(264 days)
Not Found
No
The summary describes a standard immunoassay system and reagent kit, focusing on chemical and analytical performance characteristics. There is no mention of AI or ML in the intended use, device description, or performance studies.
No
This device is an in vitro diagnostic (IVD) test used for the detection of pregnancy by measuring Beta-hCG levels, rather than providing therapy or treatment.
Yes
The Alinity i Total ß-hCG assay is used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy, which is a diagnostic purpose.
No
The device description clearly outlines a physical analyzer system (Alinity i System) that uses hardware components (SCM, RSM, processing module) and a reagent kit to perform the immunoassay. This is not a software-only device.
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 Alinity i Total ß-hCG assay is used for the "quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma". This indicates that the device is intended to be used in vitro (outside the body) to examine human specimens (serum and plasma) for diagnostic purposes (early detection of pregnancy).
- Device Description: The description of the Alinity i Total ß-hCG Reagent Kit and the Alinity i System confirms that they are used to perform laboratory tests on human samples.
- Performance Studies: The detailed performance studies (Precision, Linearity, Limits of Detection, Specificity, Method Comparison, etc.) are typical evaluations performed for IVD devices to demonstrate their analytical performance and suitability for diagnostic use.
- Predicate Device: The mention of predicate devices (ARCHITECT Total ß-hCG and ARCHITECT i System) with K numbers (indicating previous FDA clearances) further supports that this device is in the category of IVDs.
The definition of an IVD generally includes reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. This device fits that description by measuring ß-hCG in human samples for the early detection of pregnancy.
N/A
Intended Use / Indications for Use
Alinity i Total ß-hCG Reagent Kit
The Alinity i Total ß-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.
Alinity i System
The Alinity i System is a fully automated immunoassay analyzer allowing random and continuous access, as well as priority and automated retest processing using chemiluminescent microparticle immunoassay (CMIA) technology. CMIA technology is used to determine the presence of antibodies, and analyte in samples.
Product codes (comma separated list FDA assigned to the subject device)
DHA, JJE
Device Description
The Alinity i Total ß-hCG Reagent Kit is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma. The kit contains microparticles coated with anti-ß-hCG (mouse, monoclonal) in TRIS buffer with protein (bovine) stabilizers and antimicrobial agents, and anti-ß-hCG (mouse, monoclonal) acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizers and an antimicrobial agent. The calibrators (Cal A through Cal F) are prepared in human serum with sodium azide as a preservative, and are referenced to the WHO 4th International Reference Standard 75/589 for ß-hCG. The kit is intended for use with the Alinity i System.
The Alinity i System (also known as the Alinity i analyzer) is a fully automated immunoassay analyzer that uses chemiluminescent microparticle immunoassay (CMIA) detection technology to measure the concentration of analytes in samples. It has a modular design, allowing multiple processing modules to be joined. Each Alinity analyzer consists of a System Control Module (SCM), Reagent and Sample Manager (RSM), and a processing module. The system allows random and continuous access, as well as priority and automated retest processing. The process involves combining sample and anti-ß-hCG coated paramagnetic microparticles, incubation, washing, adding anti-ß-hCG acridinium-labeled conjugate, incubation, another wash cycle, and finally adding Pre-Trigger and Trigger Solutions to measure the resulting chemiluminescent reaction as relative light units (RLUs). There is a direct relationship between the amount of ß-hCG in the sample and the RLUs detected. The system also includes a dedicated pretreatment lane and dedicated wash cups for sample and reagent pipettors.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
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 (study type, sample size, AUC, MRMC, standalone performance, key results)
Within-Laboratory Precision (20-Day):
Study Type: Precision study based on CLSI document EP05-A2.
Sample Size: 398 to 400 replicates across different panel members.
Key Results: The within-laboratory (total) imprecision (within-run, between-run, and between-day) was ≤ 10 %CV for the Low, Medium, and High Controls (target range from 25 to 5000 mIU/mL). The highest observed %CV was 7.6% for sample B (mean 5.33 mIU/mL).
