On-going complex integration schemes and developments in processes present significant challenges to lithography in manufacturing advanced semiconductor integrated circuits. Although APC solutions are in place to assist in achieving robust CD control and overlay, there is a great need to increase the 'knowledge' of the system with respect to other contributors impacting the process. The problem becomes more complex in case of an ASIC Prototyping Fab where there is no big runner concept. This leads to the need of a product effect management requirement (Product layout and reticles impact). For this reason, we developed the multivariate R2R controller. This paper discusses the multi-variant methodology and results of a new R2R regulation algorithm in a 65nm node process. Specifically, parameters such as linear combinations of terms, alignment variation for overlay modeled parameters (inter-field / intra-field), CD impacts (reticles, process, tool, STI stack etc) are studied. New solutions for future technology nodes are presented in this paper. It includes for each contributor a multivariate method to assess vector responses and noise contribution. This is being applied on CD and Overlay measurement feedback. For each source of variation (or "Contributor"), the multivariate controller provides the estimated level of compensation requested to meet the target and the level of noise induced on lot processing. At the moment the multivariate R2R controller runs in production. A real evaluation of the existing sources of variations and noise is possible and demonstrated. The result is a significant regulation performance improvement.