IDS SS-A/Ro; IDS SS-A/Ro 60 kDa; IDS SS-B/La

{0} [LOGO] FDA U.S. FOOD & DRUG ADMINISTRATION ### 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ### I Background Information: ### A 510(k) Number K253817 ### B Applicant Immunodiagnostics Systems Limited ### C Proprietary and Established Names IDS SS-A/Ro IDS SS-A/Ro 60 kDa IDS SS-B/La ### D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | LLL OBE PET | Class II | 21 CFR 866.5100 – Antinuclear Antibody Immunological Test System. | IM - Immunology | ### II Submission/Device Overview: ### A Purpose for Submission: New devices ### B Measurand: Anti-SS-A/Ro IgG autoantibodies Anti-SS-A/Ro 60 kDa IgG autoantibodies Anti-SS-B/La IgG autoantibodies ### C Type of Test: Automated semi-quantitative chemiluminescent immunoassay Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} ### III Intended Use/Indications for Use: #### A Intended Use(s): See Indications for Use below. #### B Indication(s) for Use: IDS SS-A/Ro The IDS SS-A/Ro test is an automated in vitro diagnostic device intended for the semi-quantitative determination of SS-A/Ro (52 kDa and 60 kDa) IgG autoantibodies in human serum on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the diagnosis of Systemic Lupus Erythematosus (SLE), Sjögren's Syndrome (SjS), and Systemic Sclerosis (SSc). IDS SS-A/Ro 60 kDa The IDS SS-A/Ro 60 kDa test is an automated in vitro diagnostic device intended for the semi-quantitative determination of SS-A/Ro 60 kDa IgG autoantibodies in human serum on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the diagnosis of Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SjS). IDS SS-B/La The IDS SS-B/La test is an automated in vitro diagnostic device intended for the semi-quantitative determination of SS-B/La IgG autoantibodies in human serum on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the diagnosis of Systemic Lupus Erythematosus (SLE), and Sjögren's Syndrome (SjS). #### C Special Conditions for Use Statement(s): Rx - For Prescription Use Only #### D Special Instrument Requirements: For use on IDS-iSYS Multi-Discipline Automated System (K091849) ### IV Device/System Characteristics: #### A Device Description: IDS SS-A/Ro The IDS SS-A/Ro kit consists of a reagent cartridge, 2 levels of calibrators, and a QR barcode contains data for the reagent kits. K253817 - Page 2 of 21 {2} The reagent cartridge contains following ready to use reagents for 100 determinations: - MP (1 bottle, 2.5 mL): Magnetic particles coated with the SS-A/Ro antigen, in phosphate buffer containing stabilizing proteins and Pro-Clin 300 and sodium azide (< 0.1%) as preservatives. - CONJ (1 bottle, 15 mL): Mouse monoclonal anti-human IgG antibody labelled with an acridine ester derivative (conjugate), in phosphate buffer containing stabilizers and sodium azide (< 0.1%) as preservative.. - DIL (1 bottle, 25 mL): Sample Dilution Solution: phosphate buffer containing bovine serum albumin, detergent, inert blue dye, and Pro-Clin 300 and gentamicin SO₄ as preservatives.. The lot specific calibrators are included with the kit: - Two levels (CAL A and CAL B): 1 vial per level. The ready to use calibrators are human serum containing 1.6 mL human antibodies to SS-A/Ro IgG in phosphate buffer containing bovine serum albumin, detergent, inert blue dye, Pro-Clin 300 and gentamicin SO₄ as preservatives. # IDS SS-A/Ro 60 kDa The IDS SS-A/Ro 60 kDa kit consists of a reagent cartridge, 2 levels of calibrators, and a QR barcode contains data for the reagent kits. The reagent cartridge contains following ready to use reagents for 100 determinations: - MP (1 bottle, 2.5 mL): Magnetic particles coated with the SS-A/Ro 60 antigen, in phosphate buffer containing stabilizing proteins and Pro-Clin 300 and sodium azide (< 0.1%) as preservatives. - CONJ (1 bottle, 15 mL): Mouse monoclonal anti-human IgG antibody labelled with an acridine ester derivative (conjugate), in phosphate buffer containing stabilizers and sodium azide (< 0.1%) as preservative.. - DIL (1 bottle, 25 mL): Sample Dilution Solution: phosphate buffer containing bovine serum albumin, detergent, inert blue dye, and Pro-Clin 300 and gentamicin SO₄ as preservatives.. The lot specific calibrators are included with the kit: - Two levels (CAL A and CAL B): 1 vial per level. The ready to use calibrators are human serum containing 1.6 mL human antibodies to SS-A/Ro 60 kDa IgG in phosphate buffer containing bovine serum albumin, detergent, inert blue dye, Pro-Clin 300 and gentamicin SO₄ as preservatives. # IDS SS-B/La The IDS SS-B/La kit consists of a reagent cartridge, 2 levels of calibrators, and a QR barcode contains data for the reagent kits. K253817 - Page 3 of 21 {3} The reagent cartridge contains following ready to use reagents for 100 determinations: - MP (1 bottle, 2.5 mL): Magnetic particles coated with the SS-B/La antigen, in phosphate buffer containing stabilizing proteins and Pro-Clin 300 and sodium azide (< 0.1%) as preservatives. - CONJ (1 bottle, 15 mL): Mouse monoclonal anti-human IgG antibody