(268 days)
No
The device description and performance studies focus on a luminescence immunoassay based on a competition principle, which is a standard biochemical method. There is no mention of AI or ML in the text.
No
The device is an in-vitro diagnostic device used to quantitatively determine Cortisol levels in human saliva, aiding in the diagnosis and treatment of adrenal disorders. It is not designed to provide or deliver therapy itself.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device "is intended for the in-vitro diagnostic quantitative determination of Cortisol in human saliva and for use as an aid in the diagnosis and treatment of adrenal disorders." This clearly indicates its use in diagnosis.
No
The device is an in-vitro diagnostic immunoassay kit, which includes physical components like a microtiter plate, standards, controls, and reagents. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is intended for the "in-vitro diagnostic quantitative determination of Cortisol in human saliva and for use as an aid in the diagnosis and treatment of adrenal disorders." The phrase "in-vitro diagnostic" is a direct indicator.
- Sample Type: The device analyzes human saliva, which is a biological sample taken from the body.
- Purpose: The purpose is to quantitatively determine Cortisol levels to aid in the diagnosis and treatment of adrenal disorders. This is a clear diagnostic purpose.
- Test Principle: The description of the luminescence immunoassay principle confirms that it is a laboratory-based test performed on a sample outside of the body.
N/A
Intended Use / Indications for Use
The IBL International Cortisol Saliva Luminescence Immunoassay is intended for the in-vitro diagnostic quantitative determination of Cortisol in human saliva and for use as an aid in the diagnosis and treatment of adrenal disorders. The device is not intended for point-of-care settings.
Product codes
NHG
Device Description
Cortisol (also known as hydrocortisone, compound F) is the main glucocorticoid in humans and is produced in the zona fasciculata of the adrenal cortex. 90 % of the circulating cortisol are bound to corticoid binding globulin (CBG, Transcortin), ca. 7 % are bound to albumin and only 1-3 % are unbound. Only the latter part represents the active form of cortisol. The free cortisol is released in saliva and is excreted via the kidneys as a small part among the metabolites of cortisol. The level of free cortisol in blood regulates mainly its secretion in the adrenal cortex in a negative feedback mechanism via CRH (corticotropin releasing hormone) in the hypothalamic region and the ACTH in the pituitary gland, but it is also affected by different situations above all by stress.
In humans, there is a physiological fluctuation of cortisol achieving the highest level in the morning and the lowest during the night. This fluctuation of cortisol plasma level is reflected in saliva normally with a peak in the first 90 minutes after waking up. The cortisol measurement is indicated in adrenal disorders. Due to the diurnal fluctuations of cortisol, a salivary sample collection is an easy method without the stress of repeated venipunctures.
Test principle:
Luminescence immunoassay based on the competition principle. An unknown amount of antigen present in the sample and a fixed amount of enzyme labelled antigen compete for the binding sites of the antibodies coated onto the wells. After incubation the wells are washed to stop the competition reaction. After addition of the luminescence substrate solution the intensity of the luminescence measured is inversely proportional to the amount of the antigen in the sample. Results of samples can be determined directly using the standard curve.
Device composition:
The device is available in two sizes, 96 tests and 960 tests.
The device consists of an antibody coated 96 well Microtiter Plate, seven Standards (range 0.015 - 3.20 µg/dL, equivalent to 0.15 - 32 ng/mL calibrated to the NIST cortisol), two Controls, Enzyme Conjugate (Cortisol coupled to peroxidase), Chemiluminescence Reagent 1 and 2, 10x concentrated Wash Buffer, Adhesive Foils.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Human saliva
Indicated Patient Age Range
Ages: 21-70
Intended User / Care Setting
Not intended for point-of-care settings.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Analytical Performance
Detection limits (LoB/LoD/LoQ): LoB study conducted over three days by one operator with high/low kit controls and five different samples, each tested five times in duplicate using two reagent lots. LoD/LoQ study similarly conducted over three days by one operator with high/low kit controls and five different human saliva samples, each tested multiple times in duplicate using two reagent lots.
Specificity: Cross-reactivity study conducted over eight days by one operator. Five runs maximum per day with high/low kit controls and three human saliva samples spiked with potential interfering substances (0, 0.1, 1, 10, 100, 1000, 10000 µg/dL). Each sample tested once in duplicate using one reagent lot. Specificity assessed on a panel of 27 members. Potential interfering substances identified as Prednisolone (≥10% from 10000 µg/dL) and 11-Deoxycortisol (≥5% from 10000 µg/dL).
