Cambridge Healthtech Institute’s 4th Annual
Overcoming Formulation Challenges for Biopharmaceutical Development
Formulation and Process Optimization, Analytics, Device Integration and New Biologics
Part of CHI's 8th Annual The Bioprocessing Summit

August 17-18, 2016 | Westin Boston Waterfront | Boston, MA

The popular fourth 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 The conference will feature case studies, especially unpublished and innovative work, on the use of the effective scale-up strategies, excipient-induced instability, process challenges, fill finish challenges, and predictive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.

Final Agenda

Wednesday, August 17

7:00 am Registration Opens and Morning Coffee


8:05 Chairperson’s Opening Remarks

Christian Schöneich, Ph.D., Takeru Higuchi Distinguished Professor and Chair, Pharmaceutical Chemistry, University of Kansas


8:15 Considerations about Development of Stable Liquid Formulations for Maytansinoid ADCs

Alex Lazar, Ph.D., Head of Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.

The attachment of the small molecules in ADCs changes the physicochemical properties of the proteins. In order to stabilize the ADCs, we need to study their behavior under different conditions in order to design appropriate formulations.

9:00 Glycoform Diversity and Antibody-Drug Conjugation Control the Chemical Stability of Antibodies

Christian_SchoneichChristian Schöneich, Ph.D., Takeru Higuchi Distinguished Professor and Chair, Pharmaceutical Chemistry, University of Kansas

Antibodies are target for a large variety of chemical degradation reactions during processing and storage. This presentation will provide new examples, where forced degradation studies have led to the characterization of novel degradation products generated during storage. Experimental evidence for the effect of glycoform diversity and antibody-drug conjugation on the chemical degradation of antibodies will be presented.

9:30 Inherent Instability of a Conjugate Type Vaccine- Cause and Mitigation Strategy

Sumit_GoswamiSumit Goswami, Ph.D., Senior Scientist, Pharmaceutical R&D, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc.

A conjugate vaccine antigen (CRM197-peptide conjugate) was observed to form visible particulates and opalescence within hours of storage at room temperature. While an alternative form of the peptide antigen (identical sequence with modified C-terminus) was used for conjugation, significant improvement in stability could be achieved. Careful evaluation of the inherent difference in the stability of these two antigens will be the focus of this work.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


10:45 Effects of Arginine Counter Ions in Solubility, Protein-Protein Interaction, and Stability of a Monoclonal Antibody

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

The most commonly used salt of arginine in protein formulation development is arginine hydrochloride. Although anions are considered to be more effective compared to cations, a limited number of studies have been performed at understanding the effects of counter ions of arginine on various solution properties of proteins. This presentation will discuss the effects of different counter ions and will shed some light on understanding the mechanism of arginine-X (X refers to counter ion) interaction with proteins.

11:15 Formulation of High Concentration Monoclonal Antibodies to Minimize Aggregation Caused by Distinctive Protein Isoforms

Ionela IliescuIonela Iliescu, M.Sc., Scientist I, Technical Development, Biogen

11:45 Automated Buffer Exchange and Concentration of Biopharmaceuticals

Taegen Clary, Vice President, Marketing, Unchained Labs

Protein formulation preparation requires either dilution or buffer exchange of a protein solution into multiple formulation buffers. Traditional approaches for buffer exchange include dialysis, desalting columns, and centrifugal UF/DF devices. While these are all relatively simple and easy they are also manual and specifically, dialysis and desalting columns, do not allow for protein concentration. Unchained Labs offers multiple systems for automated buffer exchange and concentration of biopharmaceuticals. In this talk we describe these systems and their application to protein formulation preparation.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:00 Session Break


1:45 Chairperson’s Remarks

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

1:50 Polysorbate 20 Degradation and Free Fatty Acid Release in a Sulfatase Drug Product: Identification of Residual Host Cell Protein as a Potential Root Cause

Nitin_DixitNitin Dixit, Ph.D., Scientist, Drug & Combination Product Development, Shire

This study investigated the root cause behind an observed free fatty acid particle formation and Polysorbate 20 loss in a sulfatase drug product upon long term storage. The current work highlights the importance of early detection of potential impurities in the protein drug substance that may contribute to polysorbate degradation to make a judicious selection of the surfactant and its optimized concentration for the final drug product.

2:20 Alternative Surfactants: A Search for Substitutes to Polysorbates

Kishore Ravuri, Ph.D., Principal Scientist, Formulation Development, Europe Biologics, F. Hoffmann-La Roche

Surfactants are often indispensable components of biologic, parenteral formulations. Polysorbates have always been the best choice till date. Recent studies have pointed towards certain disadvantages which Polysorbates might pose if not carefully monitored. This could range from surfactant degradation to peroxide induced Drug Product oxidation. With the increasing number of novel protein formats entering the research pipeline, it is worthwhile to look for potential alternatives to polysorbates which can overcome challenges which polysorbates tend to pose. The current talk focuses on our evaluation of alternatives to polysorbates.

2:50 i-Raman Portable Spectrometer to Identify Raw Materials and Active Components of Novel Vaccines

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

The topic of this presentation is Raman Spectroscopy method development to identify biological raw materials for a novel recombinant adjuvanted vaccine, and active components and excipients of novel viral vaccine during the formulation. The advantages of using i-Raman portable spectrometer will be discussed.

