When was the last time you wrote a research or term paper? Were you evaluated on requirements like font size and theme? Spacing? And who could forget a word count? Often, extraneous requirements intended to guide continuous improvement and corrective action tasks, like investigations, cloud the value of effective analysis and investigational writing. Yes, space-conscious editors may still require them for publication in trade journals, but this is not the same for all industries.
When it comes to addressing events in Life Sciences compliance, standards and guidelines are not beholden to these requirements. Instead, compliance standards should put more emphasis on the investigation process such as an in-depth investigation with conclusions, action items, and improvement.
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Quality Investigation Standards and Controls
In the Life Sciences compliance systems, regulatory standards do not define rigid process steps for investigations or non-conformances. Like most quality-related issues, the governing body provides recommendations fit for a company to comply with the current quality philosophy. This openness can be an issue. How much analysis is needed for a complaint investigation? Certain standards provide a recommended workflow on top of usually looking for formal documentation, follow-up actions, and monitoring of these actions’ effects.
The FDA provides pharmaceutical companies manufacturing in the U.S. with the Agency’s current thinking for investigations in out-of-specification results for production. This is defined in 21 CFR Parts 210 and 211. 21 CFR Part 211 §192 and requires that any unexplained discrepancy be thoroughly investigated, documented, maintained no matter where in the process the discrepancy occurred and that it includes conclusions and follow-up.
The European Union (EU) provides companies producing medicinal products with rules and regulations that govern the production of these products in the EU. EudraLex Volume 4 (Chapter 8) details the process for when a quality defect investigation is initiated, and the minimum procedures for an investigation. The defect must be described, the extent determined in broad scope, samples needed, risk assessment(s), action planning, assessment of further impact, communication, root cause analysis, and implementation of actions (Corrective and/or Preventive).
Outside of the FDA and the EU, the International Organization for Standardization also has its requirements for non-conformity investigation in many of its management standards. ISO 9001:2015 (Clause 10) requires that when a non-conformity occurs, including arising complaints, the organization shall react and evaluate the need for action to eliminate the cause(s) of the nonconformity. Documentation of the nonconformance, any actions taken, and the results of those actions must be retained.
But effective operating procedures for investigations or other types of continuous improvement aren’t copied and pasted from regulations issued by the industry governing bodies. Common standard wording like “appropriate” or “applicable” are intended to make us think and invest in our processes, not leave us infuriated or confused. As such, the best way to address investigational events is to take a risk-based approach to determine which root cause analysis model is most appropriate. Choosing the most appropriate investigation tool enables a company to discover the root cause of the event in an efficient manner without undue burden.
Guidelines provide a great baseline for a company’s investigation process but still give leeway for exactly how to carry out an effective investigation. Some editing controls may be needed but forms or eQMS field requirements shouldn’t slow down the process. To be effective, a quality investigation must be thorough, timely (documented in a timely manner), unbiased, well-documented, and scientifically sound.4 Investigations must take the problem presented and provide the cause of the problem through analysis. Once the cause of the investigation is determined, actions are taken to mitigate the reoccurrence of the issue at hand. Three common investigation models are “5 Why” Investigation model, Failure Mode and Effect Analysis (FMEA), and the Fishbone/Ishikawa Diagram. All have their respective benefits and limitations. So, how do we determine what model fits your company’s needs when investigating events?
Why Life Science Compliance Needs Quality Investigation
How do you know how to properly determine the process for an effective quality investigation within your company? That’s the million-dollar question! Taking a risk-based approach to determining this answer can provide clarity on the in-depths of the investigation to take.
Risk is defined as the combination of the probability of occurrence of an event and the severity of this event. For example, if you have one batch out of 150 containing microbial growth, the occurrence would be low as occurrence is 0.7%. The severity of this failure could lead to patient harm so this non-conformity is a high severity.
This example gives numerical values to the occurrence (O) and severity (S) and using them together gives us a risk ranking. Depending on this risk ranking, we can categorize and choose which models to use for an effective investigation. For low-risk events, a simpler model can be used to determine the root cause. For higher-risk events, a model that looks at the process more in depth and action items that mitigate or prevent the risk will yield an effective and compliant investigation. If a root cause cannot be identified, all probable root causes should be investigated and addressed through necessary actions.
Concluding a Quality Investigation
Now that the root cause has been investigated, the next step is to create action items that will be implemented to reduce the occurrence of the event. Action items can fall into two different types: corrective or preventive.
Corrective actions are defined as, “Solutions meant to reduce or eliminate the identified undesirable event(s) and prevent recurrence”6, whereas preventive actions are defined as, “action(s) taken to prevent the occurrence of a potential undesirable event(s)”6. Corrective actions are commonly implemented after a non-conformance occurs where the action is reactive (i.e. After a non-conformance is discovered).
Preventive actions are commonly implemented for issues that could arise from a particular workflow (i.e.. In the design of a cleaning validation). To have an effective action implementation process, companies should utilize a balance of the two types of actions and monitor the effectiveness of actions taken.
Monitoring and Continuous Improvement
Just because a quality investigation has been conducted and actions taken, does not mean you’re in the clear. All the guidelines discussed require continuous improvement or follow-up actions, which themselves may seem vague too.
Continuous improvement is a company’s dedication to improving in the suitability, adequacy, and effectiveness of the quality management system. A common way for a company to monitor their events is through trend analysis. A trend analysis is utilized by collecting current and historical data for a specific amount of time (yearly/quarterly, etc.) to identify a pattern. This can be applied to the analysis of complaints, non-conformances, and audit findings. Applicable parties should review the trends and come up with corrective and/or preventive actions. Continuous Improvement is not to just comply with the standards set forth but also to help with a company’s efficiency and employee satisfaction!