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Key Sessions

Alfred Del Grosso, Ph.D.

Regulatory Expectations for Analytical Methods During Product Development

U.S. FDA

Arulvathani Arudchandran, Ph.D.

Patient Centered Specifications for the Life Cycle Management of Biologics: A Regulator’s View

CDER - FDA

Lokesh Bhattacharyya, Ph.D.

Performance Monitoring of Analytical Methods - Life-cycle Approach

CBER - FDA

7:00am - 8:00am

Coffee & Registration

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8:00am - 8:15am

Chairperson’s Remarks

  • John Alvino - Senior Manager, Global RA-CMC, GRAPSQA, Astrazeneca
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Showing of Streams
9:45am - 10:10am

Networking and Refreshment Break in Poster and Exhibit Hall

More
Showing of Streams
Showing of Streams
Showing of Streams
Showing of Streams
Showing of Streams
3:00pm - 3:25pm

Networking Refreshment Break in the Poster and Exhibit Hall

More
Showing of Streams
5:00pm - 6:00pm

Networking Cocktail Reception in Poster and Exhibit Hall

More
6:00pm - 6:05pm
Close of Day One

Close of Day One

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7:00am - 8:00am 60 mins
Coffee & Registration
8:00am - 8:15am 15 mins
Chairperson’s Remarks
  • John Alvino - Senior Manager, Global RA-CMC, GRAPSQA, Astrazeneca
8:15am - 8:45am 30 mins
Plenary Session
Regulatory Expectations for Analytical Methods During Product Development
  • FDA Speaker Alfred Del Grosso, Ph.D. - Team Leader, Analytical Chemistry, Division of FDA/CBER/OCBQ/DBSQC, U.S. FDA
8:45am - 9:15am 30 mins
Info
Plenary Session
Patient Centered Specifications for the Life Cycle Management of Biologics: A Regulator’s View
  • Arulvathani Arudchandran, Ph.D. - Microbiologist & Product Quality Reviewer OBP, OPQ,, CDER - FDA

For Biotechnological and Biological License Applications (BLA), ICH Q6B provides recommendations for setting specifications with acceptance criteria justification centered on clinical and manufacturing experience.  Specifications are an integral part of the control strategy since they confirm that the manufacturing process produces a consistent product that is pure, potent, stable, and safe when administered to patients.  Adjusting specifications throughout the product life cycle as clinical and manufacturing knowledge increases is recommended for the establishment of patient centered specifications.  Leveraging the knowledge to the product’s mechanism of action, clinical experience, product characterization, and to the manufacturing process in addition to risk management strategies is important in establishing patients centered specifications in the original BLA. Case studies to support the establishment of scientifically justifiable patient centered specifications at approval and throughout the product life cycle will be presented.

9:15am - 9:45am 30 mins
Plenary Session
Performance Monitoring of Analytical Methods - Life-cycle Approach
  • FDA Speaker Lokesh Bhattacharyya, Ph.D. - Lab Chief, CBER - FDA
9:45am - 10:10am 25 mins
Networking and Refreshment Break in Poster and Exhibit Hall
10:10am - 10:15am 5 mins
Modality Specific Characterization & Strategies for Diverse Products: Analytical Methods for ADCs, Bispecifics, and Fusion Proteins
Chairperson’s Remarks
  • John Alvino - Senior Manager, Global RA-CMC, GRAPSQA, Astrazeneca
10:10am - 10:15am 5 mins
Areas & Applications of Characterization: Host Cell Proteins
Chairperson's Remarks
  • Satish Sharma, Ph.D. - Scientist II, Bristol-Myers Squibb
10:10am - 10:15am 5 mins
Biological Assays: Lifecycle Approaches and Strategies for Bioassay Development
Chairperson’s Remarks
10:15am - 10:45am 30 mins
Info
Modality Specific Characterization & Strategies for Diverse Products: Analytical Methods for ADCs, Bispecifics, and Fusion Proteins
A Platform Approach for Characterization and Analysis of Symmetric Architecture scFY-IgG Bispecific
  • Mingyan Cao, Ph.D. - Senior Scientist II, Analytical Biochemistry, MedImmune

