Non-Compliance Reports for European Manufacturers of Sterile Medicinal Products

Recommendation

18/19 June 2024
Copenhagen, Denmark

Environmental Monitoring
Compliant and Reasonable

Non-Compliance reports are published by national competent authorities in the EudraGMDP database of the European Medicines Agency (EMA). They relate to inspections both within and outside the European Community (European Union). The Non-Compliance reports are entered into the database by the national competent authorities independently using a standardised form. Such a Non-Compliance report has serious consequences for the company concerned until the deficiencies have been rectified. A suspension of the marketing authorisation as well as product recalls can be ordered.

On 2nd February 2016, the Spanish competent authority published a Non-Compliance report for the Spanish company Farma Mediterrania S.L. Beside deviations in the areas of secondary packing and QC, considerable deficiencies with regard to sterile manufacturing have been criticised. One of them relates to sterility tests: their results have been accepted uncritically although no investigation had been performed to determine the root cause of previous OOS sterility tests. Furthermore, the following major deficiencies were found:

• Media Fills haven't been performed every six months and samples used in the simulation haven't been incubated at the right temperature.
• The air treatment system hasn't been sufficiently qualified as it is only checked when it is "at rest" but not "in operation".
• No test performed of growth promotion of culture media used in the sterility testing, in Media Fill and in microbiological environmental monitoring

On 19 January 2016, the Polish competent authority (GIF) released a Non-Compliance report for the Polish subsidiary Agila Specialities Polska Sp. z o.o. This Non-Compliance report relates almost exclusively to "sterile topics" and lists 29 major deficiencies - among them:

• Design and qualification of the HVAC, laminar air flow system and clean areas
• Cleaning and maintenance of clean areas
• Production and batch release didn't fulfil the GMP requirements
• Change controls for significant modifications of the filling lines. No re-qualification after the changes have been made.
• Pressure differential between clean areas B and C < 10 Pa
• Inexistent or insufficient maintenance in the cleanrooms
• The filtration process was not fully validated.
• Lack of A grade in a lyophilizer

Source: EudraGMDP Database of the EMA