Detaljerad miljöinformation

Tecartus, brexucabtagene autoleucel, is a genetically modified autologous cell-based product containing T cells transduced ex vivo using a retroviral vector expressing an anti‑CD19 chimeric antigen receptor (CAR). Therapy is initiated under the strict direction and supervision of an experienced healthcare professional.

Treatment consists of a single dose for infusion, administered only in qualified treatments centres by experienced healthcare professionals who have been trained in handling live human cells and are aware of local biosafety guidelines related to hygiene and standards for safety and infectious materials handling. The product is transported in hermetically sealed, break‑proof containers frozen in the vapour phase of liquid nitrogen (≤ − 150°C). At the administration site, brexucabtagene autoleucel is thawed and infused into the patients.

Standard biosafety guidelines are locally followed by medical facilities when handling biological products such as brexucabtagene autoleucel and the waste of human-derived material. These include special precautions for disposal and handling, restricted access, secure storage, and training of personnel, personal protective equipment established routine practices for dealing with potentially infectious waste such, as patient samples/fluids and medical waste (autoclaves, sharps bins, incinerators, disinfectants, and appropriate cleanable surfaces).

Unless frozen, the T-cells expressing anti CD19 CAR, which comprise brexucabtagene autoleucel, cannot survive outside of the intended recipient. It is not possible to self inoculate with brexucabtagene autoleucel and there is only a hypothetical risk of exposure to humans after a spillage incident. The patients’ own T cells are not shed from the patient into the environment after administration. Brexucabtagene autoleucel is an autologous T cell therapy. These cells would be recognised as ‘foreign’ due to the mismatching of human leukocyte antigens and therefore eliminated through the individual’s innate (i.e. complement mediated lysis and phagocytic cells) and adaptive immune system (i.e. secreted antibodies and B  and T cells). Adverse effects would be limited to a normal immune reaction to foreign with no specific adverse effected related to the genetic modification of the cells expected.

There is a theoretical possibility that brexucabtagene autoleucel could persist if transmitted to an immunocompromised individual. In this highly unlikely case, the theoretical adverse effect would be the same as the possible adverse effects in patients.

The retroviral vector used for the manufacture is integrated stably into the cellular genome and is not present as free infectious particles. There are no expected immediate and/or delayed, direct or indirect environmental impacts of the specific techniques used for management of brexucabtagene autoleucel.

In conclusion, use of Tecartus - brexucabtagene autoleucel has been considered to result in insignificant environmental impact.

References

• EMEA/CHMP/SWP/4447/00 corr 2. Guideline on the Environmental Assessment of Medicinal Products for Human Use. EMEA, June 2006.

• Tecartus Environmental Risk Assessment - GMO.

• Tecartus summary of product characteristics.