Bispecific antibodies (BiS Abs) represent an emergent class of biologics that has seen increasing interest, as demonstrated by numerous BiS Ab therapeutics entering clinical studies in recent years. To date, there have been three approved BiS Abs to enter the market: Removab®, Blincyto®, and Hemlibra®. There are many bispecific formats reported in literature, most of which broadly fall into three categories: Fc-less bispecific, IgG-like with asymmetric architecture, and appended IgG with symmetric architecture. For appended IgG bispecific antibody molecules, single chain variable fragments (scFv) are linked to or inserted in different locations of an intact IgG molecule to confer dual epitope binding. To improve biochemical stability, cysteine residues are frequently engineered on the heavy and light chain regions of the scFv to form an interchain disulfide bond. While this disulfide bond often improves stability, it potentially introduces other unexpected challenges. In this work, we report on size variants that were observed for an appended scFv-IgG bispecific antibody. Structural characterization studies showed the origin of the size variants to be a result of the engineered disulfide bond on the scFv, whereby the engineered disulfide was found to be either open or unable to form an inter-chain disulfide bond due to cysteinylation and/or glutathionylation of the cysteines. Furthermore, the scFv engineered cysteines also formed inter-molecular disulfide bonds, leading to the formation of highly stable dimers and aggregates. As both the monomer variants and dimer showed lower bioactivity, they are considered product related impurities must be controlled. Due to small difference in size between the variants, a high-resolution SEC method was developed and optimized using a statistical design of experiments methodology. The SEC assay was demonstrated to be robust, linear, accurate and precise. Lastly, as similar impurities can be anticipated for other BiS Abs that share similar architecture and incorporate an engineered disulfide bond in the scFv, this SEC method has potential to form the basis of a platform approach for monitoring and control of BiS Ab size variants.

10:15am - 10:45am 30 mins
Areas & Applications of Characterization: Host Cell Proteins
HCP Risk Assessment and Mitigation Strategy from CMC and Clinical Safety Perspective
10:15am - 10:45am 30 mins
Biological Assays: Lifecycle Approaches and Strategies for Bioassay Development
How to Use Statistics in A Lifecycle Approach
  • Steven Walfish - Principal Science & Standards Liaison, United States Pharmacopeia (USP)
10:45am - 11:15am 30 mins
Info
Modality Specific Characterization & Strategies for Diverse Products: Analytical Methods for ADCs, Bispecifics, and Fusion Proteins
Mass Spectrometric Analysis of ADC Quality Attributes to Support Process Development
  • Lintao Wang, Ph.D. - Associate Director, Immunogen

As a class of novel cancer therapeutic agents, antibody drug conjugates (ADCs) are complex biomolecules that are made of monoclonal antibodies linked with potent cytotoxic compounds. Mass spectrometry has been used to address some unique analytical challenges for process development due to structural complexity of ADCs.

10:45am - 11:15am 30 mins
Info
Areas & Applications of Characterization: Host Cell Proteins
Alternative to HCP ELISA Analysis: Evaluation of New Technology for Process Development and PAT Environment
  • Satish Sharma, Ph.D. - Scientist II, Bristol-Myers Squibb

In this presentation I will talk about evaluation of a new technology platform that offers a faster and simpler HCP analysis as compared to traditional ELISA. The new assay has several advantages over traditional ELISA and shows comparable results for in-process samples. Hence, the assay has promising application in process development and PAT environment.

10:45am - 11:15am 30 mins
Biological Assays: Lifecycle Approaches and Strategies for Bioassay Development
Analytical Quality by Design Approach in the Development and Qualification Lifecycle Stages of a Biological Analytical Procedure
  • Richard Burdick, Ph.D. - Chief Statistician, Elion Labs, a division of KBI Biopharma, Inc.
11:15am - 11:45am 30 mins
Modality Specific Characterization & Strategies for Diverse Products: Analytical Methods for ADCs, Bispecifics, and Fusion Proteins
Challenges for Bispecific Fusion Protein Characterization - from Glycosylation Heterogeneity to Disulfide Bond Variants
  • Chunlei Wang - Senior Research Investigator, MedImmune
11:15am - 11:45am 30 mins
Info
Areas & Applications of Characterization: Host Cell Proteins
Direct qPCR Methods for Monitoring Viral RNA and Host DNA Clearance in Purification Process Development for Biologics
  • Musaddeq Hussain, Ph.D. - Principal Scientist, Merck Research Laboratories

Biologics manufacturers need to show during purification clearance of retro-virus-like particles (RVLP) and host DNA and demonstrate safe levels in purified drugs.  Instead of nucleic acid extraction followed by PCR, we have developed extraction-free ‘direct’ methods, for quantification of RVLP and host DNA, which are streamlined and easier to run.

