34th SQA Annual Meeting and Quality College

FF-1   EMA Bioequivalence Inspections in the US - What to Expect and How They Differ from US FDA Bioequivalence Inspections

Abstract:
As an international contract research organization studies conducted by Covance are submitted to various regulatory authorities.  The resulting inspections differ significantly and come with different challenges.  During this session details related to the planning, conduct and follow up from one EMA/FDA inspection will be reviewed and discussed.

Category:
Bioanalytical

Level of Content:
Intermediate

FF-2  Bioanalytical Audit Due Diligence and Risk Management

Abstract:
In this session we will discuss how CROs prepare to host and respond to audits: Pre-Qualification, Re-Qualification, and Data (BA/BE & Pivotal Studies) - by identifying the risks sponsors are looking to mitigate, and how Bioanalytical CROs address real and perceived risks.

We will hear from Sponsors, Auditors, and CROs, and their real life experiences.

Category:
Bioanalytical

Level of Content:
Intermediate


FF-3  Investigation of incurred sample reanalysis failure 

Abstract:
5-fluorouracil (5-FU) is a chemotherapy agent for treating breast and colon cancers.  Capecitabine is also a chemotherapy agent for treating those cancers and it is a prodrug which is enzymatically converted to the active drug 5-FU within the tumor.  Incurred sample reanalysis (ISR) of 5-FU were performed for patients dosed with either 5-FU or capecitabine in one clinical trial. ISR analysis on samples from patients that were dosed with 5-FU met acceptance criteria. However, ISR analysis on samples from patients that were dosed with capecitabine in the same study was failed. It was suspected that capecitabine and its upstream metabolites 5’-DFCR or 5’-DFUR, alone or in combination, may convert to 5-FU following sample collection. An investigation was performed. Blank plasma was spiked individually with capecitabine, 5’-DFCR and 5’-DFUR at potential Cmaxconcentrations and were left at testing conditions before analysis for 5-FU. It was confirmed that 5’-DFUR was continuing to convert to 5-FU even after samples had been frozen. To prevent the conversion, a further investigation was performed using different conditions with various inhibitors such as 5-nitrouracil, 7-deazaxanthine or tetrahydrouridine with formic acid, acetic acid, and citric acid. This investigation led to the development of a specialized sample collection procedure. A bioanalytical method was then developed and validated for the determination of 5-FU in human plasma from patients dosed with capecitabine utilizing the above sample collection procedure. This new approach has resulted in acceptable ISR results for 5-FU from patients dosed with capecitabine.

Category:
Bioanalytical

Level of Content:
Advanced