Cambridge Healthtech Institute第11回年次

Optimizing Bioassays for Biologics
(バイオロジクスに対するバイオアッセイの最適化)

新興モダリティ時代におけるバイオアッセイ開発成功の実証

2023年10月4日〜5日

細胞および遺伝子治療を含む新たな薬剤モダリティ、免疫治療、抗体治療は、より優れた検査とバイオアッセイ開発改良の必要性を推し進め続けています。これら多くの形式では新たな課題が提起されています。今年で11年目を迎えるCHIの「バイオロジクスに対するバイオアッセイの最適化」カンファレンスはバイオアッセイ開発、バイオプロセシング、生物学的分析で活躍する産学界の登壇者が一堂に会します。このフォーラムでは、最先端のケーススタディを紹介し、米国や欧州の機関の新たなモダリティでの検査の見解を議論し、新規、もしくはこの分野に参入する将来の科学者を教育します。バイオアッセイ開発、検証、転写、保守における共通の課題をエキスパートである登壇者がどのように克服したか、この10月にご聴講ください。

10月4日(水)

Registration Open12:00 pm

BIOASSAY DESIGN AND POTENCY ASSAY DEVELOPMENT
バイオアッセイデザインとポテンシーアッセイの開発

12:25 pm

Chairperson's Opening Remarks

Faye Vazvaei, Executive Director, Merck

12:30 pm KEYNOTE PRESENTATION:

Comparing Four Parameter Logistic Regression with Log Log Linear Models in Clinical Luminex Assays

Jianfang Hu, Senior Director, Pfizer

Linear regression is a commonly used model for sample concentration calculation in multiplex clinical Luminex assays. In theory, four parameter logistic regression (4PL) is preferred when percent recovery based on linear regression is not satisfying in desired assay range. We compared percent recovery and assay precision from both models, and our results indicate that four parameter logistic regression may not perform as well as expected.

1:00 pm

Phase-Appropriate Potency Assay Development for mAbs Targeting Viral Pathogens 

Vaishali Vinod Sarode, Senior Scientist, Vir Biotechnology

Development of potency assays for infectious diseases comes with a unique set of challenges. Fc engineered monoclonal antibodies require development of multiple bioassays that reflect the complex mechanism of action (MOA), such as virus neutralization and clearance via effector function. Potency assays need to be in place for early clinical development and validated at a later stage. This presentation will discuss the development of bioassays to support late-stage programs including the challenges faced and lessons learned.

1:30 pm

Change of Drug Product Formulation-Mediated Innovation for Potency Development and Calculation

Jan Amstrup, PhD, Principal Scientist, Novo Nordisk AS

A potency assay used for several years showed not to be sensitive to low-affinity insulin analogs as well as impacted by the Drug Product matrix. A story regarding implementation of two new potency assays as well as the learnings will be described.

Sponsored Presentation (Opportunity Available)2:00 pm

Refreshment Break in the Exhibit Hall with Poster Viewing2:30 pm

3:10 pm

Bioassay Development and Establishment

Kate Getliffe, PhD, Principal Scientist, Akamis Bio

3:40 pm

Functional Antibodies in Dried Blood to Measure Protection against RSV

Jonne Terstappen, MD, PhD Candidate, Pediatric Infectious Diseases, Wilhelmina Children's Hospital

The respiratory syncytial virus (RSV) prevention landscape has rapidly expanded, with 33 candidates currently in clinical development. We have demonstrated RSV neutralization on dried blood as an alternative for serum.  Functional antibodies in dried blood is a patient-centered solution that may replace serology testing in vaccine trials in LMICs and potentially be used as a tool to monitor protection against RSV globally.

STANDARDS AND REFERENCE MATERIALS
基準と標準物質

4:10 pm

Supporting Global Harmonisation and Traceability of Biological Medicines: The Role of WHO Bioassay Standards at Different Stages of a Product’s Lifecycle

Sandra Prior, PhD, Senior Scientist, National Institute for Biological Standards and Control (NIBSC, a Centre of The Medicines and Healthcare products Regulatory Agency)

Bioactivity characterisation and bioassays, in addition to reference standards, are essential for regulatory approval throughout the lifecycle of Biotherapeutics. However, harmonisation and traceability of bioactivity data depend on the availability of public reference standards to “translate” manufacturer’s proprietary units into “international units” to understand bioactivity, both longitudinally and across products, whilst using different assay platforms. We are developing a panel of reference reagents to benchmark assays which are used to characterise Fc-interactions. 

Close of Day4:40 pm

Dinner Short Course Registration5:00 pm

Recommended Dinner Short Course*5:30 pm

SC5: Advice on Putting Together an Integrated Summary of Immunogenicity
*Separate registration required. See short course page for details.

10月5日(木)

Registration and Morning Coffee7:30 am

LIFECYCLE MANAGEMENT OF BIOLOGICS
バイオロジクスのライフサイクルマネジメント

7:55 am

Chairperson's Remarks

Steven Walfish, Owner, Statistical Outsourcing Services

8:00 am FEATURED PRESENTATION:

Life Cycle Management of an ADA Assay: PC Selection, Critical Reagents Bridging and Assay Comparability Between Labs

Linlin Luo, PhD, Director, Merck

Anti-drug antibody (ADA) testing is required to evaluate immunogenicity against a biotherapeutic. ADA assay development and its life cycle management is crucial to a drug’s launch and post-market success. Many key factors need to be considered, including: positive control selection to aid detection of clinically meaningful immunogenicity, critical reagents bridging to ensure assay continuity, and cross-lab assay comparability evaluation to support pooling of immunogenicity data in global studies?.

