C. Standardization and Certification of Methods by Manufacturers:
1. Standardization of Methods Prior to Certification of Traceability: The process by which a method is standardized to the Reference will depend on the specific method and is determined by the manufacturer, e.g. standardization may be accomplished by re-assignment of calibrator values or by conversion equation since the method may or may not include calibration by the end user. Manufacturers may request assistance from the any network laboratory to 1) help determine the best approach to standardization, 2) recommend or to evaluate different calibrator materials 3) assign preliminary values to calibrators with the understanding that an adjustment in the values may have to be made based on results of fresh sample comparisons, and/ or 4) perform analyses of fresh samples to provide the manufacturer with data on the new method's values compared to reference values in order to provide a basis for calibrator value assignments.
2. Certification of Traceability to the Reference Method: Manufacturers desiring certification of their method must contact the NETCORE. The NETCORE will then assign a SRL based on manufacturers preference, method type, and/or potential conflicts of interest. A method comparison must be performed for certification of a method as traceable to the DCCT Reference. Before pursuing certification through the SRL, manufacturers should establish that their analytical instrument systems / methods:
Manufacturers must participate in a fresh blood sample comparison (n=40) for estimation of bias from the SRL. Manufacturers may perform the precision and comparison analyses at the manufacturing site or they may choose to have a laboratory (that is NOT an NGSP network laboratory) using their system perform the testing. For the sample comparison, one set of fresh samples may be split and used to evaluate several applications or methods, thus necessitating only one evaluation by the SRL. Collection of patient samples may be done either by the manufacturer (or designated laboratory) or by the SRL as long as sample stability requirements for both the SRL and the manufacturer's method can be met. All data should be sent from the manufacturer and the SRL directly to the NETCORE.
In order for a commercial method to be considered traceable to the CPRL, the 95% CI of the differences between methods (test method and SRL method) must fall within the clinically significant limits of ±0.85% GHB (1).
All data analysis will be performed by the NETCORE following Bland and Altman Assessment of Agreement (1). Outliers will be analyzed for informational purposes only; an outlier is defined as > mean + 3SD of the absolute differences between pairs. All outliers will be investigated by the NETCORE to determine if the discrepancy could be due to characteristics of the specimen rather than the assay method. If results show that a discrepancy could be due to characteristics of the specimen, then the manufacturer will be asked to submit a new specimen and the data will be reanalyzed.
Manufacturers are awarded Certificates of Traceability for successfully completing fresh sample comparisons for the specific reagent lots, calibrator lots and instrumentation used. Traceability to the DCCT applies only to results from fresh or fresh frozen blood samples. Analysis of processed (e.g. lyophilized) material may be subject to matrix effects and any comparisons to the DCCT using results from processed specimens should be made with caution. Final certification of traceability is issued by the NETCORE. Methods should be re-certified annually. A new certification is also recommended in the event of significant changes, such as those that would require a new 510(k) form to be filed with FDA.
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