Cleaning Validation in the Manufacture of non-sterile Medicinal Products: new Information from the EMA

In our news "Microbiological Contamination Control of Non-Sterile Medicinal Products – EMA Q&A", we drew attention to the EMA Q&A document "What are technical and organisational measures that should be taken into consideration to prevent microbial contamination of non-sterile medicinal products". Designed as a Q&As document, it also addresses cleaning validation in relation to microbiology. What does the EMA expect in this regard?

It clearly states that microbiological sampling should be covered as part of cleaning validation for non-sterile dosage forms, specifically for product-contact surfaces. This also includes documentation in which the sampling locations and techniques are clearly recorded.

The EMA also points out that other parameters of the cleaning process should be taken into account in cleaning validation. One example given is a drying step that prevents residual moisture which could lead to microbial contamination.

The microbiological tests used to analyse active substances, excipients, water, primary packaging materials, equipment, the environment and finished products should be validated. In the event of microbiological contamination, the use of validated cleaning and disinfection procedures is also required.

Interestingly, the document also recommends the principles of the Contamination Control Strategy (CCS) from Annex 1 for sterile medicinal products as a possible option for non-sterile medicinal products. Consequently, many sub-sections of Annex 1 are included in the references. The references are listed in great detail in the document:

• EU GMP Chapter 5, 5.21, Technical Measures: vii (e.g. polishing brushes), viii, ix, x, xi, xii, xiii
• EU GMP Chapter 5, 5.21, Organisational Measures: iii, v, vi, vii, viii, ix, x
• EU GMP Annex 1 (with appropriate modifications): 4.5, 4.7, 4.8, 4.34, 4.35, 6.18, 7.7, 7.8, 7.9, 7.13 (iii & iv), 9.4 (i & ii), 9.5, 9.6, 9.8, 9.11, 9.12, 9.13, 9.30 (Grade D), 9.31 (Grade D), 10.2, 10.9, 10.10
• EU GMP Annex 15: 10
• EU Guideline 2015/C 95/02
• EU Guideline CHMP/CVMP/QWP/496873/2018, Guideline on the quality of water for pharmaceutical use
• ICH Q9 Quality Risk Management

You can find the document on the EMA website.

In summary: among other things, the EMA document provides tips on cleaning validation with regard to microbiology in the manufacture of non-sterile dosage forms. The possible integration of Contamination Control Strategy principles in the non-sterile area is a relatively new approach.

At the ECA event Cleaning Validation, taking place online from 24-26 November 2026, you will learn about the current state of the art in cleaning validation. A post-conference course explicitly addresses the impact of Annex 1 on cleaning validation.