2019 Archived Content
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Cambridge Healthtech Institute’s 11th Annual

Optimizing Biologics Formulation Development

Exploring the Future of Tools and Techniques for Formulating Novel Biologic Drug Products

January 14-15, 2019

 

Cambridge Healthtech Institute’s 11th Annual Optimizing Biologics Formulation Development is an essential international gathering of analytical and formulation scientists from leading industry companies, providing an exchange of scientific developments and emerging technologies in an environment that encourages discussion with colleagues. For 2019, the conference offers perspectives on the future of biotherapeutics formulation development. Presenters will address the formulation challenges of new modalities and delivery systems, consider strategies for accelerating and streamlining this stage of development and examine best practices for applying new technologies and analytical platforms.

 

The formulation meeting kicks off the weeklong PepTalk Formulation & Stability Pipeline, which also includes separate meetings on Lyophilization and Drying Technologies and Protein Aggregation. By attending, you may also participate in the full set of eight PepTalk pipelines, including three-meeting sets on analytics and impurities, process technologies, protein engineering, antibody therapeutics and more.

Final Agenda

SUNDAY, JANUARY 13

4:00 - 6:00 pm Pre-Conference Registration (Sapphire West Foyer)

MONDAY, JANUARY 14

7:00 am Registration and Morning Coffee (Sapphire West Foyer)

The Next Generation of Protein Delivery
Aqua D

9:00 Welcome by Conference Organizer

Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

Zhenyu Gu, PhD, Director, Developability, Denali Therapeutics


KEYNOTE PRESENTATION

9:10 How Next-Generation Biotherapeutics Will Influence Formulation and Device Development

Kerstin Walke, PhD, Head, Pharmaceutical Development Biologicals, Boehringer Ingelheim

Patient self-administration is now expanding and the threshold limits for high concentrated formulations are driving development of high-volume delivery devices. Co-formulations of multiple monoclonal antibodies into a single drug product also offer patient convenience but drives the need for new analytical methods. There is also a trend toward advanced therapy medicinal products (ATMPs), a challenging new area for pharmaceutical development. This presentation will explore the impact of these trends on the formulation function.

9:50 Progress and Remaining Challenges in Formulating High Concentration Proteins for Patient Administration

Gu_ZhenyuZhenyu Gu, PhD, Director, Developability, Denali Therapeutics

High-concentration protein formulation poses considerable challenges to the formulation and assay development. Manufacturing aspects including concentratability, viscosity and stability need to be considered in the early development. In this presentation, practical challenges and solutions to the molecule selection, formulation and analysis will be discussed for the formulation development of high protein concentrations.

10:20 Networking Coffee Break (Sapphire & Aqua West Foyer)

Mixtures and Co-Formulations
Aqua D

10:45 Quality by Design and Design Control for Combination Product Development: Crossroads of Design Control and Manufacturing Risk Assessment

Leigh Bohack, PhD, Formulation Scientist, Pfizer

By developing an assembly, labeling and packaging (ALP) process Failure Mode and Effect Analysis (pFMEA), the fulfillment of user, product and regulatory requirements can be traced through the ALP process and identified risks can be mitigated. Utilizing engineering, PQ and PV manufacturing data is essential for building an understanding of this process and the impact to the combination product. This process generates a well-controlled process and quality product.

11:15 Analytical Strategies for Co-Formulated Products

Svitel_GeorgeGeorge Svitel, PhD, Principal Scientist, Merck

Co-formulating multiple mAbs into a single drug product brings benefits including combined therapeutic effect, streamlined manufacturing/distribution and elevated patient convenience. But co-formulated products also bring additional product characterization challenges. Analytical methods originally developed for individual products need to be further developed for co-formulated products. There are also questions regarding mechanisms of degradation, aggregation pathways and possibility of creation of mixed aggregated species in co-formulated products.

11:45 Peptide Mixtures: Biophysical Characterization of Self-Association and Hetero-Oligomers

Pedersen_MarieMarie Østergaard Pedersen, PhD, Specialist, Protein & Peptide Biophysics, Novo Nordisk, Denmark

Many peptides are prone to form oligomers with size and distribution depending on sequence, chemical modifications and formulation conditions. For mixtures of two different peptides, hetero-oligomer formation has the potential to alter stability properties and/or change pharmacokinetic profiles. Thus, a thorough biophysical understanding of each individual component, and their interactions, is required. This talk will present an overview of biophysical techniques relevant to the study of peptide mixtures.

12:15 pm Sponsored Presentation (Opportunity Available)

12:45 Session Break

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

Next-Generation Viscosity Prediction
Aqua D

2:00 Chairperson’s Remarks

Prakash Manikwar, PhD, Scientist II, MedImmune

2:05 Molecular Dynamics for Assessment of Candidate Developability

Zarzar_JonathanJonathan Zarzar, Technical Development Scientist, Genentech

Shortening development timelines requires earlier decisions on biologics developability, and thus the need to predict a molecule’s chemical liabilities with little or no material. Here we summarize our approach of using molecular dynamics simulations to generate various descriptors that can differentiate labile and non-labile residues.  This type of in-silico approach could be applied early in the development cycle and help guide molecule design.  


