Cambridge Healthtech Institute’s 5th Annual
Early Analytical Development for Biotherapeutics
Optimizing Preclinical Analytical Development for Emerging Biotherapeutics
Part of CHI's Ninth Annual The Bioprocessing Summit
August 23-24, 2017 | Westin Copley Place | Boston, MA

The analytical steps conducted in preclinical development following the handoff of a lead candidate are vital on many levels in determining the fate of that program. This complex effort shapes the optimization of the new product, requires the use of expensive and scarce resources and supports the voluminous regulatory filing that is the early IND application. It is imperative that companies reach this important milestone as quickly and efficiently as possible, while positioning the organization to move rapidly into the GMP production needed for early phase clinical trials. Early Analytical Development for Biotherapeutics will present best practice case studies of how industry companies have approached the most important analytical studies occurring during this stage, focusing on the development and optimization of key assays, the application of automation and the challenges of analytical development for novel modalities.

Final Agenda

Wednesday, August 23

7:00 am Registration Open and Morning Coffee

8:05 Chairperson’s Opening Remarks

Steven LaBrenz, Ph.D., Scientific Director, Cell and Developability Sciences, PDMS, Janssen R&D

8:15 KEYNOTE PRESENTATION:

Early Analytical Profiling to Facilitate Biologics Development

Tao He, Ph.D., Associate Research Fellow, BioMedicine Design, Pfizer, Inc.

Early analytical profiling has become an integral component in biologics discovery & development. This presentation will highlight the recent technology development and their applications to facilitate selection and engineering of biologics leads. Approaches to minimize risk associated chemical degradation and other biophysical properties will be discussed.

METHODS AND INSTRUMENTS

9:00 Rapid Development of HPLC-UV Based Multiple Quality Attributes Method

Zhi Chen, Ph.D., Senior Scientist, Molecular and Analytical Development, Global Manufacturing & Supply, Bristol-Myers Squibb

Transferability to QC is challenging for mass spectrometry (MS) based multiple quality attributes (MQA) methods. While HPLC-UV based peptide mapping methods can provide an alternative solution with potentially better accuracy and QC-friendly feature, the chromatographic separation of peptides of interest is not easy. In this presentation, the speaker will demonstrate case studies using HPLC modeling software and automation to facilitate rapid development of MQA methods.

9:30 Multidimensional Chromatography Characterization of Drug Load Variants in a Thiol Linked Antibody-Drug Conjugate

Catherine Eakin, Ph.D., Principal Scientist, Seattle Genetics

We developed three MS compatible 2D-LC methods for HT characterization of HIC peaks without manual fractionation. These methods are complementary and provide DAR confirmation by intact mass, identification of drug-load isomers and post-translational modifications by denaturing mass analysis, and localization of post-translational modifications to specific subunits by denaturing reduced mass analysis. Results demonstrate an efficient mechanism for characterization of ADC HIC peaks using multidimensional chromatography methods with in-line MS.

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

10:45 Integrated Development Environment for Production of Monoclonal Reference Material

Steven LaBrenz, Ph.D., Scientific Director, Cell and Developability Sciences, PDMS, Janssen R&D

The focus on quality is primarily from the protein perspective. Quality however refers to both the raw materials and the product. There is a need to test the outcome (product quality and CQAs) alongside the impacting parameters (raw materials, formulation materials, process parameters). The concept of an integrated development environment (IDE), where the growth, formulation and analysis of the protein are performed alongside the analysis of the raw materials, is presented.

11:15 Biophysical Characterization and Formulation Development of Live Viral Vectors as Vaccine and Immunotherapy Candidates

Ozan Kumru, Ph.D., Research Assistant Professor, Macromolecule and Vaccine Stabilization Center, University of Kansas

Numerous live attenuated viruses and viral vectors are being developed as vaccine and immunotherapy candidates, yet their use can be challenging due to their inherent complexity and instability. Case studies will be presented in which various physical assays were used as part of formulation development to determine the extent of loss of viral particles due to environmental stresses and then compared to viral titer results.

11:45 Analytical Method Toolbox for Biotherapeutics: Platform Assays for Efficient Development and When to Step Out of the Box

Jason Barker, Ph.D., Associate Principal Scientist, Group Leader, Analytical Development, FUJIFILM Diosynth Biotechnologies

Platform analytical methods are efficiently leveraged for efficient support monoclonal antibody and other recombinant protein throughout their development lifecycles. Method toolbox provides a stable baseline for development, yet stepping outside the method toolbox to develop methods for unique proteins or improve method robustness for long term use maybe required.

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

1:00 Session Break

EMERGING MODALITIES

1:45 Chairperson’s Remarks

Lintao Wang, Ph.D., Principal Scientist and Mass Spec Group Leader, Analytical and Pharmaceutical Science, ImmunoGen, Inc.

1:50 Comparative Assessment of Physical and Chemical Stability of Bispecific Antibodies Using Different Analytical Tools

Prakash Manikwar, Ph.D., Scientist, MedImmune

Mab-based bispecific antibodies (BiSAbs) offer a unique development challenges due to the presence of an additional single chain variable fragment (scFv) domain. We investigated physical and chemical stability of various BiSAb formats which differed in the location of scFv and antigen specificity using different analytical tools. Here, we compare the rate constants derived from different methods across the constructs and similarities between specificities along with analytical challenges and mechanistic understanding.

2:20 Early Analytical Support for Novel Site-Specific ADC Development by Mass Spectrometry

Lintao Wang, Ph.D., Principal Scientist and Mass Spec Group Leader, Analytical and Pharmaceutical Science, ImmunoGen, Inc.

