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

August 21-22, 2017 | Westin Copley Place | Boston, MA

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 fifth annual Rapid Methods to Assess Quality & Stability of Biologics conference brings together experts in analytical and formulation development to discuss regulatory expectations, prediction and manipulation for protein stability and instabilities caused by particles, higher order structures and impurities. Conference will provide platform to share case studies, unpublished and innovative work on methods employed in real time and accelerated stability studies, protein aggregates and effective use of DoE for assessment and data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 21

8:00 am Short Course Registration Open

9:0011:30 Recommended
Morning Short Courses*

SC4: Accelerated Stability Testing of Biologics

* Separate registration required

11:30 Main Conference Registration Open


1:00 pm Chairperson’s Opening Remarks

Christopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, University of Delaware

Developing Competitive Biologics Products Necessitates Combining Formulation Design, Process Development, and Device Integration

Yatin_GokarnYatin Gokarn, Ph.D., Head, Global Pharmaceutical Development Biologics, Sanofi

There is a increasing need for designing and developing competitive biologics drug products in today’s biotherapeutics marketplace when many new modalities and new product formats are making their way to market and many promising leads continue to fill the research and development pipelines. A competitive patient-centric product necessitates a holistic product development strategy that takes into consideration formulation design, process development, analytics and device integration.

1:45 How Well Can We Predict Protein-Protein Interactions and Aggregation Propensity Using Molecular Models during Candidate and Formulation Assessment?

Christopher_RobertsChristopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, University of Delaware

The presentation will focus on approaches for identifying aggregation-prone proteins and formulation conditions based on different structural models and molecular simulation, compared to experimental results for protein-protein interactions and aggregation rates. Examples will include monoclonal antibodies and globular proteins at low and high concentrations, with a view to both candidate selection and formulation development.

2:15 Divide and Conquer: Comparison of Statistical and Probabilistic Tools for Risk Assessment in Multi-Stage Processes

Olga_YeeOlga Yee, Ph.D., Principal Scientist, Drug Product Science and Technology, Bristol-Myers Squibb

Faster decisions imply acceptance of risks associated with accelerated development of compounds. In this presentation, a risk of success for a drug to meet a specification limit is quantified for a three-stage process using three approaches: worst-case scenario, variance transmission model, and the novel approach of “divide and conquer.” A case study for a biologic drug product lifecycle from drug substance to final delivery is presented.

2:45 Refreshment Break

3:15 Connecting Prescreening Studies to Commercial Product Stability and Integrity

Mark_BraderMark Brader, Ph.D., Research Fellow, Moderna Therapeutics

Evaluating conformational and colloidal stability represents distinct aspects in the development of scalable bioproducts. An effective early development program will incorporate a diverse set of screening methodologies to evaluate drug candidates and their responses to solution conditions. Traditional and emerging approaches to the accelerated prediction of long term product stability will be reviewed and a perspective presented on leveraging biophysical methods to more effectively support comparability and biosimilarity assessments.

Halo Labs3:45 High Throughput, Low Volume Subvisible Particle Screening

Mark_BraderBernardo Cordovez, Ph.D., President, Halo Labs

Halo labs will present a subvisible particle screening tool, the HORIZON, with detailed explanation of its Backgrounded Membrane Imaging (BMI) technology. A comparative analysis between HORIZON and flow imaging will be presented and key performance indicators including sample volume, throughput, dynamic range, instrument repeatability will be evaluated.

WuXi-App Tec NEW4:00 Approaches to Extractables/Leachables for Single Use Systems: Case Studies Using a Risk-based Approach

Sandi_SchaibleSandi Schaible, Director, Analytical Chemistry, WuXi AppTec

There are a number of approaches when it comes to Extractables/Leachables testing for Single Use Systems in bio manufacturing. We will discuss taking a customized approach based on the risk of each component in your system.


