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Welcome to Bioassays 2018: Scientific Approaches & Regulatory Strategies On behalf of the Scientific Organizing Committee and CASSS, we are excited to welcome you to Bioassays 2018: Scientific Approaches & Regulatory Strategies and look forward to your participation and input April 16-17, 2018 at the DoubleTree by Hilton Hotel in Silver Spring, Maryland. The CASSS Bioassays meeting has established itself as a premier conference and unique opportunity for participants and opinion leaders to discuss and debate current regulatory and industry topics regarding bioassays. Bioassays are a critical component of the analytical control strategies for biologics and other complex molecules. The ability of an assay to characterize and demonstrate biological activity is essential and developing such bioassays is becoming more difficult as biologic drugs are engineered to be more complex and/or have multiple modes of action. Companies are continuously challenged with developing assays that are biologically relevant for the analysis of multiple potential mechanisms. Bioassays are also used for lot release, stability, comparability and characterization studies, which requires that the assays be robust and, in most cases, suitable for a QC lab. Bioassays 2018 is structured to encourage attendee interaction. Each session includes case study presentations followed by a panel discussion allowing for lively dialogue between attendees from academia, industry and regulatory agencies. As in previous years, we expect this format to result in additional focus on the technical and regulatory details of the topic. Regulatory participation from the US FDA, Health Canada and various European agencies has been strong each year. In addition, an exhibitor showcase at the end of day one and a dedicated poster session on day two will give attendees the opportunity to present additional topics and continue the day's discussion in an informal setting. We would like to thank the speakers and the panel members who are giving generously of their time and resources and to you for your attendance. We would also like to acknowledge the generosity of our program partners for the continued support of the CASSS Bioassays meeting: Amgen Inc.; Biogen; Eli Lilly and Company; F. Hoffmann-La Roche Ltd.; Genentech, a Member of the Roche Group; MedImmune, A member of the AstraZeneca Group; Pfizer, Inc.; Sanofi. We are grateful for the expert management from CASSS and the audio-visual expertise of Michael Johnstone from MJ Audio-Visual Productions. Their experience and guidance in the preparation of this meeting has been invaluable. We are sure you will find Bioassays 2018 to be informative and productive, and that it will provide you with current perspectives on bioassays.

Scientific Organizing Committee: Thomas Arroll, Seattle Genetics, Inc., USA Evangelos Bakopanos, Health Canada, Canada Katrin Buss, BfArM-Federal Institute for Drugs and Medical Devices, Germany David Cirelli, Pfizer, Inc., USA Jill Crouse-Zeineddini, Amgen Inc., USA Chana Fuchs, CDER, FDA, USA Denise Gavin, CBER, FDA, USA Stephen Hartman, AbbVie Inc., USA Xu-Rong Jiang, AstraZeneca, USA

Helena Madden, Biogen, USA Bruce Meiklejohn, Meiklejohn Consulting, USA Thomas Anders Millward, Novartis Pharma AG, Switzerland Bhavin Parekh, Eli Lilly and Company, USA Michael Sadick, Catalent Pharma Solutions, USA Sally Seaver, USA Max Tejada, MedImmune, A member of the AstraZeneca Group, USA Marcel Zocher, Bristol-Myers Squibb Company, USA

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The Scientific Organizing Committee gratefully acknowledges the following program partners for their generous support of Bioassays 2018:

STRATEGIC DIAMOND PROGRAM PARTNER

F. Hoffmann-La Roche Ltd.

Genentech, a Member of the Roche Group

STRATEGIC PLATINUM PROGRAM PARTNERS

Amgen Inc.

Biogen

MedImmune, A member of the AstraZeneca Group

STRATEGIC GOLD PROGRAM PARTNERS

Eli Lilly and Company

Pfizer, Inc.

STRATEGIC SILVER PROGRAM PARTNER

AbbVie, Inc.

BRONZE PROGRAM PARTNER

Sanofi

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EXHIBITOR PARTNERS

acCELLerate GmbH

Envigo Analytics Ltd.

Euro Diagnostica AB

Eurofins Lancaster Laboratories

Eurofins Pharma Discovery Services

Labcyte, Inc.

Pall FortéBio LLC

Promega Corporation

Stegmann Systems GmbH

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The Scientific Organizing Committee gratefully acknowledges the following media for their promotional consideration of Bioassays 2018:

MEDIA PROGRAM PARTNERS

American Laboratory American Pharmaceutical Review

The Analytical Scientist BioPharm International

Genetic Engineering & Biotechnology News International Pharmaceutical Quality

The Pathologist Pharmaceutical Outsourcing

Technology Networks

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CASSS Mobile App Does the printed program look a little bit thinner this year? That’s because we’re going mobile. This year, we are pleased to once again offer the CASSS Mobile App for Bioassays 2018! Top Reasons You Need to Have the App:

o Connect and network with fellow attendees, speakers, and exhibitors o View the schedule and create a personalized agenda o Download speaker abstracts and handouts o Take notes during the presentations and export later o Receive all the latest information on schedule changes or updates o View poster abstracts and connect with poster presenters o Have all your questions answered during sessions through the message board

Log on and be a part of the Bioassays Community! STEP 1 OPTION 1: On your mobile phone, go to the App Store (Apple App Store, Google Play Store) and search "CASSS 365 OPTION 2: Use a QR code reader to scan the QR code on this page. OPTION 3: To use the HTML version of the app, go to the internet browser on your mobile phone, tablet, or computer and go to the link www.tripbuildermedia.com/apps/casss365 STEP 2: Follow store instructions to download the CASSS 365 mobile app. STEP 3: Open the app. It will ask for your username and password. THIS IS THE SAME INFORMATION YOU USE TO REGISTER FOR A CASSS MEETING. STEP 4: Go to Events and select "Bioassays" from the list. Enter your username and password again. This is the same username and password used in step three.

You now have access to the entire schedule, session abstracts, speaker handouts and bios – as well as the ability to connect with your fellow attendees.

Need Help? Still not sure how to sign in and get the most out of the mobile app? You can also contact CASSS Meeting Coordinator Julie Fowle (jfowle@casss.org) or stop by the registration desk located in the foyer.  