labelled with an acridine ester derivative (conjugate), in phosphate buffer containing stabilizers and sodium azide (< 0.1%) as preservative.. - DIL (1 bottle, 25 mL): Sample Dilution Solution: phosphate buffer containing bovine serum albumin, detergent, inert blue dye, and Pro-Clin 300 and gentamicin SO₄ as preservatives.. The lot specific calibrators are included with the kit: - Two levels (CAL A and CAL B): 1 vial per level. The ready to use calibrators are human serum containing 1.6 mL human antibodies to SS-B/La IgG in phosphate buffer containing bovine serum albumin, detergent, inert blue dye, Pro-Clin 300 and Gentamicin SO4 as preservatives. ### B Principle of Operation: The assays are based on chemiluminescence technology. Diluted samples, controls or calibrators are incubated with magnetic particles coated with the SS-A/Ro, SS-A/Ro 60 kDa, or SS-B/La antigens to allow reactive antibodies to bind. Following a washing step after the first incubation, a mouse anti-human IgG monoclonal antibody labelled with acridinium is added, followed by a subsequent incubation step. The magnetic particles are captured using a magnet and a wash step performed to remove any unbound antibodies. Trigger reagents are added; the resulting light emitted by the acridinium label is proportional to the level of anti-SS-A/Ro, SS-A/Ro 60 kDa, or SS-B/La antigen-reactive IgG antibodies in the sample. ### V Substantial Equivalence Information: ### A Predicate Device Name(s): ORGENTEC ANTI-SS-A(RO) ELISA QUANTA Flash Ro60 QUANTA Flash SS-B ### B Predicate 510(k) Number(s): K962054 K141328 K141210 ### C Comparison with Predicate(s): K253817 - Page 4 of 21 {4} | Device & Predicate Device(s): | K251440 (Candidate) | K962054 (Predicate) | | --- | --- | --- | | Device Trade Name | IDS SS-A/Ro | ORGENTEC ANTI-SS-A(RO) ELISA | | **General Device Characteristic Similarities** | | | | Intended Use/Indications For Use | The IDS SS-A/Ro test is an automated in vitro diagnostic device intended for the semi-quantitative determination of SS-A/Ro (52 kDa and 60 kDa) IgG autoantibodies in human serum on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the diagnosis of Systemic Lupus Erythematosus (SLE), Sjögren's Syndrome (SjS), and Systemic Sclerosis (SSc). | The Orgentec Anti-SS-A(Ro) ELISA is intended for the in vitro semi-quantitative determination of autoantibodies against cytoplasmic antigen, SS-A(Ro) in human serum or plasma to assist in the diagnosis of system lupus erythematosus (SLE) and other connective tissue diseases such as Sjögren's Syndrome. | | Antigen | Purified recombinant Ro60 kDa and Ro52 kDa | Same | | Shelf Life | 12 months | Same | | **General Device Characteristic Differences** | | | | Assay Principle | Chemiluminescent immunoassay | Enzyme-linked immunosorbent assay | | Assay Format | Automatic | Manual | | Sample Type(s) | Serum | Serum or plasma | | Solid phase | Paramagnetic microparticles (beads) | 96-well plate | | Conjugate | Mouse monoclonal anti-human IgG antibody labelled with an acridinium ester derivative | Anti-human IgG HRP labelled | | Assay Measuring Interval | 5.3 – 640.0 AU/mL | 0 – 200 U/mL | | Cut-off | Negative: < 10.0 AU/mL Positive: ≥ 10.0 AU/mL | Negative: < 15 U/mL Equivocal: 15 to 25 U/mL Positive: > 25 U/mL | | Unit | AU (arbitrary units) | U/mL (arbitrary units) | K253817 - Page 5 of 21 {5} | Device & Predicate Device(s): | K251440 (Candidate) | K141328 (Predicate) | | --- | --- | --- | | Device Trade Name | IDS SS-A/Ro60 kDa | QUANTA Flash Ro60 | | **General Device Characteristic Similarities** | | | | Intended Use/Indications For Use | The IDS SS-A/Ro 60 kDa test is an automated in vitro diagnostic device intended for the semi-quantitative determination of SS-A/Ro 60 kDa IgG autoantibodies in human serum on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the diagnosis of Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SjS). | QUANTA Flash Ro60 is a chemiluminescent immunoassay for the semi-quantitative determination of IgG anti-Ro60 autoantibodies in human serum. The presence of antiRo60 autoantibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of Systemic Lupus Erythematosus and Sjögren's Syndrome. | | Assay Methodology | Solid phase (heterogeneous) immunoassay | Same | | Assay Principle | Chemiluminescent immunoassay | Same | | Sample Type | Serum | Same | | Antigen | Purified recombinant Ro60 antigen | Same | | Shelf Life | 12 months | Same | | Assay Format | Automatic | Same | | Solid Phase | Paramagnetic microparticles (beads) | Same | | **General Device Characteristic Differences** | | | | Conjugate | Monoclonal mouse anti-human IgG antibody marked with an acridinium ester derivative. | Isoluminol conjugated anti-human IgG | | Cut-off | Negative: < 10 AU/mL Positive: ≥ 10 AU/mL | Negative: < 20 CU Positive: ≥ 20 CU | | Assay Measuring Range (AMR) | 2.9 – 640.0 AU/mL | 4.9 - 1374.8 CU | | Unit | AU (arbitrary units) | CU (Chemiluminescent units) (arbitrary) | K253817 - Page 6 of 21 {6} | Device & Predicate Device(s): | K251440 (Candidate) | K141210 (Predicate) | | --- | --- | --- | | Device Trade Name | IDS SS-B/La | QUANTA Flash SS-B | | **General Device Characteristic Similarities** | | | | Intended Use/Indications For Use | The IDS SS-B/La test is an automated *in vitro* diagnostic device intended for the semi-quantitative determination of SS-B/La IgG autoantibodies in human serum on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the diagnosis of Systemic Lupus Erythematosus (SLE), and Sjögren's Syndrome (SjS). | QUANTA Flash SS-B is a chemiluminescent immunoassay for the semi-quantitative determination of IgG anti-SS-B autoantibodies in human serum. The presence of anti-SS-B autoantibodies, in conjunction with clinical findings and other laboratory tests is an aid in the diagnosis of Sjögren's Syndrome and Systemic Lupus Erythematosus. | | Assay Methodology | Solid phase (heterogeneous) immunoassay | Same | | Assay Principle | Chemiluminescent immunoassay | Same | | Sample Type | Serum | Same | | Antigen | Purified recombinant SS-B antigen | Same | | Shelf Life | 12 months | Same | | Assay Format | Automatic | Same | | Solid Phase | Paramagnetic microparticles (beads) | Same | | **General Device Characteristic Differences** | | | | Conjugate | Mouse monoclonal anti-human IgG antibody labelled with an acridinium ester derivative | Isoluminol conjugated anti-human IgG | | Cut-off | Negative: < 10 AU/mL Positive: ≥ 10 AU/mL | Negative: < 20 CU Positive: ≥ 20 CU | | Assay Measuring Range | 4.6 – 640.0 AU/mL | 3.3 – 1550 CU | | Unit | AU (arbitrary units) | CU (Chemiluminescent units) (arbitrary) | ### VI Standards/Guidance Documents Referenced: The following Clinical and Laboratory Standards Institute (CLSI) guidelines were used: - CLSI EP05, 3rd Edition, Evaluation of Precision of Quantitative Measurement Procedures, K253817 - Page 7 of 21 {7} - CLSI EP06, 2nd Edition, Evaluation of the Linearity of Quantitative Measurement Procedures - CLSI EP07, 3rd Edition, Interference Testing in Clinical Chemistry - CLSI EP17, 2nd Edition, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures - CLSI EP25-A2, Evaluation of Stability of In Vitro Diagnostic Reagents - CLSI EP28-A3c, Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory - CLSI EP34, Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking - CLSI EP37, Supplemental Tables for Interference Testing in Clinical Chemistry ### VII Performance Characteristics (if/when applicable): #### A Analytical Performance: ##### 1. Precision/Reproducibility: Precision of the IDS SS-A/Ro, SS-A/Ro 60 kDa, and SS-B/La assays was evaluated following the CLSI Guideline EP05-A3. Within-Laboratory Precision: To evaluate within-laboratory precision of the IDS SS-A/Ro, SS-A/Ro 60 kDa, and SS-B/La assays, a total of seven serum samples spanning the analytical measuring interval (AMI) of each assay were tested in duplicate, twice a day for 20 days on one IDS system using one lot of assay reagent, yielding a total of 80 measurements per sample. The standard deviation (SD) and %CV of the within-run, between-run, between-day, and total within-laboratory imprecision were calculated for each sample. The results are summarized in the following tables. IDS SS-A/Ro: | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Within-Day | | Between-Day | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 80 | 8.0 | 0.5 | 6.5% | 0.1 | 1.7% | 0.6 | 7.6% | 0.8 | 10.2% | 0.5 | 6.5% | | 2 | 80 | 10.5 | 0.4 | 3.7% | 0.4 | 3.5% | 0.6 | 6.1% | 0.8 | 8.0% | 0.4 | 3.7% | | 3 | 80 | 16.0 | 0.9 | 5.9% | 0.7 | 4.4% | 0.8 | 5.1% | 1.4 | 9.0% | 0.9 | 5.9% | | 4 | 80 | 79.9 | 1.6 | 2.0% | 1.4 | 1.7% | 2.6 | 3.2% | 3.3 | 4.2% | 1.6 | 2.0% | | 5 | 80 | 140.3 | 3.1 | 2.2% | 3.4 | 2.4% | 3.2 | 2.3% | 5.6 | 4.0% | 3.1 | 2.2% | | 6 | 80 | 306.4 | 5.7 | 1.9% | 4.5 | 1.5% | 6.2 | 2.0% | 9.6 | 3.1% | 5.7 | 1.9% | | 7 | 80 | 509.7 | 12.7 | 2.5% | 6.9 | 1.4% | 14.9 | 2.9% | 20.8 | 4.1% | 12.7 | 2.5% | K253817 - Page 8 of 21 {8} # IDS SS-A/Ro 60 kDa: | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Within-Day | | Between-Day | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 80 | 8.3 | 0.5 | 6.6% | 0.5 | 5.7% | 0.1 | 1.4% | 0.7 | 8.8% | 0.5 | 6.6% | | 2 | 80 | 10.5 | 0.5 | 4.4% | 0.5 | 4.7% | 0.7 | 6.8% | 1.0 | 9.4% | 0.5 | 4.4% | | 3 | 80 | 15.2 | 0.6 | 4.2% | 1.1 | 7.5% | 0.6 | 4.1% | 1.4 | 9.5% | 0.6 | 4.2% | | 4 | 80 | 66.3 | 1.7 | 2.5% | 2.9 | 4.4% | 2.4 | 3.7% | 4.2 | 6.3% | 1.7 | 2.5% | | 5 | 80 | 169.8 | 3.1 | 1.8% | 4.4 | 2.6% | 5.5 | 3.2% | 7.6 | 4.5% | 3.1 | 1.8% | | 6 | 80 | 338.2 | 8.0 | 2.4% | 10.2 | 3.0% | 8.7 | 2.6% | 15.6 | 4.6% | 8.0 | 2.4% | | 7 | 80 | 544.7 | 17.6 | 3.2% | 20.5 | 3.8% | 12.5 | 2.3% | 29.8 | 5.5% | 17.6 | 3.2% | # IDS SS-B/La: | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Within-Day | | Between-Day | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 80 | 7.1 | 0.6 | 9.2% | 0.2 | 3.1% | 0.4 | 6.3% | 0.8 | 11.6% | 0.6 | 9.2% | | 2 | 80 | 10.3 | 0.6 | 6.3% | 0.6 | 6.1% | 0.5 | 4.6% | 1.0 | 9.9% | 0.6 | 6.3% | | 3 | 80 | 13.7 | 0.7 | 4.8% | 