Successful Bioanalysis Outsourcing In Support Of Drug Development Program: Key To Risk Mitigation Planning For Mid-Study Method Transfer

We have developed processes to enable consistent method performance during method transfer. This has ensured timely method transfer validation and study sample analysis in support of new drug development and product commercialization. However, there were occasions based on business requirements when a mid-study transfer to another bioanalytical laboratory was required. In this circumstance, a staged approach to ensure proper mitigation of risks and that regulatory requirements for cross-validation are met, transfer processes were designed and implemented to confirm method comparability irrespective of the location for bioanalysis.

In general, we recommend assessment of spiked and pooled clinical samples; however, due to the unique circumstances of the mid-study transfer we were limited to use of unpooled clinical samples. Use of pooled clinical samples ensure patient confidentiality and reflect true study samples. In addition, pooled clinical samples account for potential changes in a patient population such as oncology and also differences in general lab processes.

Following departmental processes for repurposing samples, we selected clinical study samples that had also been used for incurred reanalysis at the reference lab (Lab A). To rule out any potential sample integrity issues, the secondary vials of the original samples still within long-term storage stability were used for the bridging experiment.

The sample size (n = 20 samples) was determined from a statistical estimation based on the method total error from each lab (± 20%) in relation to the desired equivalence interval. This sample size set provided a 92% power for analysis.

Expected values for the samples covered the analytical range of the method where 2/3 required dilution. Therefore, the analyst involved in the bridging experiment at the comparator lab (Lab B) was blinded to the identity of the samples but provided with the necessary dilution factor to allow the samples to recover within the analytical range.