Cambridge Healthtech Institute’s 2nd Annual
Early Analytical Development for Biotherapeutics
Optimizing the Selection and Performance of Preclinical Analytical Studies
August 5-6, 2015
Part of CHI's 7th Annual The Bioprocessing Summit

August 3-7, 2015 | Westin Copley Place Hotel | Boston, Massachusetts

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.

Wednesday, August 5

7:00 am Registration and Morning Coffee

8:05 Chairperson’s Remarks

Mario Hubert, Ph.D., Principal Scientist, Bristol-Myers Squibb

Early Analytical Development of Biotherapeutics; Case Studies and Lessons Learned

Eric Kwei
Ivan Correia, Ph.D., Senior Principal Research Scientist; Head, Global Protein Sciences, AbbVie Bioresearch Center

The pre-clinical effort to identify and advance therapeutic molecules is challenging as resources are scarce for enabling rapid first-in-human studies. High throughput automation, platform methods and adopting best practices are all important. However, a commitment to innovate is needed to rapidly advance therapeutic programs. This presentation will use case studies and lessons learned to illustrate how AbbVie is rapidly advancing best in class therapeutics for patients.



9:00 Early Developability Screen of Therapeutic Antibody Candidates Using Taylor Dispersion Analysis and UV Area Imaging Detection

Alexandra Lavoisier
Alexandra Lavoisier, Scientist, Biologics Center, Novartis, Switzerland

Therapeutic antibodies represent one of the fastest growing segments in the pharmaceutical market. Early quality control and risk assessment of their biophysical parameters help prevent failure in later stages of development, reducing costs and time consumption. We report on a novel micro-capillary-based instrument (Viscosizer) for measuring both the hydrodynamic radius and the absolute viscosity of antibodies based on Taylor dispersion analysis and UV area imaging using nanoliters of samples.


9:30 Biophysical Analysis of the Compatibility of Monoclonal Antibodies in Intravenous Infusion Solutions to Overcome Possible Adverse Effects During Clinical Practice

Haripada Maity
Haripada Maity, Ph.D., Research Advisor, Eli Lilly and Company

Administration of therapeutic monoclonal antibodies through the intravenous route can involve dilution of drug product using intravenous infusion solutions such as saline or 5% dextrose. As a result, the original drug product is diluted with potential changes in physical and chemical stability of the API. This presentation will discuss structural characterization, protein-protein interaction, concentration dependent inverse correlation of aggregation, and methods to monitor time-dependent self-association in intravenous infusion solutions.


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


10:45 Strategies and Challenges for Early Bioassay Method Development and Specification Setting

Debra Meyer
Debra Meyer, Senior Principal Scientist, Analytical R&D, Pfizer

Pfizer has a robust pipeline of biotherapeutics including multiple modalities.   Supplying biologically relevant bioassays across a large portfolio requires an evolution of a strategic, resource-flexible approach.  Case studies will be used to illustrate a strategy for staged method development that delivers fit-for-purpose bioassays for early product development.  The challenges and issues setting percent relative potency specification ranges for qualified bioassays early in development (prior to ICH validation) will be emphasized.


11:15 Biophysical Assays for Study of Aggregation and Subvisible Particles

Mario Hubert
Mario Hubert, Ph.D., Principal Scientist, Bristol-Myers Squibb

The presence of subvisible particles can have a critical impact on drug product efficacy and potentially induce immunogenicity. Strategies and health authority expectations for characterization of particles below 10 um are evolving. This talk describes high throughput assay development for subvisible particle concentration and characterization. Flow imaging technique, supported by fluorescence and Raman microscopy was used to develop the assay. A statistical model is used to evaluate assay precision and recommended minimum sample sizes.


11:45 Featured Poster Presentation: Determination of Multiple Product Attributes with a High-Throughput Automated Purification

Jasmine Wang, Scientist, MedImmune  

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Session Break


1:55 Chairperson’s Remarks

Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company

2:00 Analytical Development for Knob-into-Hole Bispecific Antibodies

Hongbin Liu, Ph.D., Scientist, Protein Analytical Chemistry, Genentech

Bispecific antibodies have shown great promise to be versatile and effective biotherapeutics. However, manufacturing of large quantity bispecifics with consistent quality remains to be a challenge. This presentation will focus on the analytical methods for a major format, knob-into-hole bispecifics, in development at Genentech. Details on method development for analyzing unique impurities, as well as overall analytical strategy for characterization and control systems will be discussed.

2:30 Analytical Development for Cell-Based Therapeutics

Gautam Banik
Gautam Banik, Ph.D., Vice President, Cellerant Therapeutics

CLT-008 is an off-the-shelf cellular product containing myeloid progenitor cells derived from adult hematopoietic stem cells that have the ability to mature into neutrophils in vivo. Cellerant is developing CLT-008 as a treatment for neutropenia caused by chemotherapy or radiation. CLT-008 is under evaluation in a Phase II clinical trial in AML patients receiving chemotherapy. This talk will discuss the development of CLT-008 with a focus on analytical techniques for lot release.


3:00 PEGylation of Antibody-Based Therapeutics with Reduced Serum Half-Lives

Nathan Brown
Nathan Brown, Ph.D., Senior Scientist, AbbVie Bioresearch Center

The influence of PEG conjugation on therapeutics above the renal clearance threshold is not well understood. We have pursued strategies for incorporating PEG onto engineered antibodies with diminished half-lives, including chemical conjugation to native, interchain disulfides as well as to engineered, unpaired thiol mutations. The engineered mutations and PEG attachments were evaluated for alterations to the protein’s biophysical properties, conjugation efficiency and specificity, antigen affinity, and in vivo half-life.


