(138 days)
FastPack® IP SHBG is a chemiluminescent immunoassay intended for the quantitative determination of Sex Hormone Binding Globulin in human serum and plasma on the FastPack® System. The FastPack® IP SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
The FastPack® IP Sex Hormone Binding Globulin Immunoassay employs a sandwich immunoassay principle. Endogenous SHBG in a patient sample, calibrator, or control is dispensed into a FastPack® reagent pack. In the reagent pack, the sample binds with a monoclonal anti-SHBG antibody covalently linked to alkaline phosphatase (ALP) and a different monoclonal anti-SHBG antibody linked to biotin will bind to streptavidin coated paramagnetic particles (PMP). After incubation, washing steps (using a Tris buffer containing detergents) occur to separate bound from unbound anti-SHBG monoclonal antibody-ALP, a chemiluminogenic substrate mixture is added to the system. This mixture contains indoxyl-3-phosphate, a substrate for ALP, and lucigenin (N,N dimethyl-9,9'-biacridinium dinitrate). ALP dephosphorylates indoxyl-3-phosphate to indol-3-ol, which subsequently undergoes oxidation. As a result, lucigenin is reduced to form a dioxetane structure that is cleaved to yield N-methylacridone. This compound produces a sustained luminescent glow following excitation. The raw relative luminescence units (RLUs) generated are measured by a photomultiplier tube in the FastPack® Analyzer and are directly proportional to the concentration of SHBG in the sample. The entire reaction sequence takes place at 37 ± 0.5 ℃ and is protected from external light.
Here's an analysis of the provided text regarding the FastPack® IP Sex Hormone Binding Globulin Immunoassay's acceptance criteria and studies:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" for all performance characteristics in a separate section. However, based on the comparative effectiveness study against a predicate device and the presented performance data, we can infer some implied acceptance ranges or targets for the new device.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (%CV) | Similar to or better than predicate (≤ 5.5% for all listed). Stated target: Within-run: ≤ 10%, Between-run: ≤ 8%, Between-day: ≤ 8% | Reagent lot 1, analyzer 1, calibrator lot 1: * Within-Run: 2.74% - 6.95% * Between-Run: 0.00% - 7.79% * Between-Day: 0.00% - 4.96% * Total: 3.21% - 7.06%Reagent lot 2, analyzer 2, calibrator lot 2: * Within-Run: 4.16% - 7.74% * Between-Run: 0.00% - 6.56% * Between-Day: 1.25% - 7.44% * Total: 5.04% - 11.53%Reagent lot 3, analyzer 3, calibrator lot 3: * Within-Run: 3.4% - 9.60% * Between-Run: 0.0% - 7.21% * Between-Day: 0.0% - 6.05% * Total: 4.0% - 12.05% |
| Linearity | Assay linear within a specified range (Predicate: 0.33 - 200 nmol/L) | Linear from LOQ (0.80 nmol/L) to 174 nmol/L |
| Interfering Substances | No interference at specified levels (similar to predicate) | No interference with listed compounds (e.g., conjugated bilirubin 40 mg/dL, hemoglobin 1.0 g/dL, lipid 1000 mg/dL, d-Biotin 0.2 mg/dL) and cross-reactants (e.g., Transferrin 0.5 g/dL, Testosterone 2.5 mg/dL, etc.) at specified concentrations. Rheumatoid factor up to 1000 IU/mL and human anti-mouse IgG up to 4 µg/mL also showed no cross-reactivity. Six known heterophile samples did not generate detectable interference. |
| Method Comparison | Strong correlation to predicate (Predicate R2 = 0.94) | R = 0.985, Slope (95% CI): 0.993 (0.967-1.019), y-intercept (95% CI): -0.614 (-2.21 to 0.982), R2 = 0.971 |
| Sample Type Equivalence | Equivalence between serum and plasma | Strong correlation between serum and lithium-heparin plasma via Passing-Bablok regression: Slope (95% CI): 0.960 (0.920-1.00), y-intercept (95% CI): 1.859 (-0.89 to 4.61), R = 0.990, R2 = 0.979. Absolute bias 1.117 nmol/L, % Bias 1.928%. |
| LOB | Not explicitly stated for acceptance, but a calculated value | 0.08 nmol/L SHBG |
| LOD | Not explicitly stated for acceptance, but a calculated value | 0.20 nmol/L SHBG |
| LOQ | Lowest sample with < 20% CV | 0.80 nmol/L SHBG |
2. Sample Size and Data Provenance for Test Set (Performance Studies)
- Precision: 7 serum patient samples, tested in duplicate over 20 non-consecutive days, resulting in 240 replicate determinations per sample.