0.6 | 4.1% | 0.7 | 5.2% | 1.1 | 8.2% | 0.7 | 4.8% | | 4 | 80 | 76.5 | 5.3 | 6.9% | 0.0 | 0.0% | 4.1 | 5.4% | 6.7 | 8.7% | 5.3 | 6.9% | | 5 | 80 | 135.7 | 9.5 | 7.0% | 4.1 | 3.0% | 3.3 | 2.5% | 10.9 | 8.0% | 9.5 | 7.0% | | 6 | 80 | 335.0 | 21.4 | 6.4% | 11.9 | 3.5% | 0.0 | 0.0% | 24.5 | 7.3% | 21.4 | 6.4% | | 7 | 80 | 497.6 | 42.8 | 8.6% | 0.0 | 0.0% | 15.6 | 3.1% | 45.5 | 9.1% | 42.8 | 8.6% | # *Between-Lot Imprecision:* To evaluate the lot-to-lot precision of the IDS SS-A/Ro, SS-A/Ro 60 kDa, and SS-B/La assays, a total of seven serum samples spanning the AMI of each assay were tested in five replicates, once a day for five days on one IDS system using three lots of reagents by one operator per system, yielding a total of 75 measurements per sample. The standard deviation (SD) and %CV of the within-run, between-run, between-lot, and total imprecision were calculated for each sample. The results are summarized in the following tables. # IDS SS-A/Ro: | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Between-Lot | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 75 | 8.2 | 0.6 | 7.2% | 0.2 | 1.9% | 0.3 | 3.2% | 0.7 | 8.2% | | 2 | 75 | 9.9 | 0.8 | 7.9% | 0.0 | 0.0% | 0.2 | 2.0% | 0.8 | 8.1% | | 3 | 75 | 13.8 | 0.8 | 5.9% | 0.9 | 6.4% | 0.2 | 1.6% | 1.2 | 8.9% | | 4 | 75 | 88.8 | 2.6 | 2.9% | 1.8 | 2.1% | 7.5 | 8.4% | 8.1 | 9.1% | | 5 | 75 | 159.5 | 3.3 | 2.1% | 4.8 | 3.0% | 12.7 | 7.9% | 14.0 | 8.8% | | 6 | 75 | 343.0 | 6.4 | 1.9% | 7.3 | 2.1% | 29.9 | 8.7% | 31.4 | 9.2% | | 7 | 75 | 563.5 | 14.9 | 2.6% | 29.3 | 5.2% | 14.5 | 2.6% | 35.9 | 6.4% | K253817 - Page 9 of 21 {9} # IDS SS-A/Ro 60 kDa: | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Between-Lot | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 75 | 8.3 | 0.5 | 5.7% | 0.4 | 5.1% | 0.3 | 3.1% | 0.7 | 8.2% | | 2 | 75 | 10.4 | 0.3 | 3.0% | 0.3 | 2.8% | 0.1 | 1.0% | 0.4 | 4.2% | | 3 | 75 | 14.6 | 0.6 | 4.4% | 0.3 | 2.4% | 0.5 | 3.3% | 0.9 | 6.0% | | 4 | 75 | 65.9 | 1.5 | 2.2% | 2.0 | 3.1% | 1.0 | 1.6% | 2.7 | 4.1% | | 5 | 75 | 164.1 | 3.7 | 2.3% | 1.2 | 0.7% | 6.3 | 3.8% | 7.4 | 4.5% | | 6 | 75 | 326.7 | 5.6 | 1.7% | 8.7 | 2.7% | 13.2 | 4.0% | 16.8 | 5.1% | | 7 | 75 | 535.5 | 19.4 | 3.6% | 14.7 | 2.7% | 24.2 | 4.5% | 34.3 | 6.4% | # IDS SS-B/La: | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Between-Lot | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 75 | 7.6 | 0.7 | 9.1% | 0.5 | 6.9% | 0.1 | 1.6% | 0.9 | 11.5% | | 2 | 75 | 10.9 | 0.8 | 7.1% | 0.4 | 3.4% | 0.7 | 6.2% | 1.1 | 10.0% | | 3 | 75 | 16.5 | 1.5 | 9.2% | 0.1 | 1.8% | 0.8 | 3.3% | 4.7 | 10.4% | | 4 | 75 | 76.5 | 4.8 | 6.2% | 3.6 | 4.7% | 5.3 | 6.9% | 8.0 | 10.4% | | 5 | 75 | 137.8 | 9.6 | 7.0% | 4.4 | 3.2% | 7.3 | 5.3% | 12.8 | 9.3% | | 6 | 75 | 335.9 | 24.3 | 7.2% | 18.1 | 5.4% | 11.4 | 3.4% | 32.4 | 9.6% | | 7 | 75 | 513.5 | 36.3 | 7.1% | 12.0 | 2.6% | 8.6 | 1.7% | 39.2 | 7.6% | # *Between-Instrument Reproducibility:* To evaluate the instrument-to-instrument precision of the IDS SS-A/Ro, SS-A/Ro 60 kDa, and SS-B/La assays, a total of seven serum samples spanning the AMI of each assay were tested in five replicates, once a day for five days using one lot of reagent on three IDS systems by one operator, for a total of 75 measurements per sample. The standard deviation (SD) and %CV of the within-run, between-run, between-instrument, and total imprecision (reproducibility) were calculated for each sample. The results are summarized in the following tables. # IDS SS-A/Ro | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Between-Instrument | | Reproducibility | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 75 | 8.1 | 0.8 | 9.8% | 0.3 | 3.9% | 0.5 | 6.2% | 1.0 | 12.3% | | 2 | 75 | 10.1 | 0.8 | 8.2% | 0.3 | 3.1% | 0.2 | 2.1% | 0.9 | 9.0% | | 3 | 75 | 15.6 | 0.8 | 5.4% | 1.4 | 9.0% | 0.5 | 3.1% | 1.7 | 10.9% | | 4 | 75 | 97.3 | 3.3 | 3.4% | 4.0 | 4.1% | 2.5 | 2.6% | 5.8 | 5.9% | | 5 | 75 | 173.6 | 3.8 | 2.2% | 9.7 | 5.6% | 4.2 | 2.4% | 11.2 | 6.5% | K253817 - Page 10 of 21 {10} | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Between-Instrument | | Reproducibility | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 6 | 75 | 400.4 | 16.0 | 4.0% | 10.9 | 2.7% | 20.6 | 5.1% | 28.3 | 7.1% | | 7 | 75 | 572.8 | 28.3 | 4.9% | 11.4 | 2.0% | 0.0 | 0.0% | 30.5 | 5.3% | # IDS SS-A/Ro 60 kDa: | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Between-Instrument | | Reproducibility | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 75 | 7.6 | 0.5 | 7.0% | 0.5 | 6.6% | 0.2 | 2.7% | 0.8 | 10.0% | | 2 | 75 | 10.3 | 0.7 | 7.2% | 0.3 | 3.3% | 0.2 | 1.5% | 0.8 | 8.0% | | 3 | 75 | 14.6 | 0.8 | 5.2% | 0.9 | 6.4% | 0.0 | 0.0% | 1.2 | 8.2% | | 4 | 75 | 60.5 | 1.4 | 2.3% | 2.5 | 4.1% | 3.4 | 5.7% | 4.5 | 7.4% | | 5 | 75 | 151.3 | 3.4 | 2.2% | 4.0 | 2.6% | 5.3 | 3.5% | 7.5 | 4.9% | | 6 | 75 | 298.4 | 6.4 | 2.1% | 8.4 | 2.8% | 11.1 | 3.7% | 15.3 | 5.1% | | 7 | 75 | 496.5 | 11.6 | 2.3% | 8.0 | 1.6% | 9.3 | 1.9% | 16.8 | 3.4% | # IDS SS-B/La | Sample | N | Mean (AU/mL) | Within-Run | | Between-Run | | Between-Instrument | | Reproducibility | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | | 1 | 75 | 7.3 | 0.5 | 6.7% | 0.3 | 4.5% | 0.3 | 4.1% | 0.7 | 9.1% | | 2 | 75 | 10.8 | 0.6 | 5.8% | 0.4 | 3.9% | 0.2 | 2.2% | 0.8 | 7.3% | | 3 | 75 | 17.7 | 1.3 | 7.6% | 0.5 | 3.0% | 0.0 | 0.0% | 1.5 | 8.2% | | 4 | 75 | 77.0 | 3.1 | 4.0% | 3.4 | 4.5% | 1.0 | 1.3% | 4.8 | 6.2% | | 5 | 75 | 141.6 | 6.2 | 4.4% | 5.9 | 4.1% | 2.1 | 1.5% | 8.8 | 6.2% | | 6 | 75 | 338.5 | 13.4 | 4.0% | 14.7 | 4.3% | 6.2 | 1.8% | 20.8 | 6.2% | | 7 | 75 | 509.2 | 27.1 | 5.3% | 5.4 | 1.1% | 10.6 | 2.1% | 29.6 | 5.8% | # 2. Linearity: Linearity for the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La assays was evaluated based on CLSI EP06, 2$^{nd}$ Ed. For each assay, two dilution series were prepared by mixing one High native serum sample with a Low native serum sample. Seven dilutions were made that overlapped other samples' dilution series. Each sample was tested with four or seven replicates on the IDS Instrument. The percent deviation from the weighted linear regression analysis was used to assess the fit of the regression for each sample and analyte. The results are summarized in the table below. # IDS SS-A/Ro: | Sample ID | Test Range (AU/mL) | Slope (95% CI) | R^{2} | % Deviation from Linearity | | --- | --- | --- | --- | --- | | Panel - 1 | 0.5 – 53.9 | 1.02 (0.99 – 1.05) | 0.99 | -10.4% to 15.5% | | Panel - 2 | 13.9 – 781.2 | 1.01 (0.97 – 1.04) | 0.99 | -9.5% to 12.3% | K253817 - Page 11 of 21 {11} IDS SS-A/Ro 60 kDa: | Sample ID | Test Range (AU/mL) | Slope (95% CI) | R^{2} | % Deviation from Linearity | | --- | --- | --- | --- | --- | | Panel - 1 | 2.6 – 53.5 | 1.00 (0.98 – 1.02) | 0.99 | -1.4% to 6.0% | | Panel - 2 | 12.2 – 740.2 | 1.02 (1.00 – 1.04) | 0.99 | -10.2% to 3.0% | IDS SS-B/La | Sample ID | Test Range (AU/mL) | Slope (95% CI) | R^{2} | % Deviation from Linearity | | --- | --- | --- | --- | --- | | Panel - 1 | 3.8 – 54.3 | 0.99 (0.96 – 1.01) | 0.99 | -2.1% to 6.2% | | Panel - 2 | 16.1 – 771.2 | 1.02 (1.00 – 1.04) | 0.99 | -7.6% to 7.2% | The data support the linearity of the following analytical measuring interval of the assay: - IDS SS-A/Ro (5.3 – 640.0 AU/mL) - IDS SS-A/Ro 60 kDa (2.9 – 640.0 AU/mL) - IDS SS-B/La (4.6 – 640.0 AU/mL). ### 3. Analytical Specificity/Interference: The potential for interference with IDS SS-A/Ro, SS-A/Ro 60 kDa, and SS-B/La by exogenous and endogenous compounds were evaluated following the CLSI EP07, 3rd Ed. The studies were performed using three human serum specimens, one positive, one near the cutoff (borderline), and one negative. Interferent or blank buffer (≤10% v/v) were spiked into the tested serum specimens. The results of samples with interferent substance were compared to the control samples without interferent substance. No significant interference was observed when the interfering substances were tested at the following threshold concentrations: Endogenous Interference: | Potential Interfering Substance | Tested Concentration | | --- | --- | | Albumin (Protein) | 6 g/dL | | Bilirubin, conjugated | 40 mg/dL | | Bilirubin, unconjugated | 40 mg/dL | | Cholesterol | 400 mg/dL | | Hemoglobin | 1000 mg/dL | | Human Anti-Mouse Antibody (HAMA) | 200 ng/dL | | Protein, Total | 15 g/dL | | Rheumatoid Factor (RhF) | 540 IU/mL | | Triglycerides | 1500 mg/dL | Exogenous Interference: | Potential Interfering Substance | Tested Concentration | | --- | --- | | Acetaminophen | 15.6 mg/dL | | Acetylsalicylic Acid | 3.0 mg/dL | K253817 - Page 12 of 21 {12} | Potential Interfering Substance | Tested Concentration | | --- | --- | | Alendronate | 0.01025 mg/dL | | Amoxicillin | 12.9 mg/dL | | Atenolol | 0.009 mg/dL | | Atorvastatin | 0.0756 mg/dL | | Azathioprine | 0.258 mg/dL | | Biotin | 3.5 mg/dL | | Diltiazem | 0.075 mg/dL | | Enalapril | 0.0819 mg/dL | | Erythromycin | 13.8 mg/dL | | Furosemide | 1.59 mg/dL | | Hydroxychloroquine | 0.01509 mg/dL | | Ibuprofen | 21.9 mg/dL | | Losartan | 0.0672 mg/dL | | Methotrexate | 205 mg/dL | | Naproxen | 36.0 mg/dL | | Omeprazole | 0.84 mg/dL | | Prednisone | 0.01 mg/dL | | Ranitidine | 1.05 mg/dL | | Rituximab | 114.3 mg/dL | The CDC (Centers for Disease Controls and Prevention) ANA human reference sera panel samples were tested using the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La kit to demonstrate the specificity of the assay. The table below outlines the results obtained: | Sample ID | Catalog No. | CDC Description | IDS SS-A/Ro (AU/mL) | IDS SS-A/Ro 60 kDa (AU/mL) | IDS SS-B/La (AU/mL) | | --- | --- | --- | --- | --- | --- | | ANA-01 | IS2072 | ANA Homogeneous Positive; Anti-native DNA Positive | 5.4 (NEG) | <2.9 (NEG) | <4.6 (NEG) | | ANA-02 | IS2073 | ANA Speckled Positive; Anti-SSB Positive | 306.1 (POS) | 292.8 (POS) | >640.0 (POS) | | ANA-03 | IS2074 | ANA Speckled Positive | 138.7 (POS) | 198.3 (POS) | 83.8 (POS) | | ANA-04 | IS2075 | ANA-U1 RNP Positive | 9.3 (NEG) | 5.7 (NEG) | <4.6 (NEG) | | ANA-05 | IS2076 | Anti-Sm Positive | <5.3 (NEG) | <2.9 (NEG) | <4.6 (NEG) | | ANA-07 | IS2105 | Anti-SS-A Positive | 552.6 (POS) | >640.0 (NEG) | <4.6 (NEG) | | ANA-08 | IS2134 | ANA Centromere Positive | <5.3 (NEG) | <2.9 (NEG) | <4.6 (NEG) | | ANA-09 | IS2135 | Anti-Scl 70 Positive | <5.3(NEG) | 8.6 (NEG) | <4.6 (NEG) | | ANA-10 | IS2187 | Anti-Jo 1 Positive | 232.0^{a} (POS) | <2.9 (NEG) | <4.6 (NEG) | | ANA-12 | IS2706 | Anti-Ribosomal P Positive | 6.5 (NEG) | <2.9 (NEG) | <4.6 (NEG) | $^{a}$ Other immunoassay methods had shown that sample ANA-10 (IS2187) was positive for Ro52. #### 4. Detection Limit: The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) were determined following CLSI EP17-A2. K253817 - Page 13 of 21 {13} Two reagent lots of IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, or IDS SS-B/La were used. The LoB was determined with 80 replicates of four undetectable single donor serum samples per reagent lot using the parametric method. The LoD of each assay was determined with four low level serum samples. Each sample was measured in four replicates, once per day for five days resulting in a total 20 measurements per sample per IDS reagent lot: a total of 80 measurements per reagent lot using the parametric method. Similarly, the LoQs were determined with 160 replicates of four undetectable single donor serum samples and four serum samples with low antibodies level per reagent lot. The claimed LoQ is the highest concentration of the sample below the precision of 20% CV. The claimed detection limits for each assay are summarized below: | | LoB (AU/mL) | LoD (AU/mL) | LoQ (AU/mL) | | --- | --- | --- | --- | | IDS SS-A/Ro | 0.0 | 1.2 | 5.3 | | IDS SS-A/Ro 60 kDa | 0.0 | 1.3 | 2.9 | | IDS SS-B/La | 0.0 | 1.1 | 4.6 | ### 5. Assay Reportable Range The assay reportable range is the same as the analytical measuring intervals (AMIs). - IDS SS-A/Ro: The AMI is 5.3 – 640.0 AU/mL. Results lower than 5.3 AU/mL will be reported as “<5.3 AU/mL”. Results greater than 640.0 AU/mL will be reported as “>640.0 AU/mL”. - IDS SS-A/Ro 60 kDa: The AMI is 2.9 – 640.0 AU/mL. Results lower than 2.9 AU/mL will be reported as “<2.9 AU/mL”. Results greater than 640.0 AU/mL will be reported as “>640.0 AU/mL”. - IDS SS-B/La: 4The AMI is 4.6 – 640.0 AU/mL. Results lower than 4.6 AU/mL will be reported as “<4.6 AU/mL”. Results greater than 640.0 AU/mL will be reported as “>640.0 AU/mL”. ### 6. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods): #### a. Traceability There are no international reference materials available for anti-SSA-Ro, anti-SSA-Ro60, and anti-SSB/La. Calibrator and Control values are traceable to in-house materials for each assay. #### b. Reagent Stability: The reagent stability studies for IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La assays were designed and conducted following CLSI EP25, 2nd Ed. K253817 - Page 14 of 21 {14} Shelf-life stability: The stability of the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La reagent kit was evaluated with a real-time study. Three lots of the IDS reagent kit were stored under recommended conditions at 2 – 8°C and tested at different timepoints using two negative and five to six positive serum samples. On-board stability: The on-board stability of the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La reagent kit was evaluated on-board the IDS instrument. One lot of the reagent kit was opened and stored on-board the IDS system and assessed over 12 time points using one to two negative and five positive serum samples. In-use stability: The in-use stability of the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La reagent kit was evaluated with an open cartridge vial on the IDS instrument. One lot of the IDS reagent kit was opened and stored on-board the IDS system and assessed over 8 time points using four positive serum samples at 2 – 8°C. Reagent cartridges were removed from the system after each time point and stored at 2 – 8°C. The studies support the following reagent stability claims for each assay: | | Reagent Stability Claim | | | | --- | --- | --- | --- | | Storage Condition | IDS SS-A/Ro | IDS SS-A/Ro 60 kDa | IDS SS-B/La | | Shelf-life (2 – 8°C) | 12 months | 12 months | 12 months | | On-board | 56 days | 56 days | 42 days | | In-use | 56 days | 56 days | 42 days | # c. Sample Stability: On-board sample stability: The sample stability was evaluated to support the stability of samples when on-board the IDS system for the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La assays using one to two negative and six positive serum samples. Samples were tested at six time points when placed on-board the IDS system. Sample stored at 5±3°C: The sample stability was evaluated to support the stability of samples when stored at 5±3°C for the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La assays using one negative and four to six positive serum samples. Samples were tested at four time points stored at refrigeration condition (5±3°C). Sample stored at room temperature (20±5°C): The sample stability was evaluated to support the stability of samples when stored at room temperature (20±5°C) for the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La assays using one negative and four to five positive serum samples. Samples were tested at seven time points on the IDS system when stored at room temperature. Sample stored at frozen condition (-20±5°C): The sample stability was evaluated to support the stability of samples when frozen (-20±5°C) for the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La assays using one negative and six to nine positive serum samples. Samples were tested at 10 time points when stored at frozen condition. K253817 - Page 15 of 21 {15} Sample stability under freeze/thaw cycle: The sample stability was evaluated to support the stability of samples when undergoing multiple freeze/thaw cycles using the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La reagent kit using one negative and five to six positive serum samples. Samples were aliquoted and tested with three freeze/thaw cycles on the IDS system. The studies support the following sample stability claims for each assay: Sample Stability Claim | Storage Condition | IDS SS-A/Ro | IDS SS-A/Ro 60 kDa | IDS SS-B/La | | --- | --- | --- | --- | | On-board | 8 hours | 8 hours | 8 hours | | 5±3°C | 14 days | 14 days | 14 days | | 20±5°C (RT) | 48 hours | 48 hours | 48 hours | | -20±5°C | 28 months | 28 months | 28 months | | freeze/thaw | 2 cycles | 2 cycles | 2 cycles | # 7. Assay Cut-Off: The three assays have the same cut-off: 100 AU/mL, with the following result interpretation: Negative: < 10.0 AU/mL Positive: ≥ 10.0 AU/mL # B Comparison Studies: # 1. Method Comparison with Predicate Device: The method comparison for each of the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La assay, the was conducted by testing the native serum samples with the candidate device and its predicate. Of the tested samples, samples within the analytical measuring interval of both candidate device and its predicate were used in the data analysis. Positive percent agreement (PPA) and negative present agreement (NPA), with 95% confident intervals were calculated for each analyte comparison. The method comparison study results for each assay are summarized in the following table: IDS SS-A/Ro: | | Predicate | | | | | | --- | --- | --- | --- | --- | --- | | | | Positive | Equivocal | Negative | Total | | IDS SS-A/Ro | Positive | 42 | 8 | 0 | 50 | | | Negative | 0 | 5 | 77 | 82 | | | Total | 42 | 13 | 77 | 132 | Equivocal as Positive PPA: 90.9% (50/55) (95% CI: 80.4 – 96.1%) NPA: 100.0% (77/77) (95% CI: 95.2 – 100.0%) K253817 - Page 16 of 21 {16} Equivocal as Negative PPA: 100.0% (42/42) (95% CI: 91.6 - 100.0%) NPA: 91.1% (82/90) (95% CI: 83.4 - 95.4%) IDS SS-A/Ro 60 kDa: | | Predicate | | | | | --- | --- | --- | --- | --- | | | | Positive | Negative | Total | | IDS SS-A/Ro 60 kDa | Positive | 62 | 2 | 64 | | | Negative | 7 | 77 | 84 | | | Total | 69 | 79 | 148 | PPA: 89.9% (62/69) (95% CI: 80.5 - 95.0%) NPA: 97.5% (77/79) (95% CI: 91.2 - 99.3%) IDS SS-B/La: | | Predicate | | | | | --- | --- | --- | --- | --- | | | | Positive | Negative | Total | | IDS SS-B/La | Positive | 75 | 1 | 76 | | | Negative | 0 | 60 | 60 | | | Total | 75 | 61 | 136 | PPA: 100.0% (75/75) (95% CI: 95.1 - 100.0%) NPA: 98.4% (60/61) (95% CI: 91.3 - 99.7%) #### 2. Matrix Comparison: Not applicable. ### C Clinical Studies: #### 1. Clinical Sensitivity and Specificity: To validate the clinical performance of the IDS SS-A/Ro, IDS SS-A/Ro 60 kDa. Amd IDS SS-B/La, a cohort of characterized samples were used. The study comprised a total of 824 samples including samples from patients diagnosed with systemic lupus erythematosus (SLE, n = 228), Sjögren's syndrome (SjS, n = 95), systemic sclerosis (SSc, n = 86), and other disease control samples (n = 415) from patients diagnosed with various autoimmune and infectious diseases. The results were summarized for each assay below. K253817 - Page 17 of 21 {17} IDS SS-A/Ro | | Diagnosis | | | | | | | --- | --- | --- | --- | --- | --- | --- | | | | SLE | SjS | SSc | Controls | Total | | IDS SS-A/Ro | Positive | 107 | 76 | 15 | 15 | 213 | | | Negative | 121 | 19 | 71 | 400 | 611 | | | Total | 228 | 95 | 86 | 415 | 824 | | | | Point Estimate | (95% CI) | | --- | --- | --- | --- | | Systemic lupus erythematosus (SLE) | Sensitivity | 46.9% | (40.6% to 53.4%) | | Sjögren's syndrome (SjS) | Sensitivity | 80.0% | (70.9% to 86.8%) | | Systemic sclerosis (SSc) | Sensitivity | 17.4% | (10.9% to 26.8%) | | Target Indications (SLE+SjS+SSc) | Sensitivity | 48.4% | (43.6% to 53.3%) | | Differential diagnosis controls | Specificity | 96.4% | (94.1% to 97.8%) | | IDS SS-A/Ro -Distribution of the clinical study sample cohort and the antibody positive rate | | | | | --- | --- | --- | --- | | Disease Category | N | # Positive | % Positive | | Target Diseases | | | | | Systemic lupus erythematosus (SLE) | 228 | 107 | 46.9% | | Sjögren's syndrome (SjS) | 95 | 76 | 80.0% | | Systemic sclerosis (SSc) | 86 | 15 | 17.4% | | Control Diseases | | | | | Antiphospholipid | 22 | 1 | 4.5% | | Atrophic