Advanced Therapy Drugs : Qualification of an autoclave for the treatment of waste from the production of Talimogène laherparepvec

Aim of the study

Any organism whose genetic material has been substantially modified is considered to be a genetically modified organism (GMO). GMOs are Advanced Therapy Medicinal Products (ATMPs) that are increasingly evaluated in clinical studies. The French High Council for Biotechnology (HCB) recommends destruction of GMOs by thermal inactivation (134 ° C, 20 to 30 minutes). Talimogene laherparepvec (TVEC) is an ATMP-GMO in clinical trials. The objective of this study was to qualify our autoclave to ensure viral inactivation of TVEC production waste in accordance with HCB recommendations.

Material and Methods

We evaluated the compact autoclave Tuttnauer® 2540. The waste corresponding to the production was placed in a box «DASRI STIL’ECO ST07030 (B)». Five configurations were tested by varying the load of the material in the box (MAX load with all the material used and MIN load with only needles, syringes and vials), the closure or not of the top seal and the sterilization time. The temperature was set at 134 ° C. To qualify the autoclave in the different configurations, 2 test were used: 1 / Bowie-Dick (BD), to evaluate the penetration of water vapor (MAX load : 2 BD in lower parts (DOW) and upper (TOP) of the box; MIN load : 1 single BD) and 2 / Prion Integrator (IP), changing color if the temperature is greater than or equal to 134 ° C, for at least 18 min; (MAX load : 2 IP, DOW and TOP, MIN load : 1 IP only). Each condition has been tested three times.

Result

Compliance (C) or Non-Compliance (NC) of the different configurations is reported below:

Discus & Conclusion

Our autoclave is only qualified in 2 configurations. As a safety measure, the configuration "Close MIN-60 min" was chosen. Bulky wastes with low infectious risk (fields, gloves) will be inactivated by soaking in sodium hypochlorite as recommended by HCB. This study highlights the necessary qualification of the charges for each new ATMP-GMO, the inactivation performance greatly depending on the configuration of the waste must be treat.