Root Cause Analysis Deficiencies

An appropriate level of root cause analysis should be applied during the investigation of deviations, suspected product defects and other problems. This can be determined using Quality Risk Management principles. In cases where the true root cause(s) of the issue cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing those. Where human error is suspected or identified as the cause, this should be justified having taken care to ensure that process, procedural or system based errors or problems have not been overlooked, if present.

Appropriate corrective actions and/or preventative actions (CAPAs) should be identified and taken in response to investigations. The effectiveness of such actions should be monitored and assessed, in line with Quality Risk Management principles.

EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Chapter 1 Pharmaceutical System C1.4(xiv)

The MHRA cited 210 companies in 2019 on failure to conduct good root cause analysis and develop appropriate CAPAs. 6 of those were critical and a 100 were major.

My guess is if I asked those 210 companies in 2018 how their root cause analysis and CAPAs were doing, 85% would say “great!” We tend to overestimate our capabilities on the fundamentals (which root cause analysis and CAPA are) and not to continuously invest in improvement.

Of course, without good benchmarking, its really easy to say good enough and not be. There can be a tendency to say “Well we’ve never had a problem here, so we’re good.” Where in reality its just the problem has never been seen in an inspection or has never gone critical.

The FDA has fairly similar observations around root cause analysis. As does anyone who shares their metrics in any way. Bad root cause and bad CAPAs are pretty widespread.

This comes up a lot because the quality of CAPAs (and quantity) are considered key indicators of an organization’s health. CAPAs demonstrate that issues are acknowledged, tracked and remediated in an effective manner to eliminate or reduce the risk of a recurrence. The timeliness and robustness of these processes and records indicate whether an organization demonstrates effective planning and has sufficient resources to manage, resolve and correct past issues and prevent future issues.

A good CAPA system covers problem identification (which can be, and usually is a few different processes), root cause analysis, corrective and preventive actions, CAPA effectiveness, metrics, and governance. It is a house of cards, short one and the whole structure will fall down around you, often when you least need it to.

We can’t freeze our systems with superglue. If we are not continually improving then we are going backwards. No steady state when it comes to quality.

Driving for Mature Quality Organizations – FDA recent perspective

Theresa Mullin, FDA’s Associate Director for Strategic Initiatives for the Center for Drug Evaluation and Research recently gave a presentation “Update from FDA CDER” at GMP by the Sea (I need to go to that that some-year).

As in other FDA presentations this presentation summarized the Quality Metrics Research Final Report by the University of St. Gallen as the appropriate steps to ensure quality maturity:

  1. Optimized set-up and cleaning procedures are documented as best practice process and rolled out throughout the whole plant.
  2. A large percentage of equipment on the shop floor is currently under statistical process control.
  3. For root cause analysis, the firm has standardized tools to get a deeper understanding of the influencing factors for problems.
  4. Goals and objectives of the manufacturing unit are closely linked and consistent with corporate objectives and the site has a clear focus.
  5. Manufacturers have joint improvement programs with suppliers to increase performance.
  6. All potential bottleneck machines are identified and supplied with additional spare parts.
  7. For product and process transfers between different units or sites,standardized procedures exist that ensure a fast, stable and compliant knowledge transfer.
  8. Charts showing the current performance status such as current scrap rates and current up times are posted on the shop floor and visible for everyone.
  9. The firm regularly surveys customers’ requirements.
  10. The firm ranks its suppliers and conducts supplier qualifications and audits.

This are some pretty low hanging fruit. They are also the pretty necessary in any organization, not just pharmaceuticals.

There was also a little discussion on the use of Q10 that really makes me wish I had been there to hear exactly what was said. I hope it was “Just freaking implement it already.”

In general, useful slides, I recommend going and checking them out.