- LOB/LOD: 180 replicate determinations of a blank sample (LOB) and 180 replicate determinations of four low-level samples (LOD).
- Linearity: 11 concentration levels generated by intermixing high and low patient samples, each tested in quadruplicate.
- Interferences: Two serum samples (low and high SHBG concentrations) spiked with known interfering concentrations.
- Serum and Plasma Equivalence: Blood collections from 54 volunteers.
- Expected Values/Reference Intervals: N=613 male (n=304) and female (n=309) apparently healthy individuals.
- Method Comparison: 158 human serum samples.
Data Provenance (Implied): The studies refer to "patient samples," "serum samples," and "human serum/plasma." While direct country of origin is not specified, it's generally understood that such studies for FDA submission are conducted under controlled laboratory conditions, likely within the US or by institutions adhering to similar regulatory standards. The data is retrospective in the sense that these are collected samples used for performance evaluation, not part of real-time clinical use for new diagnoses in a prospective clinical trial.
3. Number of Experts and Qualifications for Ground Truth
This device is an in vitro diagnostic (IVD) immunoassay that measures a biomarker (SHBG concentration). The concept of "ground truth" here is the true concentration of SHBG in a sample, or the accuracy of the measurement against a reference method.
- No human experts (like radiologists reading images) are used to establish ground truth for individual measurements of SHBG concentration.
- For Method Comparison: The "ground truth" or reference standard for comparison is the predicate device (Beckman Coulter Access Sex Hormone Binding Globulin assay K083867). This predicate device itself had previously established performance.
- For Reference Intervals (Expected Values): "Apparently healthy individuals with no known pre-existing endocrine disorders" were used. The reference intervals (2.5th-97.5th percentiles) are derived statistically from a population, rather than established by individual expert diagnosis for each sample.
4. Adjudication Method for the Test Set
Not applicable. As described above, the "ground truth" for this IVD is either the measurement by a predicate device or statistically derived normal ranges, not expert interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an automated immunoassay for quantitative determination of a biomarker, not an imaging device or AI algorithm that assists human readers in interpreting cases. There is no "human-in-the-loop" component in the direct measurement process to be evaluated for improvement with AI assistance.
6. Standalone (Algorithm Only) Performance
Yes, the studies presented are all standalone performance evaluations of the FastPack® IP Sex Hormone Binding Globulin Immunoassay system (device + assay + analyzer). The device operates independently to provide quantitative results.
7. Type of Ground Truth Used
- For Method Comparison: The measurements from the predicate device (Beckman Coulter Access Sex Hormone Binding Globulin assay) served as the comparative "truth" or reference.
- For Limit of Quantitation (LOQ): Defined by statistical criteria (lowest concentration with < 20% CV).
- For Linearity: Based on spiked samples with known concentrations and statistical fit to a linear model.
- For Interfering Substances/Cross-reactivity: Based on known spiked concentrations of potential interferents and lack of significant deviation from unspiked controls.
- For Expected Values/Reference Intervals: Statistically derived from a large population of apparently healthy individuals.
- Traceability: The assay is traceable to WHO 082/266 reference material, which serves as a primary reference for SHBG concentration.
