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Cambridge Healthtech Institute’s Second Annual
Overcoming Formulation Challenges for Biopharmaceutical Development
Optimizing Dosage Form and Process Development for New Biotherapeutics
Part of CHI’s 6th Annual The Bioprocessing Summit

August 18-19, 2014 | Renaissance Waterfront Hotel | Boston, Massachusetts


Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 

Tuesday, August 19

7:30 am Registration and Morning Coffee


CHALLENGES IN PROCESS DEVELOPMENT
& FILL FINISH OPERATIONS

7:55 Chairperson’s Remarks

Paul DiGregorio, Ph.D., Director, Strategic Accounts, Freeslate, Inc.

8:00 Strategy for Mitigating Particulate Risks during Product Manufacturing and Clinical Administration of a Biologic for Use in Phase I Clinical Studies

ZhiqingZhuZhiqing Zhu, Ph.D., Research Investigator, Drug Product Science and Technology Department, Bristol-Myers Squibb Co.

Protein particulate formation often presents a challenge to drug product development process, especially during manufacturing operations and clinical compounding and administration. Here, we present a case study where phase-appropriate approaches (e.g. scale-down model, syringe/needle combination selection) were utilized to facilitate the successful development of a biologic for use in Phase I studies. Although the molecule had a history of particulate formation, the approaches adopted successfully and can be readily applied or adapted to similar situations.

8:30 Protein Oxidation during Formulation and Fill Finish Operations

MarkYangMark Yang, Ph.D., Director, Fill Finish Development, Commercial Process Development, Genzyme, a Sanofi Company

Hydrogen peroxide (HP) is present ubiquitously in water and excipients, and is generated by formulation and fill finish processes. Even at sub-ppm concentration, HP can cause significant protein oxidation and impact drug product quality. HP spiking study is often used to evaluate the effect of residual HP on a given protein formulation. Data from a new spiking study will be presented.

9:00 Challenges in the Filtration of High-Concentration Formulations during Fill Finish Operations

CurtissSchneiderCurtiss P. Schneider, Ph.D., Senior Engineer I, Protein Pharmaceutical Development, Biogen Idec

Late stage changes in equipment and process design for fill finish operations can result in filtration challenges that are often not well understood or previously observed. In the case study presented here, an overview is given for a filter fouling event never before seen during the manufacture of a high-concentration mAb product. A combination of tank mixer configuration, contact interfaces, and hold times will be discussed as implicated root causes for the observation.

9:30 Selected Poster Presentation: Application of Formulatrix Liquid Handler in Protein Formulation Development

Adnan Zunic, Senior Associate Scientist, Protein Pharmaceutical Development, Biogen Idec

In this talk, the use of the Formulatrix’s Formulator liquid handling system as an aid in protein formulation development (for solubility and excipient screens) will be described.

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


HIGH-THROUGHPUT MEASURES TO OVERCOME FORMULATION CHALLENGES

10:30 Lipase Hydrolysis of Polysorbate 80 in High Concentration mAb Formulations

StevenLeBrenzSteven LaBrenz, Ph.D., Scientific Director, Drug Product Development, Janssen R&D





11:00 Impact of High Concentration Protein Formulation on Particulate Matter Analysis

MiteshAcharyaMitesh Acharya, Ph.D., Manager, Quality Control, Regeneron Pharmaceuticals, Inc.

The emphasize on sub-visible particles measurement has increased in last 10 years in biopharma industry. There have been several attempts made to evaluate multiple methods to confirm true numbers of particles. We attempted to evaluate the impact of sample preparation on the particle measurement by LO and MFI techniques by manipulating the dilution of the samples. For high concentration protein formulations, particulate matter analysis without dilution leads to significant underestimation due to refractive index.

11:30 Automated, High-Throughput Approaches to Protein Formulation

DiGregorio_PaulPaul DiGregorio, Ph.D., Director, Strategic Accounts, Freeslate, Inc.

Case studies that examine the utilization of automated, high-throughput systems with integrated analytics to assess protein formulations.

