(170 days)
No
The summary describes a standard immunoassay and its performance characteristics. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis focuses on chemical reactions, light measurement, and statistical analysis of results against a cut-off.
No
This device is a qualitative, fully automated, chemiluminescent immunoassay used for the detection of IgG antibodies to aid in determining the risk for heparin-induced thrombocytopenia (HIT). It provides diagnostic information rather than treatment.
Yes
The device is described as a "qualitative, fully automated, chemiluminescent immunoassay (CIA) for the detection of IgG antibodies" that "aids in determining the risk for heparin induced thrombocytopenia (HIT) when used in conjunction with other laboratory and clinical findings." This clearly indicates its purpose is to provide diagnostic information about a patient's condition.
No
The device is a chemiluminescent immunoassay kit consisting of physical reagents (magnetic particles, assay buffer, tracer, sample diluent, calibrators, controls) used on a specific instrument (ACL AcuStar). While the instrument likely contains software for operation and data processing, the device itself is a physical kit, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the assay is for use in human plasma and serum to detect IgG antibodies that react with Platelet Factor 4 (PF4) when complexed to heparin. This is a test performed on a biological sample taken from the human body.
- Purpose: The result aids in determining the risk for heparin induced thrombocytopenia (HIT) when used in conjunction with other laboratory and clinical findings. This indicates the test is used to provide information about a patient's health status.
- Setting: The assay is for use "in a laboratory setting," which is a common environment for IVD testing.
- Device Description: The description details the reagents and components used to perform the test on the sample, which is characteristic of an IVD kit.
- Performance Studies: The document includes performance studies like method comparison and cut-off determination, which are standard for demonstrating the analytical and clinical performance of an IVD.
- Predicate Device: A predicate device (K071255) is listed, which is another IVD used for similar testing.
- Reference Device: A reference device (Serotonin Release Assay - SRA) is mentioned, which is a common reference method for HIT testing.
All of these factors align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
HemosIL AcuStar HIT-IgG(PF4-H) is a qualitative, fully automated, chemiluminescent immunoassay (CIA) for the detection of IgG antibodies that react with Platelet Factor 4 (PF4) when complexed to heparin. The assay is for use in human 3.2% or 3.8% citrated plasma and serum on the ACL AcuStar instrument in a laboratory setting.
The result provided by the assay should be interpreted as either positive or negative based on the assay cut-off (1.00 U/mL). The positive or negative result aids in determining the risk for heparin induced thrombocytopenia (HIT) when used in conjunction with other laboratory and clinical findings.
Anti-PF4/Heparin antibodies are commonly found in patients with HIT. For use in adult population suspected of HIT. Not for use in isolation to exclude HIT.
HemosIL AcuStar HIT Controls are for the quality control of the HemosIL AcuStar HIT-IgG(PF4-H) assay as performed on the ACL AcuStar.
For prescription use.
Product codes (comma separated list FDA assigned to the subject device)
LCO, GGN
Device Description
The HemosIL AcuStar HIT-IgG(PF4-H) assay is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with PF4 complexed to polyvinyl sulfonate (PVS) which capture, if present, the PF4/Heparin antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgG antibody is added and may bind with the captured PF4/Heparin IgG on the particles. After a second incubation, magnetic separation, and a wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL AcuStar optical system. The RLUs are directly proportional to the PF4/Heparin IgG concentration in the sample.
The HemosIL AcuStar HIT-IgG(PF4-H) kit consists of:
R HIT-IgG(PF4-H) Cartridge for 25 determinations: Cartridge containing 1 vial of magnetic particle suspension coated with PF4/PVS complex, 1 vial of assay buffer, 1 vial of tracer consisting of an mAb anti-human IgG antibody labeled with isoluminol, and 1 vial of sample diluent used for the regular predilution of the sample. The reagents are in a phosphate or Tris buffer containing bovine serum albumin, bovine fetal serum, PF4/PVS complex, mouse monoclonal IgG, stabilizers, and preservative.
C1 HIT-IgG(PF4-H) Calibrator 1: Barcoded tube of a solution with humanized mAb anti-PF4-Heparin in Tris buffer containing bovine serum albumin, stabilizers and preservative.
C2 HIT-IgG(PF4-H) Calibrator 2: Barcoded tube of a solution with humanized mAb anti-PF4-Heparin in Tris buffer containing bovine serum albumin, stabilizers, and preservative.
The calibrators are lot specific and they cannot be used with other lots of reagents.
The Low and High HIT Controls are prepared by means of a dedicated process and contain different concentrations of humanized monoclonal anti-PF4-Heparin.
Low HIT Control: Control intended for the assessment of precision and accuracy of the HemosIL AcuStar HIT-IgG(PF4-H) assay below the cut-off.
High HIT Control: Control intended for the assessment of precision and accuracy of the HemosIL AcuStar HIT-IgG(PF4-H) assay above the cut-off.
Use of both controls is recommended for a complete quality control program.
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
Adult population suspected of HIT.
Intended User / Care Setting
Laboratory setting.
