(65 days)
The Nichols Advantage Aldosterone Assay is intended for in vitro diagnostic laboratory use with the Nichols Advantage® Specialty System for quantitative measurement of aldosterone in human serum, EDTA plasma, and extracted urine. Aldosterone measurements are intended for use in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.
The Nichols Advantage® Aldosterone Assay is a competitive immunochemiluminometric in vitro diagnostic laboratory immunoassay (IVD device) that utilizes a biotinylated mouse monoclonal anti-aldosterone antibody as the capture reagent and an acridinium ester labeled aldosterone as a tracer reagent. This Aldosterone IVD device immunoassay is intended for use for the measurement of aldosterone in human serum, EDTA plasma, and extracted urine, as an extended diagnostic method utilized within the Nichols Advantage® Specialty System.
Here's an analysis of the provided text regarding the Nichols Advantage® Aldosterone Assay, focusing on acceptance criteria and study details:
Acceptance Criteria and Device Performance
The submission doesn't explicitly state quantitative acceptance criteria in a dedicated section. Instead, the performance characteristics are presented as evidence of the device's capabilities and are implicitly compared to the predicate device or general laboratory expectations. The method comparison to a predicate device serves as the primary "acceptance criterion" for demonstrating substantial equivalence.
Implicit Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Implicit / Contextual) | Reported Device Performance (Nichols Advantage® Aldosterone Assay) | Predicate Device (DSL-8600 ACTIVE® Aldosterone Coated-Tube Radioimmunoassay Kit) |
|---|---|---|---|
| Method Comparison (Urine) | |||
| Correlation (Pearson's r) | High correlation (e.g., >0.90) with predicate device | 0.96 (95% CI: 0.94 to 0.97) | N/A (this is the comparator) |
| Slope (Passing Bablok) | Should be close to 1 (indicating proportional agreement) | 1.23 (95% CI: 1.2 to 1.28) | N/A |
| Intercept (Passing Bablok) | Should be close to 0 (indicating constant agreement) | -1.19 (95% CI: -1.43 to -0.81) | N/A |
| Range of Values (Urine) | Comparable to clinical needs and predicate device | 0.4 to 66.7 µg/24 Hr | 0.8 to 80.2 µg/24 Hr |
| Analytical Performance | |||
| Analytical Sensitivity | Sufficient for clinical measurement (comparable or better than predicate) | 1.2 ng aldosterone/dL | 0.7 ng aldosterone/dL |
| Within-run (%CV) | Low variability (e.g., <10%) | 1.6 to 6.1% | 3.3 to 7.4% |
| Total Precision (%CV) | Low variability (e.g., <15-20%) | 10.2 to 15.3% | 5.1 to 6.4% |
| Recovery (%) | Close to 100% (e.g., 90-110%) | 93% to 110% | 92% to 138% |
| Linearity (%) | Close to 100% (e.g., 80-120%) | 85% to 116% | 89% to 111% |
| Specificity | Limited or no cross-reactivity with structurally similar compounds | Undetectable for most tested compounds; 0.85% for Estradiol | Not specified in detail, but assumed to be acceptable |
| Urine Extraction Efficiency | Close to 100% recovery for spiked samples | 98% to 103% | Not explicitly detailed for predicate |
| Expected Values (Reference Range) | Establishment of a normal reference range | 0.7 to 23.0 µg/24 hours (for 24-hr urine) | Not explicitly detailed for predicate |
Study Information:
The primary "study" described is a method comparison and performance characteristic evaluation against a legally marketed predicate device.
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Sample sizes used for the test set and data provenance:
- Method Comparison (Urine): n = 118 urine samples.
- Expected Values (Urine): n = 80 healthy adults (41 females, 39 males, age: 18 to 78 years).
- Reproducibility for Urine: 4 urine samples, assayed in duplicate, once per day over 20 days.
- Parallelism for Urine: 5 urine samples, serially diluted and assayed in duplicate.
- Recovery for Urine: 3 sets of high and low urine samples mixed in various ratios, assayed in duplicate.
- Urine Extraction Efficiency: 3 spiked urine samples, tested in n=8 replicates per level.
