How institutional biosafety committees contribute to safety, capacity and regulatory approvals in cell and gene therapy trials

Abstract

Background & Aim In Australia clinical trials of viral vector gene therapies or gene modified (GM) viruses are required to be licenced by the Office of the Gene Technology Regulator (OGTR). Institutional Biosafety Committees (IBCs) play a crucial role by reviewing applications before they go to the OGTR for decision. IBCs also advise on cell therapy trials that do not require a licence and on laboratory research. Their advice covers safety, compliance and governance to meet the objective of the Australian Gene Technology Act 2000, which ‘is to protect the health and safety of people, and to protect the environment, by identifying risks posed by or as a result of gene technology, and by managing those risks through regulating certain dealings with GMOs [Genetically Modified Organisms]’. Methods, Results & Conclusion Royal Prince Alfred Hospital (RPAH) IBC contributes to cell and gene therapy capacity building within Sydney Local Health District. Since 2008 it has advised on over 22 clinical trials; 14 of which required an OGTR licence. It has reviewed 6 licence applications and local risk management for 7 licences obtained via other IBCs. The number of trials advised on is increasing (5 in 2008-2015, 9 in 2016-2019 and 4 as at March 2020). They cover adeno-associated viral vectors for haemophilia, adenoviral vectors for mesothelioma, oncolytic GM human HSV-1 for melanoma and squamous cell carcinoma, oncolytic GM vaccinia virus vaccine strain for liver and kidney cancer, autologous cells transduced ex vivo with lentiviral vectors for beta-thalassemia (CD34+ cells) and adult diffuse large B-cell lymphoma (chimeric antigen receptor T cells targeting CD19) and allogeneic CRISPR Cas-9 engineered T-cells for B cell malignancies. The IBC conducts science-based risk assessments, facility inspections, assists organisations to prepare for cell and gene therapy clinical trials and contributes to policy and national reviews. It assists applicants and liaises with the OGTR. It has answered infection control queries, educated sponsors, developed a GMO-waste management training program with environmental services; ensured eye-wash, autoclave maintenance and spills management training are provided; assisted with corrective actions; and provided risk prevention advice. The members are scientists, researchers, health professionals, engineers and lay persons. The committee has processes for managing confidential information and dualities of interest and assesses new technologies, policies and regulations as they emerge.