Background & Aim Major complications of allogeneic stem cell transplantation are GvHD and infections. T cell depletion (TCD) can effectively prevent GVHD, however it may prolong immune reconstitution and increase the risk of infections. Depletion of TCRab+ T cells combined with the transfer of CD45RA− donor memory T cells can ameliorate the infection risk and simultaneously decrease the risk of GVHD. To generate robust, fully automated and scalable cell manufacturing procedures for high quality personalized grafts, we report the development of a single automated process on the CliniMACS Prodigy®. Methods, Results & Conclusion The CliniMACS Prodigy currently employs two separate applications: The combined depletion of TCRab+/CD19+ cells and the depletion of CD45RA+ cells. The novel integrated CliniMACS Prodigy LP-TCRab-19-45RA depletion process merges these two strategies in one process. Depending on the desired cell composition of the graft, the user can choose to perform either a sequential depletion of CD45RA+ and TCRab+ cells with or without simultaneous depletion of CD19+ cells, a depletion of TCRab+ cells with or without simultaneous CD19+ cells alone or a CD45RA+ cell depletion only. Every application case generates separate memory T cell and stem cell products that can be combined to a final cell product, according to the patient need (personalized graft). With this process, we can effectively deplete 2.4 × 109 CD45RA+ cells from up to 6 × 109 total WBC, and 48 × 109 total TCRab+ cells plus 15 × 109 total CD19+ cells from up to 120 × 109 total WBC. The depletion performance was tested by inhouse verification and external validation runs (n=10) and yielded a mean depletion of 5.8 log (range 5.1 – 6.5) for CD45RA+ cells and 4.2 log (range 3.5 – 5.2) for TCRab+ cells with a stem cell viability and recovery of over 85%. Preliminary results indicate that combined depletion of CD19+ cells resulted in comparable values for depletion, yield, recovery and WBC viability of the target products. For quality control an automated Express Mode flow cytometric analysis software using the MACSQuant® Analyzer was developed enabling fast, accurate and reproducible results. In summary, the novel automated CliniMACS Prodigy LP-TCRαβ-19-45RA depletion process is capable to deplete CD45RA+, TCRab+ and CD19+ cells efficiently from apheresis products with a mean recovery of CD34+ cells of 85%. The performance verification and submission to an European notified body for CE mark are the important next steps.