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Key Sessions

Nadine Ritter, Ph.D.

Physical or Functional: Which is the Most Important Analytical Characteristic of a Biotech or Biosimilar Product?

Global Biotech Experts, LLC

Alfred Del Grosso, Ph.D.

Top 10 Analytical Inadequacies in IND or BLA

U.S. FDA

IND Managed Review Process and Expedited Programs

7:00am - 8:10am

Coffee & Registration

8:10am - 8:15am
Chairperson’s Remarks

Chairperson’s Remarks

Showing of Streams
Showing of Streams
10:15am - 10:55am

Networking and Refreshment Break in Poster and Exhibit Hall

Showing of Streams
Showing of Streams
Showing of Streams
Showing of Streams
3:15pm - 3:45pm

Networking Refreshment Break in the Poster and Exhibit Hall

Showing of Streams
5:15pm - 6:15pm

Networking Cocktail Reception in Poster and Exhibit Hall

6:15pm - 6:20pm
Close of Day One

Close of Day One

7:00am - 8:10am 70 mins
Coffee & Registration
8:10am - 8:15am 5 mins
Chairperson’s Remarks
8:15am - 8:45am 30 mins
Plenary Session
Physical or Functional: Which is the Most Important Analytical Characteristic of a Biotech or Biosimilar Product?
  • Nadine Ritter, Ph.D. - President and Analytical Advisor, Global Biotech Experts, LLC
more
8:45am - 9:15am 30 mins
Plenary Session
Top 10 Analytical Inadequacies in IND or BLA
  • FDA Speaker Alfred Del Grosso, Ph.D. - Team Leader, Analytical Chemistry, Division of FDA/CBER/OCBQ/DBSQC, U.S. FDA
more

Procedures to support the identity, strength, quality, purity and potency of drug products and drug substances are an important component of new product applications reviewed by the FDA. Deficiencies in submissions related to analytical procedures often involve failure to provide procedural details, failure to adequately validate recommended analytical characteristics for the type of procedure and in the interpretation of validation data.  A summary of FDA expectations for analytical procedures and validations will be presented along with commonly encountered inadequacies.

9:15am - 9:45am 30 mins
Plenary Session
IND Managed Review Process and Expedited Programs
more

The US Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review (OVRR) evaluates the safety and efficacy of vaccines and related products used for infectious disease indications in the U. S.   This presentation will discuss the IND managed review process and Expedited Programs for serious conditions as it relates to vaccine development.

9:45am - 10:15am 30 mins
Technology Workshop A
Overcoming the Challenges of Biosimilar Development with the Latest in Ultra-High Field NMR and Ultra-High Resolution Mass Spectrometers
more

Attendees of this technology seminar will hear about the latest advancements in ultra-high field NMR and ultrahigh-resolution time-of-flight hardware and their application to the analytical challenges facing innovators and biosimilars characterization labs.  Innovations in hardware, software and application specific workflows will be highlighted. Several biotech-relevant case studies will be presented to highlight:

  1. the latest in high-mass detection, 
  2. simplified higher order structure determination, and 
  3. rapid glycoprofile for determination of ideal growth conditions during manufacturing. 
9:45am - 10:15am 30 mins
Technology Workshop B
Technology Workshop Available for Sponsorship
more

For more information, contact Kristen Schott at kristen.schott@knect365.com

10:15am - 10:55am 40 mins
Networking and Refreshment Break in Poster and Exhibit Hall
10:55am - 11:00am 5 mins
Well Characterized Biologics: Analytical Characterization Strategies for ADCs, Bispecifics, Fusion Proteins
Chairperson’s Remarks
  • Chairperson Suzanne Hudak, M.S. - Scientist, MedImmune
more
10:55am - 11:00am 5 mins
Biological Assays: QbD and DoE Approaches to Bioassay Development
Chairperson’s Remarks
  • Kenneth Miller, Ph.D. - Senior Scientist, Bioassay Development, Analytical Sciences, Biopharmaceutical Development, MedImmune
more
11:00am - 11:30am 30 mins
Well Characterized Biologics: Analytical Characterization Strategies for ADCs, Bispecifics, Fusion Proteins
Analytical Assay Development for Biopharmaceutical Proteins Using Automated Capillary Electrophoresis (CE) Western Blot
more

