Evaluation of sources to document extended shelf lives of compounded cytostatics

Abstract

Due to the increasing demand for compounded cytostatics, future compounding of these drugs has to include automated production and improved logistics, and in both cases batch production for stockholding is needed. This set-up would also meet future staff shortages. Stockholding requires documentation of extended shelf lives in the range of minimum 1-3 months. Documentation is often provided by summary of product characteristics, data provided by the industry which is not included in the summary of product characteristics and data from literature. To evaluate the quality of the three main stability data sources used by hospital pharmacies when assessing extended shelf lives of compounded cytostatics. A total of 150 summary of product characteristics for fluorouracil, cyclophosphamid, oxaliplatin, cisplatin, doxorubicin, paclitaxel, vincristin, irinotecan, epirubicin, gemcitabin, docetaxel, carboplatin and cytarabin were examined regarding available information on how to handle the compounded product. A survey of literature for shelf lives for cyclophosphamide, fluorouracil, oxaliplatin and gemcitabine has been made. Dialogues with 14 suppliers of cytostatica have been conducted to clarify the possibility of expanding the fluorouracil information on shelf lives to include information on extended shelf lives of compounded products. The analysis showed that often the information on shelf life stated in the summary of product characteristic is very short and sparse in basic information regarding the compounded product. The dialogues with the companies revealed that longer shelf lives will probably not be stated in the summary of product characteristic, and the literature review revealed very different stability data and uncertainty on the validity of the obtained data. None of these data sources can be applied as documentation for extended shelf lives and it is crucial to document the extended stability yourself.