11:15am - 11:45am 30 mins
Biological Assays: Lifecycle Approaches and Strategies for Bioassay Development
Regulatory Perspectives on CMC Biological Assay Development throughout the Product Lifecycle
  • Graeme Price, Ph.D. - Research Microbiologist, CBER-FDA
11:45am - 12:15pm 30 mins
Biological Assays: Lifecycle Approaches and Strategies for Bioassay Development
Rush to Validation - The Good, the Bad, and the Ugly
  • Brian Peterson, MSc. - Consultant, Bioassay Solutions LLC
12:15pm - 1:25pm 70 mins
Info
Luncheon Roundtable A
The Past, Present and Future of Biosimilars: Statistical Considerations and Intechangeability
  • John Schiel, Ph.D. - Research Chemist, IBBR, National Institute of Standards and Technology

No PowerPoint slides here! Join interactive discussion around your challenges, roadblocks, ideas, and solutions to the biggest issues in characterization and bioassay development!

12:15pm - 1:25pm 70 mins
Info
Luncheon Roundtable B
Reference Standards Strategies
  • Santosh Yadav, Ph.D. - Principal Scientist, GVBC-BA, Merck & Company Inc

No PowerPoint slides here! Join interactive discussion around your challenges, roadblocks, ideas, and solutions to the biggest issues in characterization and bioassay development!

12:15pm - 1:25pm 70 mins
Info
Luncheon Roundtable C
Method Qualification to Expedite Biologic Development
  • Jihong Wang, Ph.D. - Principal Scientist, MedImmune

No PowerPoint slides here! Join interactive discussion around your challenges, roadblocks, ideas, and solutions to the biggest issues in characterization and bioassay development!

12:15pm - 1:25pm 70 mins
Info
Luncheon Roundtable D
Development for Bioassays In House vs. Using Commercial Available Kits - What Are the Challenges and Benefits?
  • Nathan Oien, Ph.D. - Senior Scientist, KBI Biopharma, Inc.

No PowerPoint slides here! Join interactive discussion around your challenges, roadblocks, ideas, and solutions to the biggest issues in characterization and bioassay development!

12:15pm - 1:25pm 70 mins
Info
Luncheon Roundtable E
How Can You Evolve An Assay From Early Clinical Phase to Late Clinical Phase?

No PowerPoint slides here! Join interactive discussion around your challenges, roadblocks, ideas, and solutions to the biggest issues in characterization and bioassay development!

12:15pm - 1:25pm 70 mins
Luncheon Roundtable F
Control Strategies - How Do You Maintain the Quality of Your Bioassay Over Time?
1:25pm - 1:30pm 5 mins
Modality Specific Characterization & Strategies for Diverse Products: Regulatory Strategies for Biologics
Chairperson's Remarks
  • Y. Diana Liu, MS - Protein Analytical Chemistry, Genentech
1:25pm - 1:30pm 5 mins
Areas & Applications of Characterization: Process and Product Variants and Impurities
Chairperson's Remarks
  • Jihong Wang, Ph.D. - Principal Scientist, MedImmune
1:25pm - 1:30pm 5 mins
Biological Assays: Applying DoE and QbD to Bioassay Development
Chairperson’s Remarks (1:15pm)
1:30pm - 2:00pm 30 mins
Info
Modality Specific Characterization & Strategies for Diverse Products: Regulatory Strategies for Biologics
CMC Strategies for Conditionally Active Biologics (CAB) Antibody Drug Conjugates (ADC)
  • Wei Chen, Ph.D., - Chief of CMC Operations, BioAtla

Case studies and lessons learnt from two approved INDs involving CAB ADC products will be presented. How a general CMC principle, biologic process/product controls and product release testing specifications that were applied to CAB ADC products will be discussed.

1:30pm - 2:00pm 30 mins
Info
Areas & Applications of Characterization: Process and Product Variants and Impurities
Evaluation of size variants methods for different biological compounds
  • Soundara Soundararajan, Ph.D. - Principal Scientist, BioProcess Development-MRL, Merck & Co.

Product related variants and impurities are present in biological products due to the unique nature of manufacturing process and also due to post translation modifications. Determination of these components and the purity of the molecule depend on the analytical methods used. This talk will discuss the analytical strategy that was applied to a non-mAb modality to determine the size variants and the analytical challenges when applying platform methods to non-platform mAbs.

