Drugs are expensive. That is something the whole world can agree on. People are spending too much on drugs and an unprecedented amount of population does not even have access to medications in the first place. Diminished access to drugs may stem from many factors, but one is certainly the expense of manufacturing the drugs. Now, scientists are addressing this by redesigning the processes with new technology — making it simpler and much more cost effective to produce drugs.
Collaboration between divisions, a pressing issue to the progression of process development, is facilitated at the annual Green Chemistry and Engineering Conference hosted by the ACS Green Chemistry Institute®. Themed sessions are held to bring together people with similar studies and motivations to foster a more united effort in our advancements to a greener and more sustainable future for all. One session in particular showed much potential for growth in this field. Continuous chemistry, quite possibly at the forefront of advancement, is being used to develop new and innovative synthetic processes to make medications more accessible around the world.
One of the talks at the Green Chemistry and Engineering Conference came from Frank Gupton, Ph.D., from Virginia Commonwealth University. Gupton was provided a grant from the Gates Foundation circa 2013 to found the Medicine for All Initiative (M4ALL), which has the goal of reducing medication costs while improving patient access to medications through the transformation of the pharmaceutical manufacturing industry.1 Since its founding, Gupton has enlisted help from the University of Washington and MIT in pursuing his efforts. The initiative focuses on the redevelopment of generic drugs. These are drugs that have outgrown their patents and have been fully vetted by regulatory institutions.4
Means of Change
Chemists find that the main cost drivers of generic drug prices are found in the starting materials, active pharmaceutical ingredients (API), and the type of production method used (batch vs. flow).1 The issue around starting materials is one observed in all divisions of chemistry as we begin to uncover the limited availability of many of the essential elements used in the chemical reactions seen in academic, governmental and pharmaceutical labs. As economics teaches us, when a low supply meets a high demand, prices will rise.
APIs are the costliest part of generic medications. These account for 65 to 75 percent of their selling price.4 The API is the ingredient that is biologically active, allowing a drug to serve its purpose within the human body, making it crucial to the overall utility of a medication. These have become exceedingly expensive, causing the drug companies themselves to begin outsourcing their production.3
The prices attached to each of these components are mainly dependent on economic factors, which make it hard for chemists to come up with many alternatives aside from developing novel methods of using less expensive starting materials or cheaper production methods. The former is an issue many green chemists are finding themselves working on as they attempt to find ways to utilize renewable biomass feedstocks rather than the limited, cheaper petroleum ones vastly used in today’s market.
As for the latter, there is a more efficient method of drug development that has been implemented in academic research labs across the world and is starting to grain ground in the pharmaceutical industry. Most drugs are currently manufactured under a batch process, which involves specific quantities of solvents, reactants and catalysts finding themselves in a container where the reaction is allowed to proceed.2
The alternative to this, as discussed at the Green Chemistry and Engineering conference, is continuous, or flow, chemistry, where reactions are done under constant motion. Rather than looking at stoichiometric ratios, we now have the ability to use flow rates to determine the yields of our chemical reactions. Under batch conditions, each reaction is different in its own way, but with flow you are capable of developing a more normalized synthetic method where you have complete control of all variables and can change them quickly at will.
This method has yet to be implemented in industry with the strength and vigor it deserves. This is not due to a lack of desire to make the change, but more a lack of the ability to do so. According the Dr. Gupton, the two main barriers come from cultural expectations and legacy investments. The issue with culture is due to how used to batch processes chemists are. Flow is more familiar to engineers who do not do most of the work in process development. Investors, on the other hand, resist change when something is working well. In a profit sense, the batch process works just fine. Regardless of the barriers to implementation, the work must be done somewhere where the benefits can be seen. This is exactly what Dr. Gupton and the M4ALL initiative is doing.4
Advances
A major success for the initiative was achieved in the development of a new synthetic process for the HIV drug Nevirapine. The condition of their grant was to reduce the cost of this drug by 10 percent. What they did reduced it by 40 percent.4
M4ALL has reached a global scale as they have been recruited by the government of the Côte d’Ivoire to help develop flow chemistry infrastructure that allows the country to develop its own medications, greatly increasing domestic access. The country has experienced much turmoil in the recent past and is exposed to a multitude of diseases. Development of this infrastructure will greatly improve the lives of its citizens and the future of the country.4
Women and men like Dr. Gupton and all the others who presented their research at the Green Chemistry and Engineering Conference are paving the path for future drug development processes. It is now our duty to encourage, help or act in any way we can to progress this science. The future relies on our adaption to sustainable and cost-effective techniques, and it is not through the effort of scientists alone that this will be achieved. Visit the ACS Green Chemistry Institute® site to find ways in which you can help advance the valiant efforts of scientists on the bench who cannot do their work without the help of others.
1 "Medicines for All Institute Initiative Advising & Introductions." The Arcady Group. N.p., 14 May 2017. Web. 21 June 2017.
2 Porta, Riccardo, Maurizio Benaglia, and Alessandra Puglisi. "Flow Chemistry: Recent Developments in the Synthesis of Pharmaceutical Products." Organic Process Research & Development (2015): n. pag. ACS Publications. Web.
3 Stone, Kathlyn. "What Is an Active Pharmaceutical Ingredient?" The Balance. N.p., n.d. Web. 21 June 2017.
4 "Dr. Frank Gupton." Telephone interview. 21 June 2017.
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