8. Sample Size for the Training Set
Not applicable in the typical AI/ML sense. This is a conventional in vitro diagnostic device, not an AI/ML system that requires a "training set" to learn from data. The device's performance characteristics are established through analytical validation studies (precision, linearity, interference, method comparison, etc.) as described. The calibration curve for the assay is established using known calibrator materials, but this is part of the daily operational setup, not a "training set" in the context of AI.
9. How the Ground Truth for the Training Set Was Established
Not applicable for the same reasons as #8. The assay relies on known concentrations of calibrators (traceable to WHO reference material) to establish its quantitative scale, not on a "ground truth" established for an AI training set.
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January 29, 2019
Qualigen, Inc. Wajdi Abdul-Ahad Vice President, Assay Development 2042 Corte Del Nogal Carlsbad. CA 92011
Re: K182521
Trade/Device Name: FastPack IP Sex Hormone Binding Globulin Immunoassay Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class I. reserved Product Code: CDZ Dated: December 20, 2018 Received: December 26, 2018
Dear Wajdi Abdul-Ahad:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4. Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
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Courtney H. Lias, Ph.D. for Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K182521
Device Name
FastPack® IP Sex Hormone Binding Globulin Immunoassay
Indications for Use (Describe)
FastPack® IP SHBG is a chemiluminescent immunoassay intended for the quantitative determination of Sex Hormone Binding Globulin in human serum and plasma on the FastPack® IP SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| --------------------------------------------------------- | -------------------------------------------------------- |
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510(k) SUMMARY
This 510(k) Summary information is submitted in accordance with the requirements of 21 CFR § 807.92.
510(k) Number: K182521
Submitter:
Qualigen, Inc. 2042 Corte Del Nogal, Suite B Carlsbad, CA 92011
| Telephone: | (760) 918-9165 |
|---|---|
| Facsimile: | (760) 918-9127 |
Contact Person:
Wajdi Abdul-Ahad PhD Vice President, Assay Development Telephone: (760) 918-9165 x234 Facsimile: (760) 918-9127 Email: wabdul-ahad@qualigeninc.com
Device Identification
| Trade Names: | FastPack® IP Sex Hormone Binding Globulin Immunoassay |
|---|---|
| Common Names: | Sex Hormone Binding Globulin Assay |
| Classification names: | Immunological Test Systems |
| Classifications: | Class I, reserved (assay) |
| Panel: | Chemistry (75) |
| Product Codes: | CDZ – SHBG Assay |
| Regulation Numbers: | 21 CFR § 862.1680 - Testosterone test system - Class I, reserved |
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Devices to Which Substantial Equivalence is Claimed
Access Sex Hormone Binding Globulin assay Beckman Coulter, Inc. 250 S. Kraemer Blvd. Brea, CA 92821 K083867
Device Description
The FastPack® IP Sex Hormone Binding Globulin Immunoassay employs a sandwich immunoassay principle. Endogenous SHBG in a patient sample, calibrator, or control is dispensed into a FastPack® reagent pack. In the reagent pack, the sample binds with a monoclonal anti-SHBG antibody covalently linked to alkaline phosphatase (ALP) and a different monoclonal anti-SHBG antibody linked to biotin will bind to streptavidin coated paramagnetic particles (PMP). After incubation, washing steps (using a Tris buffer containing detergents) occur to separate bound from unbound anti-SHBG monoclonal antibody-ALP, a chemiluminogenic substrate mixture is added to the system. This mixture contains indoxyl-3-phosphate, a substrate for ALP, and lucigenin (N,N dimethyl-9,9'-biacridinium dinitrate). ALP dephosphorylates indoxyl-3-phosphate to indol-3-ol, which subsequently undergoes oxidation. As a result, lucigenin is reduced to form a dioxetane structure that is cleaved to yield N-methylacridone. This compound produces a sustained luminescent glow following excitation. The raw relative luminescence units (RLUs) generated are measured by a photomultiplier tube in the FastPack® Analyzer and are directly proportional to the concentration of SHBG in the sample. The entire reaction sequence takes place at 37 ± 0.5 ℃ and is protected from external light.
