Biomedical Engineering Reference
In-Depth Information
preparation and fast chromatography do not necessarily guarantee a robust and reli-
able bioanalytical method suitable for regulated analysis. The development of a robust
bioanalytical method requires the careful consideration of many critical parameters.
A complete regulated method validation minimally requires three interday preci-
sion and accuracy runs and various stability and reproducibility experiments. It is
normally executed in approximately one or two weeks and involves the laboratory,
Quality control (QC) and Quality Assurance (QA) departments. Run failures during
method validation are especially costly in terms of time, effort, and perception. The
best practice to ensure the success of method validation is to conduct a thorough and
comprehensive method development process. With this approach, the actual method
validation itself should be a matter of formality, as there is an extremely high level
of confidence that all validation tests will pass. The final evaluation of any high
quality bioanalytical method is not complete until it passes the ultimate test of regu-
lated sample analysis and incurred sample reanalysis. A rugged method is a prereq-
uisite. However, regulated sample analysis and incurred sample reanalysis will not
be successful without proper planning and sound execution.
Unlike basic research in academic laboratory setting in which an individual
researcher works on a single project from beginning to end, regulated bioanalysis
process typically involve multiple individuals, departments, or companies. Typically
a principle investigator (PI) or study director (SD) is responsible for monitoring
project status, reviewing data and reports, and communicating with the client.
Multiple scientists will be responsible for the project at different stages. Multiple
departments will also be involved to perform required activities such as Sample
Management, laboratory, Quality Control (QC) and Quality Assurance (QA), and
Data Management. Regulatory inspections are routinely conducted by internal QA
auditors, external QA auditors, consultants, or even regulatory (FDA) auditors.
Because all study records must be clearly documented and properly maintained to
ensure the integrity of the study, it is therefore vital to build a system that there pro-
duces a clear hand off between each stage of laboratory activity and a centralized
location to retrieve and review data. In our laboratory, the solution is to use forms
(checklists) for each of three important stages during method development and vali-
dation and sample analysis. Overall, these checklists provide the required details
necessary for conducting projects in a regulated environment. These checklists
ensure that all required documentation is recorded and retained, eliminate the need
to rely on the memory of a single individual at any time, increase the confidence of
our clients based on the timely and successfully completion of contracted work, and
most importantly, ensure the integrity of all studies in all circumstances.
References
1. Shah VP, Midha KK, Dighe S et al (1992) Analytical methods validation: bioavailability,
bioequivalence, and pharmacokinetic studies. Pharm Res 9:588-592
2. FDA/CDER, Guidance for the industry: Bioanalytical method validation, May 2001, US
Department of Health and Human Services, FDA (CDER) and (CVM), Rockville, MD, USA
