GLP HSR-TIGET Test Facilities
Several gene therapy clinical trials using gene-modified hematopoietic stem cells have shown therapeutic efficacy in multiple disease areas. As this therapeutic strategy is applied to an increasing number of monogenic diseases, rigorous studies in appropriate non-clinical models are needed to assess the risk/benefit ratio and fulfil the requirements for clinical trial applications and future market approvals.
Good Laboratory Practice (GLP) is a quality system related to the organizational processes and conditions under which health safety studies are planned, performed, monitored, recorded, archived and reported (D.Lgs.50, 2 marzo 2007:G.U.86, 16 aprile 2007 and OECD Principles of Good Laboratory Practice N.1, as revised in 1997, ENV/MC/CHEM (98)17).
GLP regulations and guidelines for the conduct of preclinical testing ensure the quality and integrity of data submitted in support to the development of new treatments, foster mutual acceptance of data in the international community and serves to minimise redundant testing, minimize animal use, and maximise protection of human health. Therefore, we have established a GLP compliant Test Facility within the San Raffaele Telethon Institute for Gene Therapy to perform studies to support our Gene Therapy Medicinal Products (GTMP) development.
The primary objective of the GLP HSR-TIGET Test Facilities is to evaluate the safety of GTMPs providing results to meet the regulatory standards and ensuring outstanding scientific significance. GLP Test Facilities in TIGET combine skills and expertise in gene therapy research, pharmaceutical research and development, pathology and quality assurance. The complexity and variability of gene therapy products development are addressed by designing fit for purpose studies to allow safety assessment of GTMPs and to fulfil GLP requirements and OECD principles.
In the Test Facility are performed in vivo and in vitro studies. Different protocols have been designed for the following activities:
- Toxicology and tumorigenicity study to evaluate the potential tumorigenicity and toxicity induced by the transplantation of hematopoietic stem cells (HSCs) transduced with a viral vector;
- Biodistribution study to monitor the distribution of human hematopoietic stem cells transduced with a viral vector to target and off target tissues;
- A variety of in vitro tests, molecular and biochemical assays and cell-based processes are validated.
All experimental activities are performed following Standard Operation Procedure (SOP). and validation studies are designed following international guidelines (ICH Q2 (R1)).
HSR-TIGET Test Facilities has been inspected on 28th March 2014 from the Italian Ministry of Health and certified to perform the following study types according to GLP OECD principles:
- Toxicity studies;
- Biotechnology and Molecular biology studies.
Protocols for hematopoietic stem cell isolation and transduction with viral vectors, mouse conditioning, transplantation, manipulation and clinical signs monitoring are optimized and applied to the GLP studies.
Biological assays are planned and developed according to GLP to produce and characterize the Test and Control Items and to proof the administered dose.
GLP Facilities include two BSL2 laboratories, one dedicated to the cellular activities and one where are run molecular biology assays; four BSL2 animal rooms in SPF animal facilities, one necropsy room, one archive, one facility dedicated to Flow Cytometry, one Pathology laboratory and one QA and Management office.
GLP HSR-TIGET Structure
HSR-TIGET GLP Test facilities include 50 GLP trained people with technical and scientific skills organized as follows:
Management, Quality Assurance unit, SOP administrator, Archivists, Study Directors, Pathologists, Designated Veterinarian and other qualified and trained.
In addition, leaders of specific lines of research are also part of this organization and give their scientific support and advice.
GLP Management, Dr. Patrizia Cristofori.
Last updated: November 2014