8:30 am

Choosing Bioassays with Evolved MOA Understanding from Start to Finish

Charisma Enam, PhD, Associate Scientist, Genentech

This presentation will discuss strategic bioassay development for different phases of a product’s lifecycle with emphasis on the bioassay considerations for undefined and/or complex MOAs at early stage development. The presentation will highlight CMC solutions for designing phase appropriate bioassays with regulatory considerations in mind.

Sponsored Presentation (Opportunity Available)9:00 am

INTERACTIVE DISCUSSIONS
インタラクティブディスカッション

9:30 amInteractive Discussions

Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Breakout Discussions page on the conference website for a complete listing of topics and descriptions.

Coffee Break in the Exhibit Hall with Poster Viewing10:20 am

NOVEL MODALITIES
新規モダリティ

11:00 am

Potency Assay Development and Analytical Strategy for a Novel Immunotherapy

Sonia Connaughton, PhD, Associate Director, Sanofi

Cancer cells can evade immune surveillance through various mechanisms, including immunosuppression pathways. These pathways stand out as notable targets for new therapies, as blocking these immunosuppression pathways can allow the body’s own immune system to destroy cancer cells. Monoclonal antibodies can be a means of blocking one such pathways. This presentation will discuss the development of bioassays to understand the mechanism of action such immunotherapies and the evolution of bioanalytical strategy from early phase to supporting late phase development.

11:30 am

Cell-Based Assays with Reporter Cell Lines for Novel Bispecific Antibodies

Natalia Kozhemyakina, PhD, Head, Bioassay Department, JSC Biocad

Biological activity is a critical authenticity and quality attribute of novel biotherapeutics. Since data that we generate attribute to the quality of our products it is critical to create precise, accurate, robust quantitative methods that at the same time reflect clinical mode of action. The development of such tests for novel bispecifics is always a big challenge. Here we describe reporter test systems development and analytical characterization of bispecific antibodies.

STATISTICAL ANALYSIS AND REPLICATION
統計解析と再現性

12:00 pm

Should I Average My Replicates before Modelling?

Matthew Stephenson, PhD, Principal Statistician, Quantics Biostatistics

In the statistical analysis of bioassays, the replicates at each dose level are often treated as independent when, in fact, they are related. This is especially relevant in the case of pseudo-replicates. One method to address this relationship is to average replicates before model fitting. We will examine the impact of averaging replicates on various aspects of the statistical analysis of bioassays, including parallelism assessment and relative potency estimation.

Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:30 pm

Session Break1:00 pm

BIOASSAY - FROM FRAMEWORK TO FAQs
バイオアッセイ - フレームワークからFAQまで

1:40 pm

Co-Chairperson's Remarks

Nancy Sajjadi, Independent Quality Consultant, Sajjadi Consulting

Steven Walfish, Owner, Statistical Outsourcing Services

1:45 pm

Bridging in the World of the Analytical Lifecycle

Tim Schofield, Owner, Consultant, CMC Sciences LLC

The concept of the analytical lifecycle has opened up new opportunities for bridging technologies, standards, and critical reagents in bioassay. Science and risk-based thinking combine to develop a program which replaces or complements traditional study-based approaches with effective use of continuous performance verification. This talk will examine and compare bridging approaches as a strategic component of the bioassay control strategy.

2:15 pm

Similarity Measures for Bioassay Acceptance

Steven Walfish, Owner, Statistical Outsourcing Services

An underlying assumption to calculate relative potency is similarity between reference and test curves. This talk focuses on different similarity metrics, and how they impact the estimate of relative potency. The talk will focus on two different models, parallel line assay and the 4-pl assay. Discussion will also include the impact of a constrained model when similarity is not met.

2:45 pm

Applying an Equivalence Model to Set Lot Release Specifications for Relative Potency

Nancy Sajjadi, Independent Quality Consultant, Sajjadi Consulting

The center of a specification for product potency represents the target value of 100%. Because assays used to measure relative potency yield lognormal data, statistical analyses must be performed on log transformed values. The center of the lot release specification becomes 0 for log base 10 transformation of relative potency 1.0 (100%). To conclude that a lot is satisfactory, statistical equivalence to 0 should be demonstrated. This requires that the reported value and its confidence interval (e.g., 90%) to fall within established equivalence bounds. Drifts in product potency, assay performance, and statistical error tolerance must be considered in setting bounds.

3:15 pm PANEL DISCUSSION:

Bioassay - From Framework to FAQs

PANEL MODERATOR:

Nancy Sajjadi, Independent Quality Consultant, Sajjadi Consulting

  • Why is the lifecycle approach to assay design, development and validation a better framework for assays in general and bioassays more specifically?
  • What is the most challenging part of adopting the lifecycle approach?
  • Given that similarity of a test sample to a reference material is fundamental to determining the relative potency of product, are there any instances where testing for this requirement is unnecessary?
  • How can the choice of a statistical hypothesis framework impact the product lot release strategy for relative potency?
PANELISTS:

Steven Walfish, Owner, Statistical Outsourcing Services

Tim Schofield, Owner, Consultant, CMC Sciences LLC

Matthew Stephenson, PhD, Principal Statistician, Quantics Biostatistics

Close of Summit3:45 pm


* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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