Cambridge Healthtech Institute’s Seventh Annual

Optimizing Biologics Formulation and Stability  

New Tools, Technologies, Case Studies, and Research Updates on Development of Novel Biologics

August 14-15, 2019

 

The seventh annual Optimizing Biologics Formulation and Stability conference will cover the latest trends and challenges in formulations development of novel biologic formats, process optimization, manufacturing, and device and packaging considerations for existing and emerging protein therapeutics. We are seeking case studies, especially unpublished and innovative work on co-formulation, formulation of novel biologics, development and delivery of high-concentration protein formulations, effective scale-up strategies, excipient induced instability, process challenges, fill-finish challenges, and predictive tools for rapid formulation and stability screening.

Final Agenda

 

August 13, 6:00-8:30 Recommended Pre-conference Dinner Short Course*

Cambridge

SC7: Protein Aggregation: Mechanism, Characterization and Consequences

Instructors:

Thomas Laue, PhD, Professor Emeritus, Molecular, Cellular and Biomedical Sciences, University of New Hampshire

Matthew Brown, PhD, Applications Manager, Bioscience, Malvern PANalytical

Protein aggregation is recognized by regulatory agencies and the biopharmaceutical industry as a key quality attribute of biotherapeutics. Various aggregates hold the potential for adversely impacting production and patients in a variety of ways. This in-depth course reviews the origins and consequences of aggregation in biotherapeutics, and then examines strategies for predicting and quantifying aggregation in biopharmaceuticals. It benefits scientists engaged in the development, production, analytical characterization and approval of biotherapeutics and who require a good working knowledge of protein aggregation.

Waterfront 1C

SC9: Impact of Impurities on Stability of Biologics

Instructors:

Diane Paskiet, MS, Director of Scientific Affairs, West Pharmaceutical Services, Inc.

Katherine E. Bowers, PhD, Principal Scientist, Group Leader, Fujifilm Diosynth Biotechnologies

Impurities in protein therapeutics can originate from a variety of unexpected sources. As the protein molecule is taken through the upstream/downstream processes, final product manufacturing (fill/finish) and even during patient delivery, there is a myriad of potential “hidden” impurities that can have an impact to the safety and efficacy of the bio-therapeutic. This course aims to answer the questions of what and where are the greatest risks for biologic impurities and how can we study the impact of these impurities on the protein molecule. Our mission is to collectively discuss how to identify, evaluate and mitigate impurity risks from early development and throughout the product life cycle.

Wednesday, August 14

6:00 - 6:45 am Seaport Fun Run/Walk (Seaport Hotel Plaza Lobby)

 

 

7:00  Registration Open and Morning Coffee

FORMULATION AND DELIVERY OF NOVEL THERAPEUTICS

Beacon Hill

8:05 Chairperson’s Remarks

Danny K. Chou, PharmD, PhD, President, Biopharmaceutical Characterization and Formulation Development, Compassion BioSolution, LLC

8:15 KEYNOTE PRESENTATION: Combinatorial Development of Biomaterials for Islet Cell Therapy

Anderson_DanDaniel G. Anderson, PhD, Associate Professor, Chemical Engineering and Institute for Medical Engineering and Science, Harvard-MIT Division of Health Sciences & Technology, Massachusetts Institute of Technology

Here we describe our work on the combinatorial development of biomaterials for the purposes of enabling islet transplantation. The fibrotic reaction to biomaterials is a fundamental challenge to the function of implanted medical devices. We have developed new materials capable of avoiding fibrosis and scar tissue formation. These show promise as vehicles for the immune-isolation of transplanted cells, for the treatment of diabetes.

9:00 Integrated Approach to Developing Patient-Centric Biologics Combination Products

Saluja_AtulAtul Saluja, PhD, Senior Director, Head Formulation & Process Development, Sanofi

Successful development of patient-centric products requires a systematic understanding of multiple factors. These range from the fundamental characteristics of the active molecule, excipients of the formulation, primary packaging components, constituent unit operations and manufacturing process parameters, and various aspects of a patient-friendly device. In essence, success depends on a seamless integration between micro and macro factors of the dosage form. Integration is all the more pertinent for novel therapies wherein the physicochemical aspects are poorly understood and the regulatory landscape is rapidly evolving. This talk touches upon a number of aforementioned factors and considerations which are instrumental in derisking and scaling up a safe, efficacious and robust biologic drug product. 

9:30 Why is Platform Formulation Obsolete? A Case Study on How to Adapt to the New Reality in Biologic Formulation Development

Chou_DannyDanny K. Chou, PharmD, PhD, President, Biopharmaceutical Characterization and Formulation Development, Compassion BioSolution, LLC

The goal in this presentation is to discuss why the use of platform formulation is a risky approach in today’s environment and how one can implement new strategies to develop more robust formulations that suit the needs of every individual molecule while adapting to new regulatory expectations.