This session discusses the use of CE Western blot (from Protein Simple) as applied in the analytical assay development for protein pharmaceuticals, including monoclonal antibodies and Fc-fusion proteins. It was a very useful tool for titer measurement in process intermediates, final drug product characterization, and host-cell-protein (HCP) impurity identification/quantitation. You’ll hear about the possibility of a process control strategy from reviewing the percentages of molecular weight variants in a final purified Fc-fusion protein can be predicted from the size-based CE Western analysis on its cell culture harvest samples. A charge-based CE Western blot was also developed to monitor the isoform distribution for a monoclonal antibody during the cell culture process and for batch-to-batch consistency.

11:00am - 11:30am 30 mins
Biological Assays: QbD and DoE Approaches to Bioassay Development
Quality by Design in the Bioassay Development Lab
  • Kenneth Miller, Ph.D. - Senior Scientist, Bioassay Development, Analytical Sciences, Biopharmaceutical Development, MedImmune
more

QbD principles, which have traditionally been used in the context of biopharmaceutical manufacturing processes, can also be applied to bioassay development. This presentation will describe how QbD elements are being used for the development of bioassays that are included as part of lot release and stability testing programs.

11:30am - 12:00pm 30 mins
Well Characterized Biologics: Analytical Characterization Strategies for ADCs, Bispecifics, Fusion Proteins
Characterizing the Physiochemical Impact of Size Variants in an Antibody-Drug Conjugate
more

Antibody-drug conjugates (ADCs) represent a unique class of drugs consisting of a monoclonal antibody (mAb) conjugated with cytotoxic small molecules through chemical linkers. Although the level of complexity and heterogeneity associated with ADCs can be challenging, ADCs can be well characterized using appropriate analytical tools to ultimately ensure patient safety and efficacy. This session presents a case study on the characterization of size variants for an engineered cysteine antibody (EC-mAb) conjugated to two pyrrolobenzodiazepine (PBD) dimer drugs via protease-cleavable linkers. High molecular weight (HMW) and low molecular weight (LMW) species were purified to a high degree of purity from size exclusion chromatography. These variants were characterized using a comprehensive set of analytical techniques. In this talk, a complete story on the physiochemical nature of the size variants will be presented for the PBD linked ADC and its drug intermediate mAb.

11:30am - 12:00pm 30 mins
Biological Assays: QbD and DoE Approaches to Bioassay Development
Use of DoE Approaches for Potency Assay Development
more
12:00pm - 12:30pm 30 mins
Well Characterized Biologics: Analytical Characterization Strategies for ADCs, Bispecifics, Fusion Proteins
Analytical Characterization Challenges of Site-Specific Antibody Drug Conjugates
more

Conventional antibody drug conjugates (ADC) are usually heterogeneous mixtures of conjugated species. Site specific ADCs with near homogenous composition often show advantages over conventional ADCs, but also present unique challenges. This presentation will describe a case study of the analytical challenges we encountered with site-specific ADCs from two different conjugation techniques.

12:00pm - 12:30pm 30 mins
Biological Assays: QbD and DoE Approaches to Bioassay Development
A Case Study of Applying DOE and Automation into a Cell-based Neutralizing Antibody Assay
more

BMS is spearheading immuno-cancer therapy with multiple biotherapeutics approved. One requirement for BLA application is neutralizing antibody (NAb) assay and cell-based functional NAb assay is highly recommended by all regulatory agencies. Although BMS has successfully developed, validated and tested clinical samples for all approved biotherapeutics, it turned out to be a pain to transfer these cell-based assay to CRO, due to sensitive cells as critical reagents and much complicated assay set up. One way to circumvent the hurdle of complicated assay transfer is automation. In this case study, we will show how DOE and automation is applied during the assay development for a cell-based functional NAb assay. This not only standardizes cell-based NAb assay development, simplifier assay validation but will also greatly facilitate assay transferring.

