International Epidemic Honors Colloquium at UMass Boston Berkeley W. Cue, Jr. PhD UMass Boston Class of 1969 October 7, 2013

Outline for Today Using green chemistry to increasing availability and lower costs for HIV AIDS drugs New technology for rapidly preparing vaccines A general Q&A session addressing the pharmaceutical industry

Using green chemistry to increasing availability and lower costs for HIV AIDS drugs A + B -> Product + Waste E-Factor = Wgt Waste/Wgt Product

Green Chemistry “…the utilization of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products.” *Source: Paul T. Anastas and John C. Warner, Green Chemistry: Theory and Practice (New York, NY: Oxford University Press Inc., 1998). ISBN

The Twelve Principles of Green Chemistry 1.Prevent waste: Design chemical syntheses to prevent waste, leaving no waste to treat or clean up. 2.Design safer chemicals and products: Design chemical products to be fully effective, yet have little or no toxicity. 3.Design less hazardous chemical syntheses: Design syntheses to use and generate substances with little or no toxicity to humans and the environment. 4.Use renewable feedstocks: Use raw materials and feedstocks that are renewable rather than depleting. Renewable feedstocks are often made from agricultural products or are the wastes of other processes; depleting feedstocks are made from fossil fuels (petroleum, natural gas, or coal) or are mined. 5.Use catalysts, not stoichiometric reagents: Minimize waste by using catalytic reactions. Catalysts are used in small amounts and can carry out a single reaction many times. They are preferable to stoichiometric reagents, which are used in excess and work only once. 6.Avoid chemical derivatives: Avoid using blocking or protecting groups or any temporary modifications if possible. Derivatives use additional reagents and generate waste. Paul T. Anastas and John C. Warner, Green Chemistry: Theory and Practice (New York, NY: Oxford University Press Inc., 1998).

The Twelve Principles of Green Chemistry 7.Maximize atom economy: Design syntheses so that the final product contains the maximum proportion of the starting materials. There should be few, if any, wasted atoms. 8.Use safer solvents and reaction conditions: Avoid using solvents, separation agents, or other auxiliary chemicals. If these chemicals are necessary, use innocuous chemicals. 9.Increase energy efficiency: Run chemical reactions at ambient temperature and pressure whenever possible. 10. Design chemicals and products to degrade after use: Design chemical products to break down to innocuous substances after use so that they do not accumulate in the environment. 11.Analyze in real time to prevent pollution: Include in-process real-time monitoring and control during syntheses to minimize or eliminate the formation of byproducts. 12. Minimize the potential for accidents: Design chemicals and their forms (solid, liquid, or gas) to minimize the potential for chemical accidents including explosions, fires, and releases to the environment Paul T. Anastas and John C. Warner, Green Chemistry: Theory and Practice (New York, NY: Oxford University Press Inc., 1998).

Increasing Access to HIV AIDS Medicine Make these drugs available to more patients by – Extending expiration dates for available medicines – Increasing drug production No real manufacturing infrastructure in many needy countries Manufacture in India and China now Build manufacturing capacity elsewhere – Lowering manufacturing cost Create competition among raw material suppliers Improve manufacturing process efficiency Invent new science for new processes – Lowering dose needed to achieve efficacy Study lower doses in patients to demonstrate safety and efficacy Design new and more efficient dosage forms

The Soviet Union launched Sputnik, the world’s first artificial satellite, on October 4, 1957

New Technology for Rapidly Preparing Vaccines

Tobacco Plants

Two Raw Materials for Vaccines

Progress to Date Predicting Health and Disease (PHD) – A mRNA-based blood test has been developed for determining who will or will not become sick after exposure to a virus many days before symptoms appear. Accelerated Manufacture of Pharmaceuticals (AMP) – Using tobacco plants and virus-like particles (VLPs) Medicago has produced ten million doses of H1N1 vaccine in 1 month and tested in an animal model Modular IMmune In vitro Constructs (MIMIC®) – The MIMIC® system will work in parallel with the AMP program to test the subunit of vaccine produced under the AMP program to ensure it is safe and immunogenic.

Next Steps Under an Investigational New Drug (IND) application the new H1N1 vaccine will be tested in people to demonstrate safety and efficacy.

A General Q & A Session Addressing the Pharmaceutical Industry