Potential Sampling Errors in Stability Studies Due to Dead Volume in Closed System Transfer Devices

Area of Science:

• Pharmaceutical Sciences
• Drug Stability Testing
• Analytical Chemistry

Background:

• Closed system transfer devices (CSTDs) are utilized to minimize healthcare professional exposure to hazardous drugs.
• Their application in stability studies for anticancer drugs, such as gemcitabine, is common.
• A specific CSTD, Tevadaptor®, was investigated for potential bias in gemcitabine stability assessments.

Observation:

• Initial aliquots of gemcitabine withdrawn using the Tevadaptor® CSTD showed a significant overestimation in concentration (26%) compared to expected values.
• This overestimation was not observed in subsequent aliquots withdrawn from the same bags using the same device.
• Using a needle instead of the CSTD to withdraw aliquots did not result in concentration overestimation.

Findings:

• The Tevadaptor® device introduced a statistically significant positive bias in the measured concentration of the first gemcitabine aliquots.
• The bias was specific to the initial withdrawal and not present in later samples or when using a needle.
• The study suggests a potential interaction or issue with the CSTD during the initial drug withdrawal process.

Implications:

• The findings underscore the critical importance of validating the performance of CSTDs in drug stability studies.
• Misinterpretation of stability data due to CSTD-induced bias could impact drug quality assessments and regulatory compliance.
• A thorough understanding of CSTD technical specifications and potential limitations is essential for accurate pharmaceutical analysis.