PZQ Manufacturing Capacity

Published by MikeGretes on 12 June 2010 - 1:04am

Subject 

Request for Help

Let's think long-term: How best to scale up production of PZQ?

This is likely most economically done in India or China (possibly Brazil or South Africa), all of which have well-established pharmaceutical manufacturing sectors.  However, building manufacturing capacity in poorer disease-endemic countries stands to have enormous benefits for economic development and potential to eventually better meet local and regional general pharmaceutical demand! 
Best places to start?  Perhaps Uganda (starting with Quality Chemicals Industries, which opened a facility in Kampala recently pre-qualified by WHO to manufacture antiretroviral HIV drugs), other relatively disease-endemic countries (e.g. Rwanda) or other regional economic powers (e.g. South Africa).

Some of the African science and drug development networks could be helpful in identifying partners and determining how best to proceed: ANDI, SSI, ISHReCA, or the Emory South Africa Drug Discovery Program.
A major challenge may lie in weak regulatory capacity (complex and difficult to navigate) in many African countries.  
Thoughts?  Comments?

Comments

Being aware of the current manufacturing situation for praziquantel and having refrained from making comment for the last 9 months, I can tell you this:

1) The precursor to praziquantel is mainly made in China for a very low price and is exported to Indian companies (and possibly South Korean ones.....) for doing the final step and formulation. From there is is sold (with a very low profit margin) into Africa for $0.06-0.07/tablet.
2) The WHO is very aware of the situation as it is partially funding Matt's work. It also published a large document of the supply situation which can be accessed from its website, though this was done in 1998 and things have moved on since then.
3) The Ugandan companies have mainly been set up as partners (fronts?) to Indian companies in order to avoid patent problems that now exist in India/further reduce costs (and use Indian processes that have been transferred). I'm sure that you are aware of the main one that I am talking about through your organisation's contacts (same one as in point 4).
4) There is a company that is already producing racemic material which is ready to go with chiral production once an economic route has been developed (more info on this, but not allowed to say!). Maybe this could be transferred at a later date to Uganda.
5) Setting up a new facility, unless supported by governments, is going to add significantly to the overall manufacturing costs. As such, it will be much better to use a pre-existing facility in a low cost manufacturing country.

To be honest, I think that manufacturing is the least of the concerns on this project; the real task is to obtain a viable, cost efficient method for its preparation and obtain a manufacturer who is willing to make very low/non-existent margins. They do exist!

I'm afraid that something that has been missed in all of this discussion is, what the situation is on getting this into the market? Normally, in a developed world disease situation, a "chiral switch" such as this would require it to be considered as a completely new drug with all of the associated toxicology and clinical studies of safety plus efficacy. Would it be that, in a situation such as this where the main recipients would be in the third world and the objective is on cost constraint, that the requirements would be relaxed and the associated studies much more limited? Clearly the drug is well tolerated, but I'm sure that there is a large group out there which would object to this approach and see it as potentially dangerous.

ndt228's picture

I agree with "guests" last paragraph.  This is a vital debate to be had, as it sets the entire context of what may need to be done to launch (R)-PZQ.  If it is got wrong, it will either cost much unecessary effort & expense, or set back the launch by years.  I have posted a new "Project Planning" thread which attempts to address this area more fully.