Oct 23, 2009 (CIDRAP News) – Questions about the tardy US supply of pandemic H1N1 vaccine have increased with the report that most of Novartis’s doses may not reach the country until early in 2010 and a European regulatory recommendation that may have implications for the global vaccine supply.Novartis Chief Executive Officer Daniel Vasella said yesterday that most of the company’s vaccine supply may not be delivered until the first quarter of 2010, Bloomberg News reported yesterday. Vasella made the comments in an interview on CNBC.Novartis has a $979 million contract to supply H1N1 vaccine to the US Department of Health and Human Services (HHS). The company is expected to supply about 35% of the total projected US supply of about 251 million doses, the Bloomberg story said.Today, the European Union’s drug regulatory agency announced it would maintain an earlier recommendation for a two-dose regimen of the three H1N1 vaccines approved in the EU, despite data showing one-dose efficacy for two of the vaccines. The recommendation raises the possibility of a major increase in European demand for the vaccines, with possible repercussions for the US supply.The vaccines covered by the EU recommendation are Novartis’s Focetria, GlaxoSmithKline’s (GSK’s) Pandemrix, and Baxter’s Celvapan. Novartis makes both its US and European H1N1 vaccines in Europe. GSK is under contract to supply some doses to the United States, but it accounts for only a small share of the total supply.Slow flow of vaccineThe flow of vaccine to US providers has been far below earlier projections. At a news briefing today, Dr. Tom Frieden, director of the Centers for Disease Control and Prevention (CDC), said a total of 16.1 million doses have become available for distribution so far. Yesterday Dr. Anne Schuchat of the CDC predicted that the number will reach 28 million doses by the end of this month.Back in July, HHS had projected that 120 million doses of vaccine would be ready in October. But in mid-August that was trimmed to a predicted 45 million doses by mid-October, after manufacturers found that the egg-based vaccine production process was not yielding nearly as much virus as expected.A factor that initially hampered accurate vaccine production projections was the lack of a good test for measuring the amount of vaccine antigen produced, said Dr. Bruce Gellin, director of HHS’s National Vaccine Program Office, at yesterday’s meeting of the CDC Advisory Committee on Immunization Practices (ACIP). He said it wasn’t until late August that an accurate assay for measuring the amount of hemagglutinin became available.At today’s CDC briefing, Frieden said that though vaccine availability is increasing steadily, it’s coming far too slowly.”Vaccine production is nowhere near where we thought it would be,” he said. “Vaccine is our strongest tool, and not having enough of it is frustrating for all of us.”He said manufacturers are working as hard as they can to get as much vaccine out as safely as possible, but vaccine production is as unpredictable as viruses. When the first doses of the vaccine were coming off production lines, he said, officials had to make a tough ethical decision: let supplies build or distribute it right away.”The alternative would be to let it stock up until we have enough for larger populations of people who wanted to get it,” he said. “Doing that would have meant it would be waiting in warehouses when people who want to get vaccinated could be protected.”The CDC is aware of reports of people not being able to get the vaccine, Freiden said. “On the flip side, there is a lot of interest in the vaccine, and we’re glad to see that,” he stated. National polls conducted earlier this fall showed lukewarm interest in the vaccine, though parents seem somewhat more willing to have their children vaccinated than themselves.A reporter asked Frieden if he thought the EU’s recommendation for a two-dose regimen of H1N1 vaccine would affect the United States’ supply of vaccine, much of which comes from Europe. He said US officials aren’t worried, because vaccine data affirm one-dose efficacy. “Our supplies are already preordered and it’s a question of when they get delivered. I don’t think that [the EU decision] would be a consideration,” he said.Dr. Michael Perdue, director of influenza and emerging diseases at the HHS Office of the Assistant Secretary for Preparedness and Response, when asked about the EU recommendation today, told CIDRAP News, “So far we haven’t been told that our order with Novartis is going to be affected in any way.” He said he couldn’t immediately comment further.The EU recommendation for two doses per person was not absolute. The Committeee for Medicinal Products for Human Use (CMPH) said it decided to maintain an initial recommendation that the three vaccines “be preferably used as two doses, three weeks apart.” However, for the Novartis and GSK vaccines, “the limited data currently available indicate that one dose may be sufficient in adults,” the committee said.Frieden, when pressed today about which companies are having production delays, reiterated that it’s not unusual for manufacturers to encounter delays, which have occurred periodically with the seasonal flu vaccine. “Each different supplier has its own challenges,” he added.Frieden said vaccine supply would become more plentiful in the next several weeks, but he held off on making any projections. “Given how far off some of the projections have been from what we have now, I would prefer to just take it one day at a time, one week at a time,” he said.Manufacturers’ assessmentsVaccine manufacturers are currently wary of making specific predictions about when they will finish producing all their doses, but they say they are working hard to meet their contracts.Novartis spokesman Eric Althoff told CIDRAP News today that the company expects to finish making bulk vaccine by the end of the year, but he declined to predict when all the finished doses will be ready.Sanofi Pasteur is under contract to make 75.3 million doses of H1N1 vaccine, about 30% of the expected US supply, at its facilities in Swiftwater, Pa. Company spokeswoman Donna Cary said today that Sanofi expects to finish making bulk vaccine in December.In an e-mailed statement, Cary said, “We have orders for 75.3 million doses of bulk antigen for anticipated delivery between October and December. We are on track to deliver this by December. In fact, of the 16 million doses HHS reports they have available, Sanofi Pasteur shipped 12 million.”Cary said the company has succeeded in “optimizing” the vaccine seed virus to improve yields. “We are pleased to report that yields are now exceeding the yield projections used in early production planning with HHS. In fact, current yields are now close to our seasonal standard. Thus, we do not anticipate the strain yield to be a factor impacting future production schedules.”The company also was able to speed up the licensure of two new filling lines that were not originally scheduled to be licensed until later, boosting filling capacity, Cary reported.MedImmune is under contract to make about 40 million doses of its intranasal, live attenuated H1N1 vaccine for HHS. The company said earlier it did not have the yield problems that other manufacturers reported.Company spokeswoman Karen Lancaster said today, “We’re pretty much on track. We had anticipated about 11 million doses by the end of October, and we’re pretty much on track to deliver that. I can also say we’ve made enough bulk vaccine to fill all the orders, and we’re now working around the clock to get those into sprayers and packaged and delivered.”She said the company’s delivery schedule goes through early 2010, but she couldn’t be more specific about a projected date for finishing production.Another US suppilier is Australian-based CSL Biotherapies. According to the Bloomberg story, a company official said on Oct 20 that the firm was on scheduled to deliver its 36 million doses.