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
Cut-Off Determination:
- Sample size: Eighty-seven (87) citrated plasma samples.
- Data source: Hospitalized patients exposed to heparin with clinical signs consistent with HIT.
- Annotation protocol: Samples were tested by the hospital with the Serotonin Release Assay (SRA). 45 samples were SRA positive and 42 were SRA negative. A Receiver Operating Characteristics (ROC) analysis was performed to establish the cut-off.
Multicenter Method Comparison:
- Sample size: 802 samples for comparison with predicate device; 790 samples for comparison with SRA.
- Data source: Samples from patients exposed to heparin that showed HIT related symptoms.
- Annotation protocol: Samples were analyzed in singlicate; no spiked samples were used in this study. Comparison was performed against the predicate device (Zymutest HIA IgG) and the Serotonin Release Assay (SRA).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Multi-Reagent Cartridge Lot Precision:
- Study Type: Internal precision study.
- Sample Size: Five (5) plasma samples (two native, three prepared pools). Each material was tested in duplicate, twice a day for 22 days, for a total of 88 replicates per level per lot.
- Key Results: Precision reported as %CV (coefficient of variation) for "Within Run (Repeatability)" and "Total (Within Device)" across three reagent lots. Aggregated data included Lot-to-Lot Variability %CV. %CV ranged from 4.1% to 13.0% for repeatability and 4.4% to 13.8% for total within device. Lot-to-Lot Variability %CV ranged from 11.8% to 19.6%.
Cut-off Precision:
- Study Type: Internal precision study.
- Sample Size: Three (3) plasma samples (one negative sample pool, three unadulterated positive samples). Each sample analyzed with three reagent lots on two ACL AcuStar instruments over five days, two runs per day, three replicates per run (N=360 per sample level).
- Key Results: Precision reported as SD and %CV for Within-Run, Between-Run, Between-Day, Between-Lot, Between-Instrument, Between-Operator, and Total variability. Total %CV ranged from 6.4% to 10.0%.
Multi-Control Lot Precision:
- Study Type: Internal precision study.
- Sample Size: Three (3) different lots of HemosIL AcuStar HIT Controls (low and high). Each level tested in duplicate, twice a day for 20 days, for a total of 80 replicates per level per lot.
- Key Results: Precision reported as %CV for "Within Run (Repeatability)" and "Total (Within Device)". %CV ranged from 2.8% to 4.6% for repeatability and 5.0% to 7.0% for total within device.
Multi-Calibrator Lot Precision:
- Study Type: Internal precision study.
- Sample Size: Three (3) different lots of HemosIL AcuStar HIT-IgG(PF4-H) Calibrator. Each calibrator lot tested in duplicate, twice a day for 20 days, for a total of 80 replicates per lot.
- Key Results: Precision reported as %CV for "Within Run (Repeatability)" and "Total (Within Device)". %CV ranged from 2.2% to 3.9% for repeatability and 3.1% to 6.3% for total within device.
Multi-Reagent Cartridge and Control Lot Reproducibility:
- Study Type: Reproducibility study.
- Sample Size: Three (3) patient citrated plasma sample pools (2 positive, 1 negative). Each material tested in triplicate, twice a day for 5 days, for a total of 30 replicates per level.
- Key Results: Precision reported as SD and %CV for Repeatability (within-run), Between-Run, Between-Day, Between Site, and Reproducibility (Total) for three reagent lots. Total %CV ranged from 7.2% to 10.7%.
Cut-Off Determination:
- Study Type: ROC analysis.
- Sample Size: 87 citrated plasma samples (45 SRA positive, 42 SRA negative).
- Key Results: Cut-off established at 1.00 U/mL (94.3% Agreement; 95% CI = 87.2% - 97.5%).
Multicenter Method Comparison (HemosIL AcuStar HIT-IgG(PF4-H) vs. Predicate Device (Zymutest HIA IgG)):
- Study Type: Method Comparison.
- Sample Size: n=802 samples from patients exposed to heparin with HIT symptoms.
- Key Results:
- PPA (Positive Percent Agreement): 35% (26/74) with Wilson 95% CI (25% - 47%).
- NPA (Negative Percent Agreement): 99% (719/728) with Wilson 95% CI (98% - 99%).
- Total Percent Agreement: 93% (745/802) with Wilson 95% CI (91% - 94%).
Multicenter Method Comparison (HemosIL AcuStar HIT-IgG(PF4-H) vs. SRA):
- Study Type: Method Comparison.
- Sample Size: n=790 samples from patients exposed to heparin with HIT symptoms.
- Key Results:
- PPV (Positive Predictive Value): 76% (26/34) with Wilson 95% CI (60% - 88%).
- NPV (Negative Predictive Value): 98% (741/756) with Wilson 95% CI (97% - рия).
- Total Percent Agreement: 97% (767/790) with Wilson 95% CI (рике% - 98%).
Multicenter Method Comparison (Zymutest HIA IgG (Predicate) vs. SRA):
- Study Type: Method Comparison.
