QUANTA Flash Jo-1, QUANTA Flash Jo-1 Calibrators, and QUANTA Flash Jo-1 Ciontrols

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K151429 B. Purpose for Submission: New device C. Measurand: Anti-Jo-1 IgG autoantibodies D. Type of Test: Semi-quantitative chemiluminescent immunoassay (CIA) E. Applicant: INOVA Diagnostics, Inc. F. Proprietary and Established Names: QUANTA Flash® Jo-1 QUANTA Flash® Jo-1 Calibrators QUANTA Flash® Jo-1 Controls G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100, Antinuclear Antibodies Immunological Test System 21 CFR §862.1150, Calibrator 21 CFR §862.1660, Quality Control Material (Assayed and Unassayed) 2. Classification: Class II, Assay and Calibrators Class I, Control 3. Product code: LLL – Extractable antinuclear antibody, antigen and control JIT – Calibrator, Secondary {1} JJX – Single (Specified) Analyte Controls (Assayed and Unassayed) 4. Panel: Immunology (82) (Assay) Clinical Chemistry (75) (Calibrators and Controls) H. Intended Use: 1. Intended use(s): QUANTA Flash® Jo-1 is a chemiluminescent immunoassay for the semi-quantitative determination of IgG anti-Jo-1 antibodies in human serum. The presence of anti-Jo-1 antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of idiopathic inflammatory myopathies. QUANTA Flash® Jo-1 Calibrators are intended for use with the QUANTA Flash® Jo-1 Reagents for the determination of IgG anti-Jo-1 antibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values. QUANTA Flash® Jo-1 Controls are intended for use with the QUANTA Flash® Jo-1 Reagents for quality control in the determination of IgG anti-Jo-1 antibodies in human serum. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use only 4. Special instrument requirements: BIO-FLASH® chemiluminescent analyzer (k083518) I. Device Description: The QUANTA Flash® Jo-1 Kit includes one QUANTA Flash® Jo-1 Reagent Cartridge with the following reagents for 50 determinations: a. Jo-1 antigen coated paramagnetic beads, lyophilized b. Assay Buffer c. Tracer IgG – Isoluminol labeled anti-human IgG antibodies in buffer {2} The QUANTA Flash® Jo-1 Calibrators set is sold separately and contains: a. Calibrator 1: Two barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrator 1 contains human antibodies to Jo-1 in buffer with concentration of 19 CU. b. Calibrator 2: Two barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrator 2 contains human antibodies to Jo-1 in buffer with concentration of 320 CU. The QUANTA Flash® Jo-1 Controls set contains is sold separately and contains: a. Negative Control: Two barcode labeled tubes containing 0.5 mL, ready to use reagent. Negative control contains human antibodies to Jo-1 in buffer with concentration of 10 CU. b. Positive Control: Two barcode labeled tubes containing 0.5 mL, ready to use reagent. Positive control contains human antibodies to Jo-1 in buffer with concentration of 50 CU. J. Substantial Equivalence Information: 1. Predicate device name(s): FIDIS Connective 10 2. Predicate 510(k) number(s): K102607 2. Comparison with predicate: QUANTA Flash® Jo-1Reagent Kit: | Similarities | | | | --- | --- | --- | | Item | Device QUANTA Flash® Jo-1 | Predicate FIDIS Connective 10 | | Intended Use | Semi-quantitative determination of anti-Jo-1 antibodies in human serum. | Same | | Antigen | Recombinant Jo-1 | Same | | Sample Type | Serum | Same | | Assay methodology | Solid phase immunoassay | Same | | Traceability | International Reference preparation is not available. Results are traceable to in-house standards | Same | | Shelf Life | One year at 2–8°C | Same | {3} | Differences | | | | --- | --- | --- | | Item | Device QUANTA Flash® Jo-1 | Predicate FIDIS Connective 10 | | Detection | Chemiluminescent immunoassay | Multiplex bead-based flow cytometric fluorescent immunoassay | | Solid Phase | Paramagnetic