Reported compliance with limits lags behind, especially at suppliers’ sites

• Supplier data often not available, but more positive signs at companies’ own sites

• Only 5.2% of supplier sites were reported as compliant with discharge limits

As the number of sites that set limits to mitigate the risk of AMR increases, the next step is to examine whether these limits are achieved in practice. The Benchmark surveyed the 17 companies in its scope to assess levels of compliance with limits, looking across companies’ own sites and those of their suppliers.

More sites regularly monitored for compliance, but a long way still to go

There are 1,057 sites in scope, consisting of 187 of the companies’ own sites (based on data from 15 companies) and 870 supplier sites (based on data from 12 companies). 

The majority of sites are reported to be subject to discharge limits. However, less than a third of all sites are reported as quantifying discharge levels to determine compliance with limits, while 13% are reported as compliant with the limits set.

Focusing in on suppliers’ sites, the ‘compliance gap’ or ‘data gap’ becomes clear. Whereas 97 out of the pharma companies’ 187 directly-operated sites included in this analysis are reported as compliant (52%), just 45 of the 870 suppliers’ sites are reported as compliant (5.2%).

Even where limits are set, quantification and compliance lags behind

Discharge limits are set at 163 of the companies’ own manufacturing sites – and of those sites, more than three quarters are reported as quantifying discharge levels. More than half are reported as compliant with discharge limits.

While 561 supplier sites are required to set discharge limits, quantification of discharge levels is only reported at 173 sites. That leaves 388 sites where, although limits have been set, no actions are reported as being taken to check whether the actual levels of antibacterial residue in wastewaters are compliant with these levels. Only 45 sites are reported as compliant with limits. 

While four sites are reported as not compliant, compliance data is not available – or has not been made available – for the majority of suppliers’ sites. It is crucial that pharma companies collect and report on compliance data across their entire supply chains.

The challenge of compliance

Companies can have over 20 manufacturing sites and 200 suppliers’ sites, making it a complex and time-consuming challenge to assess standards at all sites. Reaching compliance is a work in progress, which makes it key for companies to have environmental standards rooted in their long-term strategies, and to assign sufficient resources.

Data and transparency

This Benchmark captures data companies’ practices at manufacturing sites along their supply chains. In future assessments, it will be important to take a step further and require companies to report on actual volumes of antibacterials that are manufactured per site to better map the risk of selection for resistance associated with manufacturing.

Which companies report the most compliant sites?

This table shows the percentage of each company's manufacturing sites, broken down by own and suppliers’ sites, which are reported as compliant with discharge limits. Some company names are covered by NDAs. Many companies do not assess or report whether manufacturing sites are compliant with discharge limits.

Aurobindo reports that all of its 15 sites are compliant with discharge limits, making up almost half of the total number of generic medicine manufacturers’ sites which are reported as compliant.

Of the 45 supplier sites reported as compliant, almost all of them were reported as such by GSK.

Case study - GSK

GSK reports that all 20 of its own sites and 37 out of 39 of its suppliers’ sites are compliant with discharge limits set in the receiving environment. For its own manufacturing sites, GSK states that the most important steps to achieve compliance involve: 

• Optimising source control and cleaning procedures to reduce losses in wastewater. This includes vacuum cleaning and pre-rinsing of manufacturing equipment. Concentrated streams are collected at the point of generation and sent for proper disposal, such as incineration.

• Installing pre-treatment technology such as pH or thermal hydrolysis, thin-film evaporation dryers, electrochemical oxidation, and multi-effect evaporation. 

GSK reports that contracts with suppliers are discontinued when suppliers are not compliant with discharge limits. To assist suppliers towards reaching compliance, GSK promotes the use of tools and guidelines that help to assess and reduce their antibacterial discharges. Furthermore, GSK provides detailed guidance to suppliers based on experiences from the company’s own manufacturing sites.

Quality management systems

Companies are expected to produce their antibacterials using the highest standards to ensure quality and minimise the risk that patients are exposed to sub-therapeutic levels, which drive AMR. While all companies have quality management systems (QMS) in place, several companies are also pushing up standards upstream.

During the period of analysis (22 June 2019 - 30 April 2021), antibacterial sites operated by Aurobindo and a subsidiary of Teva have received a GMP non-compliance inspection result of ‘Official Action Indicated’ (OAI) from the FDA. Due to the COVID-19 pandemic, re-inspections by the FDA are delayed.