- Data Provenance: Not explicitly stated, but given the manufacturer (Nichols Institute Diagnostics) and context, it is highly likely that the data was collected retrospectively or prospectively as part of an internal validation study for the device, presumably in the US or a region with comparable regulatory standards. It is retrospective in the sense that existing urine samples might have been used, but the testing itself would have been a prospective application of both assays.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is an in vitro diagnostic immunoassay, not an AI/medical imaging device that requires radiologist or clinician interpretation for establishing ground truth for individual cases. The "ground truth" for the test set (the 118 urine samples) is the measurement obtained from the predicate device (DSL-8600 ACTIVE® Aldosterone Coated-Tube Radioimmunoassay Kit), which is itself a laboratory assay.
- For the Expected Values study, "80 healthy, prescription expected forchoo fangedults (41 females and 39 males, age:18 to 78 years)" were used. The 'ground truth' here is their healthy status, presumably determined by routine medical screening, not by expert consensus on specific diagnostic cases.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is not a study involving human readers or expert consensus on case interpretation that would require adjudication. The method comparison uses quantitative measurements from two different laboratory assays.
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If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This is an IVD device, not an AI algorithm for image interpretation or diagnosis that would involve human readers.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, this is an intrinsic performance study of the standalone device (the Nichols Advantage® Aldosterone Assay). Its performance is evaluated objectively through analytical characteristics (precision, recovery, linearity, specificity) and compared to a predicate device. There is no human-in-the-loop component in the measurement process itself; a laboratory technician operates the system, but the device provides the quantitative result.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the method comparison study, the "ground truth" for the 118 urine samples was the measurement obtained from the predicate device (DSL-8600 ACTIVE® Aldosterone Coated-Tube Radioimmunoassay Kit).
- For other analytical performance studies (precision, recovery, linearity, specificity, extraction efficiency), the "ground truth" is established through known concentrations of analytes (e.g., spiked samples, reference materials) or by the absence/presence of cross-reactants.
- For establishing the Expected Values, the "ground truth" was the clinical health status (healthy individuals) of the sampled population.
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The sample size for the training set:
- Not applicable in the conventional sense of machine learning. This is a traditional immunoassay, not an AI/ML algorithm that requires a "training set" to learn from data. The assay's performance is based on its chemical and immunological design.
-
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" in the context of an immunoassay. The device is built based on established biochemical principles.
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12.0 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS
This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
510(k) Number: K050784
1. Name of Submitter, Contact Person and Date Summary Prepared:
Nichols Institute Diagnostics 1311 Calle Batido San Clemente, CA 92673 Phone: 949-940-7358 Fax: 949-940-7313
Contact Person: Xie Qiyi, MD., MPH, Director of Clinical and Regulatory Affairs Date Prepared: 5/13/2005
2. Device Name and Classification
| Trade/Proprietary Name: | Nichols Advantage® Aldosterone Assay |
|---|---|
| Common/Usual Name: | Aldosterone Immunoassay |
| Classification Name: | Radioimmunoassay System, Test, Aldosterone |
| Classification: | Class IIRegulation Number: 862.1054Product code: CJM, Clinical Chemistry |
- DSL-8600 ACTIVE® Aldosterone Coated-Tube 3. Predicate Device: Radioimmunoassay Kit.
4. Device Description:
The Nichols Advantage® Aldosterone Assay is a competitive immunochemiluminometric in vitro diagnostic laboratory immunoassay (IVD device) that utilizes a biotinylated mouse monoclonal anti-aldosterone antibody as the capture reagent and an acridinium ester labeled aldosterone as a tracer reagent. This Aldosterone IVD device immunoassay is intended for use for the measurement of aldosterone in human serum, EDTA plasma, and extracted urine, as an extended diagnostic method utilized within the Nichols Advantage® Specialty System.
5. Intended Use
The Nichols Advantage Aldosterone Assay is intended for in vitro diagnostic Inhoratory use with the Nichols Advantage® Specialty System for quantitative measurement of aldosterone in human serum, EDTA plasma, and extracted urine. Aldosterone measurements are intended for use in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.