Additional Precision Data: Nine samples assayed in replicates of at least 22 on 2 runs in a single day on 2 instruments and reagent lots. The Alinity i Total ß-hCG assay demonstrated acceptable precision.
Linearity:
Study Type: Linearity evaluation based on CLSI document EP06-A.
Key Results: The assay was linear across the range of 2.42 to 15,000 mIU/mL.
Limits of Blank, Detection, and Quantitation (LoB, LoD, and LoQ):
Study Type: LoB, LoD, and LoQ study based on CLSI document EP17-A2.
Sample Size: n ≥ 60 replicates of zero-analyte samples for LoB; n > 60 replicates of low-analyte level samples for LoD; n ≥ 60 replicates of low-analyte level samples for LoQ.
Key Results: LoB ranged from 0.00 to 0.20 mIU/mL. LoD ranged from 0.16 to 0.67 mIU/mL. LoQ ranged from 1.10 to 2.42 mIU/mL (at 25% TEa).
Specificity (Cross-Reactivity):
Study Type: Evaluation of potential interference from cross-reactants based on CLSI document EP07-A2.
Key Results: Cross-reactivity was less than 10% for each cross-reactant (TSH, LH, FSH, hCG alpha subunit) when evaluating samples with ß-hCG concentration > 25 mIU/mL. The assay is not susceptible to interference from these cross-reactants.
Potentially Interfering Substances – Bilirubin, Hemoglobin, Triglycerides, and Total Protein:
Study Type: Evaluation of potential interference from endogenous substances based on CLSI document EP07-A2.
Key Results: Percent interference for Total ß-hCG samples was ≤ 10% for each potentially interfering endogenous substance (bilirubin, hemoglobin, triglycerides, total protein) at specified levels. The assay is not susceptible to interference effects from these interferents.
Potentially Interfering Exogenous Substances - Drugs:
Study Type: Evaluation of potential interference from exogenous substances based on CLSI document EP07-A2.
Key Results: Percent interference for Total ß-hCG samples was ≤ 10% for each potentially interfering exogenous substance at specified levels. The Alinity i Total ß-hCG assay is not susceptible to interference effects from these interferents.
Method Comparison (Quantitative):
Study Type: Comparison study using serum specimens based on CLSI EP09-A3 with Weighted Deming regression.
Sample Size: 210 serum samples.
Key Results: Correlation Coefficient of 1.00, Intercept of 0.12, Slope of 1.01. Concentration Range: 2.40 – 14,866.03 mIU/mL.
Method Comparison (Qualitative):
Study Type: Concordance analysis.
Sample Size: 381 Alinity i Total ß-hCG qualitative results.
Key Results: Concordance table provided. Discordant specimens: 24.42 mIU/mL (Alinity i) vs 26.41 mIU/mL (ARCHITECT); 5.25 mIU/mL (Alinity i) vs 4.58 mIU/mL (ARCHITECT); 5.06 mIU/mL (Alinity i) vs 4.62 mIU/mL (ARCHITECT); 5.16 mIU/mL (Alinity i) vs 4.80 mIU/mL (ARCHITECT). The method comparison data was acceptable.
Within-Assay Sample Carryover:
Study Type: Sample carryover evaluation.
Key Results: The difference between protected and unprotected samples was 0.22 mIU/mL, indicating the assay is not susceptible to within-assay sample carryover.
Tube Type Equivalency (Matrix Comparison):
Study Type: Evaluation of acceptable blood collection tube types.
Sample Size: 43 unique positive pregnant donor's serum specimens + 45 unique female non-pregnant whole blood specimens.
Key Results: The following blood collection tube types are acceptable: Serum (separator tube), Dipotassium EDTA, Tripotassium EDTA, Lithium heparin, Lithium heparin (separator tube), Sodium heparin.
