Here is a provocation: Quality practices in the pharmaceuticals industry today are what they were in other industries 15 to 20 years ago. It is time to catch up. The regulators recognize it. Pharmaceutical business leaders recognize it.

Six Sigma is an opportunity for operations and quality professionals to modernize quality practices. Those who get there first will experience the triple bonus of lower risk processes that yield significantly higher product quality at dramatically lower costs. There is a clear need for a cultural, or mind-set, change about quality in the industry. Six Sigma is a leadership opportunity to achieve both technical and cultural breakthroughs.

How Far Behind Is Pharmaceuticals Industry?

Between 5 and 10 percent of medicines produced do not meet specification and have to be reworked or discarded. That compares to 0.0001 percent in the semiconductor industry, according to an article in The Wall Street Journal.

Closer to home, the food industry is an example of how far behind the pharmaceuticals industry is in quality practices. Take for example, liquid coffee creamer in single-serving plastic containers. They are filled aseptically. The plastic container is thermoformed at the same time as the contents is steamed, thus sterilizing both, and then it is put together in a laminar flow process.

By contrast, take a packaging line for vials in the pharmaceuticals industry: It is not possible to sterilize in-line, so the line is validated to show compliance to good manufacturing practices, while at the same time accepting a certain, though very low, level of contamination. A much better way would be to understand the parameters that ensure sterility, to do parametric releases rather than sterility tests and to show the regulators certificates of analysis. This has been common practice for years in other industries.

The Compliance Fortress

For fear of getting on the wrong side of the regulators, quality people in the pharmaceuticals industry have become fanatics about compliance and have lost the drive for quality through process capability. They have built a fortress of paperwork, showing compliance, to protect themselves from the regulators. Worse still, they are demonstrating compliance to practices they, and the regulators, know do not guarantee quality. For example, it is common practice to declare a process stable if the company can successfully produce three full-scale batches. This is not statistically valid, but it is done anyway, and compliance to that process is religiously documented even for years afterwards.

And when there is evidence that the process can be improved, it is often not done for fear of attracting the scrutiny of the regulators. How often has it been said, “We can’t change the process because it has already been validated”? “Valid” certainly does not mean stable or capable, which is what the regulators are really interested in.

Science-Based Process Control

Here is a quote from the U.S. Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research in March 2004:

“Neither the CGMP (Current Good Manufacturing Practice) regulations nor FDA policy specifies a minimum number of batches to validate a manufacturing process. Having identified and establishing control of all critical sources of variability, conformance batches are prepared to demonstrate that under normal conditions and operating parameters, the process results in the production of acceptable product. The agency encourages the use of science-based approaches to process validation.”

The FDA has introduced the notion of “safe harbor.” For companies coming forward with science-based evidence that they can improve existing processes, there are no penalties. On the contrary, the practice is encouraged and, in the eyes of the authorities, helps separate the progressive companies from the laggards. Another quote from an FDA paper entitled “PAT – A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance,” August 2003, says: “Continuous learning through data collection and analysis over the life cycle of a product is important. Data can contribute to justifying proposals for post approval changes.” The paper goes on to encourage companies to:

1. Identify and measure critical material and process attributes relating to product quality.
2. Develop mathematical relationships between product quality attributes and measurements of critical material and process attributes.
3. Design a process measurement system to allow real-time or near real-time monitoring of all critical variables.
4. Design process controls that provide adjustments to ensure control of all critical variables. Has there ever been a better invitation to apply Six Sigma to pharmaceutical processes?

Six Sigma and Lean for Pharmaceuticals

By improving process capability, Six Sigma sets the stage for leaner organizations. As published in Pharmaceutical Manufacturing in fall, 2004, Novartis has cut costs by 40 percent and improved cycle-times by 70 percent at its site in Suffern, New York. The company has done it by applying Lean principles not only in the direct labor areas but in supporting functions like quality, IT and maintenance. It has eliminated the need for supervisors by integrating those functions into line teams. Six Sigma is entirely compatible in that it removes the roots causes of deviations which otherwise slow up processes and add to overhead costs.

Leading the Change

The role of business leaders is to create the vision, supply state-of-the-art tools, provide the resources and manage the cultural change. Those business leaders just starting the journey should ask themselves:

• Is there a sufficient sense of urgency to change?
• Do senior managers share a common vision of Six Sigma processes and a Lean organization?
• Where can examples be created as references to demonstrate what is possible and provide opportunities to learn?

Those business leaders who are 12 to 24 months down the road should ask themselves:

• Are enough people being involved to reach the tipping point of 15 to 20 percent of the total population?
• Have first-line managers been sufficiently educated in what is expected of them? Have they been given the opportunity to learn by doing (i.e., be Six Sigma project leaders)?
• Do the company’s managers believe sufficiently in people’s creative potential and the power of teams to help build the future? If it is clear that some will not succeed, then help them find a place where they will be successful.

Those business leaders with 24 to 36 months culture change experience should ask themselves:

• How could the company’s roles and responsibilities be better aligned with the vision of a Lean organization?
• What leading indicators for performance can be used as a dashboard to drive continuous improvement?
• Have process teams been set up to manage the white spaces on the new organization chart on a day-to-day basis?

At no stage along the way, can the leadership for cultural change be delegated.

The Rewards of Six Sigma

FDA Commissioner Mark B. McClellan is quoted in The Wall Street Journal as saying, “Other high-tech industries have achieved enormous quality and productivity gains in the last 25 years. We should expect nothing less from the pharmaceuticals industry.”

Six Sigma is an opportunity for pharmaceutical companies to show leadership. It applies not only to operations processes but to all supporting processes. It will set the stage for transforming companies into truly Lean organizations. The challenge is as much cultural as it is technical, since the two are intertwined. A company cannot expect changes in attitude unless it simplifies and improves the capability of processes people use day in and day out. Six Sigma is not for the feint of heart. But, those who have the courage to combine it with a clear vision and lead a cultural quality change in their businesses will reap the rewards.