Laboratory-developed tests analytical verification

This system includes measures and activities related to laboratory procedures, testing, analytical methods development and validation or verification, and the stability program. 

Many clinical laboratories find it necessary to develop methods to detect various infectious agents for which there are no commercially available methods or systems. Laboratory-developed tests (LDT), formerly known as home-brew assays or in-house developed assays, are those assays tliat have been fuUy developed and validated by the laboratory that offers the testing. Usually, these assays use a combination of reagents that are purchased separately from various manufacturers. The analytical and clinical verification of the LDT is the responsibility of each laboratory, and this verification procedure is more complex than verification of an FDA-cleared or FDA-approved test. 

Metal speciation procedures, which have been verified under controlled laboratory conditions and evaluated by means of bioassays, will require further verification in order to determine their ecological effects. For example, how does the response of the bioassay test species to a toxic metal fraction relate to the toxicity to larger organisms such as fish in the natural environment Bioaccumulation of metals in populations has been very difficult to relate to metal speciation measurements. There is a challenge for analytical chemists to develop metal speciation procedures that are relevant to ecotoxicology (Morrison and Wei, 1991). 

Analytical method validation should track closely to the stages of development of the method itself However, it is not realistic to expect complete and thorough validation of the method until its development cycle is complete. An exception to this would be a situation where an accepted compendial method is applied to clinical material (such as a dissolution test or release testing of a compendial component). In these cases, companies must be prepared to demonstrate that consistent acceptable results can be obtained when using the compendial method in the company s laboratory (also known as methods verification). The obvious... 

The process for the transfer of analytical methodology is, on the surface, a relatively simple operation. In its most common form, analytical method transfer is the verification that a method or test procedure works in an equivalent fashion at two or more different sites or laboratories and meets all acceptance criteria. This process is driven by compliance and governed by a statistical treatment of the resulting data. This interlaboratory transfer aspect of the overall transfer process has been covered comprehensively by McGonigle, who stressed that successful transfers are linked to the method validation process. Method transfer was defined in this case as the introduction of a validated method into a designated laboratory so that it can be used in the same capacity for which it was originally developed. The second portion of the technology transfer... 

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. 

---