Cambridge Healthtech Institute’s 3rd Annual
Overcoming Formulation Challenges for Biopharmaceutical Development:
Formulation and Process Optimization, Analytics, Device Integration and New Biologics
August 3-4, 2015
Part of CHI's 7th Annual The Bioprocessing Summit

August 3-7, 2015 | Westin Copley Place Hotel | Boston, Massachusetts

The popular third annual Overcoming Formulation Challenges for Biopharmaceutical Development conference will cover latest trends and challenges in biologic formulations development, process optimization, manufacturing, and device and packaging considerations for existing and emerging protein therapeutics. The conference will showcase case studies, especially unpublished and innovative work, on the use of the effective scale up strategies, excipient induced instability, process challenges, fill finish challenges, and predictive tool for rapid formulation and stability screening. We invite you to attend to learn from and network with the leading experts from around the world in the field of biologics formulation development.

Monday, August 3

8:00 am Pre-Conference Registration and Morning Coffee

9:00-11:30 Recommended Short Course

Accelerated Stability Testing of Biologics

11:30 Main Conference Registration


1:00 pm Chairperson’s Opening Remarks

Sandeep Yadav, Ph.D., Scientist, Late Stage Pharmaceutical Development, Genentech, Inc.

1:10 Polysorbate 80 Hydrolysis and Rationale for Determining the Effective Level of Polysorbate 80 in a High Concentration Monoclonal Antibody Formulation

Vincent Corvari, Ph.D., Senior Research Advisor, Bioproduct Research & Development, Eli Lilly & Company

During the development of a solution formulation for a high concentration monoclonal antibody, a reduction in the content of polysorbate 80 occurred on stability. Further evaluation demonstrated the reduction resulted from hydrolysis of the fatty acid side chains. The focus of this presentation is to describe the knowledge gained while identifying this degradation pathway and the development work conducted to define the effective level of polysorbate 80 required to maintain product quality.

1:45 Is PS-80 a Critical Excipient? A Short History and Case Studies

Michael T. Jones, Ph.D, Research Fellow, Biotherapeutics Pharmaceutical Sciences, Analytical R&D, Pfizer, Inc.

Polysorbates are ubiquitous as excipients in protein formulations. These surfactants are added to the formulation to help maintain the stability of the drug product (DP). There has been an increased interest in the biopharmaceutical industry to understand the fate of these surfactants over the shelf-life of the DP. This talk will highlight some of the issues with polysorbates and provide case studies on the criticality of PS80 addition to a protein DP.

2:15 Critical Considerations for Surfactant Stability in Biopharmaceutical Formulations

Sandeep-YadavSandeep Yadav, Ph.D., Scientist, Late Stage Pharmaceutical Development, Genentech, Inc.

Polysorbate is commonly used excipient in biotherapeutic formulations for protection against interfacial stress and surface adsorption. In this work we present evidence of Polysorbate degradation over long-term 5OC storage that may subsequently result into visible and subvisible particles in protein formulation. A number of challenges associated with characterizing particulates, identifying potential reasons for Polysorbate degradation, novel methods to quantify the degradants as well as the solubility characteristics of the PS20 degradants are discussed.

2:45 Refreshment Break

3:15 Challenges in Co-Formulating Polysorbates and Preservatives in Multi-Use Biologics Formulations

Shuai-ShiShuai Shi, Ph.D., Associate Principal Scientist, Sterile Product and Analytical Development, Merck

The compatibility between polysorbates and m-cresol was thoroughly investigated in this study. It was found that both PS20 and PS80 are compatible with m-cresol (at 2.8 mg/mL) when their levels were not greater than 20 ppm. Significant losses of polysorbates were observed when PS20 and PS80 concentrations were above 50 ppm. Also, it was demonstrated that factors such as the presence of salt, the order of addition, and the hydrophobicity of surfactants could also impact compatibility. Furthermore, the agitation study demonstrated that even trace levels of PS20 and PS80 (e.g., 20 ppm) could stabilize the protein against fibrillation and aggregation.

