HIV Drug Availability and Potential Manufacturing Opportunity

Global spread of HIV/AIDS has been and is a cause of alarm. Approximately 33.4 million people are estimated to be infected with HIV/AIDS and about 30% of this population can use the antiretroviral therapy (ART). Of this number about 42% are getting the treatment. This could be due to pricing and/or their availability or a combination of both. There are methods and means to lower the cost and increase availability. I have used AZT (Azidothymidine/Zidovudine) an ART component as an example to illustrate the need for manufacturing technology innovation that can lower prices and increase availability.

In general majority of the active pharmaceutical ingredients (API) are manufactured using batch processes. This is more due to tradition rather than the process chemistry and economics. This holds true for high and low volume actives. Some of the actives due to their chemistry and volume have become commodity chemicals and are produced by continuous processes. However, batch processing is still the preferred method of API manufacture in China and India irrespective of their volume.

Under Clinton Foundation HIV/AIDS Initiative (CHAI), prices of some of the HIV/AIDS drugs have been negotiated with the suppliers from India and China. AZT (300 milligram) tablet is priced at 13.3 cents.

Doing a reverse calculation and using about 80% tablet formulation yield, one can calculate potential bulk selling price of the azidothymidine. Using two 300-milligram tablets per day about 2.4 million pounds of azidothymidine would be needed for about 4 million patients. At $25.00 per kilo, the cost of the API content would be about 1.88 cents per tablet. If the formulation, excipient cost and profit were considered to be 5 times the cost of API (an estimate), the cost of finished tablet would be about 11.25 cents per tablet compared to 13.3 cents from CHAI. Thus the assumption of $25.00 per kilo for bulk API is not un-reasonable. All of the AZT in the above consideration is produced using batch processes.

In the coming years under the new World health Organization guidelines, if the number of people needing treatment grows to 14 Million, there would be a supply problem. The capacity of the existing batch processes would have to be increased to about 8.5 million pounds of AZT per year. Similar steps would be needed to increase capacity of other members of the ART cocktail. Other alternate is to develop and commercialize continuous processes.

A continuous process would not only increase throughput but also will lower the manufacturing cost and consistently produce product of high quality. Combination of improved manufacturing technology and throughput can easily lower costs by 20-25%. Based on the reported chemistry, it should be feasible to develop a continuous process. We should never forget that most of the actives are fine chemicals first and drugs second. Acceptance of this fact might facilitate development of better manufacturing technologies. If better technology drops the price of AZT from 11.25 cents per tablet to 9 cents this would be a significant improvement.

A continuous process would have much higher throughput than the batch processes facilitating availability of the needed drug. Plants can be ramped up and down to meet the market demand. Three plants using continuous processes and operating at about 400 pounds per hour (24/350 at 85% on-stream-time) could meet the global demand of AZT and give the operators higher profit margin. Strategy discussed above could be extended for other components of the HIV/AIDS cocktail. It would be a win-win.