A catalyst for organizational change
The last three years have seen a strategic shift in business strategy in the pharmaceutical and biotechnology market that heralds a new era of remarkable change. The status quo is confronted with the emergence of qualified, low-cost manufacturing capability for APIs and finished products in India and the portent of parallel possibilities from China. This has moved the threshold for U.S. and European manufacturers to strive for unprecedented levels of efficiency just to remain competitive. Add to this the FDA's shift to a risk-based approach to product development, and the rules and expectations of manufacturers and regulatory authorities alike are under fire to demonstrate that their processes and products are under control.

Regulatory authorities around the world have embraced the need for greater scientific understanding as the foundation for new product development. Several key guidance documents from The International Conference on Harmonization (ICH) are at the center of this global mindset shift, namely, ICH Q8 (Pharmaceutical Development), ICH Q9 (Quality Risk Management) and the impending ICH Q10 (Quality Management). Each articulates an important imperative of this new approach to drug development and quality. ICH Q8 conveys a more scientific framework for process and product development - termed Quality by Design (QbD) - based on understanding which key drivers affect process stability and ultimately product performance, rather than quality oversight. ICH Q9 outlines a methodology for assessing, mitigating and controlling risk and presents the industry with the opportunity to concentrate quality efforts on only those elements that matter. Still under review, ICH Q10 endeavors to describe a method for integrating ICH Q8 and Q9 requirements into our quality management systems. Together these form the foundation for a new approach to drug development and quality.

In response to this shifting paradigm the industry has looked to Operation Excellence initiatives such as Six Sigma* and Lean Manufacturing to catalyze change within an organization's culture and processes. The reality is stark: an undertaking that purports to change overall organizational philosophies - entrenched in 50 years of regulatory mandates - and move the industry mindset is proving more difficult than it looks. This article describes the use of a focused improvement process called "Kaizen" to rapidly catalyze change within an organization.
Operational Excellence
The fact is, drivers for organizational change can come from many sources within an organization. Jack Welch, General Electric's legendary former CEO who adopted Six Sigma as the foundation for business excellence, highlighted the impact that persistent senior management support and firm commitment to vision have on an organization. Other industries, concerned with compliance as well as productivity, looked to Lean Manufacturing at the shop floor level to achieve their strategic business objectives. Extending classical analysis tools such as Kepner-Tregoe, TRIZ1 and Quality Functional Deployment (QFD) as part of the product development process has allowed organizations to shift away from subjective process and product development toward a more structured, objective approach to business performance management. Operational excellence frameworks such as these share several common elements indicative of systems which are successful in changing organizational thinking:

– Structured methodology: measurable milestones
– Data driven decision making
– Risk based optimization techniques
– Cross-functional effort

Integrating these elements is the challenge that faces most firms attempting the transformation to a high-performing organization.
Lean Manufacturing

Figure 1 (Click image for larger version.)
While Six Sigma programs focus upon eliminating process variation, Lean initiatives essentially focus upon efficiency. Founded by Taiichi Ono at Toyota in Japan, the science of Lean Manufacturing centers on identifying those tasks which bring value to the customer and eliminating, to the extent possible, all activities which are non-value-added in the eyes of the customer. Lean principles do not require statistical analysis; rather they rely on a simple set of tools to address inefficiencies within an operation. The tools within the House of Lean are shown below in Figure 1.

Lean principles attempt to align process productivity with market demand, striving to eliminate finished goods inventory. Tools within the Lean toolkit include:

– Quality, Cost, Delivery
– Shorten Production Flow by Eliminating Waste Just in Time
– The Right Part at the Right Time in the Right Amount
– Continuous Flow
– Pull Systems
– Level Production Built-in Quality
– Error Proofing
– Poka Yoke
– 5S, Visual Controls Operational Stability
– Standardized Work
– Robust Products and Processes
– Total Productive Maintenance
Lean Kaizen
One of the great advantages of Lean is its ability to rapidly realize results. Unlike Six Sigma projects which can often take six months to a year before beginning to realize profits, Lean applies these tools within the context of a rapid problem-solving framework. This rapid framework for continuous improvement is called Kaizen. Kaizen is the Japanese term for continuous improvement and is often interpreted to mean "to take apart and put back together in a better way". The beauty of this approach is that all levels of an organization can participate in a Kaizen – from the CEO down to shop floor technicians and operators. This affords many levels of an organization to focus upon a common improvement goal. Combining focused, cross-functional organizational effort with the rapid deployment timeframe, Kaizen efforts are often termed a "blitz", designed to rapidly realize improvement.

