Sample analysis protocols, documentation

A validation plan or protocol (Section 10.3.1) that specifies the experiments to be run on each day should be prepared prior to validation sample analysis. This document should specify how the validation should be conducted and, for validations that are conducted over multiple days, the plan should specify what experiments should be run on each day. Prior to the initiation of work, the protocol should be reviewed. Any questions or discrepancies should be resolved and, if necessary, an amendment should be prepared to resolve these issues. 

It is very likely that incomplete or missing records would prevent the verification of data integrity. Source records should be complete to facilitate an understanding of actual study conduct for critical phases of method development, method validation, and subject sample analysis. The records should confirm whether the testing was conducted in an appropriate manner, with well-designed and optimally controlled experiments. The documentation of actual laboratory events should demonstrate that the quantitative measures are suitable to achieve the objectives of the clinical or nonclinical protocol. The records should confirm that the reported results accurately reflect the actual concentration of the analyte in the biological matrix. It should be noted that the failure to adequately document critical details of study conduct has resulted in rejection of bioanalytical data for regulatory purposes. 

Some river basin districts in Spain have developed guidance documents on biological sampling and analysis protocols in accordance with the Water Framework Directive. 

The a priori identification of specific risk hypotheses leads to the ability to take some of the methodology normally applied to hypothesis testing of efficacy results and apply it to safety assessment. The most important difference between these two analysis domains is that in the case of efficacy, outcomes of interest are identified a priori with great specificity, and clear statistical hypotheses are laid out in advance with complete analysis and decision rules documented in the clinical protocol. In practice, only a few efficacy variables are identified as primary, and only a few others as second-ary. Sensitivity, statistical power, and sample size are all carefully analyzed in advance to assure the trial will have a high probability of detecting differences of interest in these few critical variables. 

For studies of more than four weeks in experimental duration, a reserve sample of each batch of the test, reference (analytical reference standard) and control substance must be retained. As this archive sample may be retained by either the sponsor or the contract facility, the responsibility should be addressed in the protocol. Additionally, a sample of the chemical should be collected prior to each application and immediately frozen for possible analysis for "storage stability of the test, reference and control substance at the test site". If the sponsor s storage stability data are inclusive of the storage conditions recorded at the test site, the GLP requirement will have been met and the above storage stability samples will not have to be analyzed (10). It should be noted that all test substance containers must be retained for the duration of the study i.e., until the study director signs the final report. A conditional exception for disposing of the containers may be obtained by writing to the OCM (11). OCM will set forth certain documentation requirements that will be required to account for the test substance containers. 

A standardization of the experimental protocols to obtain standard sample is desirable in order to compare database acquired in different laboratories. In this context, several initiatives, carried out by the Standard Metabolic Reporting Structures group, were focused to produce draft policy documents covering all aspects of a metabolomic study that are recommended for recording, from the raw biological sample, the analysis of material from that sample, and che-mometric and statistical approaches to retrieve informaticHi from the sample data [19-21]. 

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