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

 

10:45 Novel Approaches for Stabilization and Formulation of Biotherapeutics

Mosharraf_MitraMitra Mosharraf, PhD, HTD Biosystems Inc.

In this presentation problems associated with formulation development and stability of different types of biological molecules will be discussed. A high throughput approach for accelerating formulation development of biotherapuetics will be presented. We will showcase the use of this approach in combination with high throughput analytical methodologies for the development of various types of biotherapeutics. 

HIGH CONCENTRATION PROTEINS FORMULATIONS

Beacon Hill

11:15 Challenges in Developing and Manufacturing High Concentration Protein Therapeutics – Case Studies

Zen_KevinKevin Zen, PhD, Executive Director, Analytical Characterization, Formulation Development and Biologics Manufacturing, AnaptysBio Inc.

Subcutaneous injections are gaining wider acceptance as an alternative to intravenous injections. The higher concentration for SC injection poses unique challenges to drug delivery, formulation development, downstream processing, particularly in ultrafiltration/diafiltration step to meet final product specification. Typically the high protein concentration challenges include protein aggregation, conformational stability, colloidal stability, potential particulate formation and high viscosity. In this talk, I will present a case study on addressing such challenges in the context of pre-filled syringes.

 

11:45 Predicting High-Concentration mAb Behavior from Measured Parameters

Laue_ThomasThomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire

A computer program is presented that predicts solution colloidal stability based on the charge, molar mass, axial ratio, salt concentration and self-association constant. Graphs of thermodynamically rigorous concentration-dependent interaction parameters are provided. Examples of how the various parameters impact colloidal stability will be presented.

12:15 Luncheon Presentation: Steer Clear of FOMO: Get More Protein Stability and Characterization Data with Uncle

Kevin Lance, PhD, Product Manager, Marketing, Unchained Labs

Novel protein therapeutics and ever-higher concentrations require the best formulations for maintaining protein stability and avoiding aggregation.  Uncle’s unique combination of static light scattering, dynamic light scattering, and full-spectrum fluorescence tells the story of your protein’s conformational and colloidal stability on the same small sample.

1:00 Dessert Break in the Exhibit Hall with Poster Viewing

HIGH CONCENTRATION PROTEINS FORMULATIONS (CONT.)

Beacon Hill

1:45 Chairperson’s Remarks

Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire

1:50 Excipients Modulate Viscosity of High Concentration Proteins in a Concentration Dependent Manner: Experimental and Computational Approaches

Rodrigues_DanikaDanika Rodrigues, Associate Scientist, BioTherapeutics Drug Product Development, Janssen Research and Development

This talk presents an experimental and computational excipient screening strategy to address viscosity and concentratability of a monoclonal antibody (mAb-A) via protein-excipient interactions. The rank order of excipients on viscosity lowering properties of mAb-A was reversed as the protein concentration increases from ~ 100 mg/mL to >175 mg/ml. These findings demonstrate the need for careful selection of excipients depending upon the target high concentration of proteins during biopharmaceutical development.

2:20 Advanced Strategies for Formulating High Concentration Antibody Products

Vishal_TopraniVishal Toprani, PhD, Development Scientist-I, Pharmaceutical Development, Alexion Pharmaceuticals

Developing high concentration monoclonal antibody formulations is challenging from both pharmaceutical as well as downstream process. Thus, formulating high concentration monoclonal antibody products requires orthogonal testing modalities for implementing modern high throughput formulation screening tools, such as with viscosity and particulate assessments in traditional and DOE study designs. This presentation will focus on a case study using this advanced strategy in combination with UF/DF step optimization to successfully achieve manufacturable high concentration protein formulations.

2:50 Development of High Concentration Frozen Formulation for Anti-Malaria Antibody

Kueltzo_LisaLisa A. Kueltzo, PhD, Director, Formulation and Stabilization Sciences, Vaccine Production Program, Vaccine Research Center, National Institute of Health

A high concentration (≥ 100 mg/mL) frozen anti-malaria mAb was formulated for Phase 1 clinical trials at the NIH. The effect of the buffer, pH and ionic strength on conformational and colloidal properties was evaluated. Excipient screening and optimization revealed that sugars, sugar alcohols and arginine increased overall stability. Selected buffers were subjected to accelerated degradation (thermal and freeze-thaw stress) and evaluated for IV solution compatibility prior to final formulation selection.

