(190 days)
The ARCHITECT SHBG assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the ARCHITECT i System. The ARCHITECT SHBG assay is used as an aid in the diagnosis of androgen disorders.
The ARCHITECT SHBG assay is a two-step immunoassay to determine the presence of SHBG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology with flexible assay protocols, referred to as Chemiflex. In the first step, sample, assay diluent, and anti-SHBG coated paramagnetic microparticles are combined. SHBG present in the sample binds to anti-SHBG coated microparticles. After washing, the SHBG binds to the anti-SHBG acridinium-labeled conjugate that is added in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). A direct relationship exists between the amount of SHBG in the sample and the RLUs detected by the ARCHITECT i System optics. The concentration of SHBG in the sample is determined by comparing the chemiluminescent signal in the reaction to the ARCHITECT SHBG calibration.
This document is primarily a 510(k) summary for a labeling change to the ARCHITECT SHBG assay. It is not about a new device or an AI/ML device, but rather an update to the "Free Testosterone Index (FTI) / Free Androgen Index (FAI)" expected values section of the existing device's labeling. Therefore, many of the requested categories for acceptance criteria and study details for AI/ML devices are not applicable.
Here's an interpretation based on the provided text, focusing on the available information:
1. Table of Acceptance Criteria and Reported Device Performance
The device itself (ARCHITECT SHBG assay) was previously cleared. The current submission is for a labeling change to update expected values for the Free Testosterone Index (FTI) or Free Androgen Index (FAI). Therefore, there are no new performance acceptance criteria for the device itself as part of this submission. The performance of the underlying assay remains as established in K060818.
However, the "study" described in the document is the generation of new FTI/FAI expected values. The implicit acceptance criterion for this study is that the calculated FTI/FAI values are representative of the studied populations and are suitable for inclusion in the device labeling. The "reported device performance" in this context refers to the generated expected value ranges.
| Acceptance Criteria (Implicit for FTI/FAI Study) | Reported Performance (FTI/FAI Expected Values) |
|---|---|
| New FTI/FAI expected values are derived from a sufficient number of representative samples across different demographic categories. | See tables below for the calculated median, 2.5th, and 97.5th percentiles for SHBG, Testosterone, and %FTI/%FAI for various demographic groups. |
| The individual SHBG and Testosterone measurements used to calculate FTI/FAI fall within the expected values of their respective ARCHITECT assays. | Samples were included if they were within the expected values of the ARCHITECT 2nd Generation Testosterone (LN 2P13) and ARCHITECT SHBG (LN 8K26) reagent inserts. |
| The labeling update does not alter the intended use, indications for use, or fundamental scientific technology of the predicate device. | Confirmed in the conclusion. RLI analysis performed, no change in performance expected. |
SHBG Expected Values (nmol/L)
| Category | N | Median | 2.5th Percentile | 97.5th Percentile |
|---|---|---|---|---|
| Males (21-49 years of age) | 163 | 31.1 | 16.2 | 68.5 |
| Males (≥ 50 years of age) | 144 | 35.3 | 13.7 | 69.9 |
| Females (Premenopausal, 21-49 years of age) | 174 | 48.6 | 14.7 | 122.5 |
| Females (Postmenopausal, ≥ 50 years of age) | 175 | 49.9 | 16.7 | 124.4 |
Testosterone Expected Values
| Category | N | Median (nmol/L [ng/dL]) | 2.5th Percentile (nmol/L [ng/dL]) | 97.5th Percentile (nmol/L [ng/dL]) |
|---|---|---|---|---|
| Males (21-49 years of age) | 163 | 15.33 [442.07] | 8.76 [252.73] | 27.85 [803.24] |
| Males (≥ 50 years of age) | 144 | 14.42 [415.85] | 8.58 [247.50] | 23.37 [674.13] |
| Females (Premenopausal, 21-49 years of age) | 174 | 1.05 [30.43] | 0.52 [14.92] | 1.72 [49.56] |
| Females (Postmenopausal, ≥ 50 years of age) | 175 | 0.76 [21.83] | 0.46 [13.34] | 1.18 [33.90] |
% FTI or % FAI Expected Values
| Category | N | Median (%) | 2.5th Percentile (%) | 97.5th Percentile (%) |
|---|---|---|---|---|
| Males (21-49 years of age) | 163 | 46.6 | 24.5 | 113.3 |
| Males (≥ 50 years of age) | 144 | 40.7 | 19.3 | 118.4 |
| Females (Premenopausal, 21-49 years of age) | 174 | 2.0 | 0.7 | 8.7 |
| Females (Postmenopausal, ≥ 50 years of age) | 175 | 1.5 | 0.5 | 4.7 |
2. Sample Size Used for the Test Set and Data Provenance
- Sample sizes:
- Males (21-49 years of age): 163 samples
- Males (≥ 50 years of age): 144 samples
- Females (Premenopausal, 21-49 years of age): 174 samples
- Females (Postmenopausal, ≥ 50 years of age): 175 samples
- Total samples: 163 + 144 + 174 + 175 = 656 samples
- Data Provenance: The document states "A new study was conducted in 2014 to calculate FTI or FAI..." It specifies "individuals in the following categories: normal males... normal females..." without explicitly stating the country of origin. The study appears to be prospective in nature, as it was specifically conducted to establish these new expected values.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- This is not applicable as the study involves quantitative measurements using an immunoassay device, not subjective expert assessment of images or clinical findings that would require ground truth established by experts.