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6. Comparison to predicate device :
The Nichols Advantage Aldosterone(Y) was compared to a commercially The Nionolo Aldosterone radioimmunoassay (X) previously cleared by the FDA using the NCCLS EP9-A procedures for method comparison and bias analysis. (n=118) urine samples were assayed by both methods following each manufacturers' directions and without modifications. The range of values observed with the commercially available kit was 0.8 to 80.2 µg/24 Hr; with the Nichols Advantage Aldosterone the range was 0.4 to 66.7µg/24 Hr . Computing the Passing Bablok regression analysis of these data yielded an equation of Y = 1.23X - 1.19 (95% confidence intervals of the slope and intercept were 1.2 to 1.28, and -1.43 to -0.81 respectively). Pearson's correlation coefficient (r) of the paired data was 0.96 (95% confidence interval was 0.94 to 0.97). User laboratories should perform their own method comparison following their inhouse procedures.
7. Similarities:
- Both assays use same specimen type [i.e., 24 hour human urine sampling] �
- Both assays use human-derived aldosterone standards and controls. .
- Both assays use a specific antibody to aldosterone, use competitive direct . immunoassay methods to measure the hormone in urine.
- The sensitivity of both assays is sufficient to measure aldostrerone levels . found in urine in the range of normal and abnormal values.
- Both assays are IVD laboratory-based medical device products. .
Differences: 8.
| DSL-8600 ACTIVE®Aldosterone Coated-TubeRadioimmunoassay Kit | Nichols Advantage®Aldosterone Assay | |
|---|---|---|
| FeatureSample Volume | 100 microliters | 250 microliters |
| Sample preparation | Extracted Urine samples | Hydrolyzed Urine Samples |
| Analyticalsensitivity | 0.7 ng aldosterone/dL | 1.2 ng aldosterone/dL |
| Analytical prinicpal | Radioimmunassay or RIA | limmunochemiluminometric Assay or ICL Assay |
| Incubation stepsand temperature | Several steps, 18 hoursat room temperature[~25°C] | 3 steps, 10 minutes eachat 37C |
REPORTING RESULTS 9.
The recommended reportable range is 3 to 120 ng/dL. Values below 3 ng/dL should be reported as "less than 3 ng/dL" (< 3 ng/dL). The highest reportable value without dilution is the value of the highest point on the Master Curve (120
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Samples reading above the Master Curve should be diluted and na/dL). ngrue, " Oumplos "rous reater than the highest value on the Master Curve. The repeated, or reported as grouter in the location of the sample in the sample printout for the accay the time in which and the time in which the assay was completed. In addition, the printout will show the RLU value for each replicate, the mean RLU, RLU %CV, %CV concentration, and the mean result in ng/dL. The mean result for all replicates should be reported.
EXPECTED VALUES (Urine) 10.
Nichols Institute Diagnostics recommends that each laboratory establish its own range of expected values for the population they serve. To establish an expected reference range, 24 hours urine samples, n= 80 healthy, prescription expected forchoo fangedults (41 females and 39 males, age:18 to 78 years), were obtained. Non of the females were pregnant, taking birth control pills, or on were obtained. Non of the square root transformation of the data, the 95% confidence interval for normal 24-hour Urine Aldosterone results are as follows. 24-hour Urine Aldosterone Reference range: 0.7 to 23.0 µg/24 hours.
| Feature | DSL-8600 ACTIVE®Aldosterone Coated-TubeRadioimmunoassay Kit | Nichols Advantage®Aldosterone Assay |
|---|---|---|
| Within-run (%CV) | 3.3 to 7.4% | 1.6 to 6.1% |
| Total Precision(%CV) | 5.1 to 6.4% | 10.2 to 15.3% |
| Recovery | 92% to 138% | 93% to 110% |
| Linearity | 89% to 111% | 85% to 116% |
PECIFIC PERFORMANCE CHARACTERISTICS 11.
