Advice Reassessment of the threshold values for the presence of free lentiviral and retroviral vector particles in clinical trials with ex vivo transduced cells

In certain gene therapies, cells from the patient are genetically altered outside the body, often using retroviral or lentiviral vector particles. Following this procedure, the vector particles are usually removed from the cell by washing before the altered cells are returned to the patient. However, when the cells are returned to the patient there is a possibility that they may still contain some vector particles. The presence of vector particles poses a potential risk if third parties are accidentally exposed to them. In such cases, the possible disruption of cell processes, which could in turn lead to cancer, cannot be ruled out. The number of vector particles that can be unintentionally transferred is therefore a key factor in the environmental risk assessment. The number of vector particles remaining in the cells to be returned to the patient can be determined experimentally or calculated using the ‘COGEM formula’. COGEM has previously recommended using a threshold value for the number of vector particles present in the cells as a basis for determining whether or not additional measures are needed to reduce to a minimum the risk of vector particles being transferred. In this advice, COGEM evaluates this threshold value and proposes amending it. COGEM considers that the presence of up to a maximum of 500 retroviral or lentiviral vector particles in the cells to be returned to clinical trial subjects poses a negligible risk to third parties.