12:30pm - 1:40pm 70 mins
Luncheon Roundtable A
Biosimilar Comparability Strategies: Effectively Comparing Reference Product to Biosimilars
  • Moderator Renuka Sivendran, Ph.D. - Principal Scientist, Biosimilars Process Development, Amgen Inc.
more

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

12:30pm - 1:40pm 70 mins
Luncheon Roundtable B
Control Strategies for Host Cell Proteins
  • Moderator Nadine Ritter, Ph.D. - President and Analytical Advisor, Global Biotech Experts, LLC
more

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

12:30pm - 1:40pm 70 mins
Luncheon Roundtable C
Setting Specifications Based on Patient Exposure
more

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

12:30pm - 1:40pm 70 mins
Luncheon Roundtable D
Bioassays for Biosimilars
more

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

12:30pm - 1:40pm 70 mins
Luncheon Roundtable E
Characterization of rAAV Gene Therapy Vectors
more

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

1:40pm - 1:45pm 5 mins
Well Characterized Biologics: Analytical Methods for Identification and Quantification of Host Cell Proteins
Chairperson's Remarks
more
1:40pm - 1:45pm 5 mins
Well Characterized Biologics: Strategies for Higher Order Structure
Chairperson’s Remarks
  • Chairperson Luke Arbogast, Ph.D. - Research Chemist, National Institute of Standards and Technology (NIST)
more
1:40pm - 1:45pm 5 mins
Biological Assays: Lifecycle Management of Bioassays and Assay Changes to Commercial Products
Chairperson’s Remarks
more
1:45pm - 2:15pm 30 mins
Well Characterized Biologics: Analytical Methods for Identification and Quantification of Host Cell Proteins
Host Residual DNA Testing: New Paradigms and New Techniques
more

The biologics manufacturer needs to demonstrate a safe level of host–residual DNA (hrDNA) in the purified drug.  Instead of DNA extraction followed by qPCR we developed extraction-free methods where CHO-derived samples were protease-digested and directly subjected to qPCR or dPCR.  We have also developed direct dPCR assays for Pichia and E. coli hrDNA.  We show that in some ways dPCR is better than qPCR

1:45pm - 2:15pm 30 mins
Well Characterized Biologics: Strategies for Higher Order Structure
Simple NMR Methods for evaluating HOS of Monoclonal Antibody Therapeutic Quinary Structure
  • FDA Speaker Kang Chen, Ph.D. - Chemist, Office of Testing and Research, CDER, Food and Drug Administration (FDA)
more

Correctly folded protein higher order structure (HOS), including secondary, tertiary, quaternary and quinary structures, is crucial for protein drug quality. For large multi-domain protein like monoclonal antibody (mAb), its oligomer can have quinary structure, association of its monomeric quaternary structure. Here, several commonly available analytical methods, i.e., size-exclusion-chromatography (SEC) FPLC, dynamics light scattering (DLS), NMR and multivariate analysis, were combined with in situ enzymatic cleavage to yield a complete profile of mAb HOS and comparable metrics. Rituximab and infliximab were chosen for method evaluation because both IgG1 molecules are known to be homologous in sequence, superimposable in Fab crystal structure and identical in Fc structure. However, herein the two are identified to be significantly different in quinary structure in addition to minor secondary structure differences. All data collectively showed rituximab was mostly monomeric while infliximab was in mono-oligomer equilibrium driven by its Fab fragment. This session with review the studies and discuss the analysis using the new in-situ enzymatic digestion method holds potential in identifying structural differences on larger therapeutic molecules using NMR.