Intended Use
FastPack® IP SHBG is a chemiluminescent immunoassay intended for the quantitative determination of Sex Hormone Binding Globulin in human serum and plasma on the FastPack® System. The FastPack® IP SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
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Comparison of new device to predicate device
| CHARACTERISTIC | Qualigen FastPack® IPSex Hormone Binding GlobulinImmunoassay | Beckman CoulterSex Hormone BindingGlobulinK083867 |
|---|---|---|
| Intended Use/Indications for Use | FastPack® IP SHBG is achemiluminescent immunoassayintended for the quantitativedetermination of Sex HormoneBinding Globulin in human serumand plasma on the FastPack®System. The FastPack® IP SHBGassay is intended for use as an aidin the diagnosis of androgendisorders. | The Access SHBG assay is aparamagnetic particle,chemiluminescentimmunoassay for thequantitative determination ofSex Hormone Binding Globulinlevels in human serum andplasma using the AccessImmunoassay Systems. TheAccess Sex Hormone BindingGlobulin assay is indicated foruse in the assessment ofandrogen disorders. |
| Assay format | Paramagnetic particle,chemiluminescent, two-sitesandwich immunoassayemploying specific monoclonalantibodies | Same |
| Assay procedure | Automated | Same |
| Components | Mouse monoclonal antibodyagainst SHBG in the capture phaseand a mouse monoclonal anti-SHBG antibody conjugated toalkaline phosphatase in the signalphase. | Same |
| Sample Type | Serum or lithium-heparin plasma | Same |
| Sample Preparation | Standard processing for serum orplasma | Same |
| Interpretation ofResults | Standard Curve | Same |
| Reagent StorageTemperature | 2-8 °C | Same |
| Testing Environment | Professional use | Same |
| Precision (% CV) | Within-run: ≤ 10%Between-run: ≤ 8%Between-day: ≤ 8% | ≤ 5.5% |
| Linearity | Assay linear from LOQ (0.80 nmol/L) to 174 nmol/L | Assay linear from 0.33 - 200 nmol/L |
| InterferingSubstances/Specificity | No interference withacetaminophen (10 mg/dL),acetylsalicylic acid (80 mg/dL),alpha-fetoprotein (500 µg/L),conjugated bilirubin (40 mg/dL),unconjugated bilirubin (30 mg/dL), d-biotin (0.2 mg/dL),cortisol (10 mg/dL), 11-deoxycortisol (0.5 mg/dL), 5-α-dihydrotestosterone (2 mg/dL),hemoglobin (1.0 g/dL), heparin(10,000 U/dL), human serumalbumin (8 g/dL), ibuprofen (600mg/dL), estradiol (4 mg/dL),GAS6 (250 µg/L), laminin (6000µg/L), Protein S (30 mg/L),testosterone (2.5 mg/dL),thyroglobulin (300 µg/L),thyroxine-binding globulin (20mg/dL), transferrin (0.5 g/dL),and triglycerides/Intralipid (1000mg/dL) | No interferences at similarconcentrations of the samesubstances |
| Comparative TestingvsEstablished Methods | FastPack® vs. AccessN = 158Range of observations:5.7 to 176.0 nmol/LPassing-Bablok regression:Slope (95% CI): 0.993 (0.967-1.019)y (95% CI): -0.614 (-2.21 to0.982)R = 0.985R2 = 0.971 | Beckman Access vs. ImmuliteN = 158Range of observations:5.7 – 184.5 nmol/LDeming regression:Slope (95% CI): 1.09 (1.06–1.12)y (95% CI): 1.84 (0.54 – 3.00)R2 = 0.94 |
| ExpectedValues/ReferenceIntervals | Males (13-50 years): 9.4-61.8Males (≥ 50 years): 13.0-86.4Females (12-46 years): 9.2-134.4Females (> 46 years): 12.2-121.2 | Males (20-50 years): 13.3-89.5nmol/LFemales (20-49 years): 18.2-135.5 nmol/LPost-menopausal females (≥50years): 16.8-125.2 nmol/L |
