The potential for manufacturing issues to severely disrupt operations remains a constant headache for vaccine manufacturers. In Europe, several major manufacturers experienced such problems during 2012.In October 2012, several EU member states suspended the use of some anti-influenza vaccines manufactured by Novartis because of suspected quality defects. Although there was no evidence of the problems impacting efficacy and safety, the authorities acted as a precautionary measure. The Italian Medicines Agency was the first to act over Novartis' Aggripal, Fluad and Influpozzi products when it received a verbal notification from Novartis. The agency subsequently warned other member states, the European Commission and the European Medicines Agency (EMA). Although Novartis provided the Italian authorities with data it believed supported the high quality, efficacy and safety of their products, other countries followed Italy's lead in banning the products (2–5). Reports of protein particulates in some vials were enough to persuade France, Austria, Germany, Spain and Switzerland to act. Canada and Singapore also followed suit.
According to Novartis, the particulates reported in the vials were all "normal and necessary components" of their influenza vaccines and that the aggregation of these proteins was not considered unusual in terms of vaccines manufacturing (6). Furthermore, Novartis stated that clinical data demonstrated similar safety and immunogenicity profiles to prior years for these products. Additional data from the ongoing seasonal vaccination campaign in Europe had also not revealed any safety signals. Nevertheless, the Italian authorities sought an explanation from Novartis as to why it had taken until October to inform them of the particulate issues, despite the company identifying such problems in July (7).
The manufacturing issues have not only proven to be damaging to Novartis' reputation, but may also represent a new financial setback for the company's vaccines unit. The unit has been underperforming financially since 2010, when it had revenues of $2.9 billion (2). In 2011, reports claimed that the company had made a $249 million operating loss on $2 billion in revenue. The 2012 manufacturing issues will inevitably dampen prospects of surpassing 2010's revenue.
The influenza vaccine manufacturing issue has led to concerns that there will be a shortage of influenza vaccines this coming winter in the UK, Germany, Switzerland and Italy, although most governments should have alternative sources and strategic reserves in place. Germany, for example, has turned to GlaxoSmithKline and Abbott to help make up any shortfall, and predictions from the German Health Ministry suggest that the number of available flu vaccines available in Germany will be 14 million, which is comparable to 2011 (5). Despite these reassurances, disruptions tend to cause controversy between governments, pharmaceutical companies and healthcare professionals about why vaccine shortages occur in the first place. With respect to the situation in Germany, pharmaceutical companies and some physicians have blamed insurance companies, whom they claim negotiate exclusive contracts with vaccine manufacturers in exchange for better rates, which puts patients at risk (5).