microparticles (beads) | Color-coded microspheres | | Conjugate | Isoluminol conjugated anti-human IgG | Phycoerythrin conjugated anti-human IgG | | Calibration | Lot specific Master Curve and two Calibrators (Sold separately) | Calibration system interpolates fluorescent intensity (included in the kit | | Cut-off | Negative: <20 CU Positive: ≥20 CU | Negative: <30 AU/mL Borderline: 31-40 AU/mL Positive: >40 AU/mL | | Assay Measuring Range (AMR) | 2.2-1147.2 CU | No claim for the reportable range | QUANTA Flash® Jo-1 Calibrators: | Similarities | | | | --- | --- | --- | | Item | Device QUANTA Flash® Jo-1 Calibrators | Predicate | | Analyte | Anti-Jo-1 antibodies | Same | | Matrix | Human serum, buffers, stabilizers and preservative | Same | | Physico-chemical characteristics | Liquid, prediluted, ready to use | Same | | Shelf Life/Storage | One year at 2–8°C | Same | | Differences | | | | --- | --- | --- | | Item | Device QUANTA Flash® Jo-1 Calibrators | Predicate | | Intended Use | For use with QUANTA Flash® Jo-1 reagents for determination of IgG anti-Jo-1 antibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values. | No separate intended use; calibrator is part of the kit. | | Unit | CU (Chemiluminescent Units) | AU/mL (arbitrary)s | {4} QUANTA Flash® Jo-1 Controls: | Similarities | | | | --- | --- | --- | | Item | Device QUANTA Flash® Jo-1 Controls | Predicate | | Analyte | Anti-Jo-1 antibodies | Same | | Matrix | Human serum, buffer, stabilizer, and preservative | Same | | Physico-chemical characteristics | Liquid, ready to use | Liquid, to be diluted | | Levels | 2 (negative and positive) | Same | | Shelf Life/Storage | One year at 2–8°C | Same | | Differences | | | | --- | --- | --- | | Item | Device QUANTA Flash® Jo-1 Controls | Predicate | | Intended Use | For use with the QUANTA Flash® Jo-1 reagents for quality control in the determination of IgG anti-Jo-1 autoantibodies in human serum. | No separate intended use; controls are part of the kit. | | Unit | CU (arbitrary) | AU/mL (arbitrary) | K. Standard/Guidance Document Referenced (if applicable): EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline, Second Edition. EP06-A, Evaluation of Linearity of Quantitative Measurement, Approved Guideline, Second Edition. EP07-A2, Interference Testing in Clinical Chemistry, Approved Guideline, Second Edition EP09-A2-IR, Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline, Second Edition (Interim Revision). EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline, Second Edition C28-A3, Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline, Third Addition L. Test Principle: The QUANTA Flash® Jo-1 assay is a microparticle chemiluminescent immunoassay designed for use on the BIO-FLASH® instrument. The instrument platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash® Jo-1 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH® instrument. {5} Purified recombinant Jo-1 antigen is coated onto paramagnetic beads. The bead suspension is lyophilized and stored in the bead tube. Prior to use in the BIO-FLASH® system, the sealed reagent tubes are pierced with the reagent cartridge lid and the beads are rehydrated and resuspended using resuspension buffer by pipetting up and down with a transfer pipette. The reagent cartridge is then loaded onto the BIO-FLASH® instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted by the BIO-FLASH® with system rinse in a small disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. Isoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 and Trigger 2 are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH® optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti-Jo-1 antibodies bound to the corresponding Jo-1 on the beads. For determining the amount of antibody in a sample, the QUANTA Flash® Jo-1 