Linearity: Experiment conducted according to CLSI EP06-A over two days by one operator. Runs performed with high/low kit controls and two human saliva samples mixed to produce intermediate concentrations. Each sample tested in duplicate using one reagent lot. Linear correlation: Determined Cortisol concentration (µg/dL) = -0.05 + 1.03 x (expected Cortisol concentration (ug/dL)), with R2 =0.99. Linear range: 0.012 µg/dL (LoQ) to 3.134 µg/dL.
Recovery: Study conducted over one day by one operator. Run performed with high/low kit controls and three human saliva samples spiked with six different cortisol concentrations. Each sample tested in duplicate using one reagent lot. Recovery range: 93.7% to 109.6% for concentrations from 0.242 µg/dL to 2.528 µg/dL.
Precision: Study conducted over 1 day of pre-evaluation and 20 days of testing (based on CLSI Guideline EP05-A3). 6 assays performed daily in a fully factorial design using 3 different reagent lots and 3 operators. Within each assay, 7 human saliva pools were used and determined in triplicate. Between lot CV range: 0.4 – 1.7%. Between operator CV range: 0.8 – 1.8%.
Interferences/Analytical Specificity: Study conducted for every possible potentially substance during one day of testing by one operator. Runs performed with high/low kit controls and 3 different human saliva samples. Each sample tested in duplicate using one reagent lot.
Sample Freezing Claim: Evaluation showed mean CV = 4.4% after freezing vs. 7.2% without freezing. Sample stability evaluated at various temperatures and durations: 37°C for 1 week, 18-25°C for 2 weeks, 2-8°C for 2 weeks,
§ 862.1205 Cortisol (hydrocortisone and hydroxycorticosterone) test system.
(a)
Identification. A cortisol (hydrocortisone and hydroxycorticosterone) test system is a device intended to measure the cortisol hormones secreted by the adrenal gland in plasma and urine. Measurements of cortisol are used in the diagnosis and treatment of disorders of the adrenal gland.(b)
Classification. Class II.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
November 25, 2015
IBL INTERNATIONAL GMBH NICOLA KAISER HEAD OF REGULATORY/ QM FLUGHAFENSTRASSE 52 A HAMBURG D-22335 GERMANY
Re: K150528
Trade/Device Name: Cortisol Saliva Luminescence Immunoassav Regulation Number: 21 CFR 862.1205 Regulation Name: Cortisol (Hydrocortisone and Hydroxycorticosterone) Test System Regulatory Class: II Product Code: NHG Dated: October 21, 2015 Received: October 22, 2015
Dear Nicola Kaiser:
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. 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.
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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Katherine Serrano -S
For : Courtney H. Lias, Ph.D. 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) K150528
Device Name
Cortisol Saliva Luminescence Immunoassay
Indications for Use (Describe)
The IBL International Cortisol Saliva Luminescence Immunoassay is intended for the in-vitro diagnostic quantitative determination of Cortisol in human saliva and for use as an aid in the diagnosis and treatment of adrenal disorders. The device is not intended for point-of-care settings.
| 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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IBL International GmbH, Flughafenstrasse 52a, 22335 Hamburg
510(k) Summary K150528
For
Cortisol Saliva Luminescence Immunoassay
1. Submission Correspondence
IBL International GmbH Flughafenstrasse 52A D-22335 Hamburg GERMANY Phone: + 49 40 532891 482 Fax: + 49 40 532891 11 Contact: Nicola Kaiser, Quality Manager/Regulatory Affairs
2. Submission Sponsor
IBL International GmbH Flughafenstrasse 52A D-22335 Hamburg GERMANY Phone: + 49 40 532891 482 Fax: + 49 40 532891 11 Contact: Geert Nygaard, Managing Director
3. Date Prepared
2015-11-24
IBL International GmbH
49 (0) 40 53 28 91-1
Geert W. Nygaar ht Hambur Account: 577 073 000 200 700 00 1 2007 0000 0577 0730 00 Umsatzsteuer ID: DE2610.
IBL International GmbH
047 510k Summary Revision D
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4. Device Name
Trade/Proprietary Name: Cortisol Saliva Luminescence Immunoassay Common/Usual Name: Cortisol Saliva LUM
5. Classification Name
Classification Name: Enzyme Immunoassay, Cortisol, Saliyary: Cortisol (hydrocortisone and hydroxycorticosterone) test system Classification Regulation: 862.1205 Product Code: NHG
6. Predicate Device
Pantex INC. AM/PM Salivary cortisol EIA K102841.
