Handling of recombinant adeno-associated virus (AAV) infected animals

In a 2005 ZKBS statement, various AAV serotypes were already classified into risk groups 1 and 2, respectively, and a safety assessment for corresponding genetic engineering work with recombinant AAV or vectors derived from them was carried out. This statement was expanded by the ZKBS in April 2021 with a passage referring to genetic engineering work with AAV-infected animals. Among the notes, it initially states that experimental animals whose somatic cells were transduced using recombinant, replication-defective AAV vector particles do not constitute GMOs. However, the animals are generally considered carriers of GMOs. The period during which infectious vector particles remain in the animal depends heavily on the administered dose and the inoculation route. It is further stated that the infected animals may re-shed the administered vector particles. This impacts the handling and inactivation of all materials (bedding, cages, feed, etc.) that come into contact with the infected animals and may therefore potentially be contaminated with recombinant AAV vector particles. However, if it can be proven with the help of data or appropriate literature for comparable systems that after a certain period of time, no further AAV vector particles are released from the treated animal, it is safe from a safety perspective if the state authorities, after a case-by-case assessment, independently set appropriate deadlines after which the animals are no longer treated as carriers (or excretors) of GMOs. It can also be assumed that the protection of the legal interests pursuant to Section 1 No. 1 GenTG is also guaranteed if the carcasses of laboratory animals inoculated with AAV vector particles of risk group 1, for which no corresponding data regarding the release of AAV have been presented, are disposed of without prior autoclaving in the manner customary in laboratory animal husbandry. Unless Section 24 Paragraph 1 No. 3 GenTSV is already applicable, the relevant licensing and monitoring authority can decide in accordance with Section 2 Paragraph 2 GenTSV that these animal carcasses be disposed of in accordance with the usual practice in laboratory animal husbandry without autoclaving, provided it is guaranteed that the animal carcasses will not enter the food and feed chain. In the case of laboratory animals inoculated with AAV vector particles of risk group 2 and for which the aforementioned data regarding GMO release were not submitted, it can be assumed that a significant accumulation of AAV vector particles has been achieved seven days after inoculation, meaning that working with the carcasses of these animals does not pose a risk potential beyond safety level 1. Here, too, the relevant licensing and monitoring authority can, after examination, determine that these animal carcasses be disposed of in accordance with the usual practice in laboratory animal husbandry without autoclaving.

The ZKBS statement can be found at File number Az.6790-10-73 can be retrieved.