Expected Values Non-Pregnant (Reference Range):
Study Type: Determination of reference interval.
Sample Size: 128 pre-menopausal, 140 peri-menopausal, and 137 post-menopausal females.
Key Results: Reference interval for pre-menopausal (
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines extending from the profiles.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 October 23, 2017
ABBOTT LABORATORIES LINDA SOHN REGULATORY AFFAIRS SENIOR SPECIALIST DEPT. 9AA. BLDG AP8 100 ABBOTT PARK ROAD ABBOTT PARK, IL 60064
Re: K170317
Trade/Device Name: Alinity i Total ß-hCG Reagent Kit Alinity i System Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: II Product Code: DHA, JJE Dated: September 19, 2017 Received: September 20, 2017
Dear Linda Sohn:
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
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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/ResourcesforYou/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,
Kellie B. Kelm -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
2
Indications for Use
510(k) Number (if known) K170317
Device Name Alinity i Total ß-hCG Reagent Kit Alinity i System
Indications for Use (Describe) Alinity i Total ß-hCG Reagent Kit
The Alinity i Total ß-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.
Alinity i System
The Alinity i System is a fully automated immunoassay analyzer allowing random and continuous access, as well as priority and automated retest processing using chemiluminescent microparticle immunoassay (CMIA) technology. CMIA technology is used to determine the presence of antibodies, and analyte in samples.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
| Representation Use (Part 201, CERCLA, Subject Property) | On-Site Service Use (21E, CERCLA) |
|---|---|
| ----------------------------------------------------------------------- | ------------------------------------------------- |
Prescription Use (Part 21 CFR 801 Subpart D)
| | Over-The-Counter Use (21 CFR 801 Subpart C)
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3
K170317
510(k) Summary (Summary of Safety and Effectiveness)
This 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.
I. Applicant Name
Abbott Laboratories Dept. 09AA, AP8-1 100 Abbott Park Road Abbott Park, IL 60064
Primary contact person for all communications:
Linda Sohn, ADD, Project Manager, Regulatory Affairs Phone: (224) 667-4846 Fax: (224) 667-4836 E-mail: Linda.Sohn@abbott.com
Secondary contact person for all communications:
Amy Ghering, Associate Director, Regulatory Affairs Phone: (224) 668-6934 Fax: (224) 667-4836 E-mail: Amy.Ghering@abbott.com
Date Summary Prepared: January 31, 2017.
Date Summary Revised: October 23, 2017.
4
II. Device Name
Alinity i Total β-hCG Reagent Kit Alinity i System
Alinity i Total β-hCG Reagent Kit
Device Classification: Class II Classification Name: Human chorionic gonadotropin (HCG) test system Governing Regulation: 862.1155 Product Code: DHA
Alinity i System
Device Classification: Class I Classification Name: Discrete photometric chemistry analyzer for clinical use Governing Regulation: 21 CFR 862.2160 Product Code: JJE
III. Predicate Device
Reagents
ARCHITECT Total β-hCG (K983424)
Instrument
ARCHITECT i System (K983212)
5
IV. Description of Device
A. Reagents
Kit Contents
Volumes (mL) listed in the table below indicate the volume per cartridge:
| REF | 07P5120 | 07P5130 |
|---|---|---|
| Tests per cartridge | 100 | 600 |
| Number of cartridges per kit | 2 | 2 |
| Tests per kit | 200 | 1200 |
| Microparticles | 6.6 mL | 32.1 mL |
| Conjugate | 4.2 mL | 9.0 mL |
- . Microparticles: Anti-ß-hCG (mouse, monoclonal) coated microparticles in TRIS buffer with protein (bovine) stabilizers. Minimum concentration: 0.06% solids. Preservatives: antimicrobial agents.
- Conjugate: Anti-ß-hCG (mouse, monoclonal) acridinium-labeled conjugate in . MES buffer with protein (bovine) stabilizers. Minimum concentration: 2.9 µg/mL. Preservative: antimicrobial agent.