| Globulin | ||
| CHARACTERISTIC | Qualigen FastPack® IPSex Hormone Binding GlobulinImmunoassay | Beckman CoulterSex Hormone BindingGlobulinK083867 |
| Approximate assay time | 8 minutes | ~28 minutes (first result) |
| Traceability | Traceable to the WHO 082/266reference which serves as thePrimary Reference Material | Traceable to the WHO 95/560reference |
Similarities between FastPack® and Beckman Coulter Access 2 Assays
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Differences between FastPack® and Beckman Access Sex Hormone Binding
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Performance Summary
Precision
Precision was evaluated following the CLSI EP5-A3 guidance. Seven serum patient samples with concentrations of ~ 5 to ~ 150 nmol/L SHBG were tested in duplicate determinations in each of two runs per day on each of three FastPack® reagent lots, one FastPack® analyzer per reagent lot (total of three Analyzers), one FastPack® Calibrator per reagent lot (total of three Calibrator lots) over a period of 20 non-consecutive days to yield 240 replicate determinations of each sample. Within-run, between-run, between-day, and total imprecision were calculated using a fully nested 2-way random factor analysis of variance (ANOVA) model. The following three tables present the results by combination of reagent lot, analyzer, and calibrator lot:
| Within-Run | Between-Run | Between-Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Sample | Mean nmol/L | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 4.85 | 0.27 | 5.55 | 0.00 | 0.00 | 0.21 | 4.37 | 0.34 | 7.06 |
| 2 | 12.56 | 0.60 | 4.82 | 0.68 | 5.46 | 0.28 | 2.19 | 0.60 | 4.82 |
| 3 | 25.59 | 1.40 | 5.46 | 1.83 | 7.14 | 0.87 | 3.40 | 1.40 | 5.46 |
| 4 | 59.49 | 3.67 | 6.16 | 1.80 | 3.03 | 2.95 | 4.96 | 3.67 | 6.16 |
| 5 | 91.33 | 5.99 | 6.56 | 7.12 | 7.79 | 0.00 | 0.00 | 5.99 | 6.56 |
| 6 | 102.26 | 7.11 | 6.95 | 3.85 | 3.76 | 4.76 | 4.66 | 7.11 | 6.95 |
| 7 | 154.79 | 4.24 | 2.74 | 0.62 | 0.40 | 2.51 | 1.62 | 4.96 | 3.21 |
Reagent lot 1, analyzer 1, calibrator lot 1
Reagent lot 2, analyzer 2, calibrator lot 2
| Within-Run | Between-Run | Between-Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Sample | Mean nmol/L | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 5.02 | 4.88 | 4.88 | 0.00 | 0.00 | 0.16 | 3.20 | 0.29 | 5.83 |
| 2 | 16.74 | 0.74 | 4.40 | 0.89 | 5.29 | 0.88 | 5.24 | 1.45 | 8.65 |
| 3 | 29.97 | 1.58 | 5.27 | 1.97 | 6.56 | 0.37 | 1.25 | 2.55 | 8.51 |
| 4 | 63.53 | 2.99 | 4.71 | 3.36 | 5.29 | 2.57 | 4.04 | 5.18 | 8.15 |
| 5 | 94.47 | 7.31 | 7.74 | 5.33 | 5.64 | 4.44 | 4.70 | 10.07 | 10.66 |
| 6 | 107.81 | 8.31 | 7.70 | 4.59 | 4.26 | 8.03 | 7.44 | 12.43 | 11.53 |
| 7 | 150.43 | 4.16 | 4.16 | 0.00 | 0.00 | 4.28 | 2.85 | 7.58 | 5.04 |
| Reagent lot 3, analyzer 3, calibrator lot 3 | ||
|---|---|---|
| -- | -- | --------------------------------------------- |
| Within-Run | Between-Run | Between-Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Sample | Mean nmol/L | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 4.90 | 0.21 | 4.2 | 0.0 | 0.0 | 0.1 | 2.0 | 0.2 | 4.7 |
| 2 | 14.26 | 0.67 | 4.69 | 0.51 | 3.56 | 0.45 | 3.13 | 0.95 | 6.67 |
| 3 | 25.47 | 1.22 | 4.78 | 1.75 | 6.86 | 0.91 | 3.58 | 2.32 | 9.10 |
| 4 | 58.56 | 3.30 | 5.64 | 4.22 | 7.21 | 2.25 | 3.85 | 5.81 | 9.93 |