3:20 A Rapid Dehydration Process for the Stability and Delivery of Biologics

Deborah Bitterfield, PhD, CEO and Founder, Lindy Biosciences, Inc.

This novel dehydration process produces spherical, dense, stable particles of a therapeutic protein, ideal for solid injectable formulations such as low-viscosity, high-concentration suspensions or encapsulation for controlled release.

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


4:45 Plenary Keynote Session View details

6:00 A Taste of New England Reception in the Exhibit Hall with Poster Viewing 

7:00 End of Day

 

Thursday, August 15

6:00 - 6:45 am Namaste@#BPSMT (Seaport Hotel Plaza Lobby)

8:00  Registration Open and Morning Coffee

EXCIPIENTS AND STABILITY

Beacon Hill

8:25 Chairperson’s Remarks

Brittney J. Mills, PhD, Senior Scientist II, NBE Development, Formulation, AbbVie, Inc.

8:30 New Excipients to Prevent Particle Formation in Antibody Formulations

Wuthrich_PhilipPhilip Wuthrich, Senior Scientist, Research, Research & Development, ReForm Biologics

Commonly used polysorbates are prone to chemical degradation, compromising formulation storage stability. Polysorbates also create processing issues, because the micelles they form are similar in size to antibodies. Here we present data for alternative excipients that can prevent particle formation in protein formulations, and we consider the chemical stability of the new excipients compared with polysorbate. Additionally, we describe the potential benefits of these alternative excipients in downstream processing applications.

9:00 Use of High-Throughput Methods for Early Stage Formulation Evaluation and their Correlation to Stability Studies

Mills_BrittneyBrittney J. Mills, PhD, Senior Scientist II, NBE Development, Formulation, AbbVie, Inc.

Early-stage evaluation of drug-like properties is completed using high-throughput methods due to the limited material available at this stage. As this data is used to screen candidates and assess potential formulations, it is important to establish that it aligns with data obtained during more extensive stability assessments that occur later in development. This presentation will focus on a comparison between our miniaturized approach for early-stage evaluation and more extensive stability assessments.

LOW CONCENTRATION FORMULATIONS, CO-FORMULATION & COMBINATION PRODUCTS

Beacon Hill

9:30 Novel Combo Vaccine – Characterization of Adsorbed Drug Product

Kirkitadze_MarinaMarina Kirkitadze, PhD, MBA, Head, Analytical Process Support & PAT Platform, Analytical Sciences, Sanofi Pasteur

The topic of this presentation is compositional and structural analysis of novel combo vaccine. Characterization of adsorbed product included thermal stability measured by nanoDSF, particle size distribution was examined by Laser Diffraction and SEM, and protein secondary structure by FTIR.

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

10:45 CMC Perspective on Clinical Trial Preparation for Low Concentration Potent Bispecifics: Case Study of Glenmark’s BEAT

Sachin_DubeySachin Dubey, PhD, Deputy Director, Formulation, Analytical and Drug Product Development, Glenmark Pharmaceuticals

One of the novel class of biologics is bispecific antibodies – multiple formats have been developed. There are approximately 130 clinical trials ongoing with different bispecifics. Improved potency has unwrapped new challenges for CMC – challenge of low concentration. New strategies are required for formulation and drug product development. Prevention against adsorption and additional controls during manufacturing are critical. Phase appropriate dosing strategies in clinic is another vital factor influencing CMC development.

11:15 Protein-Excipient Interactions Evaluated via NMR Studies in Multi-Dose Formulations: Influence on Antimicrobial Efficacy and Potential Study Approach

FURTMANN_BrittaBritta Furtmann, PhD, Section Head – Formulation and Process Development, Biologics Drug Product, Sanofi

Preservatives are excipients essential for multi-dose formulations to prevent microbial growth. However, they are known to interact with non-ionic surfactants like polysorbate and potentially with active pharmaceutical ingredients. In the current study those interactions were successfully analyzed via NMR and correlated to the stability and antimicrobial activity of the formulations. As an outcome, NMR is proposed as a powerful tool to support the development of multi-dose formulations using minimal testing volumes.

11:45 Challenges and Strategies for Co-Formulation Development of Biologics in Combination Products

Mosharraf_MitraMitra Mosharraf, PhD, HTD Biosystems Inc.

Combination therapy of two molecules that have complimentary pharmacological effect has led to an increased interest in development of co-formulation products. These drugs are formulated into a stable product consisting of multiple active drugs to reduce the number of injections and improve patient experience. In this presentation the challenges with such approach and potential strategies to overcome these challenges are discussed using several case studies.

12:15 pm Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Last Chance for Poster Viewing 

1:55 End of Conference