B. Calibrators
Contents
Cal A through Cal F prepared in human serum. Preservative: Sodium azide.
| | | Total β-hCG
Concentration | |
|------------|------------|------------------------------|--------|
| Calibrator | Quantity | (mIU/mL) | (IU/L) |
| A | 1 x 3.0 mL | 0 | 0 |
| B | 1 x 3.0 mL | 10 | 10 |
| C | 1 x 3.0 mL | 250 | 250 |
| D | 1 x 3.0 mL | 1000 | 1000 |
| E | 1 x 3.0 mL | 7500 | 7500 |
| F | 1 x 3.0 mL | 15,000 | 15,000 |
6
Standardization Statement
The calibrators are manufactured gravimetrically and referenced to the World Health Organization (WHO) 4th International Reference Standard 75/589 for β-hCG at each concentration level.
C. Controls
Contents
The controls recommended for use with the Alinity i Total ß-hCG assay were cleared under K983424 with the name ARCHITECT Total β-hCG Controls. The Total ß-hCG assay on the Alinity i System uses the same ARCHITECT Total ß-hCG Controls with no change to formulation or container. Therefore, Abbott is not seeking a new clearance for the Alinity i Total ß-hCG Controls in this submission because only the branding has changed.
Control L. Control M. and Control H contain hCG prepared in human serum. Preservative: Sodium azide.
The following target concentration ranges may be used for individual replicate control specifications on the Alinity i analyzer:
| Control | Quantity | Total ß-hCG
Concentration
(mIU/mL)
(IU/L) | Range
(mIU/mL)
(IU/L) |
|-----------|------------|----------------------------------------------------|-----------------------------|
| Control L | 1 x 8.0 mL | 25 | 16 – 34 |
| Control M | 1 x 8.0 mL | 750 | 488 - 1013 |
| Control H | 1 x 8.0 mL | 5000 | 3250 - 6750 |
7
D. Alinity i System
The Alinity i System (also known as the Alinity i analyzer) uses chemiluminescent microparticle immunoassay (CMIA) detection technology to measure the concentration of analytes in samples. The modular design of the Alinity family of analyzers allows multiple processing modules, which perform all sample processing activities, to be physically joined to form a single workstation or system. The selection of processing module(s) determines the configuration of the system.
Each Alinity analyzer, regardless of type, consists of a System Control Module (SCM), Reagent and Sample Manager (RSM), and processing module.
E. Principles of the Procedure
The Alinity i Total ß-hCG assay is a two-step immunoassay for the quantitative and qualitative determination of ß-hCG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.
The Alinity i analyzer processes Total ß-hCG test orders as follows:
-
- Sample and anti-ß-hCG coated paramagnetic microparticles are combined and incubated.
-
- The ß-hCG present in the sample binds to the anti-ß-hCG coated microparticles.
-
- The mixture is washed.
-
- Anti- B-hCG acridinium-labeled conjugate is added to create a reaction mixture and incubated.
-
- Following a wash cycle, Pre-Trigger and Trigger Solutions are added.
-
- The resulting chemiluminescent reaction is measured as relative light units (RLUs). There is a direct relationship between the amount of ß-hCG in the sample and the RLUs detected by the system optics.
8
V. Intended Use of the Device
The Alinity i Total β-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.
The Alinity i System is a fully automated immunoassay analyzer allowing random and continuous access, as well as priority and automated retest processing using chemiluminescent microparticle immunoassay (CMIA) technology. CMIA technology is used to determine the presence of antigens, antibodies, and analytes in samples.
9
VI. Comparison of Technological Characteristics
The Alinity i Total β-hCG assay (candidate assay) utilizes a chemiluminescent microparticle immunoassay (CMIA) methodology for the quantitative and qualitative determination of Total ß-hCG and is intended for use on the Alinity i analyzer.