1:45pm - 2:15pm 30 mins
Biological Assays: Lifecycle Management of Bioassays and Assay Changes to Commercial Products
Lifecycle Management for Bioassay Development and Validation
more

Lifecycle management for bioassay development starts with procedure design and continues through validation based on QbD. The concept of QbD is understood as a systematic approach that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management (ICH Q8). An overview of variability and measurement uncertainty to align decisions with results generated by a procedure will be presented.

2:15pm - 2:45pm 30 mins
Well Characterized Biologics: Analytical Methods for Identification and Quantification of Host Cell Proteins
Identification and Quantification of HCP's in mAbs, Recombinant Proteins and Biosimilars by Mass Spectrometry
more

Gel-free, label-free mass spectrometry (MS) enables identification and quantitation of total and individual HCP in biotherapeutic products, and represents an orthogonal method to ELISA. This session will present examples showing the use of semi-quantitative HCP discovery (LC-MS/MS) and absolute quantitation of HCP (LC-MRM/MS) as applied to monitoring of process changes, improvements, scale-up, batch uniformity, clearance, and comparison of Biosimilars vs. Innovators.

2:15pm - 2:45pm 30 mins
Well Characterized Biologics: Strategies for Higher Order Structure
CD Spectroscopy of Protein-Dye Complexes as a Characterization Tool for Protein Higher Order Structure
more

CD spectroscopy plays an important part in the development of protein pharmaceuticals, as a means to examine purified proteins for structural integrity and proper folding, and also to study relative conformational stabilities in response to changing pH, ionic strength, and other formulation variables. During production of biological products, CD spectroscopy can provide a non-invasive and non-destructive means of monitoring stability and checking batch-to-batch consistency of the drug product. CD spectroscopy in the near-UV wavelength region provides a tertiary structure fingerprint, including information on aromatic residues and disulphide bridges. This session will discuss how aromatic dyes or similar compounds can serve as probes of protein higher order structure, what these changes show, and the overall beneficial effects of the method.

2:15pm - 2:45pm 30 mins
Biological Assays: Lifecycle Management of Bioassays and Assay Changes to Commercial Products
Change or Replace? Lifecycle Management of Bioassays for Commercial Products
more

Case studies will be presented to discuss implementing changes to bioassays already approved for commercial products. The focus will be on making decisions on whether to make modifications to the existing assay, or to develop a new, better assay.

2:45pm - 3:15pm 30 mins
Technology Workshop A
Glycans Before Lunch: Rapid N-Glycan Sample Preparation Workflows for Liquid Chromatography and Capillary Electrophoresis Platforms
more

Glycosylation is frequently a critical quality attribute of biotherapeutics, making the characterization of N-glycans an essential part of the development process. We present a rapid N-glycan sample preparation platform with a choice of labels for LC, LC-MS and CE applications. The Gly-Q CE platform enables relative N-glycan quantification for up to 96 cell culture samples within a single workday.

2:45pm - 3:15pm 30 mins
Technology Workshop B
Robust and Simple Potency Bioassays for Biologics and Biosimilars
more
3:15pm - 3:45pm 30 mins
Networking Refreshment Break in the Poster and Exhibit Hall
3:45pm - 4:15pm 30 mins
Well Characterized Biologics: Analytical Methods for Identifying, Monitoring and Controlling Product and Process Variants and Impurities
Analytical Methods in Development: Robust Strategies for Charge Variants, Size-Exclusion Methods and other Methods
more

Since its implementation, Quality by Design (QbD) has become an integral part of the pharmaceutical product development process. More and more, those principles also apply to analytical method development to ensure method appropriateness and robustness. Case studies for development approaches across different analytical techniques will be shared.

3:45pm - 4:15pm 30 mins
Biological Assays: CMC Biological Assay Case Studies
MoA-reflective Bioassays for a Monoclonal Antibody Targeting a T Cell Co-Stimulatory Receptor
more

Generating anti-tumor immune responses with antibodies that activate T-cell co-stimulatory receptors while at the same time modulating interactions with Fcγ receptors is a promising approach in cancer immunotherapy. We have characterized a monoclonal antibody (mAb) with the capacity to modulate FcγR interactions and target a co-stimulatory T cell receptor. For assessment of a molecule with multiple mechanisms of action (MoA), it is important to consider characterization strategies that fully capture the functional capability of the therapeutic protein. Challenges and approaches to design relevant in-vitro assays for therapeutic antibodies with complex MoA will be presented.

