Big hope for the production of Tamiflu - a bird flu drug - on large scale
Elias Corey, professor at Harvard University and Nobel Prize winner in 1990 for chemical synthesis, is co-author of a letter published in the Journal of the American Chemical Society in May describing a cheap and efficient chemical synthesis to produce Tamiflu. He answers Scitizen?s questions.
Few
words about the context first: in a case of a bird flu pandemic, is there any
vaccine or drug available at the moment?
There is no vaccine available for the virus that would infect humans because
that virus hasn't formed yet as far as we know. The only avian flu virus that
exists now is infective for birds. It would be a totally new virus that would
have to arise through a mutation that would become infective for humans. Without
knowing what that virus is, it's not possible to develop a vaccine. Once the
virus does begin to infect humans, it may take some while for a vaccine to be
produce, it could be anywhere from 1 year to 5 years, so even though vaccine
allows a very desirable preventative for bird flu, it is not the ideal solution
at this point.
What about drugs?
There is a kind of drug that blocks the entry of flu virus into human cells. There
are 2 versions of that: one is in form of an oral pill and the other is given
by inhalation of a spray. It is the oral drug that seems to be the more
effective and the more practical. It is that compound that we have enabled to
synthesize in a way that should make it more widely available.
Making this drug, called Tamiflu, is slow and hard. Why?
It is a complex organic structure and, as it's usually the case with such
structures, you need to have an appropriate starting point for chemical
synthesis. The synthesis must be carried out in several stages, it cannot all
be done in one operation. At each stage some material is lost. In the case of
Tamiflu, the starting material that has been used in the past is a very
expensive complicated molecule. Its supply is limited. The synthesis process
itself is long and the amount of material obtained at the end is not large. Finally,
in the current manufacturing process, as I understand it, there are two steps
that involve explosive intermediates. It is very dangerous to carry out those
chemical steps on large scale. So at present, those two steps represent
bottlenecks in the production.
In your article, you describe a new method to make this drug.
Yes. Our method uses some brand new chemistry that allows us to start with two
very inexpensive ingredients obtained from petrol chemicals. These are also
very widely available. The course of chemical synthesis is efficient and the
recovery at the end is quite high. The number of steps involves in the overall
process is lower than for the previous manufacturing process and also there are
no bottleneck steps. So we think that this method can be carried out on quite
large scale, and we think it should be more cost effective as a manufacturing
process. It's our hope that the suppliers of Tamiflu will be greatly increased
by the use of this synthesis process.
Do you think it can be scaled up easily? Can it be done shortly?
I believe it can be scaled up without any insurmountable problem but it does
take time to carry out an industrial scale up of a chemical process. I don't
know what the timetable will be. That depends on so many things. In the end,
the questions are who does the manufacturing, where is it manufactured and how
long does it take to get the regulatory approval of the method of
manufacturing. That I don't know.
Did you file for an international patent?
No, I did not.
Why not?
I think that in situations like this where the issue is a humanitarian issue,
involving possible lost of many human lives, most important thing is to do
anything one can to minimize those dangers and to increase the supply of the
drug which should result in lowering the costs. So to me, it's just common
sense that in a matter of public health one should do everything one can to
make sure lives are saved.
Prof Elias Corey, thank you.
Elias
Corey works at the Department of Chemistry and Chemical Biology at Harvard
University. He won a Nobel Prize in 1990 for chemical synthesis.
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