3:20 Storage and Delivery of Biopharmaceuticals: Identifying Risk in Early Development Stages

Diane Paskiet, Senior Director of Global Scientific Affairs, West Pharmaceutical

The quality of biologic products can be influenced by the propensity of the formulation to extract chemicals from contact materials. It may not be evident that a stability issue could be due to a chemical leaching or a change in material surface chemistry. Correlating component chemistry data with the intended use is key for protecting biologics over the product lifecycle. This presentation will discuss the regulatory expectations for systems used to contain and deliver biologics; examples of the PQRI approaches for leachables assessments will be given.

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Plenary Keynote Session

6:00 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

Thursday, August 18

8:00 am Registration Opens and Morning Coffee


8:25 Chairperson’s Remarks

Mark L. Brader, Ph.D., Independent Consultant - Protein Drug Product Formulation and Biophysical Characterization

8:30 Bringing Back the Good Stuff: X-Ray Crystallography to Accelerate Biologics Drug Development

Mark_BraderMark L. Brader, Ph.D., Independent Consultant - Protein Drug Product Formulation and Biophysical Characterization

X-ray crystallography enables atomic-level insight into protein structure, function, and mechanistic pathways in biology. It plays a prominent role in structure-based lead discovery yet is largely ignored as a characterization tool during development. This presentation will examine some common myths surrounding protein crystallization and x-ray crystallography, and explore how recent advancements allow this technique to be applied in new and creative ways to aid the development of complex therapeutic biomacromolecules.

9:00 QbD Based Forced Degradation -- The Key of Efficient Drug Product Development

Yu Tang, Ph.D., Principal Scientist, Drug & Combination Product Development, Shire

Forced degradation is widely used through the life cycle of biological product development. Implementation of properly designed forced degradation studies can improve the efficiency of product development. This presentation focuses on application of QbD strategy to assist the design and implementation of forced degradation studies for efficient product development. A case study will be provided to demonstrate the QbD strategy based study design, implementation time, and application of data package.

9:30 Analytical Challenges and Control Strategies for High Concentration Formulations and Associated Delivery Devices

Abbas Razvi, Ph.D., Formulation Development, Lonza AG

Biological drug products are complex systems comprised of several components in addition to the API, including excipients, stabilizers, a container and container closure system. High concentration formulations pose challenges related to API stability and stabilizer and excipient degradation. Successful high concentration formulation and delivery systems require an effective control strategy that addresses all aspects of this complex drug product. This presentation will review current knowledge on high concentration formulations and associated analytical challenges.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Selected Poster Presentation: Implementation of USP Antibody Standard for System Suitability in Capillary Electrophoresis Sodium Dodecyl Sulfate (CE-SDS) for Release and Stability Methods

Abbie L. Esterman, Ph.D., Senior Scientist, Molecular and Analytical Development, Biologics Manufacturing & Process Development, Bristol-Myers Squibb

11:00 Selected Poster Presentation:Exploring Inline Raman Method Development through Better Understanding of Spectral Interferences

Dimuthu Jayawickrama, Ph.D., Sr. Research Investigator II, Drug Science Product & Technology, Bristol Myers Squibb

Raman spectroscopy is increasingly used as a real-time spectroscopic tool in mammalian cell culture bioreactors for monitoring of nutrients and metabolites. Generally the Raman calibration methods for bioreactors are developed with spectral data generated with multiple batches manufactured under similar conditions. This approach is practical at manufacturing where process is well understood and controlled. However this approach of developing methods may not be suitable during process development where materials and process conditions can vary greatly. Therefore, an alternative approach of method development has been explored. The objective is to develop robust methods independent of or less sensitive to cell type, cell population, and cell debris and fluorescence background. This work describes a series of experiments designed to isolate and study various interferences as described above. Potentially remedies to eliminate these interferences are presented.

11:15 Overcoming Freeze-Thaw Agglomeration of a Meningococcal Vaccine

Chris_MenschChristopher Mensch, Scientist, Vaccine Drug Product Development, Merck

The purpose of this work was to investigate the susceptibility of an aluminum adjuvant and an aluminum-adjuvanted native outer membrane vesicle (nOMV) vaccine formulation to freeze/thaw–induced agglomeration using static light scattering and micro-flow Imaging analysis; and to evaluate the use of propylene glycol as a vaccine formulation excipient by which freeze/thaw–induced agglomeration of a nOMV vaccine formulation could be mitigated. Our results indicate that including 7% v/v propylene glycol in a nOMV containing aluminum adjuvanted vaccine formulation, mitigates freeze/thaw–induced agglomeration.

11:45 FEATURED TALK: Antibody Drug Product Formulation: Current Status and Future Directions

Dingjiang_LiuDingjiang Liu, Ph.D., Director, Formulation Development, Regeneron Pharmaceuticals, Inc.

Over the last 30 years, the US FDA has approved over 50 monoclonal antibody related drug products. This presentation will summarize and analyze these drug product formulations.The industrial trends in formulation excipients, protein concentrations, dosage forms and routes of administration for monoclonal antibody drug products will be discussed along with current challenges and future directions in product formulations development.

12:15 Lunch Available for Purchase in the Exhibit Hall

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

1:55 End of Conference