In structuring a Kaizen event it is important to establish that the objective of the improvement initiative is relevant to the business strategy. This ensures that the benefits of the improvement activity will be valued by management and helps solidify the purpose behind the focused effort. One approach is to integrate the chartering activity from the Six Sigma roadmap at the outset of the Kaizen blitz. The chartering exercise is crucial at the beginning of a Lean Kaizen in order to establish clear project success metrics, definition, expectations, communication, and milestones. Simply put, if the metrics for success are not clear then the likelihood of project success is low.

Figure 2 (Click image for larger version.)
When initiating a Kaizen blitz with a new team, some training in the basic tools and philosophy of lean is recommended. Training can then be followed by the chartering exercise. The Kaizen event relies upon iterative, real time characterization, evaluation and improvement. Making sure that improvements are measurable is a key component in defining the process. Keep in mind that if the improvement cannot be measured then it cannot be improved. A framework for executing a Kaizen blitz is shown in figure 2.

Vital elements in promoting a shift in organizational thinking include the project review at the end of the exercise and recognition of the effort by the team toward achieving the goal. Therefore, the final management review should include cross-functional management representation spanning all the departments that participated in the exercise along with middle and senior management. The second critical ingredient in energizing an organization to embrace continuous improvement is to reward the participants for their efforts. Rewards can span the spectrum from peer and management recognition to monetary compensation. These costs should be included at the outset of the project during the payback calculation.
Transforming an organizational culture in the absence of strong senior management vision can be very difficult. Adopting a Lean Kaizen approach to continuous improvement, focusing upon the tactically relevant projects that impact an organization's business strategy provides an ideal framework to rapidly energize the individuals concerned. Integrating the project chartering step from the Six Sigma roadmap will help ensure that project success metrics are clearly understood and agreed to along with project milestones. Such a framework can act as a catalyst for breaking down the resistance to change, which is omnipresent in pharmaceutical organizations today. In addition, it has the power to motivate and reward individuals to embrace the concepts of operational excellence and continuous improvement.
References and Resources
1. Forrest W. Brefogle III, Implementing Six Sigma, ISBN 0-471-29659-7, Wiley and Sons, 1999.
2. Wheeler, Donald, Understanding Variation: The Key to Managing Chaos, ISBN 0-945320-35-3, SPC Press, Knoxville, TN.
3. W.G. Cochran and G.M. Cox, Experimental Designs, ISBN0-471-16203-5, Wiley and Sons, 1957.
4. L. Holpp, and P.Pande, What is Six Sigma?, New York, N.Y.: McGraw-Hill Books, 2002
5. M. George, J. Maxey, M. Price, D. Rowlands, The Lean Six Sigma Pocket Toolbook, New York, N.Y.: McGraw-Hill Books, 2005
6. M. Bremer, L. Daniels, O. Gupta, T. McCarty, The Six Sigma Black Belt Handbook, New York, N.Y.: McGraw-Hill Books, 2005
7. ICH Harmonized Tripartite Guideline, Pharmaceutical Development,Q8, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, November 2005
8. ICH Harmonized Tripartite Guideline, Quality Risk Management Q9, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, November 2005
9. ICH Harmonized Tripartite Guideline, Pharmaceutical Quality System Q10, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, November 2005. Released for consultation May, 2007.
10. James P. Womack and Daniel T. Jones, Lean Thinking, ISBN:0-7432-4927-5, Free Press, 1996
1 TRIZ is a romanized acronym for Russian "Teoriya Resheniya Izobretatelskikh Zadatch," meaning "Theory of solving inventive problems" or "Theory of inventive problem solving".
*Six Sigma is a registered trademark of the Motorola Corporation