4:30 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. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Topic: Biologics Formulation and Stability

Moderator: Haresh T. More, Ph.D., Research Investigator I, Parenteral Science and Technology, Bristol-Myers Squibb

  • Current Formulation development in biologics, protein and peptides
  • High Concentration Protein Formulation
  • High Throughput methods, new technologies in protein biophysical assessment

Topic: Management of DP temperature excursions during shipping and in clinic

Moderator: Tatiana Nanda, Ph.D., Biopharm Product Development Investigator, Biopharm Product Sciences, GlaxoSmithKline

  • Ways to allocate the allowable temperature excursion perids
  • Ways for self-management of temperature excursions in clinic

Topic: Use of a platform formulation versus innovative formulation approaches for accelerated development

Moderator: Radhakrishna Maroju, Ph.D., Senior Scientist, Biologics CMC, Teva Biopharmaceuticals USA

  • Risk-based analysis in the decision process.
  • Unique formulation challenges for novel biologic modalities
  • QbD applications in development of drug products – formulation to container closure selection

Topic: New Tools for Characterization of Protein Aggregation and Stability

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

  • Novel 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 22

7:30 am Registration Open and Morning Coffee


7:55 Chairperson’s Remarks

Sandi Schaible, Director, Analytical Chemistry, WuXi AppTec

8:00 High Throughput Sialic Acid Analysis

Yimin Hua, Ph.D., Scientist II, Global Manufacturing Science and Technology - Analytical Science and Technology, Sanofi

The level of sialic acid is a critical quality attribute for therapeutic proteins. The level of sialic acid can be measured through glycan profiling which typically involves lengthy sample preparation procedure and challenges in separation of various glycans. This presentation will talk about a high throughput method with simple procedure for the determination of sialic acid level in glycoproteins. This method is not only QC user friendly, but also can be used for fast screening in product and process development.

8:30 Rapid Minor Variants Identification in Therapeutic Antibodies by an Automatic Off-Line 2D-LC/Q Exactive® System

Jin_LiJin Li, Ph.D., Senior Research Associate, Analytical Development and Quality Control, Genentech, Inc.

Understanding the chemical nature of minor variants in therapeutic proteins is critical for process development and product quality control. The current techniques for minor variant characterization typically require manual fractionation to enrich the low abundance species followed by desalting procedures to make the sample MS compatible. Herein we developed a rapid and automatic off-line 2D-LC/Q Exactive® MS workflow for mass analysis of the minor variants in a therapeutic antibody.

9:00 High-Throughput Analytics from RoboColumn Purification to Product Quality Screening

Hardip_GopaniHardip Gopani, Development Associate III, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.

With the increased use of automation in cell line screening and small scale upstream process development, demand for high-throughput analytics continues to grow. The right assay platforms and strategic choice of product quality to screen enabled us to meet these needs. We will share our experience with setting up an automated RoboColumn purification platform for the testing of antibody harvest cell culture fluid (HCCF) samples.

Wyatt9:30 High-Throughput Light Scattering Tools for Characterizing and Formulating Macromolecules and Nanoparticles

Hardip_GopaniJulia Deuel, Applications Scientist, Wyatt Technology

From aggregates to conjugates, peptides to polysaccharides, light scattering detectors provide a comprehensive suite of biophysical characterization tools. The light scattering toolkit determines molar mass, size, charge, interactions, and conjugation of macromolecules and nanoparticles. This seminar presents an overview of the instrumentation and example applications, focusing on µSEC-MALS-DLS, and HT-DLS.

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

10:30 Novel Approach towards the Evaluation of Critical Quality Attributes and Stability of Proteins

Belinda_PastranaBelinda Pastrana, Ph.D., Full Professor, Department of Chemistry, University of Puerto Rico, Mayaguez Campus

Therapeutic proteins are highly complex molecules; their CQAs require diverse bioanalytical techniques to comply with reporting requirements to regulatory agencies. Ideally a multivariate analysis would also be needed to address stability, yet even under the current state of technology, including proteomic and high resolution, techniques can be costly and time consuming. We have developed a DOE, label free method using Best-in-Class platform technology to aid in addressing this concern.

11:00 Rapid Method for Total Protein Measurement Using SoloVPE Technology – Challenges and Solutions

Hsin-I_PengHsin-I Peng, Ph.D., Associate Manager, Quality Control, Regeneron Pharmaceuticals, Inc.

SoloVPE technology presents a unique platform for protein concentration measurement with key benefits including “no dilution” and “rapid reading.” When exploiting SoloVPE, protein concentration under-estimation is experienced for highly concentrated samples, posing challenges for accurate protein concentration measurement. Our studies show standard curve data collected outside the Beer’s law linear region can unfavorably result in protein under-estimation. Challenges and solutions when using SoloVPE technology for protein measurement will be discussed.