REPRODUCIBILITY FOR URINE
The within-run and total imprecision performance for the aldosterone assay was estimated using the NCCLS EP5-A method (Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline)18. The data represent one run per day over 20 days with 4 urine samples assayed in duplicate. The study was performed on a single system.
| UrineSample | Mean | Within-Run | TotalImprecision | ||
|---|---|---|---|---|---|
| (ng/dL) | SD | %CV | SD | %CV | |
| Sample A | 8.6 | 0.53 | 6.1 | 1.32 | 15.3 |
| Sample B | 17.6 | 0.4 | 2.3 | 1.95 | 11.1 |
| Sample C | 37.4 | 0.61 | 1.6 | 3.84 | 10.3 |
| Sample D | 61.2 | 1.32 | 2.2 | 6.21 | 10.2 |
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PARALLELISM FOR URINE
Urine samples were extracted following the normal protocol. The reconstituted extracts were serially diluted with Nichols Advantage Aldosterone Urine Sample Diluent and assayed in duplicate.
| Sample | Dilution | Observed(ng/dL) | Expected(ng/dL) | % Recovery |
|---|---|---|---|---|
| Neat | 67.4 | |||
| 1 | 1:2 | 34.3 | 33.7 | 102% |
| 1:4 | 17.9 | 16.9 | 106% | |
| 1:8 | 7.2 | 8.4 | 85% | |
| Neat | 82.2 | |||
| 2 | 1:2 | 41.3 | 41.1 | 100% |
| 1:4 | 20.5 | 20.5 | 100% | |
| 1:8 | 9.4 | 10.3 | 92% | |
| Neat | 92.3 | |||
| 3 | 1:2 | 49.1 | 46.1 | 106% |
| 1:4 | 24.9 | 23.1 | 108% | |
| 1:8 | 13.3 | 11.5 | 116% | |
| Neat | 86.2 | |||
| 4 | 1:2 | 46.4 | 43.1 | 108% |
| 1:4 | 23.7 | 21.6 | 110% | |
| 1:8 | 11.4 | 10.8 | 106% | |
| Neat | 74.7 | |||
| 5 | 1:2 | 40.8 | 37.3 | 109% |
| 1:4 | 20.0 | 18.7 | 107% | |
| 1:8 | 9.0 | 9.3 | 96% |
RECOVERY FOR URINE
A high and low urine sample was extracted and assayed in duplicate. The reconstituted extracts from the high and low urine samples were mixed in 2 to 1, 1 to 1, and 1 to 2 ratios and assayed in duplicate
| Sample | Observed (ng/dL) | Expected (ng/dL) | % Recovery |
|---|---|---|---|
| Sample A | 53.5 | ||
| 1:1 | 30.7 | 32.9 | 93% |
| 1:2 | 28.0 | 26.0 | 108% |
| 2:1 | 36.9 | 39.6 | 93% |
| Sample B | 12.5 | ||
| Sample C | 49.9 | ||
| 1:1 | 33.1 | 31.1 | 107% |
| 1:2 | 27.4 | 24.8 | 110% |
| 2:1 | 37.2 | 37.3 | 100% |
| Sample D | 12.5 | ||
| Sample I | 62.4 | ||
| 1:1 | 39.7 | 40.7 | 97% |
| 1:2 | 35.8 | 33.5 | 107% |
| 2:1 | 44.3 | 47.8 | 93% |
| Sample J | 19.3 | 99% |
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SPECIFICITY FOR URINE
| Crossreactant | Highest Amt.Tested(µg/dL) | Apparent Amt.Detected (ng/dL) | %Crossreactivity |
|---|---|---|---|
| 17-HydroxyCorticosterone(Cortisol) | 5000 | 23.9 | Undetectable |
| 17-HydroxyCorticosterone(Cortisol) | 2500 | 24.2 | Undetectable |
| 17-HydroxyCorticosterone(Cortisol) | 1250 | 27.5 | Undetectable |
| Cortisone | 45.00 | 26.0 | Undetectable |
| Cortisone | 22.50 | 25.3 | Undetectable |
| Cortisone | 11.25 | 25.4 | Undetectable |
| 17-Ketosteroids(DHEA) | 9000 | 21.7 | Undetectable |
| 17-Ketosteroids(DHEA) | 4500 | 27.0 | Undetectable |
| 17-Ketosteroids(DHEA) | 2250 | 27.0 | Undetectable |
| Estradiol | 9.00 | 26.6 | Undetectable |
| Estradiol | 4.50 | 27.4 | Undetectable |
| Estradiol | 2.25 | 28.9 | 0.85% |
| Estriol | 59.00 | 26.3 | Undetectable |
| Estriol | 29.50 | 27.8 | Undetectable |
| Estriol | 14.75 | 28.3 | Undetectable |
| Aldosterone | 2.9 | 37.5 | 102% |
| Aldosterone | 1.5 | 43.9 | 98% |
URINE EXTRACTION EFFICIENCY
Extraction efficiency is determined by spiking known quantities of Aldosterone into urine and measuring the recovery of the spiked Aldosterone. Different amounts of a pure Aldosterone stock solution are spiked into a normal urine sample. Each sample is then hydrolyzed, extracted and tested in n=8 replicates per level.
