Over time, industry came to believe that validation had to include a broader range of equipment and processes and a greater
level of detail, and as a result, validation costs went up. In response, the industry attempted to distribute the responsibility
for validation among participants in the quality process. For example, industry suddenly decided that validation had to include
commissioning activities and engineering pre-cursor activity to equipment qualification, so they started requiring that contractors
and subcontractors test and document various aspects of IQ. The approach of requiring increased involvement from vendors also
extended to factory acceptance tests. Such tests—which have ranged from simple vendor testing and certification to constructing
simulator panels to mimic the actuation of automated components—have also ranged in their true relevance to the validation
Market drivers completely unrelated to the field of validation often have determined the amount of effort put into validation.
For example, when equity markets dried up in the late 1990s, emerging biotech companies shifted their emphasis from scientific
investigation to bringing product to market as quickly as possible. The industry looked for cheaper and faster ways to push
through the validation process to move programs forward quickly. The result was simpler process validation studies that focused
on building three validation lots to demonstrate process predictability, rather than focusing on true process understanding.
Likewise, companies began buying more equipment from suppliers who offered "canned" validation protocols that could be purchased
and implemented, rather than developing their own protocols to challenge the equipment and thus increase the probability the
equipment would meet the needs of the process. The implication of these shifts was that validation was necessary, but not
essential to sound process development.
This short-cut approach to validation resulted in processes that were less stable at the commercial scale. FDA's recent revelations
about high-profile, approved products that may be unsafe, such as Vioxx and Serevent, and Congress's pressure on industry
to find ways to reduce the cost of drugs to the general public, have impacted both Big Pharma and biotech. In response, the
industry has recognized the need for a better way to reduce process and product risk.
The answer was a shift to a more scientifically driven development approach, often referred to as "Operational Excellence,"
or "Process Excellence." This approach integrates process, quality, and business requirements to promote the science of development.
These quality initiatives integrate Six Sigma, Lean Manufacturing, Kepner-Tregoe, Theory of Constraints, Design of Experiments,
and Balanced Scorecards to establish process understanding. These methodologies emphasize the need to objectively define,
measure, and characterize critical variables that affect a process. While testing and data collection are integral components,
verification is the final culmination of the quality assessment—not the basis of quality.
Looking closely at these approaches, however, reveals that they based in a large part upon an approach that has been integral
to our quality systems for over 70 years—Walter Shewhart's cycle of Plan, Do, Check, Act (PDCA).
PLAN, DO, CHECK, ACT
Walter Shewhart, an enterprising statistician who worked at Bell Laboratories in the US during the 1930s, developed the science
of Statistical Process Control. An offshoot was the PDCA Cycle, often referred to as "the Shewhart Cycle." This tool was adopted
and promoted from the 1950s on, by W. Edwards Deming, the renowned quality management authority, and as a result the tool
also became known as "the Deming Wheel" (Figure 1).
Figure 1. PDCA "The Shewhart Cycle"
The PDCA Cycle was the first tool broadly adopted as a framework for continuous improvement. PDCA is a four-step quality improvement
cycle that promotes continuous improvement based on the method of design (plan), execution (do), analysis (check), and evaluation
(act). Sometimes referred to as plan/do/study/act, the cycle emphasizes the constant attention and reaction to factors that