Viability of selected microorganisms in parenteral preparations for novel systemic anti-cancer therapy

by Selleckchem | Nov 18 2023

Background: Risk factors for aseptic preparation of parenteral medicines encompass the growth-promoting nature of the preparation. Although many aqueous parenteral preparations do not have growth-promoting properties, inadvertently introduced microorganisms may remain viable. Knowledge about the viability of microorganisms in parenteral preparations can add useful information for assigning shelf life to preparations used to treat cancer patients.

Aim: The aim of the study was to assess the viability of four different facultative pathogenic microorganisms in 20 ready-to-administer parenteral preparations aseptically prepared in hospital pharmacies.

Methods: Samples of 20 different biologics and small molecules for systemic anti-cancer therapy were inoculated either with different bacteria (i.e., Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecium) or with Candida albicans suspension. The resulting test concentrations were 104-105 microorganisms per mL. Aliquots of inoculated test solutions were transferred in duplicate to tryptic soy agar plates at the time points 0, 4, 24, 48, 144 h. The plates were incubated for 24 h (bacterial strains) and 72 h (C. albicans) at 37 °C and colony forming units (CFUs) were counted.

Results: In most test solutions, especially in monoclonal antibody solutions, increased CFU counts of P. aeruginosa and unchanged or increased CFU counts of E. faecium and S. aureus were registered. Pronounced nutritive properties of monoclonal antibodies and filgrastim were not registered. Azacitidine, pixantrone and vinflunine containing test solutions revealed species-specific bacteriostatic and even bactericidal activity. All test solutions, except nivolumab and pixantrone containing solutions, showed constant or increasing CFU counts of C. albicans after incubation.

Conclusion: Viability of the selected pathogenic microorganisms was retained in most of the tested biological and small molecule preparations used to treat cancer patients. Therefore, in pharmacy departments strict aseptic conditions should be regarded and the lack of antimicrobial activity should be considered when assigning shelf life to RTA parenteral preparations.

Comments:

**Title:** **Assessment of Microorganism Viability in Aseptically Prepared Parenteral Preparations for Cancer Patients: Implications for Shelf Life Determination**

**Abstract:**

**Background:** Aseptic preparation of parenteral medicines is critical for patient safety. Although many parenteral preparations lack inherent growth-promoting properties, inadvertent introduction of microorganisms remains a concern, especially in cancer therapy. Understanding microorganism viability provides essential insights for assigning shelf life to these preparations.

**Aim:** This study aimed to evaluate the viability of facultative pathogenic microorganisms in 20 ready-to-administer (RTA) parenteral preparations aseptically prepared in hospital pharmacies.

**Methods:** Twenty systemic anti-cancer therapy solutions were inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecium, or Candida albicans. Test concentrations ranged from 10^4 to 10^5 microorganisms/mL. Aliquots were sampled at 0, 4, 24, 48, and 144 hours, plated on tryptic soy agar, and incubated. Colony forming units (CFUs) were counted after 24 hours (bacteria) or 72 hours (C. albicans).

**Results:** Most solutions, especially monoclonal antibodies, exhibited increased CFU counts of P. aeruginosa and unchanged/increased counts of E. faecium and S. aureus. Monoclonal antibodies and filgrastim did not demonstrate pronounced nutritive properties. Azacitidine, pixantrone, and vinflunine solutions exhibited species-specific bacteriostatic and bactericidal activity. Except for nivolumab and pixantrone solutions, C. albicans counts remained constant or increased.

**Conclusion:** Viability of selected pathogenic microorganisms persisted in tested cancer therapy preparations. This underscores the importance of stringent aseptic practices in pharmacy departments. Additionally, lack of antimicrobial activity in certain solutions emphasizes the need for careful consideration when determining the shelf life of RTA parenteral preparations.

**Keywords:** Aseptic Preparation, Parenteral Preparations, Microorganism Viability, Cancer Therapy, Shelf Life Determination, Patient Safety, Aseptic Conditions, Antimicrobial Activity.