4:15pm - 4:45pm 30 mins
Well Characterized Biologics: Analytical Methods for Identifying, Monitoring and Controlling Product and Process Variants and Impurities
Leveraging a Mass Spectrometry Based Multi-Attribute Method Platform for Monitoring Product Variants and Impurities
more

Current paradigms for monitoring biopharmaceutical variation during production and processing call for the use of multiple analytical platforms. The traditional methods report an indirect measure of a limited number of attributes per assay. A mass spectrometry-based multi-attribute method (MAM), however, has the power to evaluate multiple critical quality attributes (CQA) in a single assay with the additional advantage of providing site-specific information. The MAM is being heavily explored in the industry to streamline the quality control process and potentially replace multiple analytical methods. The MAM platform has the potential to reduce both analytical turn-around time and the use of multiple workflows and thus may reduce the analytical burden on the quality control lab. Co-Authors of this data are John Schiel, Research Chemist, NIST/IBBR; Richard Rogers, Scientist 4, Just Biotherapeutics

4:15pm - 4:45pm 30 mins
Biological Assays: CMC Biological Assay Case Studies
Development of a Murine Reporter Cell Line System to Support Potency Assays Targeting Immuno-Modulatory Receptors
more

A murine reporter cell line system was designed to have a broad application to Immuno-Modulatory Receptors potency assays. In the system, a 3A9 T cell line was engineered with IL2-luciferase and co-expresses an IMR, and a LK35.2 B cell line that expresses inhibitory receptor ligand. Bridging study demonstrated 3A9 cell line system has comparable suitability to equivalent mammalian cell line system. Further study showed the system possessed superior linearity (25%-200%), intermediate precision (GSD 4.3%), sensitivity and robustness.

4:45pm - 5:15pm 30 mins
Well Characterized Biologics: Analytical Methods for Identifying, Monitoring and Controlling Product and Process Variants and Impurities
Characterization of Antibody Charge Variants Induced by Metal-Catalyzed Oxidation
more

Characterization of charge variants is important for evaluating product quality attributes of monoclonal antibodies,and for ensuring the safety and efficacy of antibody drug products. Recently, we reported a correlation between formation of charge variants and metal-catalyzed oxidation during production and storage of monoclonal antibodies. However, to date, the charge variants and the related mechanism have not been elucidated in the literature to explain the observed correlation. In this work, charge variants of an antibody stressed by metal-catalyzed oxidation were fractionated by ion exchange chromatography. A wide range of physicochemical assays was subsequently applied to characterize these fractions at both protein and peptide levels. Several novel charge variants were identified. These findings help explain the observed correlation and provide valuable information for a critical assessment of the induced charge variants. This work also demonstrates that metal-catalyzed oxidation represents a new degradation mechanism for inducing charge heterogeneity on monoclonal antibodies

4:45pm - 5:15pm 30 mins
Biological Assays: CMC Biological Assay Case Studies
Quantitative Cell-based Bioassays to Advance Immunotherapy Programs Targeting Immune Checkpoint Receptors
more

Quantitative and reproducible bioassays are critical for antibody-based drug development. Existing methods employ primary cells and complex protocols that are not well-suited for quality-controlled environments. We have developed functional cell-based reporter bioassays for immune checkpoint targets (PD-1, CTLA-4, LAG-3, TIM-3, 4-1BB, GITR, OX40, etc.). Here we describe the development and application of MOA-based bioassays for biologics drug discovery and development.

5:15pm - 6:15pm 60 mins
Networking Cocktail Reception in Poster and Exhibit Hall
6:15pm - 6:20pm 5 mins
Close of Day One