 

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Bioassays 2018: Scientific Approaches & Regulatory Strategies Scientific Program Summary

Monday, April 16, 2018 07:30 – 17:30 Registration in the Pinnacle Grand Foyer 07:30 – 08:30 Continental Breakfast in the Discovery Ballroom 08:30 – 08:45 CASSS Welcome and Introductory Comments in the Pinnacle Grand Ballroom Stephanie Flores, CASSS

Bioassays 2018 Welcome and Introductory Comments in the Pinnacle Grand Ballroom

Helena Madden, Biogen

Fundamentals of Bioassay Workshop Session One in the Pinnacle Grand Ballroom

Session Chairs Jill Crouse-Zeineddini, Amgen Inc., Bhavin Parekh, Eli Lilly and Company and Max Tejada, MedImmune, A member of the AstraZeneca Group

08:45 – 08:50 Introduction 08:50 – 09:15 3-in-1: Increasing the Efficiency of Potency Assay Development via DoE Johannes Solzin, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an

der Riss, Germany 09:15 – 09:40 System and Sample Suitability Assessment for Potency Methods

Ruojia Li, Bristol-Myers Squibb Company, Pennington, NJ USA 09:40 – 09:45 Stretch Break 09:45 – 10:10 Minimization of Bioassay Test Result Shift When Implementing New

Reference Standard Batches Matthew Borer, Eli Lilly and Company, Indianapolis, IN USA

10:10 – 10:35 Successful Analyst Assay Training and Assay Transfers - Basics and

Recommendations to Achieve These Goals Alexander Knorre, Eurofins BioPharma Product Testing Munich GmbH, Planegg / Munich, Germany

10:35 – 11:20 Networking Break – Visit the Exhibits and Posters in the Discovery Ballroom 10:35 – 11:20 First Time Attendee Network Event in the Connection Ballroom

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Monday, April 16 continued… 11:20 – 12:20 PANEL DISCUSSION – Questions and Answers

Matthew Borer, Eli Lilly and Company, USA Alexander Knorre, Eurofins BioPharma Product Testing Munich GmbH, Germany Ruojia Li, Bristol-Myers Squibb Company, USA

Sandra McSheffrey, Health Canada, Canada Rachel Novak, CDER, FDA, USA Johannes Solzin, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany

Zenobia Taraporewala, CBER, FDA, USA 12:20 – 13:25

Lunch and Learn: Exhibitor Partner Scientific Showcase in the Pinnacle Grand Ballroom Session Chairs: Helena Madden, Biogen and Sally Seaver

ATTENDEES: Grab your lunch in the Discovery Ballroom and return

12:50 – 12:55 Introduction

12:55 – 13:05 Assay Simulation as a Supporting Technique for Equivalence Margin

Development Ralf Stegmann, Stegmann Systems GmbH, Rodgau, Germany

13:05 – 13:15 Increased Data Quality in Smaller Volumes: Bioassays using the Labcyte® Echo® Liquid Handler Jacyln Greimann, Labcyte, Inc., San Jose CA, USA

13:15 – 13:25 Controlling Cell-based Bioassay Performance Through Controlled

Preparation of Thaw-and-Use Cells Mei Cong, Promega Corporation, Madison, WI USA

13:25 – 14:00 Networking Break – Visit the Exhibits and Posters in the Discovery Ballroom

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Monday, April 16 continued…

Blazing a New Path: Are New Generation Biotherapeutics Giving You a Complex (Bioassay)? Workshop Session Two in the Pinnacle Grand Ballroom

Session Chairs: Thomas Arroll, Seattle Genetics, Inc., Stephen Hartman, AbbVie, Inc. and Michael Sadick, Catalent Pharma Solutions

14:00 – 14:05 Introduction 14:05 – 14:30 Oncolytic Viruses: A New Challenge for Bioassay

Ruth Sims, Amgen Inc., Cambridge, MA USA 14:30 – 14:55 Potency Assessment in Kymriah™ Cell Therapy Product Erik Rutjens, Novartis Pharmaceuticals Corporation, Morris Plains, NJ USA 14:55 – 15:00 Stretch Break 15:00 - 15:25 A Dual Target Reporter Cell-based Assay for a Bispecific Antibody

Shihua Lin, MedImmune, A member of the AstraZeneca Group, Gaithersburg, MD USA

15:25 - 15:50 Development of a Lentiviral Vector Potency Assay for CAR-T

Debaditya Bhattacharya, bluebird bio, Inc., Cambridge, MA USA 15:50 - 16:15 Networking Break – Visit the Exhibits and Posters in the Discovery Ballroom 16:15 - 17:15 PANEL DISCUSSION – Questions and Answers

Debaditya Bhattacharya, bluebird bio, Inc., USA Bazarragchaa Damdinsuren, CDER, FDA, USA Denise Gavin, CBER, FDA, USA Shihua Lin, MedImmune, A member of the AstraZeneca Group, USA Adelheid Rohde, F. Hoffmann-La Roche Ltd., Switzerland Erik Rutjens, Novartis Pharmaceuticals Corporation, USA Ruth Sims, Amgen Inc., USA

17:15 – 17:30 Mini-break

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Monday, April 16 continued…

Exhibitor Partner Scientific Showcase in the Pinnacle Grand Ballroom Session Chairs: Helena Madden, Biogen and Sally Seaver

17:30 – 17:35 Introduction 17:35 – 17:45 Accelerating Biologics Development from Bench to Clinic with Ready-to-use

Robust and Simple Bioassays Jane Lamerdin, Eurofins Pharma Discovery Services, Fremont, CA USA 17:45 – 17:55 Envigo – More Than Just a Preclinical CRO William Stimpson, Envigo Analytics Ltd., Huntingdon, United Kingdom 17:55 – 18:05 iLite® Cell-based Reporter Gene Assays - Technology and Key Features Frida Pauly, Euro Diagnostica AB, Malmö, Sweden 18:05 – 18:15 Turning Cells into Reagents – Assay Ready Cells in GMP Bioassays Oliver Wehmeier, acCELLerate GmbH, Hamburg, Germany 18:15 – 19:30 Exhibitor and Poster Reception in the Discovery Ballroom 19:30 Adjourn Day One

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Tuesday, April 17, 2018 07:30 – 08:45 Continental Breakfast in the Discovery Ballroom 08:00 – 17:00 Registration in the Pinnacle Grand Foyer

Structure Function Assessment for Monoclonal Antibodies and Beyond Workshop Session Three in the Pinnacle Grand Ballroom

Session Chairs: David Cirelli, Pfizer, Inc., Xu-Rong Jiang, AstraZeneca and Marcel Zocher, Bristol-Myers Squibb Company

08:45 – 08:50 Introduction 08:50 – 09:15 Understanding Mechanisms of Action and Structure Function Relationships:

A Regulator's Perspective Marjorie Shapiro, CDER, FDA, Silver Spring, MD USA

09:15 – 09:40 Use of Bioassays for Structure Function Studies to Understand Criticality of

Product Quality Attributes Carl Co, Biogen, Cambridge, MA USA 09:40 – 09:45 Stretch Break 09:45 – 10:10 Functional Assessment of Post-translational Modifications of Monoclonal

