Thursday, October 27: 6:30 – 9:30 pm

Dinner SC3: Advice on Putting Together an Integrated Summary of Immunogenicity

Instructors:

Joao Pedras-­Vasconcelos, Ph.D.,Biotech Quality and Immunogenicity Reviewer, Office of Biotechnology Products, CDER-­FDA

Paul Chamberlain, NDA Advisory Board

Purpose

The purpose of this workshop is for to share experience gained in preparing and reviewing the “Integrated Summary of Immunogenicity”, with case examples to illustrate the multi-­disciplinary information that is most useful for the regulator assessing the scale of risk of undesirable immunogenicity for overall clinical benefit vs. risk.

Background

Information relevant for the assessment of the impact of undesirable immunogenicity of therapeutic proteins on overall clinical benefit vs. risk balance is distributed across many different sections of the regulatory dossier. This can make it difficult for regulatory reviewers to located the requisite data. Moreover, essential background information to describe the intrinsic immunogenic potential of the molecule, and how extrinsic factors (product quality, patient variables, dose regimen etc.) might interact to influence clinical manifestations, is often missing. Although there might be valid reasons for applying a particular strategy for evaluating immunogenicity, the Sponsor’s rationale is often not clearly explained. For this reason, the recent draft revision to the main EU immunogenicity guideline has formally endorsed the concept of including a summary document in the MAA dossier, with the objective of collating the essential information required by the regulatory assessor.

Who should attend?

This workshop is relevant to anyone who is involved in generating and compiling the input data for immunogenicity-­related sections of regulatory dossiers, including CMC, bioanalytical, non-clinical, clinical and regulatory specialists.

Suggested agenda topics

Part 1 – Defining the gap: João Pedras-­Vasconcelos

• Priorities for the regulator
• Common gaps in dossiers
• Examples of Agency questions triggered by missing information
• The regulator’s “wish-list”

Part 2 – Addressing the gap: Paul Chamberlain

• Suggested structure of the Integrated Summary of immunogenicity
• Relationship to other parts of the dossier
• What, where and how? Examples to illustrate how to present relevant information, including:
• Intrinsic immunogenicity and systems biology
• Linkage to product quality control strategy
• Rationale for extent of evaluation
• Correlation of bioanalytical and clinical signals

Part 3 – Interactive discussion: Using the Integrated Summary of Immunogenicity to minimize regulatory questions at the Marketing Authorization stage

Discussion topics to be driven by participant’s questions and case examples

Joao Pedras-Vasconcelos, Ph.D., Biotech Quality and Immunogenicity Reviewer, Office of Biotechnology Products, CDER-FDA

Dr. Pedras-Vasconcelos has been a quality and immunogenicity reviewer with the Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drugs- FDA for 12 years, first as a researcher-reviewer (6 years) and then as a full time reviewer (6 years). He received his B. Sc. Honours in Microbiology in 1990, and an M. Sc. in Microbiology in 1993 from The University of Saskatchewan, Canada. He received his Ph. D. in Immunology in 1999 from Cornell University, Ithaca. Afterwards he completed a post-doctoral research fellowship at the Institute of Biological Sciences, National Research Council of Canada, and had a position as a term-Research Scientist at the Canadian Food Inspection Agency, both in Ottawa Canada. He joined the FDA in 2002, first with CBER and then CDER and has extensive regulatory experience in reviewing cytokines, fusion proteins, therapeutic toxins, hormones, immunomodulatory extracts, and enzyme replacement therapies. Joao is a standing member of the OBP immunogenicity coordinating group and the AAPS NAb White Paper working group.

Paul Chamberlain, NDA Advisory Board

Paul CHAMBERLAIN is a biopharmaceutical product specialist who specializes in presenting immunogenicity risk assessments to European and North American regulatory agencies. He works with Sponsors to develop strategies for evaluating the probability that a product might induce an undesirable immune response, as well as preparing expert reports on signal interpretation to support.