Cambridge Healthtech Institute’s Fifth Annual
Overcoming Formulation Challenges for Biopharmaceutical Development:
Formulation and Process Optimization, Excipients, Analytics and Device Integration
Part of CHI's Ninth Annual The Bioprocessing Summit
August 21-22, 2017 | Westin Copley Place | Boston, MA

The popular fifth 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.

Final Agenda

Monday, August 21

8:00 am Short Course Registration Open

9:00 – 11:30 Recommended
Morning Short Courses*

SC4: Accelerated Stability Testing of Biologics

* Separate registration required

11:30 Main Conference Registration Open

FORMULATION & ANALYTICAL STRATEGY FOR DEVELOPING COMPETITIVE BIOLOGICS PRODUCTS

1:00 pm Chairperson’s Opening Remarks

Christopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, University of Delaware

1:10 KEYNOTE PRESENTATION:
Developing Competitive Biologics Products Necessitates Combining Formulation Design, Process Development, and Device Integration

Yatin Gokarn, Ph.D., Head, Global Pharmaceutical Development Biologics, Sanofi

There is a increasing need for designing and developing competitive biologics drug products in today’s biotherapeutics marketplace when many new modalities and new product formats are making their way to market and many promising leads continue to fill the research and development pipelines. A competitive patient-centric product necessitates a holistic product development strategy that takes into consideration formulation design, process development, analytics and device integration.

1:45 How Well Can We Predict Protein-Protein Interactions and Aggregation Propensity Using Molecular Models during Candidate and Formulation Assessment?

Christopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, University of Delaware

The presentation will focus on approaches for identifying aggregation-prone proteins and formulation conditions based on different structural models and molecular simulation, compared to experimental results for protein-protein interactions and aggregation rates. Examples will include monoclonal antibodies and globular proteins at low and high concentrations, with a view to both candidate selection and formulation development.

2:15 Divide and Conquer: Comparison of Statistical and Probabilistic Tools for Risk Assessment in Multi-Stage Processes

Olga Yee, Ph.D., Principal Scientist, Drug Product Science and Technology, Bristol-Myers Squibb

Faster decisions imply acceptance of risks associated with accelerated development of compounds. In this presentation, a risk of success for a drug to meet a specification limit is quantified for a three-stage process using three approaches: worst-case scenario, variance transmission model, and the novel approach of “divide and conquer.” A case study for a biologic drug product lifecycle from drug substance to final delivery is presented.

2:45 Refreshment Break

3:15 Connecting Prescreening Studies to Commercial Product Stability and Integrity

Mark Brader, Ph.D., Research Fellow, Moderna Therapeutics

Evaluating conformational and colloidal stability represents distinct aspects in the development of scalable bioproducts. An effective early development program will incorporate a diverse set of screening methodologies to evaluate drug candidates and their responses to solution conditions. Traditional and emerging approaches to the accelerated prediction of long term product stability will be reviewed and a perspective presented on leveraging biophysical methods to more effectively support comparability and biosimilarity assessments.

 3:45 High Throughput, Low Volume Subvisible Particle Screening  

Bernardo Cordovez, Ph.D., President, Halo Labs

Halo labs will present a subvisible particle screening tool, the HORIZON, with detailed explanation of its Backgrounded Membrane Imaging (BMI) technology. A comparative analysis between HORIZON and flow imaging will be presented and key performance indicators including sample volume, throughput, dynamic range, instrument repeatability will be evaluated. 

4:00 Approaches to Extractables/Leachables for Single Use Systems: Case Studies Using a Risk-based Approach

Sandi Schaible, Director, Analytical Chemistry, WuXi AppTec

There are a number of approaches when it comes to Extractables/Leachables testing for Single Use Systems in bio manufacturing. We will discuss taking a customized approach based on the risk of each component in your system.

