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The development of hospital manufactured ready-to-use cefazolin 100 mg/mL injections

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European Statement

Production and Compounding

Author(s)

Bojan Žagar, Matej Vehovc, Mateja Tršan, Blaž Vehar

Why was it done?

Cefazolin injection 100 mg/mL is a sterile pharmaceutical formulation comprising cefazolin sodium and water for injections. Traditionally, cefazolin injections were prepared on hospital wards by reconstituting cefazolin sodium powder for injections with water for injections and subsequent dilution before intravenous administration.

What was done?

Establish a semi-automatic aseptic preparation process, ensure the production of final products that meet quality standards, develop analytical methodologies for in-process and final product quality control, ensure the reliability and validity of test results, and conduct a stability study to confirm long-term storage.

How was it done?

Product materials include: Pharmacy Bulk Package of Cefazolin for Injection, USP, water for injections, Luer Lock 20 mL sterile polypropylene syringes, steribags. Product is prepared with aseptic technique within a laminar flow unit situated in a pharmaceutical cleanroom. Bulk package is connected to a dispensing device, followed by reconstitution with water for injections. In-process samples are collected and volume-adjusted based on density. Following the preparation and dispensing, syringes undergo labeling and packaging into steribags. They are then promptly stored at -30°C within 4 hours. Final product samples are obtained and analysed (pH value, cefazolin content, endotoxins, sterility) prior to product release.

What has been achieved?

Preparation of cefazolin sodium injections in a controlled, aseptic environment utilizing pre-prepared bags containing the appropriate cefazolin concentration (100 mg/mL) has successfully addressed critical concerns surrounding the safety, efficacy, and quality of these pharmaceuticals when administered on hospital wards. Challenges related to stability and shelf life are being addressed with the storage approach at -30°C within the pharmacy, followed by a carefully monitored transition to ward storage at 5°C for up to 28 days, and subsequent patient administration at room temperature within 2 days.

What next?

This approach not only streamlines the process but also safeguards the well-being of patients, marking a significant advancement in pharmaceutical preparation within our healthcare setting. We are conducting an ICH-compliant stability study with the objective of establishing a combined shelf life of 90 days at -30°C, followed by 28 days at 5°C, and an additional 2 days at room temperature.

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