Pete is way more generous with his advice given the information you provided. Unfortunately, for me, you haven't provided near enough context. I have some thoughts, but they are just guesses.
Where are you in the knowledge continuum? You ran 1 DOE and think you have arrived at a useful prediction formula? (unlikely, typically model development requires iteration). You only have 1 Y (response variable, unlikely since we live in a multivariate world)? My guess is you mean Least Squares model in addition to neural network? These are two completely different strategies for model building. One based on knowledge and the other based on probability (patterns in the data). How similar are they? How useful are they? How well do they actually predict? What do the residuals look like?
Since you introduced a new tool and saw an effect, what is your hypothesis? Realize, you may not be able to just "add" for the shift as the new tool may interact with other factors in the model. Also, how sure are you it was the new tool explaining the shift? Did anything else change?
I am suspicious you haven't identified all the possible factors that might affect the response(s). Perhaps you should go back to screening and increase your inference space (more factors across changing noise) and continue sequential iterations to build your model.
"All models are wrong, some are useful" G.E.P. Box