The Alinity i System is a fully automated immunoassay analyzer allowing random and continuous access, as well as priority and automated retest processing using chemiluminescent microparticle immunoassay (CMIA) technology. CMIA technology is used to determine the presence of antigens, antibodies, and analytes in samples.
The similarities and differences between the candidate assay and the predicate assay and the candidate instrument and the predicate instrument are presented in Tables 1 through 4 starting on page 8.
10
Comparison of Candidate Alinity i Total β-hCG to Predicate ARCHITECT Total β-hCG
Table 1: Reagent Similarities
| Candidate Assay | Predicate Assay (K983424) | |
|---|---|---|
| Characteristics | Alinity i Total β-hCG | ARCHITECT Total β-hCG |
| Technical Characteristics | ||
| Methodology | Chemiluminescent Microparticle Immunoassay | |
| (CMIA) | Same | |
| Intended Use/ | ||
| Indications for Use | The Alinity i Total β-hCG assay is a | |
| chemiluminescent microparticle immunoassay | ||
| (CMIA) used for the quantitative and qualitative | ||
| determination of beta-human chorionic gonadotropin | ||
| (β-hCG) in human serum and plasma for the early | ||
| detection of pregnancy on the Alinity i analyzer. | The ARCHITECT Total β-hCG assay is a | |
| Chemiluminescent Microparticle Immunoassay | ||
| (CMIA) for the quantitative and qualitative | ||
| determination of beta human chorionic gonadotropin | ||
| (β-hCG) in human serum and plasma for the early | ||
| detection of pregnancy. | ||
| Specific Analyte | ||
| Detected | Total β-hCG | Same |
| Formulation | Microparticles – Anti-β-hCG (mouse, monoclonal) | |
| coated microparticles in TRIS buffer with protein | ||
| (bovine) stabilizers. Minimum concentration: 0.06% | ||
| solids. Preservatives: antimicrobial agents. |
Conjugate - Anti-β-hCG (mouse, monoclonal)
acridinium-labeled conjugate in MES buffer with
protein (bovine) stabilizers. Minimum concentration:
2.9 µg/mL. Preservative: antimicrobial agent. | Same |
| Assay Protocol | 2-step | Same |
11
| Supplement to K170317 Alinity i Total β-hCG 510(k) October 2017 | Cha Cal
Typ Spe Per Wit
Pre | | | | | |
| ----------------------------------------------------------------- | ------------------------------------------- | -- | -- | -- | -- | -- |
|---|
Table 1: Reagent Similarities
| Candidate Assay | Predicate Assay (K983424) | |
|---|---|---|
| Characteristics | Alinity i Total β-hCG | ARCHITECT Total β-hCG |
| Calibration Curve | ||
| Type | 6-point | |
| 4 Parameter Logistic Curve fit data reduction method | ||
| (4PLC, Y-weighted) | Same | |
| Specimen Type | Serum and plasma | Same |
| Performance Characteristics | ||
| Within-Laboratory | ||
| Precision (20-Day) | The within-laboratory (total) imprecision (within-run, | |
| between-run, and between-day) was ≤ 10 %CV for | ||
| the Low, Medium, and High Controls (target range | ||
| from 25 - 5000 mIU/mL). | Same | |
| Linearity | This assay is linear across the measuring interval of | |
| 2.42 to 15,000 mIU/mL (2.42 to 15,000 IU/L). | The assay range is 1.2 to 15,000 mIU/mL. | |
| Measuring Interval | The measuring interval is 2.42 to 15,000.00 mIU/mL | |
| (2.42 to 15,000.00 IU/L). | ||
| Note: The measuring interval is defined as the range | ||
| of values in mIU/mL (IU/L) which meets the limits of | ||
| acceptable performance for bias, imprecision, and | ||
| linearity. The inputs to the measuring interval include | ||
| precision, linearity, and the quantitation limit. | The ARCHITECT Total β-hCG assay was designed | |
| to have an analytical sensitivity of ≤ 1.2 mIU/mL, | ||
| with an Assay Range of 1.2 mIU/mL to 15,000 | ||
| mIU/mL. | ||
| Detection Limit: | ||
| Limit of Detection | ||
| (LoD) and | ||
| Limit of | ||
| Quantitation (LoQ) | • The highest observed LoD value was | |
| 0.67 mIU/mL (IU/L). | ||
| • The highest observed LoQ value at 25% TEa | ||
| was 2.42 mIU/mL (IU/L). | The analytical sensitivity is ≤ 1.2 mIU/mL. | |
| Note: The LoQ was not measured for ARCHITECT. |
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| Table 1: Reagent Similarities |
|---|
| ------------------------------- |
| Characteristics | Candidate Assay