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

7:00 Close of Day

Tuesday, August 22

7:30 am Registration Open and Morning Coffee

EXCIPIENTS & SURFACTANT STABILITY IN BIOPHARMACEUTICAL FORMULATIONS

7:55 Chairperson’s Remarks

Andrea Hawe, Ph.D., CSO, Coriolis Pharma

8:00 Trends on Analytical Characterization of Polysorbates and Their Degradation Products in Biopharmaceutical Formulations

Andrea Hawe, Ph.D., CSO, Coriolis Pharma

Polysorbate 20 and 80 are the most common surfactants in biopharmaceutical products. Structural heterogeneity, presence of degradants, impurities, and tendency for degradation may impact their functional properties and pose a challenge for the analytical characterization of PS at different stages of product development. The talk focuses on methods and strategies for the analytical characterization of PS, their degradants and other impurities within neat PS and in biopharmaceutical formulations.

8:30 Understanding the Impact of Histidine and Polysorbate 20 Degradation in Stainless Steel Containers on Protein Aggregation and Stability

Adithi Chandrasekhara, Research Associate, Late Stage Pharmaceutical Development, Genentech, Inc.

Histidine and polysorbate 20, commonly used in biologics formulations, degrade substantially when stored in stainless steel containers at accelerated temperatures (≥25°C). The observed degradation is catalyzed by metal ions leaching from the containers and is synergistic and rapid when both histidine and PS20 are present. The impact of these degraded excipients on protein aggregation and stability was characterized to assess the risk of accelerated temperature exposure to stainless steel containers.

9:00 Polysorbate Interactions with Monoclonal Antibodies as Probed by 2D NMR

Krishna M.G. Mallela, Ph.D., Associate Professor of Biophysical Chemistry, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus

We examined how polysorbates affect the structure of a monoclonal antibody using 2D NMR. Both bind to the antibody with a millimolar affinity. Binding induced changes in the tertiary structure with no changes in the secondary structure. The Fab region showed significant changes in the NMR spectrum compared to no changes in the Fc region, which indicates that polysorbates preferentially interact with the Fab region rather than the Fc region.

9:30 Sponsored Presentation (Opportunity Available)

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

CHALLENGES OF LOW & HIGH CONCENTRATION FORMULATIONS

10:30 Intravenous Administration of Low Concentration Formulations

Ian Lent, MS, Development Associate II, MacroGenics, Inc.

Dart® molecules are bi-specific antibody-based proteins developed for various indications including immune-oncology. These molecules are manufactured using conventional antibody platforms, and demonstrate product quality and stability comparable to conventional antibodies. The increased potency and lower concentration formulations of certain bi-specific molecules present new challenges for intravenous administration. Case studies will be presented regarding approaches for IV administration of low concentration protein formulations that highlight diluent, administration and analytical challenges.

11:00Transformational Science: Moving from Challenges of High Concentration Protein Formulations Development to Meet the Needs of Highly Potent Bispecifics

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

11:30 Designing a Low Viscosity, High Concentration Protein Formulation

Sarah Altinoglu, Ph.D., Post-Doctoral Scientist, Bioproduct Research and Development, Eli Lilly and Company

Although a universal formulation strategy to decrease viscosity of protein drugs is unrealistic, a better understanding of the connection between molecular properties and viscosity can help to reduce the complexity and time commitment involved in high concentration protein formulation. Here, we have studied this connection and analyzed how these findings can guide future protein formulations.

12:00 pm An Assessment of Self Interaction Chromatography as a Rapid Tool to Investigate Protein-Protein Interactions and Its Application in Formulation Screening Workflows

Sanket Patke, Ph.D., Research Investigator, Drug Product Science and Technology, Pharmaceutical Development, Bristol-Myers Squibb

Protein-protein interactions influence colloidal stability parameters such as solubility and aggregation. Measurement of osmotic second-virial coefficients, B22, provides one method to quantify protein interactions at the molecular level. Self-interaction chromatography is a novel method of measuring B22 with modest material and time requirements. Here we discuss the application of this approach to investigate protein–protein interactions in mAbs. This approach can potentially be used as a tool during formulation screening.

  12:30 Luncheon Presentation: Up Your Game in Protein Quantitation - Higher Throughput and Concentrations  

Tony Montoye, Director, Product Marketing, Unchained Labs

See how Unchained Labs brings micro-volume DNA/RNA and protein quantification to the next level by eliminating all manual prep, dilutions or risk of cross-contamination. All you need is 2 μL and 5 minutes to measure up to 96 samples, even at high concentrations. Get biologics and genomics UV/Vis quantification on the money every time.

