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 will bring 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. We are seeking case studies and strategies, especially unpublished and innovative work on methods employed in real time and accelerated stability studies, protein aggregates and effective use of DoE for assessment and data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 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

FORMULATION & ANALYTICAL STRATEGY FOR DEVELOPING COMPETITIVE BIOLOGICS PRODUCTS

1:00 pm Chairperson’s Opening Remarks

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

1:10 KEYNOTE PRESENTATION:
Developing Competitive Biologics Products Necessitates Combining Formulation Design, Process Development, and Device Integration

Yatin Gokarn, Ph.D., Head, Global Pharmaceutical Development Biologics, Sanofi Genzyme

There is a higher need for designing and developing competitive biologics drug products in today’s competitive 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 requires 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 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 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 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.

3:45 Sponsored Presentation (Opportunity Available)  

4:00 Pre-Formulation Approaches to Understand Instabilities in Protein Solution

Ashlesha S. Raut, Ph.D., Senior Scientist, Biologics and Vaccine Formulation, Merck

The aim of formulation development of protein therapeutics is to produce efficacious products wherein the protein remains in the solution and maintains stability across its shelf life. With the ever-growing biologics pipeline, continual efforts are directed towards the implementation of high throughput approaches to select robust candidate and formulation. This presentation discusses the impact of formulation and key process parameters on the protein stabilities and formulation selection strategies in the early stages of development.

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.

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

RAPID METHODS FOR STABILITY AND PRODUCT QUALITY SCREENING

7:55 Chairperson’s Remarks

Czeslaw Radziejewski, Ph.D., Senior Principal Research Scientist, Biophysical Chemistry, AbbVie

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 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

Sonia Taktak, Ph.D., Development Scientist 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.

9:30 Sponsored Presentation (Opportunity Available)  

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 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 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 PANEL DISCUSSION: Analytical Techniques for Automation, Rapid In-Process Parallel Monitoring, Analysis and Data Management

Moderator:

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

Panelists:

Czeslaw Radziejewski, Ph.D., Senior Principal Research Scientist, Biophysical Chemistry, AbbVie

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

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

Sonia Taktak, Ph.D., Development Scientist III, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.

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

12:00 pm Presentation to be Announced



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

HIGHER ORDER STRUCTURE, COMPARABILITY, PARTICLES AND STABILITY

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 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 Advanced Methods to Characterize Solution Behavior and Higher Order Structure of Antibodies and Antibody-Antigen Complexes

Czeslaw Radziejewski, Ph.D., Senior Principal Research Scientist, Biophysical Chemistry, AbbVie

The presentation will focus on the application of transmission electron microscopy, spectroscopic and scattering techniques to biopharmaceuticals and will demonstrate power of such approaches to understand structure and solution behavior of antibodies and antibody-antigen complexes.

3:00 Application of Spectral Similarity Analysis for Product Comparability Exercises

Thomas F. Lerch, Ph.D., Principal Scientist, Analytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc.

During the development of an antibody therapeutic, manufacturing process changes can affect protein structure, and consequently, drug function, efficacy and stability. As a result, comparability assessments are designed and implemented to evaluate product attributes before and after process changes. Established biophysical methods are lacking in quantitative evaluation of higher order structure (HOS) comparability. Strategies for evaluating HOS comparability in biotherapeutics and applying statistical analysis for biophysical comparability will be discussed.

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 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

OutlookYouTubeFacebookLinkedInTwitter #BPSMT

Japan-Flag Korea-Flag China-Simplified-Flag China-Traditional-Flag  


Event at a Glance
Event at a Glance


Celebrating 25 Years


 

Premier Sponsor

Unchained Labs(1)