| 5 | 91.40 | 8.78 | 9.60 | 3.70 | 4.05 | 5.53 | 6.05 | 11.02 | 12.05 |
| 6 | 105.25 | 7.42 | 7.05 | 5.21 | 4.95 | 0.00 | 0.00 | 9.07 | 8.61 |
| 7 | 148.44 | 5.04 | 3.4 | 0.8 | 0.5 | 3.0 | 2.0 | 5.9 | 4.0 |
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Limits of blank, detection, and quantitation
The limit of blank (LOB, the highest measurement likely to be observed for a blank sample), limit of detection (LOD, the lowest amount of analyte in a sample that can be detected with type I and II error rates set to 5%), and limit of quantitation (LOQ, the lowest amount of analyte in a sample that can be reliably detected) were determined according to CLSI EP17-A2 for the FastPack® IP Sex Hormone Binding Globulin Immunoassay. In this study, the limit of blank was determined from 180 replicate determinations of a blank sample tested on six different FastPack® analyzers using three reagent lots. Raw RLUs from the assays were converted to apparent nmol/L based on the calibration curve for each assay. The LOB was determined as the 171.5th rank of the sorted distribution of values. This value was 0.08 nmol/L SHBG.
The LOD was estimated from 180 replicate determinations of four low level samples. Per the CLSI EP17-A2 guideline, the parametric LOD calculation was utilized and the LOD was 0.20 nmol/L SHBG.
The LOO was determined as the lowest sample which provided < 20% CV the value was 0.80 nmol/L SHBG.
Linearity
Linearity was determined following CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approved Guideline. A high patient sample was intermixed with a low sample to generate 11 concentration levels each tested in quadruplicate determinations. Linear results were compared to 2nd and 3rd order polynomial fits against a pre-specified allowable error. The linearity range was found to extend from the LOQ (0.80 nmol/L) to 174 nmol/L.
Interferences
The effect of endogenous interferences on quantification of SHBG was investigated by preparation of two serum samples with differing SHBG concentrations (a low and high) with known concentrations of conjugated bilirubin, unconjugated bilirubin, hemoglobin, lipids, and d-biotin. The value obtained for the sample with each interfering substance was compared to the value obtained for the sample without the interfering substance and the percentage recovery in nmol/L SHBG determined. These compounds did not show interference at the levels indicated in the following table. Higher levels may cause interference.
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| Compound | Highest level demonstrating no interference |
|---|---|
| Conjugated Bilirubin | 40 mg/dL |
| Unconjugated Bilirubin | 30 mg/dL |
| Hemoglobin | 1.0 g/dL |
| Lipid | 1000 mg/dL |
| d-Biotin | 0.2 mg/dL |
The effect of potentially cross-reacting substances on quantification of SHBG was investigated. Again, two serum samples with differing SHBG concentrations (a low and high) with known concentrations of spiked cross-reactants were prepared. The value obtained for the sample with each potentially cross-reacting substance was compared to the value obtained for the sample without the substance and the percentage recovery in nmol/L SHBG determined. These compounds did not show cross-reactivity at the levels indicated in the following table. Higher levels may cause cross-reaction.
