Planting hubs around the world
Friede introduces the concept of a Center of Excellence, or ‘hub.’ Traditionally, technology transfer is a bilateral agreement between a MNC and a manufacturer, or between a university and a manufacturer, he says.
“This has been the common case for most technologies in developing countries but it is not very resource effective. Because the know-how goes to a single site,” he explains.
Instead, the team has established technology hubs that teach multiple manufacturers how to make the product, such as the influenza vaccine. And not only do multiple manufacturers acquire the technology, national regulators are also invited to visit the hubs to learn about the technology.
“There is very little point teaching a manufacturer how to make a product, if a national regulator does not know how to regulate this. This is in harmony, it goes hand in hand,” he says.
In this model, as long a manufacturer is able to build his factory appropriately, meet national regulatory requirements, and present a coherent business plan, he will likely make a product that results in improved health, Friede says.
The first such hub, he says, was the Netherlands Vaccine Institute (NVI), now called National Institute of Public Health and Environment (RIVM), where manufacturers from countries such as Mexico, Kazakhstan, India, Thailand, Vietnam, and Indonesia learnt how to develop the influenza vaccine “from A-to-Z.”
Everyone from the technicians, managers, directors, to national regulatory agencies could be trained how to make the product under Good Manufacturing Practices (cGMP) and also how to test and approve the products, he said.
Indeed, the process may expedite technology transfer and localize the know-how, but who pays for all of this?
Friede explains that in the case of the influenza hub, they issued a call for proposals from developing country vaccine manufacturers, who also needed to provide a letter from their government requesting for WHO assistance for that manufacturer.
Selected manufacturers then receive seed grants which vary from one country to another, leveraging on local public or private buy-in which is usually 17-20 times of the original funding. In one instance, the Indonesian government contributed 50 times of WHO seed funding.
“So some countries we were able to leverage; we provided the seed grants, and the local institutions behind contributed much more,” he says.
One success story is India, he says. According to Friede, the manufacturers they worked with had no experience in influenza vaccine development at the start of the project. Just two years later, the Serum Institute of India (SII) received approval for a locally made influenza pandemic vaccine.
“They are really an example of how a well trained workforce, commitment by the industry, plus some assistance from WHO enabled them to make a very good vaccine very quickly. We provided them a seed strain and negotiated a royalty free license for public sector sales to the technology,” he said.
Friede relates the story of his team’s work in Vietnam, which lacked a chicken farm and thus the supply of chicken eggs for viral production. In that particular case, the WHO contribution was straightforward: they simply financed the construction of a chicken farm as well as a water-treatment facility.
In another story, Indonesian adjuvant manufacturers learnt how to produce an oil-in-water emulsion adjuvant from the adjuvant technology transfer hub at the University of Lausanne in Switzerland. They are now performing clinical trials for the locally produced vaccine, he says.
Affordable rabies treatments
Another pet project of the team is the rabies monoclonal antibody technology transfer hub in Geneva, Switzerland.
“Rabies is a big problem in Asia. If you have been bitten by a dog, you have to assume that the dog has got rabies. You will receive first of all a rabies vaccine. But also, if the bite is more than superficial, you should receive post-exposure prophylaxis (PEP),” Friede explains.
PEP treatment of rabies these days takes place in the form of an immunoglobulin which is very expensive, he says. In addition, the immunoglobulin may also be derived from horses, and may result in dramatic allergies.
“So what we have been developing is a cocktail of monoclonal antibodies which will be as effective as the rabies immunoglobulin. We have collected various hybridomas which would appear to be needed to create this cocktail from WHO collaborating centers and we have provided this to two companies in India, and now to a research center in South Africa,” Friede says.
The South African research center is producing the antibodies in tobacco leaves, he says. Called plantibodies, the team hopes that the plant-derived antibodies may be cheaper to produce than those from hybridoma cell lines.
“But no plantibody that we are aware of has been injected into people. Plantibodies have been tested in trials by oral delivery, but not by injection,” he notes.
