Facility inspections continue to be on the minds of both drug manufacturers and regulators. Over the past year, we’ve discussed the challenges surrounding inspections in our Maintaining Quality and Supply During COVID-19 blog post, as well as providing an update on current Regulatory Guidance for Facility Inspections.
While the official guidance relating to inspections during the pandemic is useful up to a point, it only goes so far in dispelling confusion and providing useful advice. So it was refreshing to see a far more candid and direct blog recently written by Callum McLoughlin, an inspector at the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) Inspectorate. This piece contains a wealth of useful insights, which are summarized below.
In this post, McLoughlin draws on his recent inspection experience and current deficiency data to highlight some of the most common issues they encounter at companies of all sizes and operating models. In particular, he stresses the importance of the Corrective and Preventive Action (CAPA) system and investigations. His preamble notes that “roughly 10% of deficiencies raised in [the most recent] period were directly attributable to poor investigations”, and that these “could also be the root cause of other deficiencies too”.
So, What Do Inspectors Observe?
When inspecting, GMP inspectors are looking for “evidence that the investigation and Corrective and Preventive Action (CAPA) system is operating in a state of control.”
Red flags that suggest this is not the case include:
- Investigations being raised long after the event occurred or taking an unreasonable time to complete
- Root cause analysis being raised as a CAPA to enable premature deviation closeout
- A large proportion of CAPAs being overdue or being extended
- Human error being listed as a frequent root cause
McLoughlin is also wary of situations where root causes are deduced based on past experience rather than evidence:
“Professionals in industry have a lot of experience and knowledge, however this can sometimes mean that a theoretical root cause can be concluded based on previous experience – this is especially true if investigators are not given freedom to apply relevant challenge to all relevant processes and systems. This can lead to conclusions being reached based on assumption rather than an evidence-based investigation.”
What About Human Error?
There’s no question that human error can be a potential root cause. But before citing human error, a thorough investigation is needed to evaluate all other system and process-related variables.
“A common manifestation of this is where companies take the view that long-standing procedures and methods work perfectly and cannot be improved, with errors associated with the task attributed to individuals not following instructions accurately. When the same or a related problem has occurred on several occasions and with different people this is a clear indicator that human error is unlikely to be the true root cause.
Human error should only be cited as root cause when all other system and process related variables have been ruled out. It is plausible that, where human error is a potential root cause, the true root cause could be deficiencies in the training system, an overly complex or difficult to follow procedure, or perhaps other factors such as inappropriate multi-tasking and distraction. It is unlikely that ‘remind/re-train the operator’ will ever be an effective CAPA in such circumstances.”
What Inspectors Like to See
In addition to the warning signs discussed above, McLoughlin also sketched out what “good” looks like from an inspector’s point of view. His inspectorate likes to see the following:
- Effective investigations — Launched with the intention of identifying the true root cause and appropriate CAPAs. McLoughlin notes that investigations should look beyond the first probable root cause to rule out other possibilities.
- Risk assessments — Evidence-based assessments should be detailed enough to cover all reasonable risks, rather than simply building cases to support prior decisions.
- Consideration of patient safety — The impact of quality, safety, and efficacy risks on patients should be central to all investigations.
- Systematic root cause analysis —McLoughlin recommends several proven approaches to root cause analysis that deliver “clear advantages.” A red flag for inspectors are the words “true root cause could not be identified” in your report.
- A well-managed system — Investigation support systems should be monitored to ensure that they deliver meaningful information. In particular, McLoughlin calls for scrutiny during management reviews and escalation to keep the system in control when things go wrong.
For more insights about the current state of inspection procedures, check out our December Update on Regulatory Guidance for Facility Inspections. You can read McLoughlin’s full post here.