(209c) Commercialization and Quality by Design: Towards An Improved Model for Pharmaceutical Development, Launch and Supply

Five years ago, in response to unprecedented and multifocal challenges in the pharmaceutical industry, Merck adopted a new business model and approach for the development and supply of our products.  This presentation will share how we have moved forward with a new Global Pharmaceutical Commercialization model integrating Lean Six Sigma and Quality by Design (QbD) to meet these challenges and enable us to develop new medicines providing value to patients around the world.

In the past we often relied on a single point of transfer?a knowledge handoff?encompassing key activities between divisions, on the critical path to pharmaceutical product registration.   The commercialization model sought to provide industry leading cycle times, productivity enhancements on a per program basis, and optimization of  the variable/fixed cost ratio by more strategically leveraging external capabilities and capacity. Through the commercialization model, we have been able to recognize these benefits by bringing manufacturing closer to development, optimizing timing of capital investments to avoid significant expenditures where product potential is uncertain, executing a product portfolio strategy that focuses on global optimum solutions that maximize business and patient value, and transforming our culture to meet these goals.

The question we had to ask and answer was "What is the best way to execute on the Commercialization model?  How can we pull together all of the Commercialization elements in a customer-focused way and with a common framework to truly change how we work on a day to day basis?".  The answer was Quality by Design (QbD), but a QbD approach augmented with Lean-Six Sigma methodology. QbD, in our view, naturally required an integrated approach to product and process development, fully aligned with our Commercialization model's aspirations. It also could provide a common framework and nomenclature from development to supply and do so in a systematic and focused way.  The Merck QbD roadmap was consequently constructed with the goal of realizing the opportunities offered by QbD throughout the product's lifecycle.  In development, we looked to the reduction of development costs through the use of prior knowledge,  technology platforms including PAT, and focus on cross-functional optimization to maximize value of process development while minimizing overall work.   Once a marketed product, we sought goals of reducing atypicals, continuous improvement of the process and overall enhancement of customer focus.  

To date, we have greatly exceeded the target of deferring capital until after commercial launch.  We have demonstrated a significant productivity increase for technical resources in our global pharmaceutical organization vs. our pre-2005 baseline while simultaneously supporting a pipeline that is  appreciably larger.   Quality by Design drove the use of the enhanced risk management/risk based development approaches that have resulted in reduced costs while improving process capability (for API, Pharm and Analytical) as measured  by CPK.  Today, all new products are developed  within the Commercialization paradigm, following the QbD paradigm.

Commercialization and QbD (with its Lean Six Sigma basis) continue to be foundational to our future success. It has provided a clear business process for getting global optima solutions codified in the development arena, and laid the foundations for feed forward and feed back processes across the development space and into supply.   The commercialization model has allowed us to create an integrated virtual organization and a global technical community.  Commercialization has also driven a culture where continuous improvement, of processes, and systems positions the organization to meet ongoing and future challenges in the industry.