Quality Risk Management (QRM) and Knowledge Management (KM) are positioned as dual enablers to an effective Pharmaceutical Quality System. While there is broad agreement QRM and KM are highly interdependent in principle, there is recognition they are not well integrated in practice, and better integration is an opportunity to better manage risk. A framework, the Risk-Knowledge Infinity Cycle (RKI Cycle), has been proposed to better integrate QRM and KM which can be applied across the entire product lifecycle. Details of the framework are explored as application of the RKI Cycle to the Commercial Manufacturing and Technology Transfer lifecycle phases is illustrated through multiple short case studies, including examples to demonstrate the benefits of effective tacit knowledge transfer. A reimagined PQS foundation is presented, enabled by QRM and KM as intentionally connected and synergistic practices, as a means to improve reduce risk and ultimately benefit patients.