Achieving Sustainable API Production in Africa Perrer N. Tosso, Ph.D. Global Innovation Manager Medicines for All Institute June 3, 2019 Africa Pharma Conference Johannesburg, South Africa

Medicines for All: Our Mission Improve Access to Critical Medicines (i.e., treatments for HIV, malaria, tuberculosis) Introduce new, easily transitioned routes to critical medicines Train the next generation of process oriented innovators Develop new methods, technology and approaches

Current State of Drug Manufacturing in the World

Drug Manufacturing in Africa & Its Constraints Improved access to affordable medicines Improved quality-assurance of medicines Cater to local health needs (e.g. increased production of TB, malaria, & NTD drugs) Sustainability of local production API: 75% cost of the finished pharmaceutical product Primary Manufacturing Production of APIs, Intermediates and Excipients Secondary Manufacturing Formulation Tertiary Manufacturing Packaging of pre-formulated products. Small scale production Three in Sub-Africa Most Common in Africa

Drug Manufacturing in Africa & Its Constraints Proposed Solutions Reinforced quality control capability Strengthen and harmonized regulatory system Targeted training of the workforce Increased production of APIs Adoption of continuous manufacturing Improved access to affordable medicines Improved quality-assurance of medicines Cater to local health needs (e.g. increased production of TB, malaria, & NTD drugs) Sustainability of local production Primary Manufacturing Production of APIs, Intermediates and Excipients Secondary Manufacturing Formulation Tertiary Manufacturing Packaging of pre-formulated products. Small scale production Constraints Small local markets Shortage of skilled human capital Lack of skilled entrepreneurs Long lead times Immature regulatory system

Drug Manufacturing in Africa & Its Constraints Proposed Solutions Reinforced quality control capability Strengthen and harmonized regulatory system Targeted training of the workforce Increased production of APIs Offering cost reduction (to be competitive) Implementing green chemistry principles Adoption of continuous manufacturing Improved access to affordable medicines Improved quality-assurance of medicines Cater to local health needs (e.g. increased production of TB, malaria, & NTD drugs) Sustainability of local production Primary Manufacturing Production of APIs, Intermediates and Excipients Secondary Manufacturing Formulation Tertiary Manufacturing Packaging of pre-formulated products. Small scale production Constraints Small local markets Lack of skilled entrepreneurs Shortage of skilled human capital Long lead times Immature regulatory system

Medicines for All Model An Approach Toward Competitive & Sustainable Production of APIs $ Process Cost of Goods Process Mass Intensity mass of reactants S starting material costs * S Yield PMI = mass of products

Current route uses the following registered starting materials. Nevirapine Example Nevirapine: Anti-HIV NNRT Inhibitor Innovator: BI Current route uses the following registered starting materials. The process has many unit operations, high PMI and costly starting materials: + 2-CAN CAPIC 2nd Generation Nevirapine Process M4ALL Nevirapine Process

Nevirapine Example PMI from 46 to 11

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