Integrating Risk Management as an Effective Approach to Root Cause Analysis - Optimize time and cost of product development by managing risk. - BioPharm International

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Integrating Risk Management as an Effective Approach to Root Cause Analysis
Optimize time and cost of product development by managing risk.


BioPharm International
Volume 22, Issue 1



The issuance of the FDA's guidance in 2004 advocating a risk-based approach to current good manufacturing practices (cGMPs) has changed the basic paradigm for quality in the biopharmaceutical industry. This guidance advocates using scientific inquiry as a foundation for developing quality initiatives that will ensure ongoing product quality. Managing risk in the product development lifecycle presents the industry with an opportunity to optimize the time, resources, and cost of developing a drug product. This same opportunity extends to the establishment of our quality argument and all of its related systems.

The challenge in embracing this new approach to quality is shifting from the traditional mindset based on blanket inspection and testing to one driven by control and monitoring. We must change our approach and quality standards for troubleshooting and prevention if we are to realize the agency's vision of quality and business synergy. In an industry where the ratio of quality to operations personnel can reach 3:1, as is often seen in large biopharmaceutical operations, the concept that quality can operate synergistically with the needs of the business is a radical departure from what we have experienced for the last 50 years.

With this shift in philosophy by both industry and the regulatory bodies, we find ourselves reinventing our approach and expectations to fundamental quality activities, such as root cause analysis (RCA). RCA is an approach to problem solving aimed at identifying the basic drivers or causes for problems or events. The philosophy behind RCA is predicated on the belief that problems are best solved by attempting to correct or eliminate root causes, as opposed to merely addressing the immediately obvious symptoms.


Figure 1. Relationship among the components of root cause analysis.
In investigating a problem or event, there are three basic components we need to understand. We have the symptom, which is the failure observed against the expected performance; the mechanism that drove the failure; the contributing state or events that may have supported the failure; and the actual root cause of the failure. Separating these components is the key to an effective root cause analysis. The relationship among these components is shown in Figure 1.

By directing corrective measures at root causes, it is hoped that the likelihood of problem recurrence will be minimized. However, we recognize that complete prevention of recurrence by a single intervention is not always possible. To be effective, RCA is often a highly iterative process, and is frequently viewed as a tool for continuous improvement.

There is no single approach to RCA: it is an amalgam of different tools, processes, and analyses applied appropriately to identify the source of the problem or event. Even so, RCA exercises have not always been completely objective. We have all seen the corrective action and preventative action (CAPA) documents which have been closed, with the recommended root cause and corrective action being operator retraining. In such cases, the problems invariably reappear later because the corrective action was off the mark. An effective corrective action based on an effective RCA should eliminate the problem or event from happening again. In the absence of this reality, the RCA was not effective.

The lack of a disciplined approach to RCA has undermined the effectiveness of CAPA programs and often leads to recurring issues with products. As a result, the focus of many FDA inspections has been the quality and defensibility of RCAs, which are often used to close out a CAPA. Nevertheless, the emphasis in the biopharmaceutical industry on moving toward a more process-centric rather than a product-centric philosophy for quality assurance has laid the groundwork for a more effective RCA exercise. The emergence of operational excellence initiatives has rekindled interest in structured problem solving techniques such as Kepner-Tregoe that methodically drive the analysis toward an objectively defensible final conclusion. But the one thing we have learned as an industry is that there is no magic bullet, no one-size-fits-all solution that we can just buy and implement to meet this shift in quality philosophy. However, a common framework defines all good investigative processes. This article describes and illustrates the application of one approach that is very effective in integrating the basic tenets of Quality by Design and risk management as purported by ICH Q10 as a methodology for an effective RCA.


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