The importance of starting materials: quality and regulatory considerations for cell-based therapies

Published: 25 March 2021
Regulatory Insight
Barbara Bonamassa,
Barbara Bonamassa
Quality Assessor, ATMPs at AIFA (Italian Medicines Agency)
Paolo Gasparini,
Paolo Gasparini
Head, Department of Advanced Diagnostics & Clinical Research, Institute for Maternal & Child Health - IRCCS Burlo Garofolo at University of Trieste
Giulio Pompilio,
Giulio Pompilio
Professor at Università degli Studi di Milano
Alessandro Aiuti,
Alessandro Aiuti
Deputy Director, Clinical Research at San Raffaele Scientific Institute
Alessandro Aiuti initially focused his research studying diseases of the coagulation and HIV infection. His research on hematopoietic stem cells (HSCs) led to the discovery of the first chemokine produced by bone marrow cells inducing migration of human HSCs. His current research is focused on pediatric hematology and immunology and specifically on primary immunodeficiencies, genetic diseases of the immune system. He pioneered the successful gene therapy clinical trial for SCID patients that lack adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. This clinical trial, now completed, introduced a conditioning regimen to favor the engraftment of gene corrected cells and is considered to be among the most important clinical result of gene therapy for genetic diseases. Gene therapy for ADA SCID has been designated as Orphan Drug in Europe and USA. His most recent research with HSCs transduced with lentiviral vectors led to the successful application of therapy for another primary immunodeficiency, Wiskott-Aldrich syndrome.
Paolo Foggi
Paolo Foggi
at AIFA (Italian Medicines Agency)

With an increasing number of cell-based therapies obtaining marketing authorization in the EU, the availability of an adequate quantity and quality of target cells for use as starting material has emerged as an important issue. Cellular starting materials exhibit variability, which has an impact on downstream processing and final product quality. On the one hand, accommodation of the variability of cell starting materials is usually essential to allow widespread patient access to innovative and life-saving therapies. On the other hand, variability in the starting material can result in inconsistent quality of the final product and failure to meet desired specifications. In this commentary, we critically review factors contributing to cell starting material variability and provide a regulatory perspective on its management.

Read now