11:30 Punch up Biologic Development with ΔG and the HUNK

Greg Manley, Ph.D., Senior Applications Scientist, Unchained Labs

Developing biologics requires identifying an ideal construct followed by assessing a wide range of formulation space to ensure stability and minimize aggregate. Assessing ΔG is a powerful approach for the quantitative assessment of conformational stability and aggregation. The HUNK automates the tedious and manual task of determining ΔG, allowing for quantitative stability assessment throughout biologic development. We'll discuss how HUNK can be used in conjunction with more traditional approaches to assessing stability and aggregation propensity.

12:00 pm High Throughput Methods to Assess Stability of Biologics During Pre-Formulation and Formulation Development

Smita_RaghavaSmita Raghava, Ph.D., Senior Scientist, Sterile Formulation Sciences, Merck

There is a growing demand in the pharmaceutical industry for developing orthogonal tools to accurately, rapidly, and reproducibly predict protein solution stability behaviors using limited material to improve formulation screening and manufacturability assessment. This presentation will focus on combination of high-throughput technologies and assays for formulation and drug product development of biologics, such as monoclonal antibodies (mAbs) and mAb-based modalities. The overview of tools, their novel implementation, and relationship to commonly conducted “stability studies” will be further discussed using examples of high-throughput workflows, pre-formulation screening, and formulation development/optimization.

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

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


1:55 Chairperson’s Remarks

Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company

2:00 Critical Considerations in the Characterization of Protein Higher Order Structure (HOS) and Its Relationship with Stability and Function

Haripada_MaityHaripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company

Higher order structure (HOS) of a protein can be altered due to both physical and chemical instabilities. Characterization of HOS is important in assessing comparability, formulation and process development. This presentation will discuss the (i) selection of techniques in characterization of HOS, (ii) quantitative and qualitative evaluation of characterization parameters and their sensitivity and precision, and (iii) the effect of chemical “mutagenesis” on HOS, stability and functional properties.

2:30 Selected Poster Presentation: Challenges in Characterization of Bioprocesses and Products using Raman spectroscopy

Nobel Vale, Research Investigator II, Drug Science Product & Technology, Bristol-Myers Squibb Company

Raman spectroscopy is a viable spectroscopic tool to analyze biological samples. Raman’s spectral specificity for molecules, insensitivity to water and ability to analyze without sample manipulation are attractive features. In this presentation challenges for two different real-time Raman applications. In one example the effect of fluorescence background, cells/debris, and spectral interference on spectra during in-situ cell culture monitoring is discussed. In another example challenges for characterization of intact protein solutions are presented.

3:00 Selected Poster Presentation: Higher Order Structural View Of The Effects Of Oxidation On The Structure, Stability, And Aggregation Of Interferon Alpha-2a

Dinen D. Shah, Ph.D Candidate, Department of Pharmaceutical Sciences, University of Colorado

Oxidation of therapeutic proteins during their formulation and shelf-life is a persistent challenge facing the biopharma industry. We used IFN-αlpha 2a to obtain a mechanistic understanding of how oxidation affects its structure, stability, aggregation and function. Using high resolution techniques such as 2D NMR helped us to pinpoint the residue level structural changes that correlate with functional changes.

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

4:15 Using Endoglycosidase and High Resolution Mass Spectrometry to Estimate the Level of MAN-5 and Afucosylation in Monoclonal Antibodies

Ming-Ching Hsieh, Ph.D., Research Advisor, BioAnalytical Science, Eli Lilly and Company

This presentation will discuss a rapid glycosylation analysis using fast fluorescent labeling for overall glycan profiles and endoglycosidases with site specific protease for estimation of MAN-5 glycan and afucosylation levels in biologics.

4:45 Understanding & Verifying Flow Imaging Particle Counters

Dean_RippleDean Ripple, Ph.D., Leader, Bioprocess Measurements Group, National Institute of Standards and Technology

Flow imaging instruments can measure particles in biotherapeutics with potentially greater accuracy than light obscuration. However, verification methods for flow imaging instruments are not yet standardized. I will present methods used to verify the performance of flow imaging particle counters. Topics will include the use of reference materials, examination of data self-consistency, and solutions to common problems. Methods to understand errors in counts and reported size will also be presented.

5:15 Close of Conference

6:008:30 Recommended
Dinner Short Course*

SC8: Protein Aggregation: Mechanism, Characterization and Consequences

* Separate registration required