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Published on 29 May 2012

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EMA confirms benefit–risk balance of MabThera


Batches of rituximab, the active substance of MabThera, produced at the Vacaville manufacturing site in the USA do not present a risk to public health, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) says.

The Committee came to this conclusion based on a quality review of the genetically engineered monoclonal antibody, which is indicated in non-Hodgkin’s lymphoma (follicular lymphoma and diffuse large B-cell lymphoma), chronic lymphocytic leukaemia (CLL) and rheumatoid arthritis.

The review of MabThera was initiated after the unexpected detection of Leptospira licerasiae at an early stage (pre-harvest) of the manufacturing process of rituximab in bioreactors at Vacaville. 

The contaminant was not detected at later stages of manufacturing of the active substance or the finished product, and all material in which the bacteria had been detected was discarded.

Leptospira licerasiae is a bacterial species that can cause leptospirosis, a water-borne disease transmitted from animals to humans.

The CHMP reviewed all available quality data provided by the company and looked for the root cause of the contamination with the aim of ensuring safe supply of the medicine to patients. 

At the request of the CHMP, the Danish Health and Medicines Authority inspected the Vacaville site, covering laboratories, warehouses, manufacturing and utility facilities and quality management systems at the site.

The CHMP concluded that L. licerasiae had most likely been introduced into the cell culture media used in the bioreactors through personnel acting as external carriers and/or through the media preparation process itself.

The Committee noted that batches of active substance produced from cultures which tested positive at pre-harvest are not being further processed and adequate corrective and preventive measures have now been introduced at the Vacaville site, which should minimise any potential contamination and help improve the detection of the bacteria.

The Committee was reassured that the findings were not associated with any clinically relevant risk for patients treated with MabThera, as no bacteria were detected in the active substance or in the finished product, and that the manufacturing process is robust enough to eliminate any bacteria and proteins released by the bacteria.

Therefore, the CHMP concluded that the benefit-risk balance of MabThera made using the active substance produced at the Vacaville site continued to be positive.

The CHMP’s recommendation has been forwarded to the European Commission for the adoption of a binding decision.

European Medicines Agency

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