ADCs continue to be a promising biotherapeutic approach for novel cancer therapies. A typical ADC is composed of several potent cytotoxic molecules covalently linked with a tumor-targeting monoclonal antibody in a site-specific or non-specific manner. SERIMAB technology has been recently explored to create site-specific novel DNA-alkylating IGN conjugates for preclinical evaluation. Mass spectrometry was efficiently used for early process optimization, early-stage product characterization and in vivo stability assessment.

2:50 Characterization of Novel General Amyloid Interaction Motif (GAIM)-Immunoglobulin (Ig) Fusions Targeting Misfolded Protein Aggregates in Neurodegenerative Diseases

Ming Proschitsky, Ph.D., Senior Scientist, Research, Proclara Biosciences

Amyloids as therapeutic targets are heterogeneous and are well known to be difficult to analyze. Nevertheless, Proclara Biosciences developed specific SPR, ELISA and aggregation inhibition assays with high quality and consistency to characterize therapeutics interaction with amyloids. This presentation will illustrate how the challenges were addressed by adapting traditional analytical assays which otherwise only work well with soluble and homogeneous targets.

3:20 Phase Appropriate Analytical Characterization of Recombinant Protein Based Vaccines

Vaneet K. Sharma, Ph.D., Analytical Scientist, Vaccine Development & Manufacturing, International AIDS Vaccine Initiative (IAVI)

This presentation will outline key considerations towards the phase appropriate analytical characterization of recombinant protein based vaccines. Analytical strategies for the assay development, assay qualification and characterizing the critical quality attributes (CQAs) relevant to Phase I/II clinical trial material will be discussed. A case study will be presented to demonstrate the application of the phase appropriate characterization to support recombinant protein based vaccines development.
Speaker Interview

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

4:45 PLENARY KEYNOTE PRESENTATION

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

7:00 Close of Day

Thursday, August 24

8:00 am Registration Open and Morning Coffee

OPTIMIZING THE SPEED AND EFFICIENCY OF EARLY ANALYTICAL DEVELOPMENT

8:25 Chairperson’s Remarks

Marina Kirkitadze, Ph.D., Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada

8:30 Insights from Native Mass Spectrometry and Ion Mobility-Mass Spectrometry for Antibody and Antibody-Based Product Characterization

Sarah Sanglier-Cianférani, Ph.D., Professor, University of Strasbourg, France

Monoclonal antibodies-based products have emerged as one of the most successful classes of therapeutics. Mass spectrometric approaches play a central role in their analytical and structural multi-level characterization. Importantly, techniques allowing the characterization of intact mAb-based products under non-denaturing conditions are attracting increasing interest. Here, I will review the current state of the art in native mass spectrometry and ion mobility methods for the characterization of mAbs and mAb-based products.

9:00 Integrating Novel Tools into Development Workflow of Biologics: NanoDSF and MST for Early Discovery and Developability Assessment

Alexey Rak, Ph.D., Head of Biostructure and Biophysics, Integrated Drug Discovery, Sanofi R&D, France

Modern drug discovery operations require characterization of biomolecular interactions to be both time- and cost-effective as well as to be highly precise and reproducible. Here we report applications of two novel predictive, precise, low protein consuming and high throughput methods: nano-Differential Scanning Fluorimetry (nanoDSF) and MicroScale Thermophoresis (MST) applied in our biologics discovery and characterization operations. Examples of the demonstrated effectiveness of the nanoDSF and MST will be discussed.

9:30 Featured Poster Presentation: Innovation of Cell Based Assay Platforms for Therapeutic mAb Against Viral Infection

Dengyun “Daisy” Sun, Ph.D., Senior Scientist, Biologics Analytical Science, Merck Research Laboratory 

There is increasing demand for mAb therapies to confer passive immunity against viral infection due to lack of vaccine or virus specific therapy. A functional cell based assay is a regulatory requirement for clinical development, commercial release and stability testing. This presentation discusses three novel cell based assay platforms in support of therapeutic mAb development against viral infection. The advantages and disadvantages of the platforms are compared.

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

10:45 High Throughput Analytical Platforms for Early Biopharmaceutical Development

Vladimir Razinkov, Ph.D., Principal Scientist, Amgen

The highly competitive landscape of the biopharmaceutical industry calls for a large number of candidates and an accelerated pipeline during early development. With constantly increasing complexity of new modalities and tight resources available at early development stage, the need for fast characterization screening of many candidates is in high demand. The presentation describes recent practices in the development and implementation of high throughput analytical methods during early candidate and formulation selection.

11:15 Development and Adaptation of Platformed Analytical Approaches

Marina Kirkitadze, Ph.D., Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada

This presentation discusses the adaptation of platform methods to characterize higher order structure of protein antigens, enable insights in formulation stability, and support process development.

11:45 Early Developability Evaluation of IgG-Based Novel Biologics Formats

Dana Filoti, Ph.D., Senior Scientist, Drug Product Development Preformulation, AbbVie

Complex IgG-based novel biologics are remarkable from a biological MOA perspective and from a drug product developability profile. Linking drug discovery to upstream development of IgG-based novel formats poses a challenging task in identifying the most relevant biophysical techniques to interrogate their development risk and molecular stability. We will discuss approaches towards implementation of a platform methodology for early biologics development to ensure a systematic and robust screening funnel selection as early as candidate selection.

12:15 pm Enjoy Lunch on Your Own

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

1:55 Close of Conference