3:45 Development of a Stability Indicating Assay for Polysorbate-80

Mark Bolgar
Mark Bolgar, Ph.D., Senior Research Fellow, Analytical and Bioanalytical Development, Bristol-Myers Squibb Co.

The extreme heterogeneity of polysorbate 80 creates challenges for its quantitation in biotheraputic formulations. Ideally, any method should distinguish between intact PS-80 and key degraded forms. Of particular concern is the degradation of PS-80 via ester bond hydrolysis This presentation will describe the development of LC/MS-based method for the determination of PS-80 which due to its very high specificity is able to effectively differentiate between intact PS-80 and its hydrolyzed forms.


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.

Topic 1: What Does It Take To Move A Formulation From Vials To Prefilled Syringes?

Moderator: Mark Yang, Ph.D., Director, Fill Finish Development, Genzyme - a Sanofi Company

  • What are the most efficient ways to evaluate the device-ability of current formulations?
  • What are the “norms” for development timelines and budget?
  • Key development steps/challenges to move from vials to prefilled syringes

Topic 2: What Constitutes A Critical Excipient?

Moderator: Michael T. Jones, Ph.D, Research Fellow, Biotherapeutics Pharmaceutical Sciences, Analytical R&D, Pfizer, Inc.

  • Are specific excipients required for a stable formulation or would similar excipients work as well?
  • What concentration of the excipient is required to guarantee it’s function?
  • At the end of shelf-life, does the DP still meet all of the specifications required regardless of excipients present?

Topic 3: Formulation Development of the Future – Can We Develop Better Formulations Faster?

Moderator: Russell Burge, Ph.D., Applications Scientist, Freeslate, Inc.

  • Can automation help accelerate formulation development? What are the best approaches to continue with rapid and innovative formulation development?
  • Are current analytics sufficient? What improvements are needed to provide better characterization faster?
  • What are the best practices for implementing QbD in formulation development?

5:15 Discussion Report-Outs

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

7:00 End of Day

Tuesday, August 4

7:30 am Registration and Morning Coffee


7:55 Chairperson’s Remarks

Kevin Constable, Director, Technology Development, Terumo- Global Pharmaceutical Solutions.

8:00 Transformational Science: Moving from the Challenges of High Concentration mAbs to Meeting the Needs of Highly Potent Bispecifics

Sachin-DubeySachin Dubey, Ph.D., Head of Formulation Development, Process Development, Glenmark Pharmaceuticals SA

Glenmark’s proprietary BEAT® technology has provided a new impetus toward developing a more efficient way of treating cancer. This highly effective therapeutic (anticipated doses ~ 1000 fold less than conventional mAbs) has conserved key IgG properties (thermostability, effector function/antibody-like pharmacokinetics etc), but at the same time has thrown up new challenges, particularly in terms of formulation/analytical development. These low-concentration related challenges were rationally understood, characterized and mitigated.

8:30 Controlling Excipients during Commercial-Scale Formulation: Modelling-Based Control Strategy Design

Rachael Lewus
Rachael Lewus, Ph.D., Scientist II, Formulation Sciences, MedImmune, Inc.

Control of excipients during commercial scale formulation is important in order to deliver a high quality drug substance and ensure release criteria are met. However, an accurate scale down model for the excipient spiking step is not readily available for experimental characterization. Monte Carlo modelling provides an alternative method for process characterization. A case study focusing on polysorbate control in a monoclonal antibody drug substance formulation will be presented.


9:00 QbD in Late Stage Formulation Optimization

Mark-YangMark Yang, Ph.D., Director, Fill Finish Development, Genzyme - a Sanofi Company

QbD is a powerful tool for late stage formulation optimization and process definition. However, there is a delicate balance between testing many variables over a wide range for a robust process and minimizing the “process changes” to be implemented. A QbD case study will be presented. After identified key excipients, the formulation was optimized by using a response surface design to include multilevelsof key excipients over a manufacturing-relevant range.