Antibodies: A Quantitative Approach to Structure Function Assessment Scott Umlauf, Bristol-Myers Squibb Company, Hopewell, NJ USA

10:10 – 10:35 Using an ADCC Reporter Bioassay in the Characterization of an Anti-Influenza A Neutralizing Antibody Arturo Orjalo, Genentech, a Member of the Roche Group, South San Francisco, CA USA

10:35 - 11:00 Networking Break – Visit the Exhibits and Posters in the Discovery Ballroom 11:00 – 12:00 PANEL DISCUSSION – Questions and Answers

Carl Co, Biogen, USA Chantal Depatie, Health Canada, Canada Ling Gu, Pfizer, Inc., USA Arturo Orjalo, Genentech, a Member of the Roche Group, USA Marjorie Shapiro, CDER, FDA, USA Scott Umlauf, Bristol-Myers Squibb Company, USA

12:00 – 13:15 Hosted Lunch in the Connection Ballroom 13:15 – 14:15 Poster Session in the Discovery Ballroom Foyer

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Tuesday, April 17 continued…

Regulators: What’s On Your Mind? Workshop Session Four in the Pinnacle Grand Ballroom

Session Chairs: Evangelos Bakopanos, Health Canada, Chana Fuchs, CDER, FDA and Bruce Meiklejohn, Meiklejohn Consulting

14:15 – 14:20 Introduction 14:20 – 14:45 Coagulation Factor Assay Discrepancies: Historical and Current

Perspectives Elaine Gray, NIBSC-National Institute for Biological Standards and Control, Potters Bar, United Kingdom

14:45 – 15:10 Coagulation Factor Products: Potency Determination and Related

Complications Mikhail Ovanesov, CBER, FDA, Silver Spring, MD USA

15:10 – 15:15 Stretch Break 15:15 – 15:40 A MHRA Perspective on Bioassays

Leonard Both, MHRA-Medicines and Healthcare Products Regulatory Agency, London, United Kingdom

15:40 – 16:05 Bioassays for Cell and Gene Therapy Products: A Canadian Regulatory Perspective and Experience

Christopher Storbeck, Health Canada, Ottawa, ON Canada

16:05 – 16:30 Networking Break in the Pinnacle Grand Foyer 16:30 - 17:30 PANEL DISCUSSION – Questions and Answers

Evelin Balbino, ANVISA-Brazilian National Surveillance Agency, Brazil Leonard Both, MHRA-Medicines and Healthcare Products Regulatory Agency, United Kingdom Elaine Gray, NIBSC-National Institute for Biological Standards and Control, United Kingdom Susan Kirshner, CDER, FDA, USA Mikhail Ovanesov, CBER, FDA, USA Christopher Storbeck, Health Canada, Canada

17:30 – 18:00 Bioassays Workshop Recap Max Tejada, MedImmune, A member of the AstraZeneca Group Closing Remarks and Invitation to Bioassays 2019 Bruce Meiklejohn, Meiklejohn Consulting 18:00 Adjournment

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Fundamentals of Bioassay Workshop Session One

Session Chairs: Jill Crouse-Zeineddine, Amgen Inc., Bhavin Parekh, Eli Lilly and Company and Max Tejada, MedImmune, A member of the AstraZeneca Group Bioassays play an essential role in development of biologics, guiding process development, formulation development, release testing, establishment of storage conditions, and product shelf-life. As such, bioassays are a critical element of the analytical control strategy. Bioassays must be relevant to the mode of action of the biologic, as well as be sufficiently precise and robust to perform appropriately in a QC lab for lot release and stability testing. Successful long-term performance of the bioassay method requires a holistic approach to making sure that all the fundamental elements that contribute to the bioassay system are sound and under control. This session will focus on the following fundamental themes:

Use of DoE to optimize bioassays; Setting phase appropriate acceptance criteria for system and sample suitability; Strategy for long term monitoring of the potency of reference standards; Basic considerations of training and transfer.

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Presenter’s Abstracts 3-in-1: Increasing the Efficiency of Potency Assay Development via DoE Johannes Solzin Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Many labs are still using classical OFAT (One Factor at a Time) approaches to optimize bioassays although DoE approaches allow detailed understanding on the parameters critical for assay performance. Typically a 3-tiered DoE approach is chosen where an initial screening DoE, performed to identify and exclude irrelevant factors, is followed by an optimization DoE to find the optimal assay settings and finally a DoE to assess assay robustness is performed. Besides the needed statistical know-how, the labor-intensity of those typical DoEs seem to be the main reason why DoE is rarely being used for assay development. This talk will discuss case studies where screening, optimization and robustness DoEs were directly combined into a single response surface model DoE (i.e. 3-in-1) allowing more statistical power and thus more information about the assay in comparison to a DoE used in the typical tiered approach. The 3-in-1 DoE approach can be performed within the same timeframe as an OFAT approach, and is faster than a typical 3-tiered DoE approach. In order to determine the assay optimum via DoE it is necessary to assess the assay quality with carefully chosen parameters. The talk will consider parameters like signal-to-noise ratio, dynamic range, mean weighted standard deviation, Z-factor, R2 etc. and discuss their advantages and limitations for different assay types. NOTES:

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System and Sample Suitability Assessment for Potency Methods Ruojia Li MedImmune, A member of the AstraZeneca Group, Gaithersburg, MD USA System and sample suitability assessment is an integral part of potency methods. Well established suitability criteria will ensure quality of potency assay results; while inappropriate suitability assessment may cause unnecessary assay and sample failures or unreliable potency results. This talk will provide an overview of things to be considered when establishing suitability criteria for potency methods. Case studies will be used to illustrate the importance of proper suitability assessment. NOTES:

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Minimization of Bioassay Test Result Shift When Implementing New Reference Standard Batches Matthew Borer Eli Lilly and Company, Indianapolis, IN USA Users of reference standards often envision them to be perfectly assigned with no negative impact the accuracy or variability of testing methods. This is an understandable expectation given that reference standards are established to be the “gold standard” or benchmark against which the “correct” answer is obtained. Unfortunately, this is an unreasonable expectation. The assigned properties of a reference standard are subject to analytical measurement error just like every other test sample. This problem is most pronounced when the test method used for assignment is highly variable, such as biological potency assays. This presentation will explore the sources of error that result in shifts in relative potency between batches of reference standards used in biological potency assays. Various assignment approaches have been simulated to illustrate the possible magnitude of shift between batches. Based on the analysis, recommendations will be made on topics such as batch selection, assay replication, and assignment strategy to minimize the inevitable shifts between reference standard batches. NOTES:

