A company gets a 483 warning letter, which among other things criticizes the company’s continued process verification (CPV) approach. The observations include inadequate sampling plans, wrong statistical methods used, and company employees not understanding the statistical methods being used. Only a single quality engineer knows how the tools are being used.
So the company scurries about figuring out how to respond including the adoption of better procedures and more clearly explaining the methods being used. So what is the problem here? Who is at fault? The quality engineer? His supervisor? The plant manager? How should this situation be remedied?
The answer is: all of the above, with the major portion of responsibility on management. Juran’s 85/15 rule says that 85 percent of the problem is in the system with the remaining 15 percent due to people working in the system. Deming says that the blend is more like 94/6. The system in question is the CPV system. This entity is owned by management, who is accountable for the effectiveness of the CPV system including the design, execution and continued enhancement of the system.
Publication of the Process Validation Guidance by the U.S. Food and Drug Administration in January 2011 (FDA 2011) with its Stage 3 addressing “Continued Process Verification” has renewed Pharma and Biotech’s interest in process monitoring. Companies are working to implement guidance, and FDA is assessing progress. There has been considerable discussion regarding what is required to implement and maintain a sustainable CPV system. The FDA document, as it should, provides guidance, not a prescription for the system.
WHAT SHOULD A CPV SYSTEM LOOK LIKE?
The stated purpose of CPV is to “demonstrate that the process is in a state of control” operationally — this means that companies need to maintain process stability and capability over time — for the life of the product or process. A popular response to this need has been to install control charts and calculate capability indices. This is a step in the right direction. Control charts and process capability indices are indeed necessary, but not sufficient.
If CPV is to be effective and serve its stated purpose, it must be implemented as a system complete with a strategy and plan for implementation and sustainability throughout the lifecycle of the process and product. We have learned the hard way that if you want a system to be effective over a long period of time, you need to have a management system in place to guide and sustain the system. This requires the active participation of senior management.
An important question is what should the CPV System look like? This, of course, depends on the organization, process and product involved. At the strategic level CPV will enable an organization to maintain process stability and capability over time enabling us to produce quality product, continually improve the process, reduce costs and remain compliant with regulations. The strategic level should also contain some goal related to maintaining competitive advantage.
At the managerial level, a procedure needs to be in place that calls for the periodic analysis, review, reporting and process improvements. Such an approach is based on the continual evaluation of process data and is done at various levels in the organization.
The operational level utilizes a variety of statistical tools such as control charts, data analytics and graphics and process variation studies to assess process performance and product quality as each batch is produced and batch-to-batch over time. Non-statistical tools such as failure modes and effects analysis are also used. These tools are linked and sequenced using documented procedures.
It has been known for ages that for a system to be effective and sustainable over time it must contain three levels of activity: Strategic, managerial and operational. A CPV approach based on only statistical tools such as control charts and process capability indices addresses only the operational level of the system. When any of the levels of activity is missing, CPV will become ineffective and fall into disrepair.
THE SECRET SAUCE – MANAGEMENT REVIEWS
The ingredient that keeps any system operating effectively — the secret sauce — is management reviews. CPV management reviews take place at several levels in the organization at different frequencies as summarized in Table 1.
The data reviewed and actions taken at each management level in the organization differs. In general, as the level of management increases in the organization the aggregation of the data increases as does the time between reviews. We also see that management review is a “team sport.” Teams conduct the reviews at each organizational level. Each team plays a role in the overall review process.
The review is not a special event. It should be an integral part of the regular management review process. A critical aspect of the reviews is the identification of the need for improvements and the assessment of recent improvement put in place. I recall a CEO admonishing his management staff to “schedule the reviews and show up. Good things will happen. In many cases you don’t have to say a word.” It is, of course, appropriate to ask questions and engage in discussion when needed.