Unchained Labs9:30 Physical and Colloidal Stability Studies of mAbs and bi-Specifics

Ralf Joseph Carrillo, Ph.D., R&D-GPMA Global Project Management, GPAS Global Pharmaceutical Analytical Sciences, Formulation, Abbvie

Biophysical properties of two monoclonal antibodies and two Dual Variable Domain Immunoglobulin (DVD-IgTM) proteins have been studied to ascertain how protein – protein interactions (B22), unfolding and aggregation onset melting temperatures and turbidity demonstrate the propensity to predict both good and poor (aggregation and phase separation) mAb and DVD-Ig formulations.

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

10:30 FEATURED PRESENTATION: Mixing Monoclonal Antibody Formulations Using Bottom-Mounted Mixers – Impact of Mechanism and Design on Drug Product Quality

Yuh-Fun Maa, Ph.D., Principal Engineer, Pharmaceutical Processing and Technology Development, Genentech, Inc. 

Although BMM is becoming a choice of mixing but impact of BBM on protein drug product is yet to be understood. This study evaluated multiple disposable BBMs to assess their impact on a shear-sensitive mAb formulation. Aggregation of mAb, and particle formation were determined after mixing. The results suggested that mixer designs with contact between the impeller and the drive unit resulted in higher particle counts. The shear-induced particles are proteinaceous but soluble aggregated protein molecules were not detected. This study fills an important gap in understanding a critical bioprocessunit operation.

Wyatt11:00 Molar Mass, Size, Charge and Conformation: Light Scattering Tools for Biophysical Characterization of Macromolecules

Champagne_JohnJohn Champagne, Ph.D., Northeast Regional Manager & Senior Applications Scientist, Wyatt Technology Corporation

This seminar describes a comprehensive suite of characterization tools based on static and dynamic light scattering, which work together with size-based separation, to provide first principles biophysical characterization of macromolecules. Some of the key applications of the light scattering toolbox include analyses of molar mass and size distributions, aggregation, branching and other measures of conformation, and the composition of complex protein systems and other conjugated macromolecules.


 Freeslate11:30 Application of Automated and High-Throughput Systems to Formulation Development of Biopharmaceuticals

Burge_RussellRussell Burge, Ph.D., Applications Scientist, Freeslate, Inc.

Biologics can be prone to degradation and instability, both of which pose challenges to drug developers. In this presentation, we describe the application of automation and high throughput data management systems to drug development workflows. Results of case studies demonstrating the ability of automated workflows to increase throughput, improve efficiency, and streamline data management.

12:00 pm Panel Discussion: Challenges and Opportunities in QbD Approach in Formulation Development and Product Quality

Moderator: Mark-YangMark Yang, Ph.D., Director, Fill Finish Development, Genzyme – a Sanofi Company



Sachin-DubeySachin Dubey, Ph.D., Head of Formulation Development, Process Development,

Glenmark Pharmaceuticals SA


Rachael LewusRachael Lewus, Ph.D., Scientist II, Formulation Sciences, MedImmune, Inc.


Yuh-Fun-MaaYuh-Fun Maa, Ph.D., Principal Engineer, Pharmaceutical Processing and

Technology Development, Genentech, Inc.




Russell Burge, Ph.D., Applications Scientist, Freeslate, Inc.

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

1:15 Session Break


1:55 Chairperson’s Remarks


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.

Unchained Labs2:30 Developability Assessment and Formulations Optimization of Biologics Using Isothermal Chemical Denaturation (ICD)

Brown_RichardRichard 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 Poster Highlight Presentation: Leveraging Automation in Development of High Concentration Protein Formulations

Aastha Puri, M.Sc., Associate Scientist II, Drug Product Science & Technology, Bristol-Myers Squibb

Formulation development of high concentration products, brings a unique set of challenges, including the potential for increased physical and chemical stability risks, as well as challenges related to handling of viscous material. This work demonstrates the utility of new automation technologies in proficiently executing experimental workflows on a viscous high concentration protein formulation and assisting a data-driven decision making process as part of a material sparing, multi-well screening methodology.

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

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

Andrew SempleAndrew Semple, 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 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.

5:15 Close of Conference

Premier Sponsors: