Critical shortage of first-line therapy for Chagas: The story of benznidazole
In 2011, there were delays in rolling out screening and diagnosis activities in communities at risk in MSF projects in rural Bolivia and Paraguay due to the shortage of benznidazole. This was not just MSF’s problem; shortages in this first-line treatment were experienced in most endemic countries also. The production of benznidazole has been undermined by discontinued production, delays, and mismanagement of distribution mechanisms.
In some ways, this cuts to the heart of the issue when it comes to neglected tropical diseases. Since 2006, when more people began to understand and recognise Chagas disease, the demand for benznidazole increased, not only in endemic countries but also in Europe and North America, where the number of patients diagnosed with Chagas disease is increasing.
In 2003, Roche Pharmaceuticals, which was, until then, the primary manufacturer of benznidazole, transferred the technology necessary for its production to LAFEPE, a public laboratory in Brazil that worked under the mandate of that country’s Ministry of Health. LAFEPE thus became the world’s sole manufacturer of this medicine.
Although LAFEPE had the industrial capacity to produce benznidazole, it did not meet deadlines or properly manage orders of the drug. It also performed poorly when it came to distributing the final product to different countries and it did not have the support of the Brazilian Ministry of Health to do so. There were delays in procuring a new source of active pharmaceutical ingredient (API) and a lack of coordination between the API supplier Nortec, LAFEPE and the Brazilian Ministry of Health. The global shortage ensued.
Mechanisms such as the demand forecasting tool has been created to estimate demand for benznidazole (and therefore estimate production needs) and to coordinate the orders and distribution of the benznidazole stocks through international organizations—PAHO for the Americas (Rotation Fund), and WHO for the European and Asia-Pacific demand—but these, too, have so far failed to prevent the disruption of the benznidazole supply chain.
In November 2011, the Brazilian Ministry of Health committed to take measures to resolve the shortage by the end of the year. By mid-January 2012, the MoH confirmed that 1.7 million tablets were produced and approved by the regulatory body, with an additional 1 million tablets produced to be held as stock. It is not clear whether this will really cover current demand, however,PAHO has never shared a plan to ensure the proper distribution of existing stocks to the countries and patients who need it most.
In February 2012, ELEA, a private pharmaceutical company based in Argentina, announced that it had produced and registered generic benznidazole. The first batch produced is being donated to treatment programmes in Argentina. Future production could be launched to respond to the needs of other Chagas endemic countries. Other initiatives in Europe are looking into new formulations of the drug.
However, these are not the only issues. At present, there is not enough of the active pharmaceutical ingredient (API) to produce future benznidazole batches in LAFEPE. The price of the API for new batches of benznidazole may increase by 40%, resulting in a 30% increase in the final product. (ELEA has not had issues in production of benznidazole as they also produce the API.)
MSF will be following all these initiatives very closely. Access to benznidazole needs to be facilitated through registration of the product in countries and its inclusion on the essential medicines list (EML) needs to be considered. The price of benznidazole needs to remain as low as possible, so that price does not become a barrier to treatment.