2001D-0044 Clinical Laboratory Improvement Amendments of 1988
FDA Comment Number : EC8
Submitter : Ms. Fiona Campbell Date & Time: 12/07/2005 09:12:21
Organization : Trinity Biotech Plc
Category : Device Industry
Issue Areas/Comments
Trinity Biotech Plc. would like to make comment of the guidance document Draft Guidance for Industry and FDA Staff: Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications Dated September 7th 2005

In general this document describes a good design validation strategy that will ensure that only robust in vitro diagnostic products will be used in a CLIA waived environment.

We have the following comments;

FDA Document page 8; demonstrating simple
FDA text; We believe that a test that is simple should not have the following characteristics: Results need to be reported to a public health department at the state or local level e.g., tests for sexually transmitted diseases, since this is not a requirement that would be explained in the device labelling.

Trinity Comment; In the US there is a very high rate of `lost to follow? up for sexually transmitted diseases test results, which has been recently addressed in part by the introduction of rapid HIV tests. Trinity Biotech Plc. believe that the requirement for reporting to the public health department could be imposed via labelling in that a very strongly worded statement should state that all positive results must be confirmed by an non rapid method.

FDA text; Under the approach recommended in this guidance, FDA considers that a simple test should have characteristics such as the following Provides instructions and materials for obtaining and shipping specimens for confirmation testing, in cases where such testing is clinically advisable.

Trinity Comment; In the case of many infectious diseases this requirement could be very problematic. Trinity Biotech Plc. believe this should only be imposed on a case by case basis on each product taking into consideration issues like shipping etc

FDA document page 26; a. General Approach for Method Comparison
Trinity Comment In this section the FDA request that a minimum of 120 positive samples be prospectively tested. For many disease states this will require that many thousands of samples need to be collected and tested (eg HIV, influenza). Trinity Biotech Plc. feels that this is a serious barrier to entry to the US market.
In addition, it is not possible in all cases to split a sample eg nasopharyngeal swab.

FDA document page 27; b. Determining Device Performance with Analyte Concentrations near the Cutoff
Trinity Comment; It is not possible in many cases to obtain sufficient quantities of patient samples to meet FDA?s requirements eg saliva specimens where special collection devices are required.

FDA document page 28; Test Performance of Qualitative Tests
FDA text; The observed positive and negative agreements between the test proposed for waiver and the CM should be 95% or greater; but in all cases the exact lower confidence bound for the two sided 95% confidence interval should be equal to or greater than 91%. See [13-15] and Statistical notes, concerning analyses of percentages, below. In some cases, a higher percent agreement and a higher value for the lower confidence bound may be needed to reasonably assure that the WM is ? accurate?.

Trinity Comments
1. The requirement to demonstrate accuracy may be very difficult to achieve if the only available reference methods are not as sensitive and specific as the investigational method.
2. In addition this requirement seems to restrict the development of advanced technologies.
3. Equivalent test may perform similarly in that they have comparable sensitivity and specificity, the requirement for positive and negative agreement does not take into account technology differences between the tests.
4. It is generally medically accepted that the availability of a rapid test result is very important even if the accuracy of that result is not as good as the gold standard. This is especially the case for nosocomial infections where quarantine may be immediately imposed.