We work in a highly regulated industry. Whether you are associated with the manufacturing of a drug, a biologic, or a device, you understand the importance of those regulations on the safety and accuracy of the final product. Much like you would not go skydiving without checking all of your equipment before AND after your dive, you do not want to implement a corrective or preventative action without planning for, and ensuring, its effectiveness before and after implementation.
The effectiveness check; a requirement after the close out of your investigation, following a deviation, suspected product defect or other problem (EU GMP Chapter 1.4.xiv). The requirement for effectiveness checks are also part of the US CFR and ICH guidelines (21CFR820.100, ICH Q10 3.2.2.).
But what exactly is the effectiveness check, and how do you apply it adequately?
The effectiveness check is the verification that the root cause was remediated and the quality objectives were met. It is performed as the final act but can be defined as soon as the root cause is known.
When performing an effectiveness check, it usually belongs to one of three different categories:
Trending for recurrence is the most common approach used. However, there are some challenges when using recurrence as an effectiveness check. The initial event(s), requiring corrective or preventative action and thusly effectiveness check, was a recurring event(s) with a known rate of occurrence. This rate of occurrence should be sufficiently high and consistent. The effectiveness check, post CAPA implementation, is aimed at waiting a set amount of time to ensure the issue doesn’t happen again. This only works if there is ample opportunity for it to happen, in case the root cause was not remediated adequately.
With respect to this time frame, this should not be an arbitrary period (3 months, 6 months), but should be based on the rate of occurrence. As a general guidance, the time required is three times the number of batches needed for 1 occurrence (e.g. if an issue occurs 1 in 20 batches, then the time frame should be approximately 60 batches).
Process data is used when the corrective actions are aimed at adjustment or improvement of systems, which are regularly or continuously monitored. This can be continuous process monitoring, like conductivity or temperature, or data that is obtained on a regular basis, like in-process measurements or QC (release) tests. In both cases, it is required to obtain a sufficient amount of data from before and after the implementation of CAPA to trend the data. Furthermore, the adjustment or improvement should introduce a significant shift in the process monitored. The shift or difference observed should be statistically relevant.
Audits and Spot Checks
Whereas the two methods described above are data-driven and provide objective evidence for the effectiveness check, these methods are not always useable. For example, when a corrective action intends to obtain a behavioral change, there is generally no data generated by a system that can be used to verify if the intended change was achieved. In this circumstance, the only reliable method is auditing – go and observe the behavior as a process witness. Although there are drawbacks to this approach, it might be the only one available. As with the other methods, the conditions and requirements for the effectiveness check must be well-defined, taking into account the risks associated with the type of effectiveness check performed.
Completion of the Effectiveness Check
When the effectiveness check is performed, and the CAPA remediated the root cause, the evidence is added to the record, and the file is closed. But what would you do when the effectiveness check fails? In that case, you have to assess where it failed. Generally, there are three possibilities:
Another point to consider is that, in a well-developed quality management system, effectiveness checks are, to a certain extent, inherently part of your system. For example, when the deviation management system includes a check on recurrence for each new event, this could replace the effectiveness check for a recurring issue. Or, when the remediation of the root cause includes a validation, and the validation includes the verification of the desired functioning of the system, this can be used as an alternative to the effectiveness check.
At the moment, the effectiveness check is still a topic that leads to a lot of worries and is not structurally implemented in many companies. Even though it is the final step and confirmation of adequate remediation, and a regulatory requirement, it is not always applied correctly, or occasionally, not applied at all.
Still struggling with effectiveness checks? Don’t hesitate to contact us!