EU GMP Annex 10 - Manufacture of Pressurised Metered Dose Aerosol Preparations for Inhalation

What it says

Manufacture of pressurised metered dose aerosol preparations requires specific attention to dose uniformity across the product's labelled number of actuations, propellant filling accuracy given the pressurised nature of these products, and valve and actuator component control given their direct role in delivering an accurate, reproducible dose to the patient.

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

What it means in practice

• Dose uniformity across the full labelled number of actuations, not just the first few doses from a canister, is a specific and significant quality concern for this dosage form, since patients rely on consistent dosing throughout the entire product life, including near-empty canisters where dose delivery can become less reliable.
• Propellant filling accuracy under pressure presents distinct manufacturing challenges compared to non-pressurised dosage forms, requiring specialised filling equipment control and verification given that filling errors are not as easily visually detected as they might be for other product types.
• Valve and actuator components function as an integral part of the drug delivery mechanism itself for this dosage form, meaning component quality control carries drug-delivery-critical importance beyond typical packaging component expectations.

What inspectors look for

• Whether dose uniformity testing data covers the full labelled number of actuations, including doses delivered near the end of canister life, not only initial actuations.
• Whether propellant filling process controls and in-process verification adequately confirm filling accuracy given the pressurised, less visually verifiable nature of this filling process.
• Whether valve and actuator component specifications and incoming quality control reflect their drug-delivery-critical function, not merely standard packaging component expectations.

Related regulations