Aim/Background: In this study, a stability-indicating method of the anticancer agent cabazitaxel was developed and validated. This method will be used to determine the chemical stability of commercially available concentrate-solvent mixture cabazitaxel (Jevtana®) to examine the possibility of multi-dosing from the same product vial after storage. The impossibility to re-use leftovers today is contributing to an unnecessary and significant financial waste. Methods: A forced degradation study of cabazitaxel was performed under different conditions to produce degradation products. Acidic, basic, oxidation, heat, and ultraviolet (UV) light conditions were tested. The method to determine the stability was developed so that potential degradation products would be shown in the UV spectra after separation from cabazitaxel with a C18 column in a high-performance liquid chromatography (HPLC) system. The only degradation product occurring during storage in room temperature and ambient light was identified by accurate mass Orbitrap Mass Spectrometry. Results/Conclusion: A stability-indicating method for cabazitaxel (Jevtana ®) concentrate-solvent mixture has been developed. We demonstrated that this method can be applied to stability studies with the purpose of multi-dosing cabazitaxel from a chemical/physical stability perspective within the tested period of time and conditions. As an addition, the only naturally occurring degradation product found has been identified and a degradation reaction has been suggested.
Background/purpose In the absence of thorough microbiological, chemical and physical stability data, high amounts of pharmaceutical products, from which the seal has been broken, are to be discarded after preparation. We performed a generic microbiological validation study for several marketed monoclonal antibody products, in order to define conditions under which leftovers from partially extracted product can be used in order to minimize loss. Methods From the daily practice of the Central Preparation Unit of the Netherlands Cancer Institute, used monoclonal antibody product vials were collected. To examine the integrity of the primary packaging, a VDT/S Vacuum Leak tester from Erweka was used. Vials were punctured with different types of spikes or a needle prior to experiments and examined for leakage afterward. In addition, microbiological monitoring was performed by broth simulation of the preparation method. Results All vials (631 vials, 18 different monoclonal antibody products) showed no leakage after puncturing with a 18 G needle. However, the use of a spike system resulted in leakage in 108 of the 435 tested vials. Results from the broth simulations confirmed a higher risk of contamination after puncturing with a spike as compared to needle-punctured vials (0.5% vs. 0.05%). Conclusion When working under aseptic preparation conditions and making use of appropriate needle, the risk of contamination is acceptably low to justify storage and reuse of leftover monoclonal antibody product from a microbiological perspective. The spikes tested lead to an unacceptably high level of loss of integrity and subsequent risk of microbiological contamination if stored in a non-classified environment. We concluded that these results could be applied generically to all monoclonal antibody products with a primary packaging composed of a glass vial and rubber stopper.
Aim/Background In this study, the prolonged physical and chemical stability of the anticancer agent cabazitaxel, commercially available as Jevtana®, was examined. Both concentrate-solvent mixture and infusion solution were examined with the aim to extend the use of multidose left-over cabazitaxel and infusion solutions and with that reduce financial and environmental waste. Methods A validated stability-indicating high-pressure liquid chromatography (HPLC) method with ultraviolet (UV) and photodiode array (PDA) detection was used to examine the purity and any degradation of cabazitaxel. The concentrate-solvent mixture and infusion solution samples that were tested had been stored out of the range of the criteria stated in the summary of product characteristics (SmPC). The concentrate-solvent mixtures were stored at 3–5°C, 18–21°C, and 40 °C, whereas the infusion solution was stored at 3–5°C. All samples were tested at t = 0, t = 1 week and t = 2 weeks. Results All samples showed that purity and concentration had remained within the criteria of <5% as stated in the European Pharmacopoeia. However, the concentrate-solvent mixtures stored at 18-21°C and 40 °C showed a degradation product forming in all the samples lowering the purity of the samples from 100% to 99.91% and 98.20% respectively, whereas all samples stored at 3–5°C remained at 100%. Conclusion Concentrate-solvent mixture and infusion solution of cabazitaxel, Jevtana®, can be used up to 2 weeks after preparation if stored at 3–5°C and prepared under aseptic conditions.
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