4. Adjudication Method for the Test Set
- Not applicable for a quantitative in vitro diagnostic assay. The results are raw numerical measurements from the ARCHITECT i System.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
- Not applicable. This is an immunoassay, not an imaging device or an AI/ML algorithm requiring human reader performance evaluation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Not applicable as this is not an AI/ML algorithm. The "standalone" performance here refers to the ARCHITECT SHBG and ARCHITECT 2nd Generation Testosterone assays themselves, which provide quantitative results directly from the instrument.
7. The Type of Ground Truth Used
- The "ground truth" in this context is the quantitative determination of SHBG and Testosterone concentrations in human serum/plasma samples using the respective ARCHITECT assays. These are measured values, not a 'ground truth' in the sense of a consensus diagnosis or pathology result. For FTI/FAI, the ground truth is derived calculation based on these assay results.
8. The Sample Size for the Training Set
- Not applicable as this is not an AI/ML device that undergoes a training phase. The study involved collecting new data to establish expected values for FTI/FAI, effectively acting as a validation/reference range study, not a training set for an algorithm.
9. How the Ground Truth for the Training Set Was Established
- Not applicable.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
BIOKIT, S.A. ANGELS ROMA, REGULATORY AFFAIRS AND MARKET SURVEILLANCE DIRECTOR CAN MALE, S/N 08186 LLICA D'AMUNT 08186 February 11, 2016 BARCELONA, SPAIN
Re: K152185
Trade/Device Name: ARCHITECT SHBG Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: I, Reserved Product Code: CDZ Dated: December 10, 2015 Received: December 14, 2015
Dear Angels Roma:
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.
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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)
Device Name
ARCHITECT SHBG
Indications for Use (Describe)
The ARCHITECT SHBG assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the ARCHITECT i System. The ARCHITECT SHBG assay is used 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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I. 510(k) Summary
The summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
Date: February 1, 2016
Applicant Name:
Ms. Angels Roma, Regulatory Affairs and Market Surveillance Director Biokit S.A. Can Malé, S/N 08186 Lliçà d'Amunt Barcelona, Spain Phone: (34) 938-609-000 Fax: (34) 938-609-029
Device Name:
Reagents
Classification Name: Radioimmunoassay, Testosterones, and Dihydrotestosterone Trade Name: ARCHITECT SHBG Governing Regulation: 21 CFR 862.1680 Device Classification: Class I Reserved Classification Panel: Clinical Chemistry Product Code: CDZ
Legally marketed device to which equivalency is claimed:
ARCHITECT SHBG assay (K060818)
Intended Use/Indications for Use:
The ARCHITECT SHBG assay is a chemiluminescent microparticle immunoassay (CMA)
for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the ARCHITECT i System.
The ARCHITECT SHBG assay is used as an aid in the diagnosis of androgen disorders.
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Description of Device:
The ARCHITECT SHBG assay is a two-step immunoassay to determine the presence of SHBG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology with flexible assay protocols, referred to as Chemiflex. In the first step, sample, assay diluent, and anti-SHBG coated paramagnetic microparticles are combined. SHBG present in the sample binds to anti-SHBG coated microparticles. After washing, the SHBG binds to the anti-SHBG acridinium-labeled conjugate that is added in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). A direct relationship exists between the amount of SHBG in the sample and the RLUs detected by the ARCHITECT i System optics. The concentration of SHBG in the sample is determined by comparing the chemiluminescent signal in the reaction to the ARCHITECT SHBG calibration.