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash® Jo-1 Calibrators. Based on the results obtained with the two Calibrators included in the Calibrator Set, an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU) from the instrument signal (RLU) obtained for each sample. ## M. Performance Characteristics (if/when applicable): ### 1. Analytical performance: #### a. Precision/Reproducibility: **Precision**: The precision of the QUANTA Flash® Jo-1 assay was evaluated by testing nine serum samples prepared to contain various concentrations of anti-Jo-1 antibody. Each sample was run in duplicate, twice a day, for 20 days with one reagent lot (total of 80 replicates per sample). All %CV values were within the manufacturer's pre-determined acceptance limit (&lt; 10%). The results are summarized in the table below. | Sample | Mean (CU) | Within-Run | | Between-Run | | Between-Day | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | | 1 | 5.5 | 0.2 | 3.4 | 0.0 | 3.2 | 0.4 | 6.8 | 0.4 | 7.6 | | 2 | 19.5 | 0.6 | 3.1 | 0.5 | 2.6 | 0.9 | 4.7 | 1.2 | 6.2 | | 3 | 20.7 | 0.8 | 3.7 | 0.3 | 1.4 | 1.2 | 5.9 | 1.5 | 7.1 | | 4 | 37.1 | 1.6 | 4.4 | 0.0 | 0.0 | 2.3 | 6.1 | 2.8 | 7.6 | {6} | Sample | Mean (CU) | Within-Run | | Between-Run | | Between-Day | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | | 5 | 42.0 | 1.2 | 2.9 | 1.0 | 2.3 | 2.4 | 5.6 | 2.8 | 6.7 | | 6 | 97.5 | 3.1 | 3.2 | 2.4 | 2.4 | 6.0 | 6.1 | 7.1 | 7.3 | | 7 | 288.2 | 10.0 | 3.5 | 8.5 | 3.0 | 19.1 | 6.6 | 23.2 | 8.0 | | 8 | 445.6 | 18.7 | 4.2 | 0.0 | 0.0 | 29.4 | 6.6 | 34.8 | 7.8 | | 9 | 879.3 | 43.6 | 5.0 | 13.2 | 1.5 | 43.8 | 5.0 | 63.2 | 7.2 | Reproducibility: A total of five samples were tested at three different sites with one reagent lot to evaluate the site-to-site reproducibility. Each sample was run in replicates of five, once a day for five days, to generate 25 data points at each site (N=75 per sample for all sites combined). Data were analyzed for within-run, between-run, between-site, and total precision. The results are summarized in the tables below. All %CV values were within the manufacturer's pre-determined acceptance limit (&lt; 15%). | Sample | Mean (CU) | Within-Day | | Between-Day | | Between-Site | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | | 1 | 9.8 | 0.5 | 4.7 | 0.5 | 4.6 | 0.8 | 8.0 | 1.0 | 10.4 | | 2 | 32.4 | 1.0 | 3.1 | 1.9 | 5.9 | 2.3 | 7.0 | 3.1 | 9.6 | | 3 | 77.3 | 3.1 | 4.0 | 3.2 | 4.2 | 6.4 | 8.3 | 7.8 | 10.1 | | 4 | 168.3 | 6.6 | 3.9 | 8.1 | 4.8 | 14.7 | 8.8 | 18.0 | 10.7 | | 5 | 854.6 | 34.4 | 4.0 | 29.7 | 4.0 | 0.4 | 6.8 | 100.0 | 11.7 | To evaluate lot-to-lot reproducibility, five samples with anti-Jo-1 antibody concentration at various levels across the measuring range (18.6, 23.3, 73.3, 382.5, and 911.9 CU) were tested. Each sample was tested in replicates of five, one run per day for five days using three difference reagent lots. Mean and %CV for each sample were calculated and %CV values were from 3.6% to 7.9% for all samples. b. Linearity/assay reportable range: Linearity: The analytical measuring range (AMR) of the assay is defined by the lowest and highest points on the master curve, e.g., 2.2-1147.2 CU. The linearity across this range was evaluated by a study according to CLSI EP6-A. Serially diluted samples with anti-Jo-1 antibody concentrations ranging from 1.7 to 1226.6 CU were prepared by diluting each of four high positive serum samples with analyte free (stripped) serum in 10% increments. Each dilution was tested in duplicate. Percentage recovery of obtained mean results was calculated compared to the expected results with the acceptant criteria of recovery between 80 and 120%, or ± 4 CU, whichever is greater. The linear regression analysis was performed using the samples falling within the master curve and the results of samples within AMR are {7} summarized as follows: | Sample | Test Range (CU) | Slope (95% CI) | Y-intercept (95% CI) | R² | % Recovery | | --- | --- | --- | --- | --- | --- | | 1 | 3.0–14.4 | 0.99 (0.96–1.02) | 0.22 (-0.09–0.52) | 1.00 | 97.1–107.2% | | 2 | 4.4–44.3 | 0.99 (0.95–1.02) | 0.27 (-0.77–1.32) | 0.99 | 90.4–113.0% | | 3 | 11.0–110.5 | 0.99 (0.98–1.01) | -1.12 (-2.08– -0.16) | 1.00 | 90.5–100.5% | | 4 | 68.7–686.8 | 1.00 (0.95–1.04) | -11.28 (-29.25–6.68 ) | 0.99 | 85.7–106.6% | | 5 | 125.2–1126.4 | 0.92 (0.89–0.96) | 31.38 (8.50–54.26) | 1.00 | 95.0–111.5% | Auto-rerun: To validate the auto-rerun function with 1:20 dilutions, two high positive specimens with anti-Jo-1 antibody concentrations above assay measuring range (8967.5 and 19914.0 CU) were run with the auto-rerun function enabled on the BIO-FLASH®. The same set of samples prepared manually with a 1:20 fold dilution was used as reference and tested with the concentration of 9815.2 and 19343.6 CU, respectively. The % recovery values for results obtained with the auto-rerun results compared to results obtained with the manual dilution were 91% and 103%, respectively. Hook effect: Two high positive samples having anti-Jo-1 antibody concentration above assay measuring range (31783.1 CU and 65625.5 CU) were examined to assess potential hook effect. No hook effect was observed up to 65625.5 CU. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: There is no recognized standard or reference material for anti-Jo-1 autoantibodies. The calibrator and control values are directly traceable to in-house standards that are used to create the master curves for the QUANTA Flash® Jo-1. Value assignment: The QUANTA Flash® Jo-1 Calibrators and Controls are manufactured by diluting human serum that contains high titer of anti-Jo-1 antibodies. The target CU is achieved through trial dilutions on small scale. Once a dilution is selected, the Calibrators and Controls are bulked, tested, and adjusted. Upon completion of the manufacturing process, the Calibrators and Controls are tested on at least two instruments, on at least two lots of reagent cartridge, in replicates of 10 to determine final value assignment. The target values and ranges for the Calibrators and Controls are listed below: {8} 9 | | Target Value (CU) | Target Range (CU) | | --- | --- | --- | | QUANTA Flash® Jo-1 Calibrators | | | | Calibrator 1 | 19 | 17–21 | | Calibrator 2 | 320 | 280–360 | | QUANTA Flash® Jo-1 Controls | | | | Negative control | 10 | 8–12 | | Positive control | 50 | 40–60 | **Stability:** **Kit stability (unopened):** The accelerated stability study was performed using three lots of Jo-1 coupled beads, calibrators, and controls. Real-time stability is on-going; the results to date support a claim of 12 months stability for unopened reagent cartridge, up to 15 months on calibrators, and up to 16 months on controls stored at 2–8°C. **On-board (In-use) stability:** On-board stability study was performed for calibrators, controls and reagent cartridge: i. Calibrators: Calibrators were placed uncapped, onboard the instrument, and calibration was performed five times over 9.5 hours. Controls and a panel of characterized patient specimens were run on each calibration curve. Each calibrator is measured in triplicate during calibration. ii. Controls: Two vials of each control were assayed twice a day for a total of 21 runs. The first run was used to establish baseline value, and then an additional 19 runs were performed. During runs, the Controls were left uncapped, onboard the instrument for 15 minutes per run. When not in use, the controls were capped, and stored at 5°C ± 3°C. iii. Reagent Cartridge: Two lots of cartridges were tested with four serum specimens (with different reactivity levels) along with the Negative and Positive Controls. The specimens were tested periodically up to 92 days. Percent