IND - Cell Therapy. Robert W. Lindblad, MD, FACEP. Where Did you Hear

Transcription

1 IND - Cell Therapy Robert W. Lindblad, MD, FACEP Where Did you Hear

2 The EMMES Corporation CRO Coordinating Center Cell Therapy PACT Production Assistance for Cellular Therapy Bone Marrow Transplant Network SCCT Specialized Centers for Cellular Therapy ITN Edmonton Islet Transplant Protocol PACT 20 applications approved products for manufacturing 14 clinical 6 translational(3 initially submitted as clinical applications) 13 currently have an active IND 2 products completed and delivered 10 products are currently being manufactured 1 product pending manufacturing commencement 5 are in the IND submission process. translational work being conducted 2 no longer pursuing manufacturing request

3 IND Process How well can you negotiate? IND Process researchcartoons.com

4 OCP Office of Combination Products Addresses product jurisdiction issues Requests for designation CTGTAC Cellular, Tissue and Gene Therapies Advisory Committee Provides FDA with outside current, reliable scientific and medical guidance to facilitate regulatory decisions pertaining to cellular, tissues and gene transfer therapies regulated by CBER

5 FDA Team Center collaboration CBER/CDRH Review Team Manager/Contact Pharm/Tox preclinical Product Clinical IND Submission Pre-IND meeting Creating a package Developing questions Pharmtox Clinical protocol Dosing CMC

6 Pre IND Planning researchcartoons.com Pre-Clinical Animal testing Toxicological assessment Comprehensive histological examination Cell survival post transplantation Cell migration Cellular fate Plasticity, Differentiation,Transdifferentiation, Fusion Tissue integration Tumorgenicity Hyperplastic or unregulated growth

7 Pre-Clinical Testing researchcartoons.com Manufacturing Process Controls Standardization and optimization of reagents and processing procedures Product characterization and development of acceptance criteria Controlling purity and impurity profile of the final product Establish specific characteristics to ensure product integrity Develop analytical approaches for evaluating proposed acceptance criteria for in process intermediates and final cellular product

8 Manufacturing Process Controls researchcartoons.com CMC for Cell Based Therapies Pre-IND package Provide as much detail as possible Characterization of the Cell Product Morphologic evaluation Detection of phenotype-specific cell surface antigens Unique biochemical markers Gene and protein expression analysis Cellular impurity profile assessment Biological activity assay Potency MHC/HLA expression - Compatibility

9 Potency CTGTAC review February 9, 2006 The relevant biological function/activity of the product Development of cell product potency assay Validate surrogate markers as predictors of intended biologic activity Specify parameters on which product dosing should be based (Number of cells, activity, molecular markers) Record Keeping Documentation of critical processes Submission of list of all SOPs Submission of critical SOPs Maintenance of records through-out the processing procedure

10 Record Keeping Poor Record Keeping researchcartoons.com researchcartoons.com

11 IND Submission A clinical hold is a failure of the Pre-IND process IND Issues Bench to clinical trial Belief in the product with inadequate supporting scientific data Skip steps to save time Inadequate characterization of the product

12 IND Issues Central manufacturing vs. distributed manufacturing Clinician trying to produce a cellular product Cell product manufacturer trying to run a clinical trial Lessons Learned Listen to FDA comments Negotiate based off of scientific data Educate The manufacturer must write the CMC section The clinician must write the clinical protocol

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