Drugmakers sprinting to develop Ebola vaccines face a series of technical hurdles if they are to get millions of doses ready for use next year — even assuming clinical trials are successful.
The challenges include finding sufficient sterile capacity for filling and packaging finished vials, getting fast quality approvals from regulators, and building a supply chain in Africa for products that must be stored at minus 80 degrees Celsius.
With the World Health Organization (WHO) now expecting vaccine efficacy trials to start in West Africa in December, a month earlier than anticipated, the development program is clearly gaining momentum.
But industry executives, health experts and governments are still grappling with a host of issues — and some differences of opinion — on topics ranging from clinical trial design to factory biosafety levels, according to people who attended a high-level meeting of officials in Geneva last week.
“There is not a funding problem,” said one person at the meeting. “The real issues are all around the practicalities.”
Because it has proved so difficult to slow the world’s worst Ebola epidemic, which has killed around half of the 10,000 officially reported cases so far, many health experts now see a vaccine as a vital tool in controlling the disease.
Far from coming too late, experts at last week’s meeting concluded that “vaccines will have a significant impact on the further evolution of the epidemic in any scenario, from best-case to worst-case”.
That has increased the pressure on all parties to expedite development, production and distribution.
Companies have pledged affordable prices as they race to develop the first vaccines for a previously neglected disease, in collaboration with donors and government agencies.
Two leading vaccine candidates from GlaxoSmithKline [fortun-stock symbol=”GSK”] and NewLink Genetics (NLNK) are already in human safety trials, and another five should begin testing in the first quarter of next year. One from Johnson & Johnson (JNJ) will start trials in January.
The three leading companies hope to make millions of doses over the course of 2015, with GSK ordering five production lines and J&J investing $200 million.
However, the exact number of doses depends on manufacturing yields — something that can vary widely, depending on how well cell cultures grow — and how much vaccine has to be injected into the arm of each person to ensure protection.
The Norwegian Institute of Public Health estimates that 10 million to 27 million doses may be needed, or considerably more if the current epidemic spreads to neighboring countries, according to a document circulated at the WHO meeting.
Biosafety Level 2
Translating bulk vaccine production into vials of product ready for widespread use in Liberia, Sierra Leone and Guinea, where the disease is still spreading rapidly, also needs a massive packaging effort.
“One of the main bottlenecks is filling capacity,” said WHO assistant director general Marie-Paule Kieny, echoing the concerns of vaccine developers.
Because Ebola vaccines use genetically modified organisms, the sterile filling of vials must be done in a so-called biosafety level 2 (BSL2) facility, which only a few companies possess.
Those with BSL2 operations include GSK, Sanofi (SNY), Merck and Novartis (NVS), but in many cases their factories are already working on other important vaccines against diseases such as measles, mumps, rubella and rotavirus.
Options now being actively pursued include sharing capacity between companies and talks with regulators as to whether the BSL2 requirement for Ebola vaccines might be relaxed, although this may cause concern given past biosafety lapses.
Another hurdle that must be overcome is accelerating the quality approval process required by regulators for finished vaccines, which typically involves lengthy checks at various stages in the production process.
The hope is to run some quality checks in parallel, rather than sequentially. That will require the buy-in not only of regulatory authorities in producing countries but also those in Africa to prevent consignments being delayed at customs.
Further consultations are planned for this week to clarify and simplify such regulatory hurdles, and also fine-tune plans for clinical trials, where a U.S.-led plan for a placebo-controlled study in Liberia has sparked some controversy.
While experts agree that testing experimental Ebola vaccines against a control or placebo shot will give the most definitive results, a number of experts question whether this is either practical or ethical in the current outbreak.
Further down the road, the final piece that needs to be put in place is a system for procuring and delivering the millions of vaccine doses that may be ready for deployment later in 2015, through a supply chain that will need specialist refrigeration.
GAVI, the global vaccines alliance, is already working to figure out how to bulk buy a future vaccine at a reasonable price and its board will consider ideas on Dec. 10-11.