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

LYOPHILIZATION OF NEW MODALITIES & PROCESS OPTIMIZATION

1:55 Chairperson’s Remarks

Haresh T. More, Ph.D., Research Investigator I, Parenteral Science and Technology, Bristol-Myers Squibb

2:00 Lyophilization of Antibody-Drug Conjugates (ADCs) Containing Highly Potent Cytotoxic Agents

Amit Gangar, Ph.D., Scientist I, Drug Product and Process Development, Immunogen, Inc.

Handling and stabilizing cytotoxic ADCs poses several challenges to formulation development scientists. While developing a lyophilized formulation is the most common approach, additional formulation and safety concerns need to be evaluated. This presentation will provide insight into developing robust lyophilized ADC formulations while minimizing risk of exposure to the developers.

2:20 Investigation of Fogging/Haze Behavior in Lyophilized Drug Product

Min Huang, Ph.D., Principal Scientist, Pharmaceutical Research and Development, Pfizer, Inc.

Experiments were performed in this study to understand the fogging phenomena in the lyophilized drug product vials. This study demonstrated that many parameters including glass vial surface, vial treatment, lyophilization process, protein concentration and drug product formulation all could potentially affect the vial fogging phenomena to some extent. In addition, the study looked into the potential impact of fogging behavior in lyophilized drug product vials to the container closure integrity.

2:40 Lyophilization Process Optimization and Identification of Design Space for Monoclonal Antibody Formulation Using Definitive Screening Design

Haresh T. More, Ph.D., Research Investigator I, Parenteral Science and Technology, Bristol-Myers Squibb

The lyophilization process optimization for any new drug formulation requires multiple runs to identify the optimal shelf temperature, chamber pressure, and primary drying time. In this study, a definitive screening DOE was used to evaluate and identify product and process design space in an integrated fashion, where the effects of eight formulation and process factors were explored with a minimal number of lyophilization experiments.

3:10 Spray-Freezing and Dynamic Bulk Freeze Drying: An Innovative Technology for Production of a Stable, Free-Flowing Bulk Powder from a High-Volume Liquid mAb Product

Deirdre Lowe, Senior Engineer I, Technical Development, Biogen

The inherent instability of protein therapeutics at room temperature often requires a cold supply chain for storage, shipping and handling. For high-volume products, cold supply chain logistics are particularly challenging and expensive. In the case study presented here, a semi-continuous process is described for converting a high-volume liquid mAb product into a free-flowing bulk powder that is stable at room temperature. This technology has many advantages compared to conventional spray-drying and freeze-drying methods that further enable multiple drug product development options. Equipment, formulation and processing considerations for implementing this technology will be discussed in detail.

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

PROCESSES, PLATFORM APPROACHES & PRODUCT QUALITY

4:15 Degradation of mAbs during Manufacturing and Filling: An Underlying Mechanism and Common Origin of the Problem Explored

Tatiana Nanda, Ph.D., Biopharm Product Development Investigator, Biopharm Product Sciences, GlaxoSmithKline

Exposure to various interfaces during production, shipment and storage may be a contributing factor in degradation of protein therapeutics. Currently there is no consensus view on whether surface interaction or shear stress, or a combination of these are causative for protein aggregation. We subjected several mAbs to shear stress/surface interactions resembling manufacturing and injection conditions. The consistency in aggregate types formed in the systems advocates for a common degradation pathway.

4:45 Challenges in Handling of the Platform Formulations from Development through Marketing Application

Radhakrishna Maroju, Ph.D., Senior Scientist, Biologics CMC, Teva Biopharmaceuticals USA

A growing trend in the industry is to use platform formulations for Phase I products and carry it over through commercialization when feasible. The talk will present the common challenges that may be encountered in use of a platform formulation especially in late phase development to support a marketing application. Use of some novel multidimensional diagrams to identify suitability of a Phase I formulation to be carried over early in late phase will be demonstrated.

5:15 Close of Conference

6:00 – 8:30 Recommended
Dinner Short Course*

SC8: Protein Aggregation: Mechanism, Characterization and Consequences

* Separate registration required