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Successful Analyst Assay Training and Assay Transfers - Basics and Recommendations to Achieve These Goals Alexander Knorre Eurofins BioPharma Product Testing Munich GmbH, Planegg / Munich, Germany Both analyst assay training and assay transfer are prerequisites for testing stability and release samples in a Quality Control GMP laboratory. This presentation will address both activities especially with regard to meeting tight timelines for assay transfer completion everyone is facing nowadays. In detail our experiences the way our bioassay analysts are trained for bioassay method performance will be shared in order to get them in a robust Quality Control working mode as soon as possible. In addition, tips from a CRO’s point of view for successful assay transfers will be presented to allow a smooth assay transfer from one lab to another especially if this activity is for many assays the first real robustness check . NOTES:

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Fundamentals of Bioassay Workshop Session One

Panel Members: Matthew Borer, Eli Lilly and Company, USA Alexander Knorre, Eurofins BioPharma Product Testing Munich GmbH, Germany Ruojia Li, Bristol-Myers Squibb Company, USA Sandra McSheffrey, Health Canada, Canada Rachel Novak, CDER, FDA, USA Johannes Solzin, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany Zenobia Taraporewala, CBER, FDA, USA The following questions will guide the panel discussion:

Life cycle approaches to assay management. Does your company execute robustness in the assay development lab or as part of validation? Do you routinely use DOE during assay development? What type of DOEs do you use for assay

optimization and robustness? Has your company implemented any Analytical Quality by Design principles in potency assays? Does your company implement default criteria to initiate assay execution? How often do you re-visit your assay and sample acceptance criteria limits? Does your company implement outlier analysis? If so, what approach is used for outlier analysis

and when is it implemented? Does your company have a dedicated group that manages Reference Standards? Does your company assign a potency of 100% to your Reference Standard if it meets the

acceptance criterion defined in the Reference Standard qualification protocol? What is your approach to setting phase appropriate specifications?

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Blazing a New Path: Are New Generation Biotherapeutics Giving You a Complex (Bioassay)?

Workshop Session Two Session Chairs: Thomas Arroll, Seattlel Genetics, Inc., Stephen Hartman, AbbVie, Inc. and Michael Sadick, Catalent Pharma Solutions Biotherapeutics are becoming increasingly more complex and diverse, both structurally and functionally. Subsequently, the bioassays used to characterize their mechanisms-of-action are also becoming progressively more challenging to develop. Furthermore, the emergence of cell and gene therapies has required the creation of entirely new approaches and strategies to enable the assessment of product safety and functional potency, as well as the need for more rapid assay output. Presentations in this session will provide examples of the challenges encountered when developing bioassays for complex biologic therapies and will stimulate discussion of the approaches used to assess the potency of these products. Topics presented and discussed will range from CAR-T therapeutics to bi-specific antibodies. NOTES:

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Presenter’s Abstracts Oncolytic Viruses: A New Challenge for Bioassay Ruth Sims Amgen Inc., Cambridge, MA USA Oncolytic viruses represent a new class of therapeutic agents that promote anti-tumor responses through a dual mechanism of action that is dependent on selective tumor cell killing and the induction of systemic anti-tumor immunity. Amgen produces IMLYGIC®, a modified human herpes simplex virus type-1 (HSV-1). IMLYGIC® was generated by deleting ICP47 from the wild type HSV-1. The two ICP34.5 genes were functionally deleted, and hGM-CSF was inserted into their former sites. The deletion of ICP47 makes the virus more immunogenic and the functional deletion of ICP34.5 impairs replication of IMLYGIC® in non-tumor tissue. IMLYGIC® is injected into melanoma tumors and causes lysis of tumor cells followed by release of tumor-derived antigens, which together with virally derived GM-CSF may promote an antitumor immune response. However, the exact mechanism of action is unknown. Potency for IMLYGIC® therefore relies upon three key functions that include [1] the ability of the virus to infect and lyse cells; [2] the expression of hGM-CSF; and [3] the activity of expressed hGM-CSF. These three mechanisms of action are tested as part of lot release and stability evaluation of IMLYGIC® drug product The ability of the virus to infect and lyse cells is measured by the plaque assay. The basis of plaque assay is that virus infects a cell and the surrounding cells will also become infected by spread of progeny virus. This focus of infection causes apoptosis which results in a hole in the monolayer with rounded cells at the periphery indicative of a cytopathic effect (CPE). This focus of infection is called a plaque and is a measure of the number of infectious particles within a viral sample. The expression of hGM-CSF is measured by infecting skin melanoma cells (SK-MEL-28), with IMLYGIC® and measuring the amount of hGM-CSF produced via a commercially sourced ELISA assay. The activity of hGM-CSF is measured by performing a relative potency assay using TF-1 cells, which are dependent on hGM-CSF for growth. A host cell line is infected with IMLYGIC® to generate hGM-CSF. The viral component is inactivated, and the hGM-CSF is added to the TF-1 cells at a range of dilutions. The activity of a sample is quantified by comparison of the sample hGM-CSF activity to the hGM-CSF activity from a concurrent identical preparation of the IMLYGIC® reference standard. NOTES:

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Potency Assessment of Kymriah™ Cell Therapy Product Erik Rutjens Novartis Pharmaceuticals Corporation, Morris Plains, NJ USA CTL019 cells are engineered T cells containing a chimeric antigen receptor (CAR) that recognizes cluster of differentiation 19 (CD19) which is a protein found exclusively on B cells. The extracellular domain of the CAR is linked to an intracellular signaling domain comprised of the T cell receptor CD3ζ signaling chain and a co-stimulatory domain derived from 4-1BB for optimal T cell activation. T-cells equipped with this CAR are capable of specifically recognizing CD19 expressing (tumor) cells, resulting in a T-cell response, involving cytokine secretion, proliferation and cytolysis of the CD19 expressing cells. As part of clinical development, several approaches to assess potency of the product were evaluated, leading to a variety of assays with different degrees of variability, as the active ingredient in our product are cells, which have intrinsic biological variability. Increasing experience and learnings about the product and assay have led to a robust release assay for commercial use as well as characterization data from other bioassays to support understanding of the product’s mode of action. The commercial release assay was fully validated and contains numerous system suitability parameters to allow for continuous evaluation and control throughout the scale up of the numbers of products being tested, as well as increase in trained analysts, which can influence the performance of complex bioassays. Due to the vast variability of product, originating from patient-to patient differences in T-cell quality, broad ranges of results have been obtained in the clinical development stage, which made setting of specifications based on historical experience a challenging exercise, which will need ongoing re-evaluation while patient experience increases over time. Despite the vast heterogeneity in regard to key product attributes such as T cell composition, activity and functional response, the product resulted in high rates of tumor remissions in both Pediatric ALL as well as in the adult DLBCL population. NOTES:

