The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has concluded, after conducting a quality review of the genetically engineered monoclonal antibody MabThera, that the batches of rituximab, the active substance of MabThera, that were produced in the U.S. at the Vacaville manufacturing site do not present a risk to public health.
The review of MabThera was initiated after Leptospira licerasiae was unexpectedly detected during an early stage (pre-harvest) of the manufacturing process of rituximab, although the contaminant was not found during later stages of manufacturing of the active substance or in the finished product. Leptospira licerasiae are bacteria that can cause leptospirosis, a water-borne disease that is transmitted from animals to humans. All contaminated material has been discarded.
MabThera is designed to treat non-Hodgkin’s lymphoma, including follicular lymphoma and diffuse large B-cell lymphoma, chronic lymphocytic leukaemia (CLL) as well as rheumatoid arthritis.
To ensure that the medicine supplied is safe, the CHMP reviewed all available quality data provided by the company and investigated the root cause of the contamination. The Danish Health and Medicines Authority carried out a site inspection at the DHMPs request, which included an inspection of laboratories, warehouses, manufacturing and utility facilities, as well as the site’s quality management systems.
The CHMP came to the conclusion that L. licerasiae had most likely been introduced into the cell culture media used in the bioreactors by personnel, that were external carriers and/or through the media preparation process itself.
The Committee points out that batches of active substance produced from cultures that tested positive at pre-harvest are no longer further processed. The management at the Vacaville site has furthermore introduced appropriate corrective and preventive measures in order to minimize any potential contamination and to help improve the detection of the bacteria.
The Committee was satisfied that the findings were not linked to any clinically relevant risk for patients who received MabThera, as no bacteria were detected either in the active substance nor in the finished product. It also found the manufacturing process sufficiently robust enough to kill any bacteria and proteins that were released by the bacteria and therefore concluded that the benefits of MabThera continue to outweigh its risks. The CHMP’s recommendation has been forwarded to the European Commission in order to come to a binding decision.
Written By Petra Rattue