7. Device Description
Summary and explanation:
Cortisol (also known as hydrocortisone, compound F) is the main glucocorticoid in humans and is produced in the zona fasciculata of the adrenal cortex. 90 % of the circulating cortisol are bound to corticoid binding globulin (CBG, Transcortin), ca. 7 % are bound to albumin and only 1-3 % are unbound. Only the latter part represents the active form of cortisol. The free cortisol is released in saliva and is excreted via the kidneys as a small part among the metabolites of cortisol. The level of free cortisol in blood regulates mainly its secretion in the adrenal cortex in a negative feedback mechanism via CRH (corticotropin releasing hormone) in the hypothalamic region and the ACTH in the pituitary gland, but it is also affected by different situations above all by stress.
In humans, there is a physiological fluctuation of cortisol achieving the highest level in the morning and the lowest during the night. This fluctuation of cortisol plasma level is reflected in saliva normally with a peak in the first 90 minutes after waking up. The cortisol measurement is indicated in adrenal disorders. Due to the diurnal fluctuations of cortisol, a salivary sample collection is an easy method without the stress of repeated venipunctures.
Test principle:
Luminescence immunoassay based on the competition principle. An unknown amount of antigen present in the sample and a fixed amount of enzyme labelled antigen compete for the binding sites of the antibodies coated onto the wells. After incubation the wells are washed to stop the competition reaction. After addition of the luminescence substrate solution the intensity of the luminescence measured is inversely proportional to the amount of the antigen in the sample. Results of samples can be determined directly using the standard curve.
5
Device composition:
The device is available in two sizes, 96 tests and 960 tests.
The device consists of an antibody coated 96 well Microtiter Plate, seven Standards (range 0.015 - 3.20 µg/dL, equivalent to 0.15 - 32 ng/mL calibrated to the NIST cortisol), two Controls, Enzyme Conjugate (Cortisol coupled to peroxidase), Chemiluminescence Reagent 1 and 2, 10x concentrated Wash Buffer, Adhesive Foils.
8. Intended Use
The IBL International Cortisol Luminescence Immunoassay is intended for the in-vitro diagnostic quantitative determination of Cortisol in human saliva and for use as an aid in the diagnosis and treatment of adrenal disorders.
The device is not intended for point-of-care settings.
| Item | Cortisol Saliva Luminescence
Immunoassay | Enzyme Immunoassay, Cortisol
Salivary |
|----------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number | K150528 | K102841 |
| Device name | Cortisol Saliva Luminescence
Immunoassay | Enzyme Immunoassay, Cortisol
Salivary |
| Analyte | Cortisol | Cortisol |
| Specimens | Saliva | Saliva |
| Method | Luminescence Immunoassay | Enzyme Immunoassay |
| Test principle | Luminescence immunoassay
based on the competition principle.
An unknown amount of analyte
present in the sample and a fixed
amount of enzyme labelled analyte
competes for the binding sites of
the antibodies coated onto the
wells. After incubation the wells
are washed to stop the competition
reaction. After addition of the
luminescence substrate solution
the intensity of the luminescence
measured is inversely proportional
to the amount of the analyte in the
sample. Results of samples can be
determined directly using the
standard curve. | The basis of the Cortisol Enzyme
Immunoassay (EIA) is the
quantitative relation between ligand
concentration and the proportion of
Cortisol (analog) enzyme conjugate
bound to the antiserum. For
example: Cortisol in the calibrators
and unknowns compete with
Cortisol coupled to peroxidase for
antibody binding sites. After
incubation, unbound components
are washed away. The reaction
between Cortisol peroxidase with
the substrate (TMB) produces a
blue color. The pre-determined time
of incubation the reaction is
stopped and a yellow color is
formed. The optical density (read at
450 nm) is inversely proportional to
the cortisol of calibrators, saliva
samples and saliva controls. |
| Detection | RLU Measurement: luminescence | OD Measurement: OD microplate |
Technology Comparison
6
| Item | Cortisol Saliva Luminescence
Immunoassay | Enzyme Immunoassay, Cortisol
Salivary |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | microplate reader | reader |
| Calculation | Quantitative | Quantitative |
| Quality control | Control low and high | Control low and high |
| Reportable range | 0.012 µg/dL – 3.0 µg/dL | 0.01 µg/dL – 3.0 µg/dL |
| Indications for
use | The IBL International Cortisol
Saliva
Luminescence
Immunoassay is intended for the
in-vitro diagnostic quantitative
determination of Cortisol in human
saliva and for use as an aid in the
diagnosis and treatment of adrenal
disorders.
The device is not intended for
point-of-care settings. | For the in-vitro diagnostic
quantitative determination of free
and protein bound salivary cortisol
in human saliva as an aid in the
assessment of Cushing Syndrome
and Addison's Disease.
