2015 BPD Header

Cambridge Healthtech Institute’s 3rd Annual
Rapid Methods to Assess Quality & Stability of Biologics:
Improving Prediction and Screening
August 3-4, 2015
Part of CHI's 7th Annual The Bioprocessing Summit

August 3-7, 2015 | Westin Copley Place Hotel | 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 the need of rapid methodologies to predict and assess the quality and stability of biologics. The third 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. We invite you to attend to learn from and network with the leading experts from around the world.

Day 1 | Day 2 | Short Courses | Download Brochure 

Monday, August 3

8:00 am Pre-Conference Registration and Morning Coffee


11:30 Main Conference Registration


1:00 pm Chairperson’s Opening Remarks

Jianmei Kochling, Ph.D., Director, Quality Science and Analytical Technology, Genzyme - a Sanofi Company

1:10 KEYNOTE PRESENTATION: Introducing Emerging Technologies into the QC Laboratory

Paul Bigwarfe, Ph.D., Director, Analytical Sciences, Regeneron Pharmaceuticals, Inc.

Introducing new and emerging technologies to the QC laboratory presents its own set of challenges. Regulatory hurdles and training are only a few of them. This presentation will address how to overcome these challenges and present case studies on where it has worked and not worked well.

1:45 Emerging Technology for Biologics Stability Testing

Jianmei Kochling, Ph.D., Director, Quality Science and Analytical Technology, Genzyme - a Sanofi Company

Biologics are monitored for purity, potency, and biological activity in stability. The use of appropriate stability-indicating physicochemical, biochemical, and immunochemical analytical methodologies permits a comprehensive characterization and monitoring the quality of the drug substance and/or drug product. The effort of introducing advanced technologies to the QC labs has positively impacted the industry, leading to improved throughput, accuracy, precision, and sensitivity, as well as reduced labor and cost. Talk will discuss some recent changes in the QC world.

2:15 A Unique High Throughput Assay for Determination of the Potency and Stability of Biologics

Michael Tovey, Ph.D., INSERM Director of Research, Laboratory of Biotechnology and Applied Pharmacology, Ecole Normale Supérieure de Cachan, France

Biologic activity is essential for the assessment of potency and stability of biologics and successful development of biologics depends upon establishment of validated and standardized assays that allow direct comparisons of the relative potency and stability between batches. A validated standardized high throughput assay platform using engineered reporter-genes allows direct comparison of drug potency and stability within two hours for structurally diverse TNF-α antagonists or closely related novel forms of human insulin and FGF-21.

2:45 Refreshment Break

3:15 Challenges to Implementing High Throughput Methods in a QC Environment

Michelle Joubert, Staff Scientist, Genzyme a Sanofi Company

3:45 Analytical Testing Strategy for Admixture Testing of Therapeutics

Shenjiang Yu, Ph.D., Associate Principal Scientist, Sterile Product and Method Development, MRL, Merck Co. & Inc.

A pharmaceutical admixture consists of a drug product mixed with a suitable diluent in a intended dosing/delivery device for the purpose of parenteral infusion to the patient. Regulatory agencies have specific requirements for the demonstration of the compatibility of the drug product with reconstitution diluents, because many of the therapeutic proteins are dosed intravenously in the form of admixtures. Therefore, analytical strategies are presented to show the compatibility with dosing/delivery device. A few case studies is discussed with the implementation of our analytical strategies.

4:15 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

Day 1 | Day 2 | Short Courses | Download Brochure 

Tuesday, August 4

7:30 am Registration and Morning Coffee


7:55 Chairperson’s Remarks

Joël Richard, Ph.D., Senior Vice President Peptides, Technical Operations, Ipsen

8:00 Strategy for Characterization and Control of Submicron and Subvisible Particles in Biologics

Nataliya Afonina, Ph.D., President and Principle Consultant, AN Biologics Consulting LLC

Aggregation of proteins, including formation of submicron (0.2 -2 µm) and subvisible (2 -10 µm) particles, is one of the major concerns in biologics drug products related to their stability, purity, and quality and is defined as Critical Quality Attribute. Finding the right risk-based approach and establishing the tractability between particle evaluation at formulation step and in final drug product is critical. New strategic approach for 0.2 -10 µm particle characterization and control including regulatory requirements, evaluation of orthogonal methods, and establishing of morphological libraries for subvisible particles will be discussed.

8:30 Addressing the Gaps in Particle Measurements for Biotherapeutic Solutions

Reema Raghavendra, MS, MBA, Scientist II, Global Protein Sciences, AbbVie, Inc.

Non-native protein structures, which are increasing in use, have potentially altered propensities to self-associate. Concerns regarding the immunogenicity of protein aggregates motivate particle characterization in the sub-visible range (0.1-100 µm). Flow cytometry holds the promise of distinguishing between particle types for sizes down to less than 1 µm. Here, we present two methods of standardizing flow-cytometry diameter readings: the use of novel protein-like standards of discrete sizes and commercial beads.

9:00 Stability Challenges for Protein Therapeutics: Anticipating Aggregation Phenomena at Early Development Stage

Joël Richard, Ph.D., Senior Vice President Peptides, Technical Operations, Ipsen

The paradigm of protein formulation development has moved from a posteriori detection and control of aggregation to the anticipation/prediction of formulation, storage and processing conditions that will lead to aggregation in a QbD approach. In order to anticipate potential aggregation issues, it is proposed to focus on the early steps of aggregation, which most of the time may involve higher order structure (HOS) alterations and loss of colloidal stability.

