We recommend conducting the reproducibility study at a minimum of 3 of the same sites that were included in the comparison study and are representative of the intended use of the waived test. To facilitate statistical analysis, the same number of untrained operators (likely 2 or 3) should be included at each site of the reproducibility study. For reproducibility study design and analysis, it is recommended that you follow FDA-recognized consensus standards (e.g. CLSI EP05, CLSI EP12). FDA recommends that you include the following sources of variability: different sites, different untrained operators, different days, different runs, different lots (if applicable), and a few replicates. If the candidate device is a unitized device, contact FDA through a Pre-Submission to discuss how you should evaluate repeatability.
Two possible study designs for evaluation of lot-to-lot variability are described below:
A reproducibility study design where each site uses a different lot is generally undesirable, especially for new technologies, because it would be impossible to determine whether observed differences are lot-related or site-related.
If specimens used with the candidate test are not stable (for example, capillary whole blood), attempts to use small-scale repeatability/reproducibility studies that use the intended use clinical samples should be explored (please contact FDA through a Pre-Submission to discuss study designs for precision/reproducibility studies).
We recommend that you include in the reproducibility study the following samples:
We recommend discussing reproducibility study design as part of a Pre-Submission prior to conducting the reproducibility study.