B Manufacturing & Production
Comparing companies’ strategies for limiting the impact of antibacterial manufacturing on resistance. This Research Area evaluates how thorough companies' environmental risk-management strategies are, whether they set limits on antibiotic discharge; and how they apply these strategies to third-party suppliers.
The process for manufacturing and producing antibiotics by pharmaceutical companies can contribute to antimicrobial resistance (AMR) in two main ways: when companies release waste into the environment that includes antibiotics or antibiotic resistant bacteria; and when they manufacture substandard antibiotics with sub-therapeutic levels of the active antibiotic ingredient. Both routes can expose bacteria to levels of antibiotics that promote the emergence of resistance.
In Manufacturing & Production, the scores near the top are closely packed. Nevertheless, six companies pull ahead of other large research-based pharmaceutical companies and the generic medicine manufacturers: GSK, followed by Johnson & Johnson, Novartis, Pfizer, Roche and Sanofi. GSK undertakes every environmental risk-management activity that the AMR Benchmark examines, with the other five companies undertaking the majority of them. All leaders make a commitment to manufacturing all antibiotic drug products in a manner consistent with Good Manufacturing Practices (GMP).
Most companies have environmental risk-management strategies in place; depth and breadth of strategies vary
The majority of companies analysed (15 of 18) show evidence of having some form of an environmental risk-management strategy that aims to minimise impact of antibiotics discharged from manufacturing processes. The depth and breadth of these strategies differ widely regarding the different aspects evaluated by the Benchmark. Six large research-based pharmaceutical companies (GSK, Johnson & Johnson, Novartis, Pfizer, Roche and Sanofi) lead the field, applying their environmental risk-management strategies most broadly, both to their own manufacturing sites and to those operated by third-party manufacturers of APIs and drug products. The performance of generic medicine manufacturers varies, with only the leaders focusing beyond their own manufacturing sites.
Fifteen companies have strategies for their own manufacturing sites, which most (14) also support with regular audits. Nearly half of those analysed (eight) report that they also apply their strategies to sites managed by third-party manufacturers of APIs and drug products. Six companies reported that they apply their strategies to external waste-treatment plants. Looking at auditing and the setting of discharge limits, fourteen companies reported that they audit their own manufacturing sites, seven audit sites managed by third parties, and three audit external waste-treatment plants. Regarding discharge limits, eight companies set these for their own manufacturing sites, four for sites managed by third-party suppliers of APIs and drug products, and two for external waste-treatment sites.
Figure: Depth and breadth of environmental risk-management strategies vary widely.
The AMR Benchmark looks at where companies are applying environmental risk-management strategies (breadth), and whether these strategies include audits and limits on antibiotic discharge (depth). Six large research-based pharmaceutical companies are leading in this area by including the most elements in their strategy. Generic medicine manufacturers mainly focus their strategies on their own manufacturing sites.
Eight companies set discharge limits for antibiotics, but none discloses actual discharge levels
Eight companies report that they have set limits on antibiotic discharge in wastewaters, but none discloses publicly its levels of actual discharges. This information is valuable and vital. Disclosing it could enhance the ability of governments, researchers and other stakeholders to understand the relationship between the discharge of active antibiotic ingredients into the environment and the development of antibiotic resistance. Four companies have set discharge limits for their own sites as well as those of third-party manufacturers of APIs and drug products, reporting that they also audit the implementation of their environmental risk-management strategies. One company (GSK) extends its discharge limits to both third-party manufacturers and external waste-treatment plants. GSK is also the only company that discloses predicted no-effect concentrations (PNEC) for resistance selection. It discloses these to the Benchmark, also giving reference to external sources for these PNECs. It does this for a subset of the antibiotics in its portfolio. The company publicly discloses safety data sheets for antibiotics, but doesn’t publicly disclose PNECs.
Only one company discloses names of third-party manufacturers
The Medicines Company is the only company identified by the Benchmark that discloses the identities of its third-party manufacturers, making it an example of best practice in this area. In its 2016 annual report, it disclosed the identity of all third-party API and drug-product suppliers for its marketed branded antibiotics minocycline (Minocin® IV), oritavancin (Orbactiv®), and meropenem/vaborbactam (Vabomere™). It also disclosed suppliers for its generic medicines, azithromycin and clindamycin. Disclosing the identities of third-party suppliers enables governments, researchers and others to assess the impact of individual manufacturing chains on antibiotic resistance. Please note: The Medicines Company was not scored in this research area. As a biopharmaceutical company in scope, it is in scope for the R&D research area only.
What and how this research area measures
In Manufacturing & Production, the Benchmark uses global antibiotic sales volumes to inform its selection of companies to analyse. It focuses on antibiotics (rather than all antimicrobial medicines). This is because antibiotic manufacturing and its potential impact on resistance is better described and understood than other areas of antimicrobial manufacturing. As such, it was possible to identify and develop metrics for this first iteration of the Benchmark.