9:30 Sponsored Presentation (Opportunity Available)

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

10:30 Investigate Protein Aggregation in Process Change through Forced Degradation Studies

Yimin Hua, Scientist II, Quality Science and Analytical Technology, Genzyme, a Sanofi Company

Aggregation is one of the main concerns of biotherapeutics when there is a process change. Detection and characterization of aggregation to identify the root cause will allow appropriate actions which will help to improve protein quality, minimize protein aggregation during process and on storage. Proteins are subjected to different stress conditions to induce aggregation in the lab. Various analytical techniques will be used to characterize the forced degraded protein samples. The results will further the understanding of leading factors that contribute to the aggregation of recombinant proteins.


11:00 Fast LC/MS Methods for Monitoring Sites of Modification in Development, PC/PV and Beyond

Amy Hilderbrand, Ph.D., Technical Development Scientist, Protein Analytical Chemistry, Genentech, Inc.

Being able to monitor site specific modifications in biological molecules is important from a process, stability and quality perspective in development. This talk will focus on rapid relative quantitation using liquid chromatography/mass spectrometry methods that are being evaluated and used to monitor sites that are vulnerable to modification.

11:30 High-Throughput Peptide Mapping to Support Early Prediction of Biologics Quality

Yan Wang, Ph.D., Scientist, Analytical Development, Biogen Idec

Peptide mapping is a sensitive and precise technique that is capable of detecting single amino acid changes and post-translational modifications (PTMs) in a single run. We have recently developed a novel high-throughput (HT) peptide mapping workflow, which targets four bottle-neck problems and enables analyst to complete multiple sample comparison in a single day starting from cell harvest to final quantitative report. Our new HT peptide mapping workflow is transferrable to assess quality of biologics in manufacturing, cell lines development and formulation development.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Luncheon Presentation: Fast and Robust Method for Charge Heterogeneity Analysis of Biologics

Scott Mack, MSc, Senior Scientist, ProteinSimple

1:15 Session Break


1:55 Chairperson’s Remarks

Hardeep Samra, Ph.D., Senior Scientist, Formulation Sciences, MedImmune, Inc.

2:00 A Novel Analytical Approach to Investigate the Effect of Methionine Oxidation on Antibody PK

Jan Stracke, Ph.D., Principal Scientist, Pharmaceutical Development & Supplies, PTD Biologics Europe, F. Hoffmann-La Roche Ltd.

Preserving the chemical and structural integrity of antibodies during manufacturing and storage is a major challenge during development. Oxidation of Fc methionines is frequently observed, which leads to reduced affinity to FcRn and faster plasma clearance if present at high levels. A novel pH-gradient FcRn affinity chromatography method was developed to isolate antibody oxidation variants from an oxidized IgG1 preparation based on their FcRn binding properties. The subsequent physico-chemical and biological characterization of these oxidation variants demonstrated the value of the new method to study structure-function relationships.

2:30 Developability Assessment and Formulations Optimization of Biologics Using Isothermal Chemical Denaturation (ICD)

Richard K. Brown, Ph.D., President, AVIA Biosystems

Stability optimization and aggregation minimization are two of the most important hurdles in the development of biologics. ICD provides the most accurate way of measuring protein stability under different formulation conditions. ICD experiments performed at different protein conc. provide a quantitative assessment of protein aggregation in the native and denatured states. ICD is ideally suited to optimize the formulation of highly concentrated formulations, bispecific antibodies and antibody drug conjugates. In this talk, the fundamentals of ICD and its application to the evaluation of protein stability and optimization of formulation conditions will be discussed.

3:00 HDX-MS Sheds Mechanistic Insights on Mutation Induced Changes in Physical Stability of an IgG1 mAb Engineered for Extended Serum Half-Life

Ranajoy Majumdar, Ph.D., Research Scientist, Biophysical Characterization, Biopharmaceutical Research and Development, Eli Lilly and Company

A triple mutation in the CH2 domain of an IgG1 mAb intended to increase in vivo half-life resulted in decreased physical stability. Although the mutation induced minimal differences in H/D exchange kinetics at the mutation sites and the FcRn binding epitopes, it increased the flexibility of an established aggregation hotspot in the CH2 domain. This case study reinforces our understanding of the correlations between mAb physical stability and its local flexibility.

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

4:15 A Comparison of Biophysical Characterization Techniques in Predicting Drug Product Stability

Geetha Thiagarajan, Ph.D., Senior Scientist, Sterile Product and Analytical Development, Merck & Co.

To predict stability behavior, solution-mediated interactions (Colloidal, self-association propensity) and key molecular characteristics of ten formulated protein-therapeutics were compared to their stability at accelerated (25C and 40C) and long-term storage conditions (2-8C) as measured by size exclusion chromatography. Our results show that colloidal stability, self-association propensity, and conformational characteristics (exposed Trp) provide reasonable prediction of accelerated stability, with limited predictive value at 2-8C stability. Other measurements (e.g., thermal unfolding temperature) did not show any correlation.

4:45 Forced Degradation Studies: An Essential Tool for the Formulation Development of Vaccines

Manvi Hasija, MS, Formulation and Stability Scientist, BioProcess Research and Development, Sanofi Pasteur

The guidelines for forced degradation (FD) regarding biologics have few to none procedural instructions on how to approach studies. There are gaps that are left to interpretation by the vaccine developer. In this presentation, we provide an overview of the methods to study FD in vaccines as well as mechanisms of degradation, analytical methodology, FD examples that are used to influence the results of new vaccine candidates.

5:15 Close of Conference

6:00-8:30 Recommended Dinner Short Course

Protein Aggregation: Mechanism, Characterization and Consequences 

Day 1 | Day 2 | Short Courses | Download Brochure