2:35 Protein-Protein Interactions and Relevance to Viscosity

Callahan_WilliamWilliam Callahan, MSc, Senior Scientist, Process Development, Amgen

Protein viscosity is known to be correlated with protein-protein interactions. Using a solubility parameter approach, we show that common properties of water miscible solvents are involved in the degree to which protein-protein interactions occur as measured by differences in viscosity. These short-range interactions are related to the dispersion energy, polar energy and hydrogen bonding energy of test solvents. It can also be shown that the viscosity can be reasonably predicted through correlation with surface tension measurements of these solvents.

3:05 Find Your Table and Meet Your BuzZ Session Moderator

3:15 BuzZ Sessions with Refreshments (Sapphire & Aqua Foyer)

Join your peers and colleagues for interactive roundtable discussions.

Click here for more details

 

Formulation Development for Novel Modalities
Aqua D

4:30 Miniaturized High Throughput Screening for Formulation Development

Smithson_DavidDavid Smithson, PhD, Scientist, Genentech

For the last four years our group has worked to develop miniaturized model systems suitable for formulation development efforts of biologics across our portfolio. These efforts have been focused in two distinct areas – physical miniaturization of our stability workflow and evaluation of improved high throughput amenable biophysical techniques for characterization of formulation candidates. We will present the current status of these efforts and discuss applicability of these techniques at various project stages.

5:00 Incompatibility of mAb Intermediate with Primary Container

Manikwar_PrakashPrakash Manikwar, PhD, Scientist II, MedImmune

During the manufacturing of an antibody drug conjugate (ADC), the monoclonal antibody (often referred to as mAb intermediate) is chemically reacted with a small molecule cytotoxic drug to form an ADC. It is important to maintain the quality of the mAb intermediate as its critical quality attributes may be carried over to the ADC drug substance and drug product. This presentation will focus on the stability of mAb intermediate in different primary containers. Data will be presented to demonstrate the challenges to assure stability and container compatibility of the mAb intermediate.

5:30 Theoretical Constraints on Design Space for High Concentration Filling: Minimizing Clogging and Increasing Filling Precision

Galas_RichardRichard Galas, PhD, Senior Scientist, Takeda

The fluid properties of many biologic formulations designed for pre-filled syringes are unique and create engineering challenges for filling systems. These products often clog the filling lines, causing costly delays while components are replaced. A theoretical fluid mechanics approach to the filling process was taken to define key parameters that impact filling accuracy and clogging. This approach identified a theoretical design space that minimizes filling variability and clogging.

6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

7:15 Close of Day

TUESDAY, JANUARY 15

8:00 am Registration and Morning Coffee (Sapphire West Foyer)

Computational and Structural Tools for Formulation Development
Aqua D

8:45 Chairperson’s Remarks

Jun Zhang, PhD, Senior Scientist, Preformulation, AbbVie

8:50 Antibody Design to Improve Physical Stability

Roberts_ChrisChristopher J. Roberts, PhD, Professor, Chemical & Biomolecular Engineering, University of Delaware

This presentation will focus on a series of coarse-grained molecular models and comparison to experimental data for predicting how changes in surface-charge distributions and formulation conditions can be used to predict protein-protein interactions and how these influence the physical stability of antibodies at low to high concentrations. Pros and cons of different modeling scales will be highlighted.

9:20 Matching pH Values for Antibody Stabilization and Crystallization Suggest Rationale for Accelerated Development of Biological Drugs

Sjuts_HannoHanno Sjuts, PhD, Postdoctoral Researcher, Protein Crystallization, Pharmaceutical Development Biologics, Sanofi, Germany

It is well known that the pH has critical influences on both a protein’s colloidal stability and it’s crystallization behavior. Here, differential scanning fluorimetry was used to determine pH values that exert highest thermal stabilities for three mAbs. Interestingly, the same pH values are required for successful crystallization of the respective mAbs. The results suggest strategies for how crystallography could be integrated into the development of novel biotherapeutic drugs for accelerated approval times.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Preformulation and Developability Screening
Aqua D

11:00 NEW: Q&A with Introduction to Biologics Formulation Development Training Seminar Instructor

Donald E. Kerkow, PhD, Director, Biopharmaceutical Development, KBI Biopharma, Inc.

11:30 Biophysical Characterization of Therapeutic Antibody Non-Specific Binding for Drug Candidate Selection and Developability Screening

Zhang_JunJun Zhang, PhD, Senior Scientist, Preformulation, AbbVie

Understanding mAb properties that affect non-specific binding in vivo are important for sequence engineering and pharmacokinetic optimization. Both hydrophobicity and electrostatic mAb properties play important roles in non-specific binding in vivo. We show that heparin binding and FcRn affinity chromatography complement hydrophobicity assessment by HIC and that incorporating these methods into molecular profiling regimens provides insight into biodistribution in addition to stability during candidate developability screening.

12:00 pm Fast Track Formulation Development and Optimization with Big Tuna

Donna Chen, Product Manager, Marketing, Unchained Labs

Buffer exchange is a ubiquitous part of working with proteins, from purification through characterization and formulation development. Conventional buffer exchange methods are labor-intensive, prone to inconsistency, and difficult to manage in large numbers. Big Tuna is an automated buffer exchange platform designed for flexibility and hands-off operation. We will describe how this new platform provides flexibility for higher throughput buffer exchange and formulation development, and enables process controls that are otherwise inaccessible by manual methods.

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Close of Optimizing Biologics Formulation Development Conference


5:45 - 8:45 Recommended Dinner Short Courses*

SC3: Protein Aggregation: Mechanism, Characterization and Consequences

Click here for more details.

*Separate registration required