15/16 February 2024
With the revision of Annex 15 in October 2015, the topic of requalification has become more important. In the former Annex 15 dated 2001, the topic of requalification was "hidden" under the general demand for revalidation (point 45). With the revision of Annex 15, the re-qualification has now its own chapter with - among other things - the requirements for :
In practice, it is sometimes difficult to establish such timelines and criteria for evaluation. In the sterile area, there are sometimes specific references from the regulations to individual devices and processes. For example, according to the FDA Aseptic Guide, HEPA filters in cleanroom class 5 should be tested twice a year. Annex 1 of the EU GMP Guidelines also provides guidelines on this subject (e.g. for sterilisation).
What about equipment in other areas?
In this case, chapter 9 of the revised ISPE Baseline No 5 Commissioning & Qualification from June 2019 on the periodic review can be helpful. The "review" approach, i.e. the evaluation, is presented in two phases.
In phase 1, the existing "direct impact systems" are categorised. Depending on the complexity of the system (complex vs. standard) and the influence on the product quality, the systems are exemplarily divided into the categories 0-3. Each category, except category 0, is then assigned to a "review " period. Category 0 refers to existing systems and the existence of monitoring data. In this respect, no review of these category 0 systems (e.g. water systems) is necessary. There are already data available to be evaluated. For systems in category 1, e.g. autoclaves, the specifications above from the sterile regulations apply. For category 2 systems, e.g. buffer storage tanks, the baseline suggests a two-year interval. For category 3 systems, e.g. tablet presses, the Baseline recommends a three-year review interval.
In phase two, the "review" is executed. The review itself takes place as a three-step process:
If this assessment raises concerns about the impact of the system on product quality, step 2 shall be followed. Otherwise, the process ends here.
If the evaluation in step 2 comes to the conclusion that a system could no longer be in qualified status, the next step, step 3, takes place. Otherwise the process ends here.
According to the baseline, the entire process should be managed by someone with a wealth of experience. The review itself should at least be approved by the system owner and the quality unit. A review form is part of the baseline as Appendix 11 and an example is given in Appendix 12.