Implementation of any significant change is difficult and challenging. Most papers over recent years support the statistic which says 70% of change projects fail. The generalized reasons for this are many fold, including, scope creep and lack of embedding and sponsorship. This paper highlights some of the specific issues and challenges that have been observed whilst engaged in major organizational changes in Pharmaceutical R&D. We will use specific references to a recent process implementation in a mid-sized pharmaceutical company as well as examples from a similar change exercised in large pharmaceutical organizations. Through contrast and comparison we will highlight some areas where all companies struggle and areas where some companies are more successful and why.