The Augsburg Confession of 1530 was a key breaking point in my opinion. From then on, Lutherans had a clearly articulated statement of faith, distinct from Catholicism. They were not simply protesting against aspects of Catholicism, but offering a replacement theology. Then in 1536 there is Calvin's Institution of the Christian Religion, serving the same purpose for the Reformed faith.
Having said that, there were some at this time who still pushed for church reform without breaking away from Catholicism, so arguably the date of total separation is later. I think the latest possible year is 1563, when the Council of Trent concluded. At that point there was no more possibility of reconciliation.