.48 allows for rapid and precise high-throughput stability screenings, while providing best-in-class high resolution thermal unfolding data for biologics, independent of buffer or protein concentration. It allows for an exact detection of aggregation onset temperatures and aggregation behavior to find the conditions in which the protein is most stable.

Barco_Joe12:15 Meet Our UNcle: the All-In-One Biologics Stability Platform
 Joe Barco, Director, Product Marketing, Marketing, Unchained Labs

Characterizing biologic stability is a wrestling match with disjointed data from sub-optimized tools. Not anymore. UNcle combines fluorescence, SLS, and DLS reads in one instrument. This allows you to quickly and efficiently characterize all the size, aggregation, thermal ramp, isothermal and viscosity information you want.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

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


1:55 Chairperson’s Remarks

Danny Chou, Ph.D., President and Founder, Compassion BioSolution; Former Senior Research Scientist, Biologics Development, Gilead Sciences

2:00 Automated and Rapid Methods to Assess Quality & Stability of Biologics: Recent Developments and the Keys to Successful Implementation in Formulation and Bioprocess Development

Danny_ChouDanny Chou, Ph.D., President and Founder, Compassion BioSolution; Former Senior Research Scientist, Biologics Development, Gilead Sciences

The goal of this presentation is to describe new developments in the field of analytical technologies for protein aggregate testing and characterization. Particular focus will be on techniques that are automated, high throughput, and capable of detecting subvisible particulates. Methods that detect changes in other quality attributes will also be discussed.

2:30 Analytical Methods in Support of High Throughput Conjugation Process Development for ADCs

Michael_FlemingMichael Fleming, MS, Scientist, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.

Assays that are suitable of providing rapid results about important ADC related attributes (e.g. size and charge variants, drug loading, residual free small molecules) will be discussed in this presentation.

3:00 Development of High-Throughput Quantitative UPLC-High Resolution Mass Spectrometry Multi-Attribute Methodology for Biologics

Pilsoo_KangPilsoo Kang, Ph.D., Scientist I, Analytical Science and Technology, Sanofi

Understanding product quality attributes is crucial in Quality by Design approach drug development. To accomplish this, appropriate analytical methodologies are required. Generally, the number of analytical methods used in protein characterization is large. To increase efficiency, we developed a quantitative UPLC-high resolution mass spectrometry-based method which permits monitoring multiple quality attributes of biologics products. This multi-attribute methodology can be applied to other products as a platform approach.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 High Throughput Biophysical and Biochemical Stability Screening for Early Stage Antibody Discovery

Yingda_XuYingda Xu, Ph.D., Director, Protein Analytics, Adimab

Problems in the development of antibodies can often be traced back to their intrinsic poor biophysical and biochemical stabilities. High throughput screening assays are developed or adapted to fit in the scope of early discovery stage to filter out candidates with poor properties.

4:45 Panel Discussion: Challenges in Adopting New Methods in QC Labs


Danny Chou, Ph.D., President and Founder, Compassion BioSolution; Former Senior Research Scientist, Biologics Development, Gilead Sciences


Michael Fleming, MS, Scientist, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.

Pilsoo Kang, Ph.D., Scientist I, Analytical Science and Technology, Sanofi

Yingda Xu, Ph.D., Director, Protein Analytics, Adimab

5:15 End of Conference

5:15 Registration for Dinner Short Course