1:30pm - 1:45pm 15 mins
Biological Assays: Applying DoE and QbD to Bioassay Development
Tech Transfer of Bioassays to Japan - Challenges, Limitations, and Impact on Lifecycle Management
  • Larisa Toulokhonova, Ph.D. - Principal Scientist, Biologics and Vaccines Analytics, Merck Manufacturing Division, Merck & Co., Inc.
1:45pm - 2:10pm 25 mins
Info
Biological Assays: Applying DoE and QbD to Bioassay Development
Development of Cell Based Assay to Access the Potency of Monoclonal Antibody Against the Immune Checkpoint Protein
  • Ping Han, Ph.D. - Associate Principal Scientist, Biologics Analytical Sciences, Merck

Modulating immune systems are effective therapeutic approaches to fight against cancer. The remarkable clinical successes of monoclonal antibodies blocking CTLA-4 and PD-1 have proven that the immune checkpoint proteins are proper therapeutic targets for tumors. A lot of interests have been focused on identifying new immune checkpoint receptors and their modulators to expand the effective therapeutic responses to more tumor types. Cell based assays have been widely used to evaluate the potency and efficacy of the candidate therapeutic molecules. A cell co-culture system mimicking the T cells and APC cells interaction in vivo was developed to assess the Mab candidate potency. Jurkat T cells stably expressing human immune checkpoint receptor and IL-2 promoter controlled Luciferase reporter gene were engineered as the effector T cells. The JY B cells stably expressing the receptor ligand were generated as the Antigen Presenting Cells (APC). When the effector cells and the APC cells are co-cultured, the ligand binds with the checkpoint receptor and send inhibitory signal to block T cell activation. Addition of Mab against the immune checkpoint protein disrupts the interaction and activates T cells in response to the stimulatory signal. The production of IL-2 drives Luciferase reporter gene expression and is measured using the Luciferase substrate. To make the cell based assay suitable for relative potency measurement, critical assay parameters were identified and evaluated. Design of Experiment (DOE) study was conducted to obtain the satisfactory assay conditions that generate good assay windows with proper slopes in the linear dose response range. A Fit-for-use study was conducted by two analysts on three different days showing that the assay has a linear measurement range between 35.5% ~200%. The overall assay accuracy and the intermediate precision (IP) meet the requirements for relative potency measurement. The cell based potency assay was employed to test the monoclonal antibodies that were manufactured and stored under the normal conditions, and the antibodies that went through forced degradation treatments. The assay is very sensitive in identifying alterations caused by some forced degradation treatments, and shows good stability indication of the monoclonal antibody. By comparing different modalities of the antibody in different assay systems, critical biophysical attributes of the monoclonal antibody that play important roles for proper cellular functions are identified.

2:00pm - 2:30pm 30 mins
Info
Modality Specific Characterization & Strategies for Diverse Products: Regulatory Strategies for Biologics
Analytical Strategies for the Regulatory Filing of Early-Phase Biotherapeutics
  • Kevin Zen, PhD - Senior Director, CMC and Manufacturing, AnaptysBio

This seminar will cover analytical testing and characterization methods for the early-phase therapeutic proteins in the context of IND/IMPD regulatory filing. This talk will overview the most commonly used analytical panel, not only for DS/DP release and stability but also for monitoring manufacturing process and facilitating formulation development: product description, purity and impurity analysis, product strength and potency, plus matrix verification of the most common process-related impurities. The characterization panel will be described: structure elucidation by mass spectroscopy, post-translational modification, biophysical characterization of higher order structure , and protein aggregates. Real-world case studies and common pitfalls will be presented during the presentation.

2:00pm - 2:30pm 30 mins
Info
Areas & Applications of Characterization: Process and Product Variants and Impurities
Assessing Antibody Quality Attributes with a Predictive in Vitro Model
  • Y. Diana Liu, MS - Protein Analytical Chemistry, Genentech

We have established an in vitro model to mimic in vivo redox environments.  The model was developed as an analytical tool to study attribute change mechanisms and predict in vivo behaviors.  Thiol-related quality attributes(QAs) for multiple therapeutic products were studied. This model replicated in vivo results for QAs with existing in vivo data. For others, potential behaviors were predictive.

