Quo vadis Cleaning Validation in Annex 15?

Recommendation

2/3 May 2024

Process Validation - Live Online Training

In the draft revision of Annex 15 of the EU GMP Guide (Validation/Qualification) there were significant changes in the chapter on cleaning validation carry over limits. These changes are based on an EMA draft "Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities" from January 2013. The draft mainly concentrated on an approach for the calculation of the PDE: Permitted Daily exposure (otherwise referred to as ADE, Acceptable Daily Exposure). In the draft revision of Annex 15 this PDE is now mentioned as the sole limit. This causes some insecurity in the industry (see ECA survey on the revision of Annex 15).

Chapter 5 (Production) of the EU GMP Guide was also in revision. Here again the draft demaned the integration of the PDE concept with the goal to prevent cross-contamination. The above-mentioned EMA guideline draft was referenced directly. In the final version of the revision of Chapter 5, this reference is omitted.

Conclusion: What does this mean for the chapter on cleaning validation in the draft of Annex 15? This, of course, will ultimately show in the release of the final version. But it can almost be taken for granted that the PDE concept will no longer be the exclusive concept. Possibly the previously mentioned limits (10 ppm, 1/1000 doses) will be maintained and will stand (equally?) next to the PDE concept? That means if the PDE concept is still to be found.