| Compound | Highest level demonstrating no cross-reaction |
|---|---|
| Transferrin | 0.5 g/dL |
| Heparin | 10,000 U/dL |
| Low Molecular Weight Heparin (LMWH) | 0.6 U/dL |
| Ibuprofen | 60 mg/dL |
| Human Albumin | Endogenous in samples + 8.0 g/dL |
| Human IgG | 1.0 g/dL |
| Thyroxine Binding Globulin (TBG) | 20 mg/dL |
| Thyroglobulin | 300 µg/L |
| Testosterone | 2.5 mg/dL |
| Laminin | 6,000 µg/L |
| GAS6 | 250 µg/L |
| Protein S | 30 mg/L |
| Estradiol | 4.0 mg/dL |
| 11-deoxycortisol | 0.5 mg/dL |
| 5α-dihydrotestosterone | 2.0 mg/dL |
| Cortisol | 10 mg/dL |
| AFP | 500 µg/L |
| Acetaminophen | 10 mg/dL |
| Acetylsalicylic acid | 80 mg/dL |
Rheumatoid factor at up to 1000 IU/mL and human anti-mouse IgG at up to 4 µg/mL do not cross-react in the FastPack® IP Sex Hormone Binding Globulin Immunoassay.
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Additionally, six known heterophile samples did not generate detectable interference in the assay.
Serum and plasma equivalence
Blood collections were obtained from 54 volunteers and processed in parallel to serum and lithium-heparin plasma. Measurements in the FastPack® IP Sex Hormone Binding Globulin Immunoassay were compared via Passing-Bablok regression and indicated equivalence between the matrices.
| Parameter | Result |
|---|---|
| N compared | 54 |
| Range of observations, nmol/L | Serum: 5.7 – 174.5Lithium-Heparin Plasma: 7.1 – 175.1 |
| Absolute bias, nmol/L | 1.117 |
| % Bias | 1.928 |
| Passing Bablok regression results | |
| Slope (95% CI) | 0.960 (0.920-1.00) |
| y-intercept (95% CI) | 1.859 (-0.89 to 4.61) |
| R | 0.990 |
| R2 | 0.979 |
Expected Values/Reference Intervals
Serum samples from N=613 male (n=304) and female (n=309) apparently healthy individuals with no known pre-existing endocrine disorders were acquired and assayed in singlet determinations. Analysis of the data relied upon determination of the nonparametric 2.5th-97.5th (central 95%) percentiles of the distributions within four reference partitions. The FastPack® IP Sex Hormone Binding Globulin reference intervals are defined below:
| Partition | N | Median (nmol/L) | Reference Interval (nmol/L) |
|---|---|---|---|
| Males 13 - 50 years | 149 | 26.6 | 9.4 - 61.8 |
| Males > 50 years | 155 | 35.9 | 13.0 - 86.4 |
| Females 12 - 46 years | 151 | 39.6 | 9.2 - 134.4 |
| Females > 46 years | 158 | 49.8 | 12.2 - 121.2 |
Method Comparison
Human serum samples were tested with the FastPack® IP Sex Hormone Binding Globulin Immunoassay and the obtained results were compared to the predicate method. A total of
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158 samples ranging from 5.7 – 176.0 nmol/L were tested in both assays. The FastPack® IP Sex Hormone Binding Globulin Immunoassay correlated well with the predicate method with correlation coefficient (R) of 0.985, slope = 0.993, and y-intercept = -0.614 nmol/L.
| Parameter | Result |
|---|---|
| Slope (95% CI) | 0.993 (0.967-1.019) |
| y-intercept (95% CI) | -0.614 (-2.21 to 0.982) |
| R2 (95% CI) | 0.971 |
| R (95% CI) | 0.985 |
SUMMARY
The information provided in this pre-market notification indicates that the FastPack® IP Sex Hormone Binding Globulin Immunoassay is substantially equivalent to the stated predicate device. The information further indicates that the FastPack® IP Sex Hormone Binding Globulin Immunoassay is safe and effective for its stated intended use.
§ 862.1680 Testosterone test system.
(a)
Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.(b)
Classification. Class I.