Comparison of Technological Characteristics:
Both the submission device (ARCHITECT SHBG) and the predicate device (ARCHITECT SHBG [K060818]) have the same technological characteristics. Both devices use a chemiluminescent microparticle immunoassay (CMIA) technology for the quantitative determination of sex hormone binding globulin in human serum and plasma. There are no technological differences between the submission and predicate devices.
Comparison of Assay Performance
The reagents, calibrators, and controls for the submission device and the predicate device are the same. The submission is to update the Free Testosterone Index (FTI) (also known as Free Androgen Index [FAI]) expected values section of the labeling. The risk assessment was performed and there is no change in the performance of the previously cleared assay. The performance data provided in K060818 still apply.
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Summary of Supporting Data:
The FTI/FAI expected values that are currently in the ARCHITECT SHBG reagent insert were calculated using ARCHITECT Testosterone (List Number [LN] 6C28, cleared under K983212) and ARCHITECT SHBG (LN 8K26) assays. A new study was conducted in 2014 to calculate FTI or FAI using ARCHITECT 2nd Generation Testosterone (LN 2P13, cleared under K120009) and ARCHITECT SHBG (LN 8K26) assay results. The %FTI or %FAI calculated as [Total Testosterone] / [SHBG] provides an index of free testosterone status. The %FTI or %FAI correlates with the value of free testosterone.
FTI/FAI Expected Values
The new FTI/FAI expected values study was performed on a minimum of 120 samples from individuals in the following categories: normal males 21-49 years of age, normal males ≥ 50 years of age, premenopausal normal females 21-49 years of age, and postmenopausal normal females ≥ 50 years of age not on hormone replacement therapy.
The following inclusion/exclusion criteria apply to the study:
Samples that were within the expected values of the ARCHITECT 2nd Generation Testosterone (LN 2P13) reagent insert and the ARCHITECT SHBG (LN 8K26) reagent insert were included in the study.
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| SHBG nmol/L | Testosterone nmol/L [ng/dL] | ||||||
|---|---|---|---|---|---|---|---|
| Category | N | Median | 2.5thPercentile | 97.5thPercentile | Median | 2.5thPercentile | 97.5thPercentile |
| Males(21-49 years of age) | 163 | 31.1 | 16.2 | 68.5 | 15.33[442.07] | 8.76[252.73] | 27.85[803.24] |
| Males(≥ 50 years of age) | 144 | 35.3 | 13.7 | 69.9 | 14.42[415.85] | 8.58[247.50] | 23.37[674.13] |
| Females(Premenopausal,21-49 years of age) | 174 | 48.6 | 14.7 | 122.5 | 1.05[30.43] | 0.52[14.92] | 1.72[49.56] |
| Females(Postmenopausal,≥ 50 years of age) | 175 | 49.9 | 16.7 | 124.4 | 0.76[21.83] | 0.46[13.34] | 1.18[33.90] |
The data from this study are summarized in the following tables.
The % FTI or % FAI values for the different groups are summarized in the following table.
| % FTI or % FAI | ||||
|---|---|---|---|---|
| Category | N | Median(%) | 2.5thPercentile (%) | 97.5thPercentile (%) |
| Males (21-49 years of age) | 163 | 46.6 | 24.5 | 113.3 |
| Males (≥ 50 years of age) | 144 | 40.7 | 19.3 | 118.4 |
| Females (Premenopausal, 21-49 years of age) | 174 | 2.0 | 0.7 | 8.7 |
| Females (Postmenopausal, ≥ 50 years of age) | 175 | 1.5 | 0.5 | 4.7 |
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Conclusion:
The submission is for a labeling change for the %FTI or %FAI Expected Values only. The risk assessment was performed and there is no change in the performance of the previously cleared assay. The performance data provided in K060818 still apply.
The submission device is substantially equivalent to the predicate device because the proposed labeling change does not alter the intended use, indications for use, or the fundamental scientific technology of the predicate device. Furthermore, the residual risk is broadly acceptable because the identified and verified control measures eliminate or reduce the potential effects of failure.
Both ARCHITECT 2nd Generation Testosterone (K152155) and ARCHITECT SHBG labeling will be updated to include the %FTI or %FAI expected values generated using these assays.
§ 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.