Appropriate Management of Chemical Substances

■ AMR

AMR (antimicrobial resistance) refers to phenomena in which bacteria (pathogens) change with the use of antimicrobials, resulting in diminishing the effect of the antimicrobials. AMR is believed to be principally caused by inappropriate or excessive administration of antimicrobials. It is also attributed to release from antimicrobial manufacturing plants as another factor. Therefore, taking action from various aspects is essential for effective AMR control.

The basic approach is to calculate the predicted environmental concentration (PEC) of antimicrobials released into the environment from data that measures the actual amount of antimicrobials lost during the manufacturing process or the wastewater constituents and compare it with the predicted no-effect concentration (PNEC) to confirm that the PEC/PNEC ratio is smaller than one.

At the Kanegasaki Plant, which is Shionogi Pharma’s main antimicrobial manufacturing plant, we have always strictly controlled the release of antimicrobials into the environment as the responsibility of a company that has been engaged in the manufacture of antimicrobials for many years. At the plant, we manufacture cephem/carbapenem antibiotics APIs and formulations. Since they are easily decomposed by alkali, wastewater from the plant is inactivated by alkali treatment and then discharged outside the plant after being neutralized with acid. The deactivated wastewater is measured by the liquid chromatography method, and the PEC is calculated from the actual measurement data. An example of analysis results is shown below, which indicate that peaks for the relevant compounds were not detected.

We plan to promote AMR measures for wastewater from antimicrobial manufacturing at manufacturing sites other than the Kanegasaki Plant.

Shionogi Pharma controls and manages the release of antimicrobials into the environment based on the Antibiotic Manufacturing Standard^*1 established by the AMR Industry Alliance.

■ Environmental Impact Assessment of Wastewater

Shionogi Pharma believes that it is its corporate responsibility to assess the environmental impact of wastewater discharged from business activities and manage it appropriately. We conduct assessment at key timings, such as the launch of commercial production, taking into account the amount of APIs used and process and other risks.

The basic approach is the same as that for AMR described above. We calculate the predicted environmental concentration (PEC) from data that measure the actual amount of APls lost during the manufacturing process for each product or the wastewater constituents and compare it with the predicted no-effect concentration (PNEC) for assessment.