recoveries were calculated compared to the day zero average values, and linear regression analysis was performed by plotting % recovery against the number of days. All results met the manufacturer’s acceptance criteria and support the following on-board stability claim: | Calibrators | 8 hours on-board; up to 4 calibrations | | --- | --- | | Controls | Up to 15 uses with 10 min on-board per use | | Reagent Cartridge | 71 days on-board | **Sample stability:** The study was performed with seven samples (two negatives, three positives, and two around the cut-off), tested at 2–8°C, and room temperature (RT). In addition, the samples were tested for the stability after up to three repeated {9} freeze/thaw cycles. The results support sample stability up to 48 hours of storage at RT, up to 14 days of storage at $2 - 8^{\circ}\mathrm{C}$ , and up to three freeze/thaw cycles when samples are stored at or below $-20^{\circ}\mathrm{C}$ . # d. Detection limit: Limit of Blank (LoB) was determined by assaying four blank samples in five replicates per sample over three days with two reagent lots. Sixty data points were generated. LoB was calculated at the 95th percentile using the non-parametric method, as the dataset showed non-normal distribution. The LoB was determined to be 337 RLU. The Limit of Detection (LoD) was determined by assaying four samples with anti-Jo-1 antibody concentration between LoB and approximately four times of LoB. Each sample was tested in five replicates over three days with two reagent lots. LoD value was calculated as the $\mathrm{LoB} + 1.645 \times \mathrm{SD}$ of the replicates for the low level samples. The LoD of the QUANTA Flash® Jo-1 assay was determined to be 409 RLU, which is below the value of the lowest QUANTA Flash® Jo-1 Master Curve standard (2.2 CU), and therefore below the AMR of the assay. # e. Analytical specificity: Endogenous Interference: Three serum samples with antibody concentrations at 11.3 CU (negative), 21.1 CU (around the cut-off), and 117.0 CU (positive) were spiked with known quantities of bilirubin (10, 5.0, or $2.5\mathrm{mg / dL}$ ), hemoglobin (200, 100, or $50\mathrm{mg / dL}$ ), or triglycerides/cholesterol (1000/224.3, 500/112.2, or $250 / 56.1\mathrm{mg / dL}$ ). Each sample was tested in triplicate and the recovery was calculated by comparing to control samples spiked with the same volume of diluents. For rheumatoid factor (RF) interference, three samples with antibody concentrations at 7.3 CU (negative), 32.5 CU, and 123 CU were tested by spiking with different proportions of a high positive RF IgM serum sample (1894 IU/mL). Each sample was tested triplicate and the recovery was calculated by comparing to control samples spiked with the same proportions of a negative serum. No interference ( $85\% - 115\%$ recovery for samples above the cutoff, and $\pm 4$ CU difference for samples below the cutoff) was detected in the samples up to the concentrations listed in the table below: | Potential Interfering Substances | Maximum Concentration | | --- | --- | | Bilirubin | 10 mg/dL | | Hemoglobin | 200 mg/dL | | Triglycerides | 1000 mg/dL | | Cholesterol | 224.3 mg/dL | | RF | 947 IU/mL | Analytical cross-reactivity: Cross reactivity of the QUANTA Flash® Jo-1 was investigated using 12 reference sera from the Center of Disease Control and {10} Prevention (CDC) with three lots of QUANTA Flash Jo-1 reagents. The ANA human reference serum #10 (for human antibodies to Jo-1) tested positive on all three lots with an average of 935.9 CU. The other reference sera in the panel were below 2.2 CU for all three lots tested. f. Assay cut-off: The QUANTA Flash® Jo-1 cut-off was determined by testing a set of samples from a reference population of 207 subjects (31 systemic sclerosis samples, 30 systemic lupus erythematosus samples, 21 Crohn's