Therapeutic Product Immunogenicity Community

Hi All,

At the Immunogenicity Discussion Group (IDG) meeting held on Wednesday 9th July, @Lauren Stevenson shared information on a planned Bioanalysis journal article series focused on the future of immunogenicity testing. Below is the proposal for the series, including the themes, potential topics, and submission details.

If you're interested in contributing or would like more information, please feel free to reach out to Lauren directly.

Best wishes,

Rob & Todd

Proposal for the series:

Refreshing the immunogenicity testing paradigm – Reflecting on the past, addressing the needs of the present and building towards a sustainable future

After over 20 years' of implementing the current 3-tiered immunogenicity testing paradigm, we have collected adequate data to allow for an informed review of our approaches and take a science-driven approach to revise accordingly. This dedicated series will explore the scientific landscape and assumptions that led to the current testing paradigm and reflect on lessons learned – what works, what doesn't and provide new thinking and approaches that will allow us to best identify and characterize clinically relevant immunogenicity for both traditional and newer, novel molecules/modalities.This requires us to develop a scientific framework that possesses both rigor and flexibility. We are in a time of change – our portfolios are filled with ever more complex molecules, yet many organizations across both industry and regulatory bodies are functioning with evolving priorities and resources. It is imperative that we focus on value-added efforts with clinical relevance front of mind.It is time to collectively evaluate approaches and consider which methodologies best serve the needs of our programs and patients. We must mindfully navigate these waters through collaborative dialogue between drug developers and regulators to ensure scientifically sound and patient-focused immunogenicity assessment strategies.

This article collection invites contributions from both industry and regulatory perspectives that offer strategies and technical solutions that will help move our science forward. We welcome a variety of submission formats including:

(i) Thought-provoking Perspectives and Editorials

(ii) Original Research Articles/Bioanalytical Challenges/Methods in immunogenicity assessment

(iii) Focused Reviews/Special reports critically evaluating existing strategies, best practices and emerging technologies

Together, these contributions will help build the future state of immunogenicity testing through balanced input from all stakeholders involved in ensuring patient safety and product efficacy.

 Tentative timelines: Call for papers in mid-August, with submissions expected late January and publications rolling out through June.

 Some potential specific topics – just to get ideas flowing…

• Case studies from completed clinical studies that retrospectively evaluate S/N from screening tier and compare and contrast conclusions drawn about development and magnitude of ADA and clinical impact from S/N vs titers from 3-tiered analysis
• Scientific perspective/proposal of development and validation approach for single-tiered ADA
• Collaborative perspective on detection of clinically irrelevant ADA – how much time, money and resource have we expended to generate a large body of clinically irrelevant responses as well as manage the perceptions and concerns of stakeholders focused on incidence rather than impact
• Scientific approaches to evaluate new modalities – defining context of use and designing approaches that address the key questions – including not misapplying guidance written for protein therapeutics to other modalities
• Technical approaches to overcome challenges in assay development
• Perspective on drug tolerance – pros and cons of highly drug tolerant methods for non-high-risk molecules
• Defining risk categories (not all drugs with an endogenous counterpart are high risk) – what is medium risk?  Clarifying risks a drug developer may want to mitigate for internal decisions regarding their platform pipeline not to be conflated with clinical/safety risks for the patient
• Why and when domain specificity matters – another example where we need to differentiate between what a sponsor may want to understand about their drug vs what will inform patient safety/clinical impact
• Perspective on statistical cut points – are they adding value?  Including case studies that demonstrate where the application of a statistical cut point caused meaningful data to be overlooked or incorrect conclusions to be drawn and/or vice versa.
• Approaches that focus on reliable detection of clinically relevant responses

Hi All,

At the Immunogenicity Discussion Group (IDG) meeting held on Wednesday 9th July, @Lauren Stevenson shared information on a planned Bioanalysis journal article series focused on the future of immunogenicity testing. Below is the proposal for the series, including the themes, potential topics, and submission details.

If you're interested in contributing or would like more information, please feel free to reach out to Lauren directly.

Best wishes,

Rob & Todd

Proposal for the series:

Refreshing the immunogenicity testing paradigm – Reflecting on the past, addressing the needs of the present and building towards a sustainable future

After over 20 years' of implementing the current 3-tiered immunogenicity testing paradigm, we have collected adequate data to allow for an informed review of our approaches and take a science-driven approach to revise accordingly. This dedicated series will explore the scientific landscape and assumptions that led to the current testing paradigm and reflect on lessons learned – what works, what doesn't and provide new thinking and approaches that will allow us to best identify and characterize clinically relevant immunogenicity for both traditional and newer, novel molecules/modalities.This requires us to develop a scientific framework that possesses both rigor and flexibility. We are in a time of change – our portfolios are filled with ever more complex molecules, yet many organizations across both industry and regulatory bodies are functioning with evolving priorities and resources. It is imperative that we focus on value-added efforts with clinical relevance front of mind.It is time to collectively evaluate approaches and consider which methodologies best serve the needs of our programs and patients. We must mindfully navigate these waters through collaborative dialogue between drug developers and regulators to ensure scientifically sound and patient-focused immunogenicity assessment strategies.

This article collection invites contributions from both industry and regulatory perspectives that offer strategies and technical solutions that will help move our science forward. We welcome a variety of submission formats including:

(i) Thought-provoking Perspectives and Editorials

(ii) Original Research Articles/Bioanalytical Challenges/Methods in immunogenicity assessment

(iii) Focused Reviews/Special reports critically evaluating existing strategies, best practices and emerging technologies

Together, these contributions will help build the future state of immunogenicity testing through balanced input from all stakeholders involved in ensuring patient safety and product efficacy.

 Tentative timelines: Call for papers in mid-August, with submissions expected late January and publications rolling out through June.

 Some potential specific topics – just to get ideas flowing…

• Case studies from completed clinical studies that retrospectively evaluate S/N from screening tier and compare and contrast conclusions drawn about development and magnitude of ADA and clinical impact from S/N vs titers from 3-tiered analysis
• Scientific perspective/proposal of development and validation approach for single-tiered ADA
• Collaborative perspective on detection of clinically irrelevant ADA – how much time, money and resource have we expended to generate a large body of clinically irrelevant responses as well as manage the perceptions and concerns of stakeholders focused on incidence rather than impact
• Scientific approaches to evaluate new modalities – defining context of use and designing approaches that address the key questions – including not misapplying guidance written for protein therapeutics to other modalities
• Technical approaches to overcome challenges in assay development
• Perspective on drug tolerance – pros and cons of highly drug tolerant methods for non-high-risk molecules
• Defining risk categories (not all drugs with an endogenous counterpart are high risk) – what is medium risk?  Clarifying risks a drug developer may want to mitigate for internal decisions regarding their platform pipeline not to be conflated with clinical/safety risks for the patient
• Why and when domain specificity matters – another example where we need to differentiate between what a sponsor may want to understand about their drug vs what will inform patient safety/clinical impact
• Perspective on statistical cut points – are they adding value?  Including case studies that demonstrate where the application of a statistical cut point caused meaningful data to be overlooked or incorrect conclusions to be drawn and/or vice versa.
• Approaches that focus on reliable detection of clinically relevant responses