2:10pm - 2:30pm 20 mins
Biological Assays: Applying DoE and QbD to Bioassay Development
Use of Analytical QbD in Early Stage Bioassay Development
  • Francis Poulin, Ph.D. - Scientific Director, Analytical Development, Sanofi
2:30pm - 3:00pm 30 mins
Biological Assays: Applying DoE and QbD to Bioassay Development
Selection Process for Parameters to be Included in DoE for Bioassays
  • Petra Bennington, MSc. - Bioprocess Development, Biologistics Analytical Sciences- Potency, Merck Research Laboratories
3:00pm - 3:25pm 25 mins
Networking Refreshment Break in the Poster and Exhibit Hall
3:25pm - 3:30pm 5 mins
Modality Specific Characterization & Strategies for Diverse Products: Case Studies of Protein Characterization and Product Comparability
Chairperson's Remarks
  • Santosh Yadav, Ph.D. - Principal Scientist, GVBC-BA, Merck & Company Inc
3:25pm - 3:30pm 5 mins
Areas & Applications of Characterization: Higher Order Structure
Chairperson's Remarks
  • Luke Arbogast, Ph.D. - Research Chemist, National Institute of Standards and Technology (NIST)
3:30pm - 4:00pm 30 mins
Info
Modality Specific Characterization & Strategies for Diverse Products: Case Studies of Protein Characterization and Product Comparability
Isolation and characterization of a mAb containing an extra heavy-light chain Fab arm
  • Dan Boyd - Associate Scientist, Gilead Sciences

Quaternary structure variants of a recombinant IgG observed by SEC-HPLC were isolated as part of identifying critical quality attributes.  This case study will describe how a truncated, non-covalently associated Fab arm was identified in one variant, the genetic origin of the variant, the impact to the variant’s potency, and its removal by a purification step.

3:30pm - 4:00pm 30 mins
Info
Areas & Applications of Characterization: Higher Order Structure
Characterization of protein therapeutics and vaccines with native LC/MS and cross-path reactive chromatography/MS
  • Igor Kaltashov, Ph.D. - Professor, UMass Amherst

Native LC (such as size exclusion and ion exchange) with on-line MS detection are powerful tools for protein characterization. Additional benefits are offered by the recently introduced cross-path reactive chromatography with MS detection. We will discuss recent advances in these fields with an emphasis on the higher order structure characterization.

4:00pm - 4:30pm 30 mins
Info
Modality Specific Characterization & Strategies for Diverse Products: Case Studies of Protein Characterization and Product Comparability
Development of High Throughput CE-SDS Method to Identify & Monitor Percentage Clipping of CAP256 mAb.
  • Deepika Gollapudi, MS - Scientist & Group Lead, Analytical Development, National Institutes of Health (NIH)

The CAP256-VRC26, broadly neutralizing antibody, was isolated from a HIV-1 clade C infected donor. It neutralizes 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency. Capillary gel electrophoresis (CE-SDS) was one of the assays that was developed and used extensively to evaluate and monitor product purity and quality. During the development, the assay detected unexpected peaks and was employed to determine root cause of the new peaks. This talk details the identification and impact of the additional peaks on the project through development of high throughput CE-SDS method.

4:00pm - 4:30pm 30 mins
Areas & Applications of Characterization: Higher Order Structure
Panel: Quantitative/Chemometrics Approaches to High Res HOS Techniques
  • Luke Arbogast, Ph.D. - Research Chemist, National Institute of Standards and Technology (NIST)
  • Frank Delaglio, Ph.D. - Principal Investigator, IBBR, National Institute of Standards and Technology and the University of Maryland
  • Mats Wikström, Ph.D. - Principal Scientist, Group Leader, Higher Order Structure, Amgen
4:30pm - 5:00pm 30 mins
Info
Modality Specific Characterization & Strategies for Diverse Products: Case Studies of Protein Characterization and Product Comparability
Analytical Ultracentrifugation Method Qualification: Determining Limits of Quantitation and Detection When Evaluating Protein Aggregation
  • John Campbell, Ph.D. - Investigator and GSK Associate Fellow, GlaxoSmithKline

Analytical ultracentrifugation (AUC) is a popular technique for evaluating protein aggregation in biopharmaceutical samples. However, establishing suitable limits of detection for AUC can be challenging. This presentation will give an overview of approaches for determining the limits of quantification for protein aggregate characterization by AUC. Our own investigation into the topic will be also be presented.

5:00pm - 6:00pm 60 mins
Networking Cocktail Reception in Poster and Exhibit Hall
6:00pm - 6:05pm 5 mins
Close of Day One