2018 Archived Content

Roundtable Breakout Discussions

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

TUESDAY, OCTOBER 23 4:40 PM

Immunogenicity Assessment & Clinical Relevance

Table 1: Cutpoints for Screening and Confirmatory Assays: Managing Change

Moderator: Mauricio Maia, PhD, Senior Scientist, BioAnalytical Sciences, Genentech, Inc.

Experiences with cut point determination
Complications experienced and means of overcoming challenges
Difficulties with analytical and biological variability
When and how to switch from "validation-based" cutpoints to "study-samples based cutpoints"
How much assay (re)validation is needed when cutpoints are changed

Table 2: Dealing with Pre-Existing Positive ADA Activity in Study Patients

Moderator: Theresa J. Goletz, PhD, Global Head, New Biological Entities and Drug Disposition, EMD Serono Research & Development Institute, Inc.

Potential complications with pre-existing antibodies
How to distinguish between pre-existing antibodies and potential immune responses to the drug and to determine a meaningful drug-induced response
Examples seen in the clinic and their relevance
Implications for humanized antibodies and novel humanized antibody products
Implications regarding PK/PD safety and efficacy

Table 3: Challenges in Developing Neutralizing Antibody Assays

Moderator: Terry P. Combs, PhD, Senior Scientist, BioMedicine Design, Pfizer, Inc.

Variables in cell- vs. plate-based anti-AAV Nab assays
Comparison of cell- vs. plate-based anti-AAV Nab assays
Dealing with poor assay sensitivity and matrix interference
Collinearity of results between cell- and plate-based anti-AAV Nab assays
Interpretation of results and risk assessment implications

Table 4: The Challenge of Drug- and Matrix-Interference in Immunogenicity Testing

Moderator: Weifeng Xu, PhD, Senior Research Investigator, Bioanalytical Science, Bristol-Myers Squibb

Clinical relevance of ADAs and the issue of drug interference in patient management
Explore various methodologies for assessment of ADAs and the impact of drug interference on each
How selecting the appropriate approach depends on the nature of the target
Current methodologies to overcome drug- and matrix-interference and their limitations
Possible alternative ways to overcome drug- and matrix-interference.

Table 5: Late Stage Clinical and Post-Marketing Strategies: Evolving ADA Assays Over Time

Moderator: Mitra Azadeh, PhD, Principal Scientist, Bioanalytical & Biomarker Development, Shire

Domain specificity testing strategies for ADA Assays
Tiered ADA assessment for nonclinical vs. clinical studies
Changing the positive controls over time
Assay development strategies with a high ADA positive rate at baseline

Table 6: Meeting Regulatory Expectations Regarding Immunogenicity Assessment

Moderator: William Hallett, PhD, Biologist, OPQ/OBP, CDER,FDA

How and when to approach the regulators: Benefits of discussion with the regulators
How much assessment is necessary? How much is too much when no additional value is gained?
Neutralizing antibody assays: When should they be carried out and why?
Challenges often encountered in translating the current guidances on immunogenicity testing for individual drug candidates

Table 7: Immunogenicity Testing for Biosimilars

Moderator: Haoheng Yan, PhD, MD, Chemist, OPQ/OBP, CDER, FDA

Challenges in assay development
Use one assay or two assays?
Demonstrating absence of clinically meaningful differences
Post-marketing surveillance plan?

THURSDAY, OCTOBER 25 9:30 AM

Immunogenicity Prediction & Control

Table 1: Practical Application of Immunogenicity Preclinical Risk Assessment

Moderator: Steve Bowen, PhD, Team Leader, Chemist, Office of Biotechnology Products, CDER, FDA

Relevant risk factors
Potential of emerging antibody products for greater immunogenicity
Features of the risk analysis and risk mitigation plan
Risk assessment at different stages of development
How to translate the identified risk into a testing strategy
Management in the clinic of products with low and high risk of immunogenicity
Experiences with reporting findings to the regulatory authorities

Table 2: Current and Emerging Predictive Tools: Selecting Candidates and Predicting Clinical Outcome

Moderator: Jad Maamary, PhD, Senior Scientist, Merck and Co., Inc.

Working in discovery – combining in silico and in vitro approaches
Applying tools in a matrix environment
Peparing for clinical success: Selecting the right tools for the question posed
Progress on the road to predicting clinical outcomes

Table 3: Application of Mechanistic Modelling to Prediction of Immunogenicity

Moderator:Timothy Hickling, PhD, Immunogenicity Sciences Lead, Biomedicine Design, Pfizer, Inc.

How to apply mechanistic modelling to the clinical development program
To what extent can individual companies coordinate their in vitro data to predict immunogenicity in the clinic?
To what extent can this help with decision making when translating to the clinic?
Which characterization studies need to be incorporated into the predictive models?
What are the implications of the ABIRISK collaboration for the industry?

Table 4: Risk of Immunogenicity of Product and Process-Related Impurities, and Leachables/Extractables

Moderators: Daniela Verthelyi, PhD, Chief, Immunology Lab, Therapeutic Proteins, CDER, FDA
Mohanraj Manangeeswaran, PhD, Therapeutic Proteins, CDER, FDA

Product-related attributes that cause the greatest concern for immunogenicity
Do level of attribute, dosing regimen, and patient population mitigate this risk?
Stringent requirements for process-related impurities and process reagents
Evidence that leachables/extractables (i.e. silicone oil) act as an adjuvant
Should product specifications be more biologically based?

Table 5: Progress towards Inducing Immunological Tolerance to Biotherapeutics

Moderator: Ronit Mazor, PhD, Scientist, Antibody Discovery & Protein Engineering (ADPE), MedImmune, Inc.

Tolerance mechanisms and different approaches for tolerance induction
Immunodominant T-cell epitopes and how these may be used as targets for tolerance induction
Methods for identification and removal of T cell epitopes and evidence for its impact on reducing immunogenicity
Tools to use with protein engineering to design non-immunogenic biotherapeutics
Applicability to enzyme-deficiency disorders, allergies, autoimmune disease and protein drugs in general

Optimizing Bioassays for Biologics

Table 6: Use of New Technologies in Bioassay Development

Moderator: Robyn Beckwith, PhD, Technical Development Scientist, Analytical Development and Quality Control, Genentech

Evaluation of new technologies (suitability for intended use)
Development strategies for automating bioassays (use of DOE, alignment with manual workflows)
Approaches for qualification/validation of automated assays

Table 7: Benefits of Optimizing Bioassays with Design of Experiments (DoE)

Moderator: Martin Kane, MS, CRE, Managing Data Scientist, Statistical and Data Sciences Practice, Exponent