gastritis | 26 | 1 | 3.8% | | Autoimmune liver disease | 21 | 1 | 4.8% | | Crohn's disease | 30 | 1 | 3.3% | | Cytomegalovirus | 6 | 0 | 0.0% | | Epstein Barr virus | 5 | 0 | 0.0% | | Granulomatosis w/polyangiitis | 34 | 1 | 2.9% | | Graves' disease | 48 | 2 | 4.2% | | Hashimoto's thyroiditis | 33 | 1 | 3.0% | | Hepatitis B | 20 | 1 | 5.0% | | Hepatitis C | 21 | 0 | 0.0% | | Idiopathic inflammatory myopathies | 27 | 3 | 11.1% | | Microscopic polyangiitis | 31 | 1 | 3.2% | | Primary biliary cholangitis | 17 | 1 | 5.9% | | Rheumatoid arthritis | 54 | 1 | 1.9% | | Ulcerative colitis | 20 | 0 | 0.0% | | Total controls | 415 | 15 | 3.6% | K253817 - Page 18 of 21 {18} IDS SS-A/Ro 60 kDa: | | Diagnosis | | | | | | --- | --- | --- | --- | --- | --- | | | | SLE | SjS | Controls | Total | | IDS SS-A/Ro 60 kDa | Positive | 105 | 71 | 9 | 185 | | | Negative | 123 | 24 | 492 | 639 | | | Total | 228 | 95 | 501 | 824 | | | | Point Estimate | (95% CI) | | --- | --- | --- | --- | | Systemic lupus erythematosus (SLE) | Sensitivity | 46.1% | 39.7% to 52.5% | | Sjögren's syndrome (SjS) | Sensitivity | 74.7% | 65.2% to 82.4% | | Target Indications (SLE+SjS) | Sensitivity | 54.5% | 49.0% to 59.8% | | Differential diagnosis controls | Specificity | 98.2% | 96.6% to 99.1% | | IDS SS-A/Ro 60 kDa -Distribution of the clinical study sample cohort and the antibody positive rate | | | | | --- | --- | --- | --- | | Disease Category | N | # of Positives | % Positive | | Target Diseases | | | | | Systemic lupus erythematosus (SLE) | 228 | 105 | 46.1% | | Sjogren's syndrome (SjS) | 95 | 71 | 74.7% | | Control Diseases | | | | | Systemic sclerosis (SSc) | 86 | 2 | 2.3% | | Antiphospholipid | 22 | 1 | 4.5% | | Atrophic gastritis | 26 | 0 | 0.0% | | Autoimmune liver disease | 21 | 1 | 4.8% | | Crohn's disease | 30 | 1 | 3.3% | | Cytomegalovirus | 6 | 0 | 0.0% | | Epstein Barr virus | 5 | 0 | 0.0% | | Granulomatosis w/polyangiitis | 34 | 1 | 2.9% | | Graves' disease | 48 | 0 | 0.0% | | Hashimoto's thyroiditis | 33 | 1 | 3.0% | | Hepatitis B | 20 | 0 | 0.0% | | Hepatitis C | 21 | 0 | 0.0% | | Idiopathic inflammatory myopathies | 27 | 0 | 0.0% | | Microscopic polyangiitis | 31 | 1 | 3.2% | | Primary biliary cholangitis | 17 | 1 | 5.9% | | Rheumatoid arthritis | 54 | 0 | 0.0% | | Ulcerative colitis | 20 | 0 | 0.0% | | Total controls | 501 | 9 | 1.8% | K253817 - Page 19 of 21 {19} IDS SS-B/La: | | Diagnosis | | | | | | --- | --- | --- | --- | --- | --- | | | | SLE | SjS | Controls | Total | | IDS SS-B/La | Positive | 44 | 40 | 7 | 91 | | | Negative | 184 | 55 | 494 | 733 | | | Total | 228 | 95 | 501 | 824 | | | | Point Estimate | (95% CI) | | --- | --- | --- | --- | | Systemic lupus erythematosus (SLE) | Sensitivity | 19.3% | 14.7% to 24.9% | | Sjögren's syndrome (SjS) | Sensitivity | 42.1% | 32.7% to 52.2% | | Target Indications (SLE+SjS) | Sensitivity | 26.0% | 21.5% to 31.1% | | Differential diagnosis controls | Specificity | 98.6% | 97.1% to 99.3% | | IDS SS-B/La -Distribution of the clinical study sample cohort and the antibody positive rate | | | | | --- | --- | --- | --- | | Disease Category | N | # of Positives | % Positive | | Target Diseases | | | | | Systemic lupus erythematosus (SLE) | 228 | 44 | 19.3% | | Sjogren's syndrome (SjS) | 95 | 40 | 42.1% | | Control Diseases | | | | | Systemic sclerosis (SSc) | 86 | 3 | 3.5% | | Antiphospholipid | 22 | 1 | 4.5% | | Atrophic gastritis | 26 | 1 | 3.8% | | Autoimmune liver disease | 21 | 0 | 0.0% | | Crohn's disease | 30 | 0 | 0.0% | | Cytomegalovirus | 6 | 0 | 0.0% | | Epstein Barr virus | 5 | 0 | 0.0% | | Granulomatosis w/polyangiitis | 34 | 0 | 0.0% | | Graves' disease | 48 | 0 | 0.0% | | Hashimoto's thyroiditis | 33 | 0 | 0.0% | | Hepatitis B | 20 | 0 | 0.0% | | Hepatitis C | 21 | 0 | 0.0% | | Idiopathic inflammatory myopathies | 27 | 0 | 0.0% | | Microscopic polyangiitis | 31 | 0 | 0.0% | | Primary biliary cholangitis | 17 | 1 | 5.9% | | Rheumatoid arthritis | 54 | 1 | 1.9% | | Ulcerative colitis | 20 | 0 | 0.0% | | Total controls | 501 | 7 | 1.4% | K253817 - Page 20 of 21 {20} ### D Expected Values/Reference Range: A negative IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La test result is expected for apparently healthy individuals. To determine the reference interval for the three assays, IDS SS-A/Ro, IDS SS-A/Ro 60 kDa, and IDS SS-B/La, a panel of 112 or 115 (56 or 58 females and 56 or 57 males, ages 19 to 65 years, with mean of 44.1 or 44.4 and median of 46.0 or 47.0 years of age) apparently healthy blood donors were tested. The results are as follows: | Assay | N | # of Samples > LoQ | # of Positive (>10 AU/mL) | % of Positive (n/N) | | --- | --- | --- | --- | --- | | IDS SS-A/Ro* | 112 | 3 | 1 | 0.89% (1/112) | | IDS SS-A/Ro 60 kDa | 115 | 3 | 0 | 0.00% (0/115) | | IDS SS-B/La | 115 | 1 | 1 | 0.87% (1/115) | *Three samples were excluded from SS-A/Ro analysis due to insufficient sample volume. ### VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. ### IX Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. K253817 - Page 21 of 21