Measurements of cortisol in saliva
are used on the diagnosis and
treatment of disorders of adrenal
gland. |
| Performance Characteristics | | |
| Expected values
(Normal range) | Ages: 21-70
AM: 0.079 - 1.290 µg/dL (N=157)
PM: 0.042 - 0.436 µg/dL (N=168) | Ages 23-68
AM: 0.258 - 1.269 µg/dL (N=152)
PM: 0.025 - 0.296 µg/dL (N=152) |
| Limit of Detection | Limit of Blank: 0.004 µg/dL | Limit of Blank: 0.00392 µg/dL. |
Analytical Performance
Detection limits
The LoB study was conducted during three days of testing by one operator. The runs were performed with high and low kit controls and with five different samples. Each sample was tested five times in duplicate each run using two reagent lots.
The LoD/LoQ study was conducted during three days of testing by one operator. The runs were performed with high and low kit controls and with five different human saliva samples. Each sample was tested times in duplicate each run using two reagent lots.
Specificity
The cross reactivity study was conducted during eight days of testing by one operator. A maximum of five runs were performed per day with high and low kit controls and with three different human saliva samples spiked with potential interfering substance in six different concentrations(0, 0.1, 1, 10, 100, 1000 and 10000 µg/dL). Each sample was tested once in duplicate using one reagent lot.
Specificity of the IBL Cortisol Saliva LUM Assay test was assessed by testing a panel of 27 members. The cross-reactivity has been defined as:
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concentration of cortisol at 50%(B/Bo)
Cross-reactivity =
concentration of cross reactant giving 50% (B/Bo)
The use of topical creams or medication containing prednisolone and 11-Deoxycortisol should be avoided as they can cause preanalytical contamination of the saliva sample.
At ≥10% Prednisolone is a potential interfering substance (from 10000 µg/dL). At ≥5% 11-Deoxycortisol is a potential interfering substance (from 10000 ug/dL).
Linearity
The linearity experiment was conducted according to the CLSI EP06-A during two days of testing by one operator. The runs were performed with high and low kit controls and with two different human saliva samples mixed up with each other to produce intermediate concentrations. Each sample was tested in duplicate using one reagent lot.
A linear correlation between the expected concentration and the determined concentration could be detected which showed the following best fit:
Determined Cortisol concentration (µg/dL) = -0.05 + 1.03 x (expected Cortisol concentration (ug/dL)), with R2 =0.99.
The linear range of the assay is defined by the LoQ =0.012 µg/dL and the highest tested Cortisol concentration of 3.134 µg/dL that showed an absence of a non-linear component.
Recoverv
The Recovery study was conducted during one day of testing by one operator. The run was performed with high and low kit controls and with three different human saliva samples spiked with six different cortisol concentrations. Each sample was tested in duplicate using one reagent lot.
The recovery showed a minimum of 93.7% and a maximum of 109.6% for all tested samples and expected concentrations. The expected concentrations ranged from 0.242 µg/dL to 2.528 µg/dL,
Precision
The Study was conducted during 1 day of pre-evaluation and familiarization period and 20 days of testing (based on CLSI Guideline EP05-A3). 6 assays were performed daily within a fully factorial design using 3 different reagent lots and 3 operators. Within each assay 7 human saliva pools were used and determined in triplicate
The between lot variation showed a CV range of 0.4 – 1.7% for the seven different concentrated human saliva samples.
8
The between operator variation showed a CV range of 0.8 – 1.8% for the seven different concentrated human saliva samples.
Interferences
Analytical Specificity
The analytical specificity study was conducted for every possible potentially substance during one day of testing by one operator. The runs were performed with high and low kit controls and with 3 different human saliva samples. Each sample was tested in duplicate using one reagent lot.
Sample Freezing Claim
The removal of the highly viscous components improves the pipetting precision. Freezing is believed to lead to the denaturation of the protein components of the viscous components. These denatured protein components were thereafter removed by centrifugation of the sample.
The mean of the coefficient of variation for freezing was lower than the mean of the coefficient of variation for samples that have not been frozen once (Mean CV = 4.4% after freezing vs. 7.2% without freezing process).
In addition the stability of Cortisol in samples was evaluated. Five samples for which the Cortisol concentration is known (low, medium and high concentration) and an acceptance range had been established were stored at the following conditions:
-
- ≤ -20°C for 3, 6 and 12 months
-
- 2-8°C for 1, 2 and 4 weeks
-
- 19-26°C (RT = room temperature) for 1, 2 and 4 weeks
-
- 36-39°C for 4 days, 1 week and 2 weeks
-
- 50°C for 1 day, 4 days and 1 week.
Within all samples stored at the above conditions, the concentration of Cortisol was determined within the predetermined acceptance range. The sample stability is listed in the following table:
| Storage | 37°C | 18-25°C | 2-8°C |