3:30 Identification of Quality Attributes in Early Biosimilar Development

Tilen Praper
Tilen Praper, Department Head, Analytical Development, Sandoz, Slovenia

Biosimilars are biologics approved via stringent regulatory pathways, following a loss of exclusivity of their originator reference products. The basis for approval is the demonstration of comparability; there must be no meaningful difference in efficacy, safety and overall quality between the biosimilar and the originator. To achieve this, it is essential to know the critical quality attributes of the molecule and to control them properly during the development and production.


4:00 Refreshment Break in the Exhibit Hall with Poster Viewing


4:45 Chair’s Remarks

Sam Ellis, Vice President, Biochemist, Thomson Instrument Co.

Meeting the Needs of Patients with Rare Diseases: Innovation in Product Development

Joanne-BeckJoanne T. Beck, Ph.D., Senior Vice President, Pharmaceutical Development, Shire Pharmaceuticals

At Shire, where the delivery of innovative medicines to patients with rare diseases and other specialty conditions is a fundamental component of the business model, creative solutions are critical to our success. Starting with the transition of drug candidates from discovery research to the clinic, followed by late phase development and eventually commercial product lifecycle management, scientists and engineers focus on both technology innovation and creative business approaches to deliver high quality therapies to the patients while decreasing development timelines and costs.


How to Innovate Product Development

  • Technologies
  • Strategies
  • Cutting Costs
  • Meeting needs
  • Utilizing creativity
  • Lessons Learned


Joanne T. Beck, Ph.D., Senior Vice President, Pharmaceutical Development, Shire Pharmaceuticals
Wayne Froland, Ph.D., Associate Vice President, Center for Biopharmaceutical Manufacturing Sciences, Merck Manufacturing Division
Stefan Schmidt, Ph.D., M.B.A., Vice President, Process Science & Production, Rentschler Biotechnologie GmbH
Haripada Maity, Ph.D., Research Advisor, Eli Lilly and Company

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

7:00 End of Day

Thursday, August 6

8:00 am Registration and Morning Coffee


8:25 Chairperson’s Remarks

Kathleen Shields, Senior Research Scientist, Pfizer

8:30 Development and Troubleshooting of Cell-Based Potency Assays to Demonstrate Drug Mechanism of Action

Peggy Criswell, Ph.D., Senior Scientist, Merck & Company

For an immunomodulatory biological therapeutic, three potency assays were developed, a competitive binding ELISA, a cell-based competitive binding ELISA, and a functional cell-based assay, utilizing a co-culture system of human Jurkat T-cells expressing the target and ligand presenting APCs. Each assay was implemented in the contract lab in parallel and validated or qualified. A case study is presented for assay implementation for product release and/or process characterization for licensure.


9:00 Method Development Guidance to Reduce Variability in Complex Cell-Based Potency Assays

Kathleen Shields
Kathleen Shields, Senior Research Scientist, Pfizer

Development of mechanistically relevant biological assays necessitates the execution of well-planned experiments. Accelerated drug development timelines and regulatory expectations for early introduction of functional bioassays in specific product categories (e.g. ADCs) challenge the method development scientist to efficiently optimize key assay parameters. A case study will be presented to illustrate the evaluation of assay parameters considered to be essential for delivery of a robust potency assay capable of supporting phase-appropriate specifications.



9:30 Application of Differential Scanning Calorimetry in Biotherapeutic Comparability Analysis

William MatousekWilliam M. Matousek, Ph.D., Staff Scientist, Protein Biochemistry, Regeneron Pharmaceuticals, Inc.

Differential Scanning Calorimetry (DSC) is a sensitive technique commonly used to define protein thermal unfolding transitions, assess relative thermal stability, and compare higher order structural content.  Multiple characteristic unfolding transitions are often observed, making the method amenable for both establishing identity and the estimation of impurities.  Thermodynamic properties such as Tm, enthalpy, and heat capacity were evaluated as indicators of structural similarity and purity.


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

10:45 A High-Throughput Capillary Isoelectric Focusing Immunoassay for Protein Sialylation Fingerprinting

Lam Raga Anggara Markely
Lam Raga Anggara Markely, Ph.D., Scientist, Biogen Idec

We developed a high-throughput method for semi-quantitative fingerprinting of protein sialylation using cIEF-immunoassay. The method is specific, sensitive, precise, and robust. It can analyze 2 µL unpurified cell culture samples within 4 hours (8 samples) to 14 hours (96 samples) without analyst supervision. It can be used for initial screening in cell line and process development, based on which a subset of samples can be further characterized by elaborate assays, such as LC and MS.


11:15 Fully Automated Host Cell Protein (HCP) Analysis using the AlphaLISA Assay for High Throughput Process Development

Zheng Ouyang
Zheng Ouyang, Automation Specialist, Biologics Process Development, Bristol-Myers Squibb

An HCP AlphaLISA was fully automated and developed to enable “best in class” HTPD program development. The improvements introduced by this accomplishment include a cost reduction of 600% as compared to the traditional approach at improved sample throughput, and provided reliable insight into the HCP impurity reduction capability and robustness. This high-throughput assay capability is instrumental to support HT process development and to meet the Fast-to-FIH timelines.


11:45 Application of High Throughput Analytical Methods and Instrumentation

Ling Santora
Ling Santora, Ph.D., Senior Scientist, AbbVie Bioresearch Center

Success of a drug discovery and development campaign depends on the adequate supply and quality of targets and other protein reagents. Scarce resources and aggressive development timelines demand the need for reliable methods to rapidly screen and select for these reagents. At AbbVie we have developed various high throughput (HT) automated multi-dimensional HPLC platforms to purify and assess the quality of protein reagents to support early target discovery and cell line development. This talk will highlight these methods.


12:15 pm Closing Q&A and Comments

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Close of Conference

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