GLP Test Facility
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 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 non-clinical health safety studies are planned, performed, monitored, recorded, reported and archived (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, serves to minimise redundant testing, minimize animal use and maximise protection of human health.
San Raffaele TIGET Institute has established GLP compliant Test Facility within IRCCS Ospedale San Raffaele to perform studies in compliance with GLP principles and data integrity to support Gene Therapy Medicinal Products (GTMPs) development.
GLP Facility include:
- two BSL2 laboratories, one dedicated to the cellular activities and one where are run molecular biology assays;
- BSL2 animal rooms in SPF animal facilities;
- one necropsy room in SPF animal facilities;
- one archive;
- one facility dedicated to Flow Cytometry;
- one Histopathology laboratory;
- one Pathology Laboratory;
- QA; Study Directors and Management offices.
SR-TIGET GLP Test facilities include full-time GLP trained staff with technical and scientific skills organized as follows: management; quality assurance; SOP administrator; archivists; study directors; pathologists; designated veterinarian; Technicians.
In addition, scientific leaders of specific lines of research are also part of this organization and give their scientific support and advice as consultants.
Primary objectives of the GLP SR-TIGET Test Facilities are to evaluate the safety of GTMPs providing results to meet the regulatory standards and ensuring data and reports are generated with high standard of quality and integrity. GLP Test Facilities combine skills and expertise in gene and cell therapy research, pharmaceutical research and development, pathology and quality assurance. The complexity of the development of cells and gene therapy products are addressed by designing tailored 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. Protocols have been designed for the following:
- 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 viral vector to target and off target tissues;
- in vitro tests to assess comparability
- Validation of molecular and biochemical assays and cell-based processes. Validation of analytical procedures is the process of determining the suitability of a given methodology for providing reliable and reproducible data
All experimental activities are performed following Standard Operation Procedure (SOP) and validation studies are designed following international guidelines (ICH Q2 (R1). SR-TIGET Test Facilities has been certified eligible to carry out studies in GLP on 28th March 2014. GLP Test Facility is part of the national GLP compliance monitoring programmes, inspected in 2016 and 2018 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
Study Plans 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 assay protocols are designed according to GLP principles to produce and characterize Test and Control Items and to proof the administered dose.