Pharmaceutical quality of docetaxel generics versus originator drug product: a comparative analysis

ABSTRACT

Introduction: The aim of this study was to evaluate the quality of 31 commercially available generic formulations of docetaxel purchased in 14 countries by comparing their docetaxel content, impurity levels and pH versus those of the proprietary product Taxotere^* (Tx).

Research design and methods: Generic formulations were purchased in 14 countries in Asia, Africa, the Middle East and Latin America. Levels of docetaxel and impurities (chromatographic peaks above 0.05%) were obtained for each sample using reverse-phase liquid chromatography with ultraviolet detection. The pH of aqueous solutions of generic docetaxel formulations and Tx was also measured. A global evaluation of quality was conducted on each product using a multicriteria desirability analysis based on standards defined by the International Conference on Harmonisation guidelines and the US Pharmacopeia paclitaxel injection monograph.

Results: Most generic formulations contained a lower than expected amount of docetaxel and/or a high level of impurities: 21 generic docetaxel formulations had an average mass of docetaxel that was <90% of the expected mass and 23 generic docetaxel formulations had a total impurity content of >3.0%, almost twice the level of impurities in Tx 20 mg. In total, 33 impurities not present in Tx were detected in the generic samples. Desirability analysis demonstrated that none of the generic docetaxel formulations had composition characteristics similar to those of Tx.

Conclusions: This study demonstrated that from an analytical point of view, 90% of the generic docetaxel formulations evaluated contained insufficient active drug, high levels of impurities or both. This has the potential to affect both efficacy and safety of the drug.

Key words: :

• Desirability analysis
• Docetaxel
• Generic
• Quality
• Reverse-phase liquid chromatography
• Taxotere

Acknowledgements

Declaration of interest: This study was funded by sanofi-aventis, Paris, France, and was conducted by the Laboratoire Environnement et Chimie Analytique. The study sponsor also assisted in collecting samples and funded editorial support provided by Adelphi Communications Ltd, Macclesfield, UK. All authors had access to the study data, and the interpretation of the results is that of the authors. JV acted as a consultant to sanofi-aventis and received funding to attend scientific symposia at which posters relating to this study were presented. None of the other authors have any conflicts of interest to declare.

In 2007, this study was presented, in part, at RDPA 33 (International Meeting on Recent Developments in Pharmaceutical Analysis) and at ASHP 34 (American Society of Hospital Pharmacy Midyear Clinical Meeting and Exhibition).

Notes

* Taxotere is a registered trade name of sanofi-aventis, Paris, France