EU GMP Annex 9 - Manufacture of Liquids, Creams and Ointments

What it says

Manufacture of liquids, creams and ointments requires specific attention to microbiological quality given the water content and physical characteristics of these dosage forms, bulk product storage and holding time controls to prevent microbial growth or physical instability, and homogeneity verification throughout batches given the potential for phase separation or settling.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• The water content characteristic of many liquid, cream and ointment formulations creates specific microbiological growth risk that this annex addresses directly, connecting to the broader objectionable organism control principles under 21 CFR 211.113.
• Bulk holding time between manufacture and final packaging is a specific control point this annex highlights, since extended holding of a water-containing bulk product before packaging creates additional microbiological and physical stability risk.
• Homogeneity throughout a batch, particularly relevant for suspensions and emulsions that can separate or settle, requires specific verification since a sample from one part of a bulk batch may not represent the whole.

What inspectors look for

• Whether bulk product holding times between manufacture and packaging are defined, controlled and supported by data demonstrating stability throughout that hold period.
• Whether preservative efficacy and microbiological control are validated specifically for the finished formulation, not assumed based on general product category expectations.
• Whether homogeneity is verified through appropriate sampling across a bulk batch, particularly for products with physical stability challenges such as suspensions.

Related regulations