| Sample | SpikedDose | µg/24 Hr | Corrected Dose(Spiked - | %Recovery. |
|---|---|---|---|---|
| Endogenous. | 0.0 | 7.0 | ||
| A | 46.1 | 53.7 | 46.8 | 101% |
| B | 31.9 | 39.7 | 32.7 | 103% |
| C | 16.6 | 23.2 | 16.2 | 98% |
12. METHOD COMPARISON
For urine samples
The Nichols Advantage Aldosterone(Y) was compared to a commercially available Aldosterone radioimmunoassay (X) previously cleared by the FDA using the NCCLS EP9-A procedures for method comparison and bias analysis. (n=118) urine samples were assayed by both methods following each manufacturers' directions and without modifications. The range of values observed with the commercially available kit was 0.8 to 80.2 µg/24 Hr; with the Nichols Advantage Aldosterone the range was 0.4 to 66.7µg/24 Hr . Computing the Passing Bablok regression analysis of these data yielded
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an equation of Y = 1.23X -- 1.19 (95% confidence intervals of the slope and intercept were 1.2 to 1.28, and -1.43 to -0.81 respectively). Pearson's correlation coefficient (r) of the paired data was 0.96 (95% confidence interval was 0.94 to 0.97). User laboratories should perform their own method comparison following their in-house procedures.
13. Conclusions:
These data, which were provided to FDA, demonstrates safety and effectiveness of the Nichols Advantage Aldosterone for its intended in vitro diagnostic use. Furthermore, based on performance characteristics, the Nichols Advantage Aldosterone assay is substantially equivalent to the predicated method in urine application.
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Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. In the center of the circle is an abstract symbol that resembles a stylized caduceus or a bird-like figure, composed of three curved lines.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUN 1 - 2005
Nichols Institute Diagnostics c/o Alfredo J. Quattrone, Ph.D., D.A.B.T. California Department of Health Services Food and Drug Branch P.O. Box 997 413 FDB Mailstop 7602 Sacramento, CA 95899
K050784 Re:
Trade/Device Name: Nichols Advantage® Aldosterone Assay Regulation Number: 21 CFR 862.1045 Regulation Name: Aldosterone test system Regulatory Class: Class II Product Code: CJM Dated: May 19, 2005 Received: May 26, 2005
Dear Dr. Quattrone:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Carol C. Benem
Carol C. Benson, M.A. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (K050784):
Device Name: Nichols Advantage® Aldosterone Assay
Indications For Use:
The Nichols Advantage Aldosterone Assay is intended for in vitro diagnostic laboratory use with the Nichols Advantage® Specialty System for quantitative measurement of aldosterone in human serum, EDTA plasma, and extracted urine. Aldosterone measurements are intended for use in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.
Prescription Use V (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
OND Concurrence of CDRH, Office of Device Evaluation (OBE)
Alberto Serta
Division Sign-Off
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
Page 1 of _ 1 _ _ 1
510(k) L050784
§ 862.1045 Aldosterone test system.
(a)
Identification. An aldosterone test system is a device intended to measure the hormone aldosterone in serum and urine. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by the excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.(b)
Classification. Class II.