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A Dual Target Reporter Cell-based Assay for a Bispecific Antibody Shihua Lin MedImmune, A member of the AstraZeneca Group, Gaithersburg, MD USA Bispecific antibodies are a fast-growing class of therapeutic molecules offering promising clinical benefits for immunotherapy. Due to the complexity of the molecular structure and potential mechanism(s) of action (MOA), which can involve more than one signaling pathway, it is critical to develop appropriate bioassays to assess the biological properties of these molecules. Here we present a dual target reporter gene bioassay for a bispecific antibody. This cell-based assay is capable of measuring the synergistic effect resulting from binding to both target antigens in a single assay and with increased sensitivity, which would not be possible using two single-target bioassays. This dual target bioassay demonstrates performance characteristics suitable for characterization as well as lot release and stability testing of the antibody. Compared to single-target assays, this dual target bioassay approach better reflects the potential MOA of the bispecific antibody and may be applicable to other bispecific antibodies as well as antibody combination therapies. NOTES:

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Development of a Lentiviral Vector Potency Assay for CAR-T Debaditya Bhattacharya Bluebird Bio, Cambridge, MA USA Malignant plasma cells commonly express B-cell maturation antigen (BCMA), a surface marker that has emerged as a selective antigen for immune system targeting for treatment of multiple myeloma (MM). Delivery of autologous human T lymphocytes (T cells) transduced with a lentiviral vector (LVV) encoding an anti-BCMA chimeric antigen receptor (CAR) is currently being studied as a potential treatment for MM. Efficient LVV transduction, stable CAR expression, and in vivo immune response upon CAR T cell activation may all affect the clinical effectiveness of CAR T cells. Therefore, a potency assay that can consistently measure the biological activity of the LVV is needed for lot release of LVV used for CAR T cell manufacturing. Here we describe the strategy for development of such an in vitro cell-based relative potency assay. NOTES:

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Blazing a New Path: Are New Generation Biotherapeutics Giving You a Complex (Bioassay)?

Workshop Session Two Panel Members: Debaditya Bhattacharya, bluebird bio, Inc., USA Bazarragchaa Damdinsuren, CDER, FDA, USA Denise Gavin, CBER, FDA, USA Shihua Lin, MedImmune, A member of the AstraZeneca Group, USA Adelheid Rohde, F. Hoffmann-La Roche Ltd., Switzerland Erik Rutjens, Novartis Pharmaceuticals Corporation, USA Ruth Sims, Amgen Inc., USA The following questions will guide the panel discussion:

How do you establish a reference standard for a CAR-T therapy product? Can you? If not, how does one quantitate potency of CAR-T therapies without a reference standard?

How do you develop a functional potency assay that can accommodate the patient-to-patient variability of CAR-T therapies?

What are the considerations for establishing potency assay specifications for cell-based therapies? Bioassay strategies for therapeutics with multiple MOAs? How to develop a bioassay for a

bispecific with a synergistic/combinatorial MOA? (i.e. 1+1=3). Is it acceptable to have two bioassays (one per target) if a single bioassay can’t be developed?

For bi-specific mAb therapeutics, is a binding assay sufficient (either multiple or combined ELISA’s or SPR/BLI analyses), or does a cell based bioassay need to be pursued?

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Structure Function Assessment for Monoclonal Antibodies and BeyondWorkshop Session Three

Session Chairs: David Cirelli, Pfizer, Inc., Xu-Rong Jiang, AstraZeneca and Marcel Zocher, Bristol-Myers Squibb Company Bioassays are broadly used for lot release and stability testing of recombinant and biological drug products. However, bioassays also have an important role in the study of the relationship between the structural attributes of a drug and their potential impact on biological activities. For novel and complex biologic therapeutics, some with multiple mechanisms of action, numerous bioassays may be required to obtain a comprehensive understanding of all potential biological activities. This work occurs in parallel with QC testing and through collaboration with other analytical, bioprocess and pharmaceutical scientists. Knowledge gained through structure-function studies informs process development, facilitates determination of product critical quality attributes, and underwrites an appropriate control strategy that includes specifications. The presentations and discussion panel will explore how, when and why structure-function assessments are performed with consideration given to the questions during the panel discussion. NOTES:

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Presenter’s Abstracts Understanding Mechanisms of Action and Structure-Function Relationships: A Regulator’s Perspective Marjorie Shapiro CDER, FDA, Silver Spring, MD USA Advances in analytical methods played an important role in considering protein therapeutics to be well characterized products, in considering a demonstration of comparability of a product when manufacturing changes are made and for assessing analytical similarity. Although the mechanisms of action for some therapeutic proteins may not be fully understood, and some therapeutic proteins may have multiple mechanisms of action, advances in the characterization of protein therapeutics has elucidated structure-function relationships for some proteins so that there is a better understanding of specific quality attributes that should be controlled to ensure patients consistently are treated with a product that is safe and effective. This presentation will provide case studies highlighting the evolving knowledge of structure-function relationships and how it informs our thinking on control strategies for our products. NOTES:

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Use of Bioassays for Structure Function Studies to Understand Criticality of Product Quality Attributes Carl Co Biogen, Cambridge, MA USA Afucosylation, glycation and HMW aggregates are examples of product quality attributes that are debated for their criticality for protein therapeutics. This presentation will describe case studies which demonstrate the necessity in carefully dissecting how the location of post translational modifications differentially impact bioactivity. Also, these case studies will highlight that it is essential to not generalize the criticality of specific glycans, such as afucosylation levels, on the biological activity of antibodies since there are multiple factors that may influence relative bioactivity. NOTES:

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Functional Assessment of Post-translational Modifications of Monoclonal Antibodies: A Quantitative Approach to Structure Function Assessment Scott Umlauf Bristol-Myers Squibb Company, Hopewell, NJ USA One aspect of structure function characterization of biologics is the functional assessment of post-translation glycosylation. Therapeutic human antibodies with cell-surface targets have the potential to mediate antibody dependent cellular cytotoxicity (ADCC). Assessment of glycan type and amount is critical at multiple stages of development as glyco-structures can impact ADCC activity. We explored a quantitative approach using ADCC activity data, supported by surface plasmon resonance (SPR) analysis to explore the role of glycosylation as a Critical Quality Attribute (CQA). NOTES:

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Using an ADCC Reporter Bioassay in the Characterization of an Anti-Influenza A Neutralizing Antibody Arturo Orjalo Genentech, a Member of the Roche Group, South San Francisco, CA USA Influenza viruses are responsible for substantial morbidity and mortality and cause annual epidemics during the autumn and winter. For those at high-risk of developing influenza complications, a highly-specific anti-influenza antibody therapy was developed as a potential universal treatment for severely ill hospitalized patients. In the following study, we investigated the ADCC activity induced by the anti-influenza antibody using a robust ADCC reporter bioassay with influenza virus-infected target cells. In the assay, the engineered NK-92 cells function as the effector cells, stably expressing an inducible NFAT-luciferase reporter and a chimera of FCGR3A (high affinity V158 variant) and FCER1G. The assay uses a model cell line that closely mimics the primary effector cells for ADCC in vivo—NK-92 cells are “natural killer-like”. We observed that the ADCC reporter bioassay using virus infected target cells is robust, accurate, precise and sensitive to changes in Fc-glycosylation. It demonstrated that ADCC was an indispensable mechanism of action for the broadly neutralizing anti-influenza antibody and offered a reliable tool to monitor ADCC activity during CMC process development. NOTES:

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Structure Function Assessment for Monoclonal Antibodies and BeyondWorkshop Session Three

Panel Members: Carl Co, Biogen, USA Chantal Depatie, Health Canada, Canada Ling Gu, Pfizer, Inc., USA Arturo Orjalo, Genentech, a Member of the Roche Group, USA Marjorie Shapiro, CDER, FDA, USA Scott Umlauf, Bristol-Myers Squibb Company, USA The following questions will guide the panel discussion:

In structure-function assessments, what bioassay methods are used routinely across industry? When are structure-function assessments performed during the product lifecycle? If a phase- or stage-based approach is used, what bioassay methods are used in early development

versus late-stage development? What platform technologies are used for structure-function studies (e.g. SPR, effector-function

assays)? How does industry assess conserved structural features within a modality (e.g. IgG1 Fc-domain)? What are regulators expectations for structure-function assessments? Are the expectations

different at FIH, Pivotal and Commercial phases? What new technologies and platforms are being developed for emerging modalities (e.g. multi-

specificity mAbs)? How are the learning from structure-function studies applied to the identification and scoring of of

CQAs, establishing Specifications and developing Control Strategies? What tools are used to assess potential impact to PK?

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Regulators: What’s On Your Mind? Session Chairs: Evangelos Bakopanos, Health Canada, Chana Fuchs, CDER, FDA and Bruce Meiklejohn, Meiklejohn Consulting Biological molecules represent a diverse group of molecules of which include: proteins, modified proteins, cells, DNA, RNA, vaccines, mixtures of molecules. The development and the manufacture of these products is an inherently complex process that may draw on novel or platform technologies as well as conventional or unique bioassay control strategies. While there are a number of regulatory guidelines for the development of biologics, their interpretation across the industry and between countries varies greatly. As a result, health regulators are faced with the daunting task of reviewing significant numbers of submissions from innovators, biosimilar, and bio-better companies each with diverse filing strategy. Regulators see and know a tremendous amount – so what’s on their mind? This session will include presentations from regulators from various countries describing bioassay case studies that highlight deficiencies in regulatory filings and/or in company practices and the subsequent outcomes. These case studies will include various aspects of CMC including, but not limited to, the use of bioassays during manufacturing, product characterization, product control and stability, and to show mechanism of action, in order to highlight the regulators’ perspectives on best bioassay practices across the industry. Suggestions about what to do better and what not to do will be discussed. Insights into what regulators are looking for will be gained through the session talks and during an interactive panel discussion workshop. NOTES:

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Presenter’s Abstracts Coagulation Factor Assay Discrepancies: Historical and Current Perspectives Elaine Gray NIBSC-National Institute for Biological Standards and Control, Potters Bar, United Kingdom Coagulation factors are complex biologicals and activity measurements are dependent on bioassay relative to an appropriate reference standard. International standards (IS) for factor VIII (FVIII) and factor IX (FIX) have been available since the 1970s. Based on the principle of biological standardisation, assaying like against like, these IS have served well for improving intra- and inter-laboratory agreement of potency/activity of FVIII and FIX replacement therapeutics manufactured by plasma fractionation. Two different types of methods, the one-stage clotting (OSC) and chromogenic (CH) methods are used for assays of these products. The suitability of the use of plasma derived IS for these therapeutics using these assay methods is endorsed through statistical validation. Slight assay discrepancies were observed with the arrival of some immunopurified and recombinant products in the 2000s. However, assay discrepancies were substantial with the newer generation of recombinant modified products such as the B-domain deleted FVIII. As the regulatory requirements for activity assays for these products differ amongst countries, up to 40% differences in the labelled potency could be observed for the same product marketed in different countries. Potency discrepancies are more marked for the latest modified recombinant and extended half-life products with significant potency disagreement, not only between OSC and CH methods, but also within a single method type. Assay discrepancies for these products also have an impact on clinical monitoring and therefore the efficacy of these products for haemophilic patients. Globally, while regulators and manufacturers are working together to harmonise approaches to potency labelling, greater efforts are still required to minimise potency discrepancies of these products. NOTES:

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Coagulation Factor Products: Potency Determination and Related Complications Mikhail Ovanesov CBER, FDA, Silver Spring, MD USA Accurate and meaningful determination of potency is essential for the safe and effective use of therapeutic products. Although most blood protein products are well characterized, and international reference standards for their biological activity are often available, discrepancies in potency assay results for both licensed and investigational coagulation factor products have been reported. The discrepancies can be attributed to the structure of the protein product; and differences in assay methodology and reagents. The newer coagulation factor products, which are structurally modified, have added another layer of complexity to this issue. In this presentation, I will discuss assay discrepancies observed in potency assignment and post-infusion monitoring of coagulation factor products and propose strategies to address the situation. Disclosure: My comments are an informal communication and represent my own best judgment. These comments do not bind or obligate FDA. NOTES:

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A MHRA Perspective on Bioassays Leonard Both MHRA-Medicines and Healthcare Products Regulatory Agency, London, United Kingdom This talk will cover regulatory considerations for bioassays from the perspective of the UK’s Medicines & Healthcare products Regulatory Agency (MHRA). The past several years we have seen much progress on bioassays in marketing authorization applications and scientific advice procedures. Some recent issues observed across these regulatory submissions are reviewed and presented in the talk, in particular issues concerning bioassays for biosimilars such as: which functional activities need to be compared, which bioassays should be applied, and what the requirements should be for this part of the biosimilar comparability exercise. In several general and product-specific European guidelines for biosimilars this has been addressed. As a general notion the bioassays should be scientifically sound and provide results that are reliable. In the context of comparability testing this would also mean that the bioassays should be sensitive, specific and sufficiently discriminatory. The full spectrum of functional activities should be compared as each of these may be key to different modes of action and several modes of actions may contribute to the clinical outcome. Moreover, the talk will address the bioassays described in the new Ph Eur monographs for etanercept and infliximab. The monographs describe appropriate common expectations for bioassays for these complex molecules. The bioassays described in these monographs include methods that are widely available, and their description is sufficiently detailed; however, some flexibility was built in to allow innovation. Finally, some other innovative technologies and approaches to bioassays such as pseudotype neutralization assays (PNA) are presented from a regulator’s perspective. NOTES:

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Bioassays for Cell and Gene Therapy Products: A Canadian Regulatory Perspective and Experience Christopher Storbeck Health Canada, Ottawa, ON Canada Cell and Gene therapy products are developing at a rapid rate holding promise for a variety of indications including cancer, genetic diseases, diseases of the eye, hematological disorders and more. These products, which range from autologous cell products, to recombinant viral vectors and oncolytic viruses, differ significantly from the typical biologic therapeutic recombinant protein in terms of pharmacokinetics, pharmacodynamics, mechanism of action and are more difficult to characterize analytically. As such, development of a reliable bioassay becomes essential to capture the mechanism of action of the therapeutic and to ensure a minimum specification for potency, and by extension, an assurance of quality with respect to this critical product attribute, for each batch manufactured. The focus of my presentation will be on the regulatory lenses through which Health Canada views and assesses Bioassays for Cell and Gene Therapy products and will draw examples from clinical trial applications, which form the bulk of our experience to date. NOTES:

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Regulators: What’s On Your Mind? Panel Members: Evelin Balbino, ANVISA-Brazilian National Surveillance Agency, Brazil Leonard Both, MHRA-Medicines and Healthcare Products Regulatory Agency, United Kingdom Elaine Gray, NIBSC-National Institute for Biological Standards and Control, United Kingdom Susan Kirshner, CDER, FDA, USA Mikhail Ovanesov, CBER, FDA, USA Christopher Storbeck, Health Canada, Canada The following questions will guide the panel discussion:

What are some of the common factors that may restrict the choice of bioassay?

What are some the common obstacles encountered during bioassay development?

What if the potency method doesn’t reflect the MOA of the product? What if the MOA is unknown?

How does one decide what the appropriate bioassay is for a cell therapy product?

How does one create a reference standard for bioassays (i.e. cell therapy)?

What about using bioassay surrogate(s) to assess product potency?

Can commercial products with years of correlation data with HPLC remove the bioassay from release testing and replace it with an HPLC?

How to monitor bioassay performance?

How should assay components, including critical reagents, be evaluated? What are the common pitfalls?

What are the challenges and concerns with the acceptance criteria being used to assess bioassay comparability?

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Exhibitor Partner Scientific Showcase

Monday, April 16, 2018 12:50 – 13:25

Pinnacle Grand Ballroom Assay Simulation as a Supporting Technique for Equivalence Margin Development Ralf Stegmann Stegmann Systems GmbH, Rodgau, Germany Assay Simulation is a powerful simple-to-use tool to support the development of a system of assay and sample suitability according to USP <1032>. It supports the decision for a certain testing strategy and allows the verification of existing test systems. NOTES:

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Increased Data Quality in Smaller Volumes: Bioassays using the Labcyte® Echo® Liquid Handler Jacyln Greimann Labcyte, Inc., San Jose CA, USA Labcyte’s revolutionary acoustic droplet ejection technology uses sound energy to transfer liquids in nanoliter increments in a non-contact, tipless manner. For nearly two decades Labcyte Echos have been used in compound management and high throughput screening groups to transfer small molecule compounds, resulting in higher accuracy and precision than existing tip-based liquid handlers. Labcyte further expanded its repertoire to include systems which translate that technology to transfer numerous fluid classes including, but not limited to nucleic acids, plasma, PCR master mixes, concentrated proteins and solutions containing up to 50% glycerol. More recently, Labcyte has developed methods impacting bioassay workflows allowing users to easily set up complex potency assays via direct dilution. This results in less reagent usage, lower transfer error and higher throughput. Furthermore, any-well to any-well dispensing provides the utmost flexibility when optimizing your bioassay design to eliminate location biases. With software to enable FDA 21CFR Part 11 compliance, Echo Liquid Handlers for Regulatory Environments allow for locking down and tracking all Echo Liquid Handler usage, protocol changes and file outputs using state-of-the-art security software. Here we present the Labcyte Echo as a solution to miniaturize bioassay workflows while maintaining or increasing data quality of potency assays. Specifically, we present data showing that the Echo liquid handler was used to transfer anti-CTLA-4 antibodies in the CTLA-4 Blockade Bioassay. From these data and others like them, we believe the Labcyte Echo will have great impact on the bioassay field by helping to increase data quality while decreasing assay volume. NOTES:

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Controlling Cell-based Bioassay Performance Through Controlled Preparation of Thaw-and-Use Cells Mei Cong Promega Corporation, Madison, WI USA Cells are considered as critical reagents in cell-based bioassays. Many factors during cell culture and cell banking can cause batch-to-batch, run-to-run variations, which in turn make assay transfer very challenging. Here I will describe the procedures that we have implemented to enable us to achieve successfully cell line transfer and manufacturing. I will describe how we have controlled their productions and benefits of such ‘cell reagents’ in bioassays. NOTES:

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Exhibitor Partner Scientific Showcase

Monday, April 16, 2018 17:30 – 18:15

Pinnacle Grand Ballroom Accelerating Biologics Development from Bench to Clinic with Ready-to-use Robust and Simple Bioassays Jane Lamerdin Eurofins Pharma Discovery Services, Fremont, CA USA Abstract was not available at the time of printing. NOTES:

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Envigo – More Than Just a Preclinical CRO William Stimpson Envigo Analytics Ltd., Huntingdon, United Kingdom Envigo has provided bioassay support services for over 30 years and in this showcase, we will provide a brief overview of the group and some case studies. These range from complex ex vivo potency assays for vaccines and gene therapies through to cell-based assays for antibody-based products. NOTES:

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iLite® Cell-based Reporter Gene Assays - Technology and Key Features Frida Pauly Euro Diagnostica AB, Malmö, Sweden Cell-based assays are a key tool for measuring the biological activity of a drug and are performed across the entire drug development continuum with applications such as screening, potency and immunogenicity. They bring the advantage of giving biologically relevant results, however, they are often inherently cumbersome, time-consuming, non-specific and highly variable. With the iLite® technology, we have developed cell-based reporter gene assays, in an Assay Ready format, that allow for sensitive and specific assays with quick turn-around times. One single iLite® assay can be used in many applications throughout drug development, all the way from screening, though potency to determination of neutralizing antibodies (NAbs). The Assay Ready format confers a high assay precision and accuracy, as will be shown using our iLite® IL-23 Assay Ready Cells. In short, using the iLite® assays, you can get the benefits of a cell-based assay, but with the ease of use and robustness normally associated with a ligand binding assay. NOTES:

