The analysis focused on active pharmaceutical ingredient (API) manufacturing, and to a lesser extent intermediate manufacturing (stage prior to API manufacturing), as these are often the bottlenecks of the supply chain.
Additionally, the API stage poses the highest risk of antibiotic discharge into the environment during the manufacturing process.
Overall, there is limited vertical integration across the antibiotic supply chain, with various manufacturing stages often outsourced. This means an antibiotic consumed or used by a patient or animal will have involved manufacturing efforts by multiple different companies.
Additionally, the antibiotic supply chain is significantly reliant on China and India, particularly at the API and intermediate stages:
• For a representative shortlist of 40 antibiotic APIs, close to 70% of the manufacturing sites are found in these two countries: 35% in India and 34% in China:
• China is the largest exporter of antibiotic APIs in the world, with 74 kilotonnes exported in 2020, accounting for 71% of global inter-regions exports (across all antibiotic APIs)
• Intermediate manufacturing is particularly reliant on China, with more than 65% of the sites manufacturing four key intermediates based in China.
A representative shortlist of 40 antibiotics was used to further characterise the impact of environmental measures on the antibiotic supply chain. Here, three antibiotic supply chain archetypes in terms of resilience of the API stage to new environmental regulation were identified. These archetypes may equally be relevant to other forms of change or disruption in the supply chain.
Supply chains resilient to new environmental regulation due to a high number of API manufacturing sites: mainly includes first-line generics with high demand. These have relatively low margins, but a high number of manufacturing sites – often geographically spread – which can reinforce supply if any sites are disrupted.
Supply chains with limited disruption risk from new environmental regulation due to high API margins: includes patented molecules, which have a limited number of manufacturing sites but high margins which gives manufacturers greater ability to absorb change.
Supply chains exposed to heightened risk from new environmental regulation due to low margins and limited number of API manufacturing sites: includes mainly antibiotics treating niche indications and last resort generics. These have low-to-medium margins and a small number of often geographically concentrated manufacturing sites which leaves manufacturers less able to absorb change and the supply more open to disruption if any sites stop manufacturing.
To better understand the impact of regulation both at a macro level and on select individual supply chains, two plausible environmental regulatory options that have been linked to current avenues of interest by policy makers for implementation were characterised. The two options differ in concentration limits, measuring location, and monitoring method:
– Option A: based on the AMR Industry Alliance Manufacturing Framework guidelines, entails antibiotic concentrations to be measured in the “mixing zone” after dilution (e.g., river water) and quantified via mass balance (whereby one calculates the amount of lost material by accounting for material entering and leaving the system) against set concentration limits.
– Option B: based on the Indian government’s draft 2020 regulation which was subsequently dropped, is overall more
stringent than Option A. It has lower (i.e. stricter) antibiotic concentration limits than Option A and requires analytical monitoring (e.g. via mass spectrometry) of the antibiotic levels in the effluent wastewater before dilution.