Italian authorities have suspended the use of about 500,000 doses of Fluad, a Novartis influenza vaccine for elderly people, following 13 recent deaths in people who had received the shot, according to company and media reports.
The problem was first reported Nov 28. In a statement today, Novartis said two batches of the vaccine, amounting to about 500,000 doses, have been put on a "precautionary hold" following the reported deaths. It said no causal link has been found between the vaccine and the deaths.
Fluad is the only flu vaccine that contains Novartis's proprietary adjuvant, MF59. It was first licensed in Europe in 1997 and is now approved in 35 countries, but not in the United States, according to a company fact sheet.
Six lots under scrutiny
Italy's drug regulatory agency, AIFA, suspended the two vaccine lots on Nov 28, after three people died within 48 hours of being vaccinated, Bloomberg News reported. On Nov 29 the number of suspicious deaths rose to 11, Bloomberg reported that day, and today the company put the number at 13.
PMLiVE, an online news service that covers the drug industry, reported today that AIFA said the 13 deaths involved people who received the vaccine between Nov 15 and 28 and that six lots of the vaccine are now under scrutiny. The story said the latest death involved an 83-year-old man who had multiple medical problems.
In today's statement, Novartis said, "All Fluad batches have passed extensive analytical and safety testing and fulfill all required quality standards. Preliminary results performed by the Italian Authorities have not detected any manufacturing defect."
The company said the deaths may have been only coincidental, since those who receive the vaccine are elderly.
"Fluad is indicated for and administered to elderly patients . . . with the highest vaccination rates in patients with underlying cardiovascular and other chronic disease, making them particularly vulnerable to sudden clinical events independent of vaccination," Novartis said. "Due to the high level of natural deaths in the target population (estimated at 500,000 per year in Italy alone) and the high number of vaccines distributed (3.5 million in Italy) timely association between natural deaths and vaccinations" does occur.
No evidence of causal link
The European Medicines Agency (EMA) said on Nov 28 that it was working with AIFA and other European authorities to investigate "the cause of serious adverse events, including deaths, in a small number of elderly patients who had received Fluad flu vaccine." The agency said there was no evidence suggesting a causal link between the vaccine and the deaths.
The EMA said the issue would be discussed by its Pharmacovigilance Risk Assessment Committee (PRAC), a panel of experts on the safety of medicines, at a meeting that started today.
Novartis distributes two flu vaccines, Flucelvax and Fluvirin, in the United States. In July the company estimated it would produce a total of about 30 million doses of the two vaccines for US distribution.
In October the company announced plans to sell its flu vaccine business to CSL Ltd., an Australian vaccine manufacturer. The sale will include Novartis's facility in Holly Springs, N.C., which makes Flucelvax, a cell-based vaccine.
Dec 1 Novartis statement
Novartis fact sheet on Fluad
Nov 29 Bloomberg story
Dec 1 PMLiVE story
Nov 28 EMA statement
Oct 27 CIDRAP News story on Novartis-CSL deal