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Turning Cells into Reagents – Assay Ready Cells in GMP Bioassays Oliver Wehmeier acCELLerate GmbH, Hamburg, Germany Mammalian cell lines of different functionality are used in bioassays to test the potency of bio-therapeutics. Traditionally, the cells are maintained in culture and prepared fresh at the day of the assay. The cultivation and preparation of cells as part of the validated assay protocol is certainly one of the most difficult to control parts of the GMP compliant process which accounts for increased assay variability. Cryopreserved cells though, when handled with care and frozen at a highly functional state, can be applied in cell-based assays instantly after thawing like a reagent. There is no need to passage, cultivate or even count the cells before use. Although it is widely accepted that the use of assay ready cells can increase the precision of a given bioassay, it is still a matter of discussion between bioassay teams and QA how these assay cell banks have to be prepared. Does the cell bank have to be produced under GMP, because the process of cell expansion is originally part of the GMP assays or do assay ready cells have to be considered as a critical biological reagent, similar to a detection antibody, its fit for propose validated for each production lot? Let’s pave the way. NOTES:

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Poster Session

Tuesday, April 17, 2018 13:15 – 14:15

Discovery Ballroom Foyer BASIC BIOASSAYS P-101 Case Study: Data and Process Applied to Establish Bioassay Control Limits for a Monoclonal Antibody Ling Gu, David Cirelli, Ned Mozier Pfizer, Inc., Andover, MA USA BIOASSAYS FOR STRUCTURE FUNCTION P-102 One Bioassay for BAbs (Bispecific Antibodies) Barbara Hebeis MedImmune, A member of the AstraZeneca Group, Cambridge, United Kingdom BIOASSAYS IN BIOSIMILAR DEVELOPMENT P-103 Comparison of Three Different Technologies for Use as a Cell-Based Potency Assay in Measuring the Biological Activity of a Drug Candidate Joseph Sergi, Junming Yie, Sandy Kashi, Jianying Su, Lucia Franco-Dilone, Kevin Gurney Merck & Co., Inc., Kenilworth, NJ, USA P-104 Development and Characterization of the Method for the Measurement of GLP1 Agonist Biopotency Bryan Teets, Brian Tash, John Smith, Christie McCracken, Evelyn Kilareski, Robert Donatelli, Weihong Wang, Jeri Ann Boose Eurofins Lancaster Labs, Lancaster, PA USA NEW TECHNOLOGIES FOR BIOASSAYS P-105 Secure and Traceable Acoustic Liquid Handling Iain Russell, Russell Burge, Harry Vlahos, Jacyln Greimann Labcyte, Inc., San Jose CA, USA P-106 Automated Removal of Phospholipids for Analysis of Membrane Proteins by Hydrogen/Deuterium Exchange Mass Spectrometry Kyle Anderson, Elyssia Gallagher, Jeffrey Hudgens National Institute of Standards and Technology (NIST), Rockville, MD USA

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P-107 Optimization of Complement Dependent Cytotoxicity Assays via Live-Cell Imaging Patrick Hussmann, Jourdain LeMaster, Christina Grigoriadou MedImmune, A member of the AstraZeneca Group, Gaitersburg, MD USA P-108 Performance Characteristics of iLite® Cell-based Reporter Gene Assays: Case Study of iLite® IL-23 Assay Ready Cells Therese Segerstein, Elsa Grenmyr, Lone Frier-Bovin, Karin Blume, Anna Pramhed Euro Diagnostica AB, Malmö, Sweden P-109 Novel, Improved Cell-Based Assays to Enable Immunotherapy Drug Development for Checkpoint Receptors Jane Lamerdin, Hanako Daino-Laizure, Mimi Nguyen, Vicki Liu, Alpana Prasad, and Jennifer Lin-Jones Eurofins Pharma Discovery Services, Fremont, CA USA P-110 Driving Robust and Reproducible ADCC and T Cell Redirection with Single-Donor Derived KILR® CD16 Effector Cells Alpana Prasad1, Lisa Blackwood2, Laura McAleer2, Hanako Daino-Laizure1, Jane Lamerdin1 1Eurofins Pharma Discovery Services, Fremont, CA USA, 2 Sartorius Stedim BioOutsource Ltd, Glasgow, United Kingdom P-111 Functional Bioassay Miniaturization is Enhanced by Using Acoustic Liquid Handling for Antibody Transfer Tracy Worzella, Jun Wang, Jey Cheng, Mei Cong, Gediminas Vidugiris, Tim Allison, John Fuller, Ruth Petersen, Cris Cowan Labcyte, Inc., San Jose CA, USA STATISTICS P-112 Near-universal Equivalence Bounds for Similarity in Bioassays David Lansky Precision Bioassay, Inc., Burlington, VT USA P-113 Strategies for Outlier Detection and Management in Bioassay David Lansky Precision Bioassay, Inc., Burlington, VT USA

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OTHER P-114 Comparison of Liquid Handlers from Different Manufactures for Suitability of Use in GMP QC Bioassay Automation Sabrina Keller, Sebastian Warnecke, Andrea Heinze, Alexander Knorre Eurofins BioPharma Product Testing Munich GmbH, Planegg, Germany P-115 Characterization and Lot Release Assays for Antibody Drug Conjugates (ADCs) Ulrike Herbrand, Sandra Bauer, Verena Sonnenberg Charles River Laboratories, Inc., Erkrath, Germany P-116 Quantitative Cell-Based Bioassays to Advance Immunotherapy Programs Targeting Immune Checkpoint Receptors Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jun Wang, Michael Beck, Jim Hartnett, Frank Fan, Mei Cong and Zhi-jie Jey Cheng, Manuela Grassi Promega Corporation, Madison, WI USA P-117 Reproducible MOA-Reflecting Reporter-Based Bioassays to Enable Drug Development of Biosimilars and Biobetters Richard Moravac, Dun Li, Jennifer Wilkinson, Frank Fan and Mei Cong Promega Corporation, Madison, WI USA P-118 Development and Qualification of a Reporter Gene Bioassay for an anti-PD-L1 Blocking Antibody Madhu Pandey, Shihua Lin and Max Tejada MedImmune, A member of the AstraZeneca Group, Gaithersburg, MD USA NOTES:

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