Alinity i Total β-hCG | Predicate Assay (K983424)
ARCHITECT Total β-hCG |
|----------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------|
| Analytical
Specificity (Cross
Reactivity, FSH,
LH, TSH, hCG
alpha subunit) | The cross reactivity was calculated as a difference in
the measured concentration of β-hCG and was shown
to be within or equal to ±10% for each cross reactant. | Same |
| Potentially
Interfering
Substances
(Bilirubin,
Hemoglobin,
Triglycerides, and
Total Protein) | Potential interference from bilirubin, hemoglobin,
total protein, and triglycerides showed a difference in
measured concentration of β-hCG within or equal to
±10% at the levels indicated below:
• Bilirubin ≤ 20 mg/dL
• Hemoglobin ≤ 500 mg/dL
• Total Protein ≤ 12 g/dL
• Triglycerides ≤ 3000 mg/dL | Same |
| Within-Assay
Sample Carryover | Carryover from a sample containing
1,000,000 mIU/mL β-hCG to an adjacent 0 mIU/mL
β-hCG sample was less than 7.5 mIU/mL β-hCG. | Same |
13
| Characteristics | Candidate Assay
Alinity i Total β-hCG | Predicate Assay (K983424)
ARCHITECT Total β-hCG |
|--------------------|------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------|
| Tube Types | Serum
• Serum
• Serum Separator | Human Serum
• Serum
• Serum Separator |
| | Plasma
• Dipotassium EDTA
• Tripotassium EDTA
• Lithium heparin
• Lithium heparin plasma separator
• Sodium heparin | Plasma
• Lithium Heparin
• Sodium Heparin
• Potassium EDTA |
| Use of Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
Table 1: Reagent Similarities
14
| Characteristics | Candidate Assay
Alinity i Total β-hCG | Predicate Assay (K983424)
ARCHITECT Total β-hCG |
|------------------------------------|------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Container and Closure Materials | | |
| Container | Polypropylene (PP)
Black colorant | High Density Polyethylene (HDPE)
• Natural (microparticles)
• Black colorant (conjugate only) |
| Closure Material
(contact only) | Sealed integrated black polyolefin elastomer septum
and moved the product contact from the cap to the septum. | F217 cap liner, Polyethylene Foam between
Low-Density Polyethylene liners, within PP cap;
white polyolefin elastomer septum (customer-placed
upon first use) |
Table 2: Reagent Differences
15
Comparison of the Candidate Alinity i System to the Predicate ARCHITECT i System
Table 3: Instrument Similarities
| Candidate Device | Predicate Device | |
|---|---|---|
| Category | Alinity i System | ARCHITECT i System (K983212) |
| Intended | ||
| Use/Indication for | ||
| Use | The Alinity i System is a fully automated, | |
| random/continuous access, immunoassay analyzer, | ||
| which utilizes chemiluminescent microparticle | ||
| immunoassay (CMIA) detection technology for both | ||
| large and small molecular weight analytes. | Same | |
| Detection | ||
| Technology | Chemiluminescent microparticle immunoassay | |
| (CMIA) | Same | |
| Sample Handling | Robotic sample handler (RSH) transport system that | |
| has random and continuous access to samples. | ||
| Autoretest Capability | Same | |
| Priority and batch sample loading | Same | |
| Reagent Handling | The on-board storage area cooler and the septum cap | |
| provide evaporation control. Continuous Reagent | ||
| Access. | Same | |
| User Interface | Continuous access to Trigger and Pre-Trigger and | |
| reconstituted Wash Buffer solutions are stored | ||
| on-board. | Same |
16
| Table 4: Instrument Differences | ||
|---|---|---|
| -- | --------------------------------- | -- |
| Characteristics | Candidate Device
Alinity i System | Predicate Device
ARCHITECT i System (K983212) |
|--------------------------------|------------------------------------------------------------------|--------------------------------------------------------------------------|
| Dedicated
Pretreatment Lane | Includes dedicated pretreatment lane | N/A |
| Dedicated Wash
Station | Dedicated wash cups for sample pipettor and reagent
pipettors | Sample pipettor and reagent pipettors do not have
dedicated wash cups |
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VII. Summary of Nonclinical Performance
Within-Laboratory Precision (20-Day)
Precision was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP05-A2.
