Use of leftovers of monoclonal antibody products after partial extraction – A microbiological safety study

Abstract

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.

Development and Validation of Analytical Methods to Determine the Prolonged in-use Stability of Anticancer Monoclonal Antibodies in Clinical Practice

“…Regarding microbiological safety, this has previously been developed and described 19 . In this previous study, 631 vials from 18 different mAb products were tested.…”

“…In conclusion, the combination of the methods shows that we can detect physiochemical and biological instabilities of mAbs with the complementing methods that are described in this research paper (see Table 9). The previous microbiological contamination research explains how the vials should be handled to maintain the microbiological stability 19 .…”

“…The microbiological stability is crucial and must be examined to ensure that there is no contamination while preparing the infusion solution for patients or when storing the samples. A study to ensure safe handling, from a microbiological safety point of view, has been conducted previously at our Institute 19 . The integrity of already opened vials was examined by the dye ingress method developing a method of safe handling of the mAb vials so that no contamination occurs, and that the integrity was assured after opening the vials.…”

Stability study of concentrate-solvent mixture & infusion solutions of Jevtana® cabazitaxel for extended multi-dosing

“…These findings demonstrate that we can re-use the cabazitaxel concentrate-solvent mixture and infusion solution bags up to 2 weeks after preparation if stored in refrigerated temperatures (3–5°C), if prepared and stored according to the established microbiological safety scheme previously developed. 13…”

“…The microbiological safety for storing opened vials and aseptic preparation has also been generically demonstrated with no signs of microbiological contamination after the tested storage conditions. 13 As an addition to the current study, 16 Jevtana V R vials were included as well.…”