Detaljerad miljöinformation

Detailed background information:

Kymriah - tisagenlecleucel is an immunocellular therapy containing tisagenlecleucel, autologous T cells genetically modified ex vivo using a lentiviral vector encoding an anti-CD19 chimeric antigen receptor (CAR). Tisagenlecleucel is administered in a qualified controlled treatment center. Therapy is initiated under the strict direction and supervision of an experienced healthcare professional.

Tisagenlecleucel is intended as a one-time infusion. Treatment is restricted to hospital centers and directed by trained specialists thus limiting the distribution of the product. The product is transported in closed, break-proof, leak-proof containers and stored frozen at <-120 °C in the vapour phase of liquid nitrogen in appropriate containers. At the administration site, tisagenlecleucel is thawed and subsequently infused to the patients.

Standard biosafety practices are typically followed by medical facilities when handling biological products such as tisagenlecleucel. 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 biohazardous materials such, as patient samples/fluids and medical waste (autoclaves, sharps bins, incinerators, disinfectants, and appropriate cleanable surfaces). No further product-specific measures are needed, as the T cells do not survive outside of the human body.

Tisagenlecleucel is not intended for direct release into the environment and it is not expected to be released in the environment. Importantly, T cells cannot survive outside of the human body and can neither propagate in exposed persons (except for the patient from whom the cells were derived) nor in the environment. Therefore, a potential negative effect of tisagenlecleucel on people or the environment is not expected. Any potential contact of the product with the health care providers during administration would be extremely limited and would not result in the expansion of the product in the exposed person.

Tisagenlecleucel is non-pathogenic and selectively target CD19-expressing B cells. Transduced T cells do not survive or colonize other species, nor are other species known to be carriers or vectors under natural conditions. Outside of the host, tisagenlecleucel is sensitive to and rapidly killed by physical inactivation, disinfectants, and lack of nutrients. The genetic modifications made on the T cells do not affect survivability in a different environment outside the host organism. Therefore, CAR + T cells are devoid of any competitive advantage. They are not able to replicate in the absence of specific antigenic stimulation or of specific cytokines and specific culture conditions. No shedding or distribution of the genetically modified sequences is expected, except in case of massive bleeding of the treated patient. Since T cells do not survive outside of the body, horizontal gene transfer is unlikely if tisagenlecleucel was released into the environment. Therefore, it is unlikely that tisagenlecleucel would interfere with the control of pathogenic microorganisms or that it would have an effect on the natural dynamics of microbial populations or the biogeochemical cycles at any given site in the environment.

In conclusion, use of Kymriah - tisagenlecleucel 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.

• Kymriah Environmental Risk Assessment - GMO.

• Kymriah summary of product characteristics