About the stability study
The British Society for Antimicrobial Chemotherapy (BSAC) sponsored a stability study of Zerbaxa (ceftolozane/tazobactam) in elastomeric infusers to facilitate the use of this drug by continuous IV infusion as part of OPAT services in the UK and further afield. The study applied the standards of the NHS Standard Protocol for Deriving and Assessment of Stability Part 1.
Assigning in-use stability
Data for ceftolozane/tazobactam (Zerbaxa) supports an extended shelf-life of up to 8 days refrigerated storage at 2 to 8°C, plus 24 hours at 32°C to allow for continuous infusion with a single infusion per 24 hours.
The data applies to ceftolozane/tazobactam (Zerbaxa) diluted in 0.9% w/v sodium chloride at 5 mg/mL and 20 mg/mL
This data applies to the following elastomeric devices tested:
- FOLFusor LV10 (Baxter Healthcare)
- Easypump® II (B. Braun Medical Ltd)
Ceftolozane/tazobactam, diluted in 0.9% w/v sodium chloride at 5 mg/mL and 20 mg/mL, was found to degrade during in-use storage at 32°C with <95% remaining after 18 hours for some device/concentration combinations. All device/concentration combinations had degraded with <95% remaining after 24 hours.
The report concluded that the data supports an extended shelf-life of up to 8 days refrigerated storage at 2 to 8°C plus 12 hours at 32°C, allowing a twice daily infusion in OPAT services.
For territories that allow a lower acceptance limit of 90% remaining for actives or a lower ‘in-use’ temperature in OPAT services, a 24 hour infusion may be achievable.
The stability assessment protocol does allow for greater than 5% degradation to be accepted for a product where the drug will still meet required clinical activity (key PK/PD targets still being met), and where the degradation product profile is well understood and there is no threat of toxicity from these degradation products.
Data provided by the product Manufacturer’s/Importation Authorisation (MIA) holder Merck Sharp & Dohme Corp (MSD) showed that after the storage period of 8 days at 2 to 8°C plus 24 hours at 32°C, the levels of degradation products and other related substances expected would still be within those stated in the Zerbaxa regulatory submission.
It should be noted that the MSD does not support the use of the product outside of the terms of its Marketing Authorisation as outlined in the product Summary of Product Characteristics.
Thank you to Mark Santillo, Pharmaceutical Consultant and Qualified Person, UHBW and UHP NHS Trusts (formerly Chair of the NHS Pharmaceutical Quality Assurance Committee and NHS Pharmaceutical Research and Development Group) for his assessment.