A summary of results is presented below:
| | | | Within-Run
(Repeatability) | | Within-Laboratory (Total)a | |
|-----------------|-----|--------------------------|-------------------------------|-----|--------------------------------|--------------------|
| Panel
Member | n | Mean
mIU/mL
(IU/L) | SD | %CV | SD (Rangeb) | %CV
(Rangeb) |
| 1 | 398 | 25.35 | 0.844 | 3.3 | 1.293
(1.154-1.416) | 5.1
(4.6-5.5) |
| 2 | 399 | 765.76 | 11.099 | 1.4 | 14.809
(11.542-17.734) | 1.9
(1.5-2.3) |
| 3 | 399 | 4971.95 | 73.079 | 1.5 | 110.173
(85.849-131.611) | 2.2
(1.7-2.7) |
| B | 400 | 5.33 | 0.269 | 5.0 | 0.408
(0.357 - 0.463) | 7.6
(7.1 - 8.2) |
| C | 400 | 165.16 | 3.680 | 2.2 | 4.583
(4.386-5.639) | 2.9
(2.7 - 3.3) |
| D | 399 | 9421.08 | 194.693 | 2.1 | 265.152
(2.14698 - 339.368) | 2.8
(2.2 - 3.5) |
| E | 400 | 13069.37 | 314.717 | 2.4 | 412.842
(372.088 - 484.306) | 3.2
(2.8 - 3.6) |
ª Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV for each reagent lot and instrument combination.
The precision of the Alinity i Total ß-hCG assay was considered acceptable if the within laboratory (total) imprecision (within run, between run, and between day) was ≤ 10 %CV for the Low, Medium, and High Controls (target range from 25 to 5000 mIU/mL).
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Nine samples were assayed in replicates of at least 22 on 2 runs in a single day on 2 instruments and reagent lots. The number of replicates within negative and positive concentrations are shown in the table below.
| Mean
Concentration
(mIU/mL)
(IU/L) | n | Negative
≤ 5 mIU/mL
(IU/L) | > 5 and
60 replicates of low-analyte level samples.
The LoQ was determined from n ≥ 60 replicates of low-analyte level samples and is defined as the lowest concentration at which a maximum TEa (Total Error allowable) of 25% was met.
Measuring Interval
The measuring interval of the Alinity i Total ß-hCG assay is 2.42 to 15,000.00 mIU/mL (2.42 to 15,000.00 IU/L).
Specificity (Cross-Reactivity)
Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2. The cross-reactivity was calculated as a percent interference for samples with a ß-hCG concentration > 25 mIU/mL (> 25 IU/L) and was shown to be less than 10% for each cross-reactant.
