Physicochemical and Microbiological Evaluation of Cefazolin Sodium under a Contamination Control Strategy

Abstract

Sterile injectable antibiotics such as cefazolin sodium require strict control of moisture, particles, sterility and process water, an expectation reinforced by the 2022 revision of European good manufacturing practice Annex 1, which requires a contamination control strategy. This study assessed the physicochemical and microbiological quality of a commercial sterile cefazolin sodium powder for injection (Mirazolin® 1 g) and of the purified water and water for injections of the manufacturing site. Analyses were performed in the manufacturer’s quality control laboratory following European Pharmacopoeia and United States Pharmacopeia procedures. Cefazolin was assayed by isocratic liquid chromatography with ultraviolet detection at 254 nm using salicylic acid as internal standard. Residual water (Karl Fischer titration), pH, identity, subvisible particles (light obscuration), mass uniformity (20 vials), sterility (membrane filtration, 14 days) and bacterial endotoxins (gel-clot, lysate sensitivity 0.125 EU/mL) were determined, together with conductivity, nitrates, oxidizable substances and microbial counts in the waters. Cefazolin content was 103.07% of the labelled amount (specification 90.0-115.0%), residual water 1.46% (≤6.0%) and pH 5.0. Mean particle counts were 70.25 (≥10 µm) and 5.25 (≥25 µm) per vial, and the maximum mass deviation was -9.57%. No microbial growth or gel formation occurred (endotoxins <0.25 EU/mg). Water for injections showed a conductivity of 0.55 µS/cm and 0 CFU/100 mL. For the batch examined, all measured attributes met the applied specifications. Such release-type results are consistent with good control of moisture, particles and water quality but cannot, by themselves, demonstrate the effectiveness of a complete contamination control strategy.