 
  
12:00 pm Enjoy Lunch on Your Own 

1:15 Session Break


RAPID SCREENING IN EARLY BIOTHERAPEUTIC DEVELOPMENT

1:55 Chairperson’s Remarks

WayneReed

Wayne F. Reed, Ph.D., Murchison Mallory Chair Professor of Physics, Department of Physics, Tulane University

 

 

 

2:00 Alternative Methods for Quantifying Temperature- and Formulation-Dependent Aggregation Rates

ChristopherRobertsChristopher J. Roberts, Associate Professor, Department of Chemical & Biomolecular Engineering, University of Delaware

Reliably predicting protein aggregation rates from accelerated storage conditions remains an outstanding challenge for formulation scientists. Issues that need to be overcome include: sufficiently accurate means to quantify how rates change with storage condition and non-linear effects that make extrapolations difficult to perform accurately. This talk presents illustrative methods to improve predictions of aggregation rates, with monoclonal antibodies as case studies, and also highlights remaining challenges for future efforts.

2:30 The Measurement of KD at Low Concentration and Its Application as a High-Throughput Screening Technique for Protein-Protein Interaction Measurements

AnthonyYoungAnthony L. Young, Ph.D., Principal Scientist, Pharmaceutical Research and Development, Pfizer, Inc.

The light scattering measurement is routinely run in a high-throughput format to quickly determine the necessary diffusion coefficient versus concentration curves. The use of a robotic liquid handler can reduce the preparation time of the dilution sequence. This talk will cover the use of the liquid handler in combination with the dynamic light scattering instrument to generate KD values that are used to screen proteins and protein formulations for development. The data from several different protein isoforms will be discussed to illustrate the screening process and show typical data.

3:00 Simultaneous Stability and Aggregation Assessment by Isothermal Chemical Denaturation

Freire_ErnestoErnesto Freire, Ph.D., Professor, Biology and Biophysics, Johns Hopkins University

Stability and aggregation are two of the most important hurdles in the formulation of biologicals. Isothermal chemical denaturation (ICD) provides the most accurate way of measuring protein stability at room, physiological or storage temperatures under different solvent or formulation conditions, yielding reliable thermodynamic stability parameters. Furthermore, ICD experiments performed at different protein concentrations provide a quantitative assessment of protein aggregation in the native and denatured states. ICD is ideally suited to optimize the formulation of proteins hard to formulate, highly concentrated formulations, bispecific antibodies and antibody drug conjugates. In this presentation, the fundamentals of ICD and its application to the evaluation of protein stability and optimization of formulation conditions will be discussed.

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

4:15 Application of DSF as a High-Throughput Tool in Protein Characterization and Formulation Development

Shuai "Sunny" Shi, Ph.D., Senior Scientist, Sterile Product Development, Merck

In this study, we benchmarked DSF against the conventional thermal technique, differential scanning calorimetry (DSC), and more importantly made an attempt to predict protein thermal aggregation kinetics by DSF. We have defined three levels of correlations between DSF/DSC transition temperature and real-time thermal aggregation kinetics which will be shown in 3 individual case studies. We will also demonstrate the unique application of DSF in studying concentration-dependent thermal behaviors especially in the high-concentration range.

4:45 Increasing the Throughput of Protein Formulation Screening Using 96-Well Plate Format

QingyanHuQingyan Hu, Scientist, Ph.D., Scientist, Formulation Development, Regeneron, Inc.

To increase throughput during formulation screening, the use of a 96-well plate format was explored for candidate selection and formulation development. Multiple mAb candidates were screened against different buffer/pH and excipients using the 96-well plate format. In addition, the stability study results obtained using the 96-well plate format was compared to the results from using glass vials. With the incorporations of an automated liquid handling system and analytical instruments compatible with 96-well plates, this approach would greatly increase the throughput of formulation screening and development.

5:15 End of Conference


5:15-6:00 Dinner Short Course Registration

6:00-8:30 Dinner Short Course*: Accelerated Stability Testing of Biologics 


*Separate registration required



Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 


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