What are those factors or predictors of success for regulatory GXP inspections? Is it possible to know how your GXP inspection will go based on certain predictive criteria? The answer to these questions is challenging and, at best, difficult to say. I have seen some plants with excellent overall operations have significant issues raised during inspections and, of course, the opposite… sites that I know had numerous vulnerabilities, yet successful regulatory inspections. However, my personal experience with several hundred regulatory inspections has revealed a number of items that I would term “predictors of success” that can help you ascertain the likely result of any specific plant inspection. Having this understanding is helpful for your existing sites, but might be especially helpful in assessing new suppliers, newly acquired operations, or for leaders when first assessing operations.
These items, in total, are predictors of regulatory GXP inspection success:
- History of both site and company inspection results – If your company or particular site has a history of compliance concerns, even if no concerns for the specific site of concern have been noted, the scrutiny and likelihood of citations increases significantly. Global GXP investigators do review the compliance history of a site and related sites for the parent company before beginning an inspection. Investigators have been trained to “connect the dots” and look for patterns across the company for non-compliance. Thus, any history of concerns at any location within the corporation elevates the risk for your site.
- Plant profile or risk level (e.g., product portfolio) – Regulators have clearly mandated that inspections and depth of review vary as the risk profile for the site increases. So, you can expect more frequent, more in-depth, and longer inspections for sites manufacturing parenteral pharmaceuticals than manufacturers of active pharmaceutical ingredient (API) manufacturers. So, generally, the higher the risk level of your products, the more complex, and the more safety risk posed (e.g., sterile versus non-sterile), the greater the potential for compliance concerns and inspection success.
- Number and severity of recent product quality or safety issues – Perhaps, the single most prevalent predictor of inspection success is the number and severity of recent product quality or safety issues, such as recalls, Field Alert Reports, issues noted in the press, etc. These events will assuredly receive significant attention during inspections and regulators will typically spend inordinate time reviewing these events. Their reviews will be deeper and more rigorous than for other systems and processes. Because of the concern with public safety, these issues are highly prone to non-compliance citations. Thus, the more of these you have experienced and the more severe risk to safety they get, the likelihood of non-compliance citations increases significantly.
- Repetitive quality or compliance issues – One certain indicator of compliance concerns is the number or repeat issues noted in your quality systems. For example, how prevalent are repeat complaints, repeat product failures, repeat inspection citations, repeat investigations, etc. The fact that you have significant issues with repeat events indicates failing or inadequate root cause analysis and/or corrective and preventive action (CAPA) systems. If these are deemed inadequate, you can nearly be certain of non-conformance citations and subsequent concerns.
- Sophistication of quality and laboratory systems – Because of regulator emphasis these days on data integrity, having sophisticated systems that remove human interaction will eliminate some of the concerns experienced by some firms. So, the more advanced these systems are, the less concern regarding data integrity SHOULD exist. Certainly, you must have robust validation of these systems, but having systems considered in the industry to be state-of-the-art (such as laboratory information management systems, electronic laboratory notebooks, enterprise quality management systems, etc.) diminishes some of the potential non-conformance concerns that we have all read about in public press.
- Trends for quality metrics – Quality metrics are another “hot topic” for GXP regulators. If your systems include the tracking, trending, regular management review, and proactive action around findings, the risks for non-compliance citations during inspections are diminished, especially if trends indicate improving results.
- “Trust” quotient for Quality leaders – You may not see this item on any other list of top concerns in anticipation of regulatory inspections. But, in my extensive experience, the ability of regulators to develop a professional and trusting raporte with the site’s Quality leaders is a profound advantage. So, if you can ascertain the “trust quotient” for your Quality leaders, you have a significant predictor of inspection success. In my opinion, factors that should be considered in this “trust quotient” include: overall competence, demeanor under pressure (cool and confident), “command” presence before and during inspections (ability to instill professionalism, confidence, and efficiency in others), and ability to “connect” with others, including regulators. So, in summary, a leader with a high “trust quotient” will exhibit these five “C’s”: competence, cool, confidence, command, and connection.
- Proactive versus Reactive culture – You can get a very accurate and quick prediction of inspection success simply by gauging whether a site has a proactive versus a reactive culture. Does the site already know its vulnerabilities and is working to remedy them? Are there systems to predict when issues are eminent and the subsequent action to prevent them? Or, is the site simply reacting to every individual event that occurs? I tend to view this in terms of offensive versus defensive. Is the site on the offensive to improve or is it simply in a defensive shell to fix issues that go wrong? Identifying this can help you predict inspection success.
- Technical competence across key functions – A strong compliance culture is often marked by a high level of technical competence across all functions, such as Manufacturing, R&D, Regulatory Affairs, in addition to Quality. When it is apparent that these other functions have strength and understanding of GXP compliance and exhibits a real sense of proactive compliance, you can be certain that the overall compliance position for the site is strong.
- Cost cutting environment not balanced by continuous improvement – Finally, cost improvement is a real factor in today’s competitive world. There is nothing wrong with a concerted effort to eliminate waste and improve costs within a GXP manufacturing arena. However, when the approach of these efforts is simply to cut costs without balancing it with continuous improvement (e.g., waste elimination, process improvement, working smarter, etc.), the risk for compliance concerns is elevated. The extent to which these efforts seek to improve costs through continuous improvement can be indicative of the culture of compliance at the site.
Certainly, these items alone cannot tell a complete story. We must certainly consider results of internal audits, industry/regulatory trends, unique vulnerabilities, quality costs, robustness of quality systems, etc. However, if you endeavor to create a relatively manageable list of items that, in concert, can predict the relative compliance posture of a site, this list of ten items can provide a highly correlated assessment of inspection risk. You can even quantify the relative risk of a site by grading the site in each of these ten items with a score that allows a rough comparison site-to-site (give each item a grade between 1 and 10, then total the score).
Understanding the relative risk of GXP inspection non-compliance can be very helpful in allocating resources, allocating funding, or decision-making regarding compliance enhancement activities. Good luck in your own assessment of inspection readiness!