Titration experiments of transmissible spongiform encephalopthies (TSE) agents, which are required for the validation of manufacturing processes of plasma derived products, involve either rapid immunochemical PrP-res detection, mostly by Western Blot (WB), or time-consuming and expensive infectivity protocols, that consist of intracerebral inoculation of laboratory rodents, which is the only validated method for the titration of infectivity. We have developed an alternative in vitro infectivity titration assay, based on the infection of MovS6 cells that can be infected with the ovine 127s strain of scrapie. This assay has shown several characteristics that make it an interesting alternative to the reference titration methods for measuring TSE infectivity : it is highly sensitive (~ 80 times more than WB, and comparable to bioassay), specific and reproducible. It is fast (less than 8 weeks), less expensive than bioassay and was shown to be suitable for the validation of manufacturing processes. Experiments are ongoing in order to increase the sensitivity of the assay and/or to reduce its duration. Work is also in progress regarding the validation of the assay for regulatory recognition (comparison to bioassay experiments and analytical validation). Latest developments of the tissue culture infectivity assay will be presented, and recognition by regulatory authorities will be discussed.