Non-Compliance with GMP to CARGILL FRANCE by French National Agency for Medicines and Health Product

Nature of non-compliance : 

Overall, 14 observations were made, including 1 critical deficiency and 4 major deficiencies:

[Critical] The management of semi-finished batches and of the mixing operations was deficient and conformity of the final batches to specifications, notably Ph.Eur. specifications, could not be guaranted.

[Major 1] The site had been manufacturing an active substance without ANSM authorisation.

[Major 2] The change control related to the suppression of one filtration step in the active substance manufacturing process was deficient.

[Major 3] The manufacturing of the active substance had not been made using master production instructions and no batch production records had been established.

[Major 4] No review of batch production records of critical process steps had been done before release of the active substance for distribution.

7 observations are related to lack of traceability, risks of contamination induced by the absence of cleanliness in the production environment, very bad condition of the production equipment and insufficient equipment cleaning procedures. The inspection’s observations also apply to the manufacture of pharmaceutical excipients and starting materials that are intended to be used as ingredients in cosmetics and medical devices, which are manufactured under the same conditions as the active substance.

Source: EUDRA GMP