Our Story

M4ALL was formed in 2014 and is the culmination of a vision first expressed in 2009 by its founder, Dr. Frank Gupton. Dr. Gupton was the former head of Boehringer Ingelheim’s North American process development, where he led the development of the large-scale manufacturing processes for nevirapine, a large-volume HIV drug. In collaboration with Dr. Tyler McQuade (Florida State University), Dr. Tim Jamison (Massachusetts Institute of Technology), Dr. Brian Marquardt (University of Washington), and Dr. Rodger Stringham (Clinton Health Access Initiative), Dr. Gupton argued that the cost of producing a wide range of pharmaceutical products is higher than it needs to be, as neither innovators nor generic manufacturers are incentivized to reduce manufacturing costs. These excess costs are illustrated in the figure below:

 

The Problem

 

Current Drug Manufacturing Processes

High Cost Starting Materials
+
High Solvent Consumption
+
Significant Waste Generation
+
Inflexible Processing Technologies

Higher Cost API

Lack of Access

Insecurity of Supply

 

Dr. Gupton explained that the broad application of novel chemical process technologies could result in a step change reduction of these excess costs across a wide range of essential medications, with profound impact on patient access to existing and new medications. With support from the Bill & Melinda Gates Foundation, M4ALL was formed to pursue and to deliver this vision.

 

Transforming Pharmaceutical Manufacturing

M4ALL’s unique approach combines novel chemistry with the fundamental elements of process intensification. These elements include:

  • Vertical integration of advanced starting materials prepared from commodity chemicals
  • Consolidation of high-yielding reactions into a minimal number of unit operations with common solvents and limited intermediate isolations
  • Evaluation of alternative manufacturing platforms

M4ALL also has created and successfully used a new, integrated model that (1) targets existing or new treatments in which transformations would most positively impact global health, and (2) ensures that M4ALL’s optimized processes can be readily translated into existing sourcing and procurement processes for immediate cost savings. The M4ALL integrated model is depicted below:

Target Molecules Identified

Cost Driver Analysis Performed

Medicines For All Institute

Chemistry
and Yield Optimization

Commodity-based Starting Materials

Solvent and Reagent Selection

Chevron Aiming Right

Telescoping

Chevron Aiming Right

Batch and Continuous Process Platform

Commercial Implementation

Batch Manufacturing
Continuous Manufacturing
 

M4ALL is working with the Clinton Health Access Initiative and other commercial implementation partners with supply chain and procurement resources to ensure (1) an efficient and effective handoff to procurers and manufacturers can occur, (2) the projected savings are actually realized, and (3) the savings are documented and tracked. M4ALL has also been cultivating similar relationships with organizations that may have the disease state-specific expertise and supply chain relationships that equip them to be effective partners for other, non-HIV drugs. To facilitate technology transfer and cost-saving market realization, particularly in an environment where multiple partners may be involved or required for full market realization, M4ALL is making efforts to ensure that its technology package is easy to understand and can be deployed with conventional process equipment, analytical support, and normal manufacturing skills.

 

Proof of Concept

The impact of M4ALL’s integrated, “end-to-end” solution has been demonstrated in initial proof-of-concept work for the HIV medication nevirapine, funded by the Gates Foundation. For its work on nevirapine, already a low cost HIV treatment, M4ALL collaborated with the Clinton Health Access Initiative to translate M4ALL’s new materials and processes to active pharmaceutical ingredient (API) manufacturers for HIV-related pharmaceuticals. This collaboration has realized significant access-enhancing cost savings in the marketplace. The impressive results of M4ALL’s efforts are shown below:

1

M4ALL Novel Chemistry

Commercial
Process

M4ALL
Process


Starting materials $100/kg

Starting Materials $60/kg

21 Unit Operations

11 Unit Operations

50% Isolated Yield

87% Isolated Yield

4 Solvent Changes

Single Solvent System

Waste-to-drug mass: 56

Waste-to-drug mass: 4

 
RESULTS: >30% lower Cost of Goods
 
2

Transfer to Manufacturers

New process Transferred to CHAI

Both major generic manufacturers in China have implemented the process

3

Track Price Reductions

Process established to monitor market price change

9% price decrease so far which translates to estimated savings of approximately $7.8M in 2015 alone

 

Reinventing the Medicine Supply Chain

The M4ALL manufacturing optimization process has the potential to significantly change the economics of the pharmaceutical supply chain, in particular for generic manufacturers. The generic marketplace is extremely competitive—with tight margins and high barriers to entry for new competitors. This is especially true for manufacturers of global health treatments, where margins are typically even more constrained. The M4ALL model provides not only an opportunity for manufacturers to reduce costs and increase efficiency, but it also provides technical innovation to serve as a competitive advantage in an already challenging marketplace. Additionally, M4ALL’s environmental benefits, based on green chemistry and reduced waste generation, not only reduce manufacturing costs but also reduce expenditures associated with waste disposal to help meet new government regulatory demands. These significant economic and other ancillary benefits provide a unique win-win: permitting lower global health costs and improved patient access while reducing manufacturing costs, preserving manufacturer margins, and improving manufacturers’ environmental impact. Together, these benefits ensure the sustainability and, indeed, vitality of the global supply chain.

Target Molecule Identification

Target Molecule Identification

The Bill & Melinda Gates Foundation establishes priorities based on market projections and established therapies for AIDS antiretroviral drugs.

Active Ingredient Optimization

Active Ingredient Optimization

M4ALL works with academic partners to discover cost-saving techniques for manufacturing an active drug ingredient.

Batch Manufacturing

Batch Manufacturing

Once M4ALL finds a low-cost batch process, they send it to the Clinton Health Access Initiative. They implement it rapidly to reduce the cost by 10-30%.

Continuous Manufacturing

Continuous Manufacturing

M4ALL designs a continuous, automated manufacturing platform for the process. This reduces cost and environment impact.

Distribution

Distribution

The Clinton Health Access Initiative coordinates distribution to under-served populations.

Training the Next Generation of Global Scientists

M4ALL operates under the auspices of the Virginia Commonwealth University School of Engineering, located in Richmond, Virginia. As a research-related institute within the university, M4ALL has a responsibility to educate and train the next generation of chemists and engineers and instill the principles and foundations that will drive accessibility to affordable and high-quality medicines. This will result in work force expansion to meet the 21st century's needs in global health care. Additionally, M4ALL is currently engaged with partner countries to explore ways to develop in-country or in-region medicine manufacturing capabilities that utilize processes developed by M4ALL. One pathway is to create a program whereby chemists and engineers from a country or region are trained with the necessary skills and expertise to build up capabilities to produce their own medicines. This would lead to reduced dependence on a few manufacturers around the world and empower a country or region to be self-sufficient in providing high quality health care to its own people.