Drug shortage - what next?

A new and unusual experience: supply bottlenecks in almost all areas

This is a new and unusual experience: supply bottlenecks in almost all areas. Press reports about the shortage of generics received particular attention. At times, up to 600 products such as propofol (muscle relaxant for intubation), fentanyl (painkiller) or synthocinone (induction of labor) were hardly or even impossible to obtain. Mind you, the supply of patent-protected original preparations was not the problem. It was the supply of generics and cheap consumer goods such as protective masks or plastic goods that caused concern during the corona crisis. This comes as no surprise since we are now completely dependent on imported products from the far east.

Generics production in Switzerland? China is Switzerland's third most important trading partner after the USA and Germany, with a significant Swiss export surplus of CHF 12 billion. It can be assumed that the value of advanced medicines exported to China also significantly exceeds the import of generics. Intermediates and bulk substances from China are frequently formulated into generics in India. In addition, production is concentrated on a few manufacturers – a cluster risk. From an economic point of view, a repatriation of generics to Switzerland is not reasonable.

What options do we have? A typical hospital pharmacy contains about 3000 medicines. A prioritization according to recognized criteria is a prerequisite. During the SATW Conference 18 March 2022 in Bern, Enea Martinelli [ https://www.enea-martinelli.ch/] suggested dividing medicines into three groups:

• Green: Medicines that can be produced anywhere.

• Yellow: Medicines that need to be manufactured in more than one country to minimize the risk.

• Red: Medicines that would have to be manufactured in Switzerland.

There are numerous Swiss companies with expertise in the synthesis and manufacture of complex, optically active organic molecules such as Azad Pharma AG, Bachem, Corden Pharma, Dottikon Exclusive Synthesis, Firmenich, Givaudan, Lonza, Max Zeller Söhne AG, Siegfried, Vifor and others. However, a "repatriation" of generics would be time-consuming and expensive. Current generic procedures are no longer possible in Switzerland for cost and environmental reasons. However, a targeted return of particularly critical active substances is feasible after a comprehensive clarification and assessment.

Innovation: New processes mandatory, biosynthesis & biocatalysis & biotransformation, process intensification, continuous processes, AI, computer-aided synthesis, cross-company innovation (blockchain) etc.

Production processes & plants: E-factor (kg waste/kg product), process material intensity, automation, process analytical technology, energy sources, reduced energy consumption, optimized logistics, etc.

Economic aspects: Lack of plants & operating personnel, technological commitment (lock-in), economies of scale, CAPEX & OPEX, sales potentials & critical market sizes, production scenarios, pricing, etc.

Strategic aspects: Product priorities, long-term availability of basic building blocks and intermediates, lack of know-how, transnational partnerships & cooperations, pricing, regulation & approval, subsidies, price war during transition phase, etc.

What next? One conclusion of the SATW platform discussion on 2 May 2022 at the Swiss Biotech Day in Basel was to expand Switzerland's leading role in the development and manufacture of advanced medicines by investing more energy and resources in sustainability [CHIMIA (2022) 76:800–804]. "Swissness" is intended to increasingly refer to effective medicines that are also produced sustainably. With regard to generics, we need new manufacturing methods that allow a significant reduction in manufacturing costs in general and labor costs in particular. SATW will work on the topic of innovation around new production processes in 2023 with partners.

Are you interested in this topic? Then contact us!

Hans‐Peter Meyer, Expertinova AG, SATW Member, Head of Scientific Advisory Board