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The Alinity i Total ß-hCG assay is not susceptible to interference from the cross-reactants when evaluated at the levels presented in the table below:
| Cross-Reactant | Cross-Reactant Level |
|---|---|
| TSH | ≤ 100 μIU/mL |
| LH | ≤ 500 mIU/mL |
| FSH | ≤ 500 mIU/mL |
| hCG alpha subunit | ≤ 500 mIU/mL |
Potentially Interfering Substances – Bilirubin, Hemoglobin, Triglycerides, and Total Protein
Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2. Interference effects were assessed by comparing test samples containing potentially-interfering endogenous substances to reference samples. The percent interference for Total ß-hCG samples was shown to be less than or equal to 10% for each potentially interfering endogenous substance.
The Alinity i Total ß-hCG assay is not susceptible to interference effects from the following interferents at the interferent levels listed in the table below:
| Interferent | Interferent Level |
|---|---|
| Conjugated Bilirubin | ≤ 20 mg/dL |
| Unconjugated Bilirubin | ≤ 20 mg/dL |
| Hemoglobin | ≤ 500 mg/dL |
| Triglycerides | ≤ 3000 mg/dL |
| Total Protein | ≤ 12 g/dL |
Potentially Interfering Exogenous Substances - Drugs
Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2. The percent interference for Total ß-hCG samples was shown to be less than or equal to 10% for each potentially interfering exogenous substance.
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| Interferent | Target Interferent Level |
|---|---|
| Acetaminophen | ≤ 20 mg/dL |
| Acetylcysteine | ≤ 167 mg/dL |
| Acetylsalicylic Acid | ≤ 66 mg/dL |
| Ampicillin | ≤ 53 mg/L |
| Ascorbic Acid | ≤ 6 mg/dL |
| Atropine | ≤ 20 mg/dL |
| Ca-Dobesilate | ≤ 200 mg/L |
| Caffeine | ≤ 20 mg/dL |
| Cyclosporine | ≤ 5 mg/L |
| Cefoxitin | ≤ 660 mg/L |
| Doxcycline | ≤ 30 mg/L |
| Ethanol | ≤ 1% |
| EDTA | ≤ 80 mg/dL |
| Ibuprofen | ≤ 50 mg/dL |
| Levodopa | ≤ 20 mg/L |
| Methyldopa | ≤ 15 mg/L |
| Metronidazole | ≤ 120 mg/L |
| Phenylbutazone | ≤ 400 mg/L |
| Rheumatoid Factor (RF) | ≤ 194 IU/L |
| Rifampicin | ≤ 64 mg/L |
| Sodium Heparin | ≤ 3000 U/L |
| Sodium Salicylic Acid | ≤ 70 mg/dL |
| Theophylline | ≤ 40 mg/L |
| Gentisic Acid | ≤ 20 mg/dL |
The Alinity i Total ß-hCG assay is not susceptible to interference effects from the following interferents at the interferent levels listed in the table below:
Method Comparison
Quantitative
A study was performed using serum specimens based on guidance from CLSI EP09-A3 using the Weighted Deming regression method.
22
The data summary below presents that data with all outliers included.
| | Sample
Type | Units | N | Correlation
Coefficient | Intercept | Slope | Concentration
Range |
|---------------------------------------------------------|----------------|------------------|-----|----------------------------|-----------|-------|------------------------|
| Alinity i Total
β-hCG vs
ARCHITECT
Total β-hCG | Serum | mIU/mL
(IU/L) | 210 | 1.00 | 0.12 | 1.01 | 2.40 – 14,866.03 |
Qualitative
A total of 381 Alinity i Total ß-hCG qualitative results were analyzed for concordance with the ARCHITECT Total ß-hCG assay. Samples below the lower limit of the measuring interval were included in the analysis.
| | ARCHITECT Total β-hCG
mIU/mL (IU/L) | | |
|----------------------------------------|----------------------------------------|--------------------|--------------------|
| Alinity i Total β-hCG
mIU/mL (IU/L) | Positive
≥ 25.00 | > 5.00 - 5.00 - 55 | 137 | post-menopausal* |