disease samples, 19 multiple sclerosis, 19 hepatitis C positive samples, 18 ulcerative colitis samples, 13 psoriatic arthritis samples, 10 syphilis positive samples, 10 healthy individuals, 9 polymyalgia rheumatica samples, 8 rheumatoid arthritis samples, 5 spondylarthritis samples, 3 Sjögren's syndrome samples and 11 other disease control samples). The cut-off was established as 20 CU (10000 RLU) based on the 99th percentile of the results obtained. | | Positive | Negative | | --- | --- | --- | | QUANTA Flash® Jo-1 | ≥20 CU | <20 CU | 2. Comparison studies: a. Method comparison with predicate device: Samples for method comparison analysis included 487 samples from the clinical validation study (see below) along with 26 additional samples contrived by diluting Jo-1 positive samples with negative serum to cover the reportable range of assay. These samples were tested on both the QUANTA Flash® Jo-1 and on the predicate FIDIS Connective 10. From the total of 513 samples, results for 105 samples were within the reportable range of the assay. The results are summarized below: | | FIDIS Connective 10 | | | | | | --- | --- | --- | --- | --- | --- | | | | Positive | Borderline | Negative | Total | | QUANTA Flash® Jo-1 | Positive | 20 | 5 | 6 | 31 | | | Negative | 2 | 2 | 70 | 74 | | | Total | 22 | 7 | 76 | 105 | Borderline as negative: Positive agreement: 90.9% (95% CI: 72.2–97.5%) Negative agreement: 86.7% (95% CI: 77.8–92.4%) Overall agreement: 87.6% (95% CI: 80.0–92.6%) Borderline as positive: Positive agreement: 86.2% (95% CI: 69.4–94.5%) Negative agreement: 92.1% (95% CI: 83.8–96.3%) Overall agreement: 90.5% (95% CI: 83.4–94.7%) {11} b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity and Clinical Specificity: A total of 487 samples were included in the clinical validation for the QUANTA Flash® Jo-1. The validation set of samples includes 206 samples from patients diagnosed with idiopathic inflammatory myopathy (IIM) and 281 samples from patients with other autoimmune diseases. Clinical sensitivity and specificity in this sample cohort are summarized in the following tables: | | Clinical Diagnosis of IIM | | | | | --- | --- | --- | --- | --- | | | | Positive | Negative | Total | | QUANTA Flash® Jo-1 | Positive | 24 | 2 | 26 | | | Negative | 182 | 279 | 461 | | | Total | 206 | 281 | 487 | Sensitivity: 11.7% (95% CI: 8.0-16.7%) Specificity: 99.3% (95% CI: 97.4-99.8%) The distribution of the cohort and the Jo-1 positivity rate for each clinical subgroup are summarized below: | Disease category | QUANTA Flash® Jo-1 | | | | --- | --- | --- | --- | | | N | # of positive | % Positive | | Target Diseases (IIM): | | | | | Dermatomyositis (DM) | 95 | 11 | 11.7% | | Polymyositis (PM) | 71 | 7 | 9.9% | | Juvenile Dermatomycotic | 7 | 1 | 14.3% | | Others (IMNM, OM, UM)* | 5 | 1 | 20.0% | | IIM not further specified | 28 | 4 | 14.3% | | Total of IIM | 206 | 24 | 11.7% | | Control Diseases: | | | | | Sjögren’s syndrome | 15 | 0 | 0.0% | | SLE | 41 | 0 | 0.0% | | Systemic Sclerosis | 44 | 0 | 0.0% | | Rheumatoid arthritis | 59 | 1 | 1.7% | | MCTD | 103 | 1 | 0.9% | | Septicemia | 19 | 0 | 0.0% | | Total of controls | 281 | 2 | 0.7% | * IMNM: Immune mediated necrotizing myopathy OM: overlap myositis UN: undifferentiated myositis {12} b. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: The expected value in the normal population is "negative". Anti-Jo-1 antibody levels were analyzed in a cohort of 400 apparently healthy blood donors (246 females and 154 males, ages 17 to 60 years, with an average age of 34.7 years and median age of 34 years) using the QUANTA Flash® Jo-1. The results showed a mean concentration of 2.3 CU with the values ranging from &lt; 2.2 to 16.3 CU. None of the samples were positive on the QUANTA Flash® Jo-1. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.