Q&A column

Q. Our laboratory uses a total protein assay from Beckman Coulter that has an analytical measurement range of 3–12 g/dL for serum determinations. The assay sensitivity states 1 g/dL of total protein. Can we loop sensitivity into our AMR and make our reporting range 1–12 g/dL? Will this make our assay a laboratory-developed test? Quite often our clinicians need assays reported to 1 g/dL, since they need to calculate the ratio of total protein serum to body fluid as per Light’s criteria. If we report to 1 g/dL, we have to loop sensitivity into our AMR.

A.The analytical measurement range on the manufacturer’s product insert is the AMR that has been approved by the Food and Drug Administration.

CLIA regulation 42 CFR §493.1253(b)(1) “Verification of Performance Specifications” states that when a laboratory introduces an unmodified, FDA-cleared or -approved test system, it must verify that the performance characteristics for which the test was approved are comparable to those established by the manufacturer. This standard is met by performing and documenting accuracy, precision, reportable range, and reference interval studies.

The instructions for use for the total protein assay from Beckman Coulter state that the AMR is 3–12 g/dL. This is the unmodified, FDA-cleared AMR.

Decreasing the lower limit of the total protein AMR to 1 g/dL modifies the lower limit. CLIA regulation 42 CFR §493.1253(b)(2) states that a laboratory “that modifies an FDA-cleared or approved test system . . . must, before reporting patient test results, establish for each test system the performance specifications” for seven performance characteristics, as applicable. Similarly, the “Test Method Validation and Verification—Nonwaived Tests” section of the CAP’s all common checklist states that “for modified FDA-cleared or approved tests and laboratory-developed tests (LDTs), the laboratory must establish accuracy, precision, analytical sensitivity, analytical specificity (interferences), reportable range, and reference intervals, as applicable; data on interferences may be obtained from manufacturers or published literature, as applicable.”

The reader indicates that they believe the assay sensitivity is 1 g/dL. This is incorrect and is a misinterpretation of the product insert’s wording. Beckman Coulter’s instructions for use for its total protein assay state, under “Sensitivity,” that the “[t]ypical change in absorbance per minute for 1 g/dL of total protein is . . . ” and then gives the amounts of change in absorbance for various models of its AU series analyzers. The reference to 1 g/dL under the sensitivity heading does not imply that the AMR’s lower limit can be decreased to 1 g/dL; rather, it is stating the typical change in absorbance per minute for 1 g/dL of total protein within the FDA-approved AMR of 3–12 g/dL.

Therefore, the answer to the reader’s question is that from 1.0 to 2.9 g/dL, the lab has a modified FDA-cleared/-approved test or laboratory-developed test that it must validate and document appropriately.

College of American Pathologists. All common checklist. Aug. 24, 2023.

Standard: Establishment and Verification of Performance Specifications. 42 CFR §493.1253(b)(1).

Standard: Establishment and Verification of Performance Specifications. 42 CFR §493.1253(b)(2).

Total protein. Instructions for use, BAOSR6X32 11. Beckman Coulter, Inc.; 2020.

Michelle K. Zimmerman, MD, MBA
Director, Clinical Chemistry, Point-of-Care Testing, Specimen Processing, and Send-out Testing
Indiana University Health
Pathology Laboratory
Associate Professor, Clinical Pathology and Laboratory Medicine
Indiana University School of Medicine
Indianapolis, Ind.