- Sample Size: n=790 samples from patients exposed to heparin with HIT symptoms.
- Key Results:
- PPV (Positive Predictive Value): 36% (26/73) with Wilson 95% CI (26% - 47%).
- NPV (Negative Predictive Value): 98% (702/717) with Wilson 95% CI (97% - 99%).
- Total Percent Agreement: 92% (728/790) with Wilson 95% CI (90% - 94%).
Conclusion for SRA testing: HemosIL AcuStar HIT-IgG(PF4-H) showed equivalent NPV and superior PPV performance to the predicate device when both assays were compared to the SRA method with the intended use adult population.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
HemosIL AcuStar HIT IgG(PF4-H) vs. Zymutest HIA IgG:
- PPA (Positive Percent Agreement): 35% (26/74)
- NPA (Negative Percent Agreement): 99% (719/728)
- Total Percent Agreement: 93% (745/802)
HemosIL AcuStar HIT IgG(PF4-H) vs. SRA:
- PPV (Positive Predictive Value): 76% (26/34)
- NPV (Negative Predictive Value): 98% (741/756)
- Total Percent Agreement: 97% (767/790)
Zymutest HIA IgG (Predicate) vs. SRA:
- PPV (Positive Predictive Value): 36% (26/73)
- NPV (Negative Predictive Value): 98% (702/717)
- Total Percent Agreement: 92% (728/790)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 864.7695 Platelet factor 4 radioimmunoassay.
(a)
Identification. A platelet factor 4 radioimmunoassay is a device used to measure the level of platelet factor 4, a protein released during platelet activation by radioimmunoassay. This device measures platelet activiation, which may indicate a coagulation disorder, such as myocardial infarction or coronary artery disease.(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/2 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" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with the profiles overlapping each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
September 8, 2017
Instrumentation Laboratory Co. Carol Marble Regulatory Affairs Director 180 Hartwell Road Bedford, Massachusetts 01730
Re: K170854
Trade/Device Name: HemosIL AcuStar HIT-IgGopp4-HemosIL AcuStar HIT Controls Regulation Number: 21 CFR 864.7695 Regulation Name: Platelet factor 4 radioimmunoassay Regulatory Class: Class II Product Code: LCO. GGN Dated: March 21, 2017 Received: March 22, 2017
Dear Carol Marble:
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
1
Part 807): labeling (21 CFR Part 801 and Part 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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and Part 809), please contact the Division of Industry and Consumer Education (DICE) 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 (DICE) 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,
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology 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) K170854
Device Name HemosIL AcuStar HIT-IgG(PF4-H) HemosIL AcuStar HIT Controls
Indications for Use (Describe)
HemosIL AcuStar HIT-IgG(PF4-H) is a qualitative, fully automated, chemiluminescent immunoassay (CIA) for the detection of IgG antibodies that react with Platelet Factor 4 (PF4) when complexed to heparin. The assay is for use in human 3.2% or 3.8% citrated plasma and serum on the ACL AcuStar instrument in a laboratory setting.
The result provided by the assay should be interpreted as either positive or negative based on the assay cut-off (1.00 U/ mL). The positive or negative result aids in determining the risk for heparin induced thrombocytopenia (HIT) when used in conjunction with other laboratory and clinical findings.
Anti-PF4/Heparin antibodies are commonly found in patients with HIT. For use in adult population suspected of HIT. Not for use in isolation to exclude HIT.
HemosIL AcuStar HIT Controls are for the quality control of the HemosIL AcuStar HIT-IgG(PF4-H) assay as performed on the ACL AcuStar.
For prescription use.
| 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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3
Image /page/3/Picture/0 description: The image contains the logo for Instrumentation Laboratory. The logo consists of a blue and green graphic on the left, followed by the text "Instrumentation Laboratory" in a gray sans-serif font. Below the company name, it says "A Werfen Company" in a smaller font.
510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
| Submitter's Information | Instrumentation Laboratory (IL) Co.
180 Hartwell Road
Bedford, MA 01730, USA | | |
|---------------------------------------------------|------------------------------------------------------------------------------------------------------------------|------------------------------------|--|
| Contact Person | Carol Marble, Regulatory Affairs Director
Phone: 781-861-4467
Fax: 781-861-4207
Email: cmarble@ilww.com | | |
| Preparation Date | August 26, 2017 | | |
| Device Trade Names | Reagent Cartridge Kit (with Calibrator) | HemosIL AcuStar HIT-IgG(PF4-H) | |
| | Controls | HemosIL AcuStar HIT Controls | |
| Regulatory Information –
Reagent Cartridge Kit | Regulation Number | 21 CFR 864.7695 | |
| | Regulation Description | Platelet Factor 4 Radioimmunoassay | |
| | Classification | Class II | |
| | Product Code | LCO | |
| | Classification Panel | Hematology (81) | |
| Regulatory Information –
Controls | Regulation Number | 21 CFR 864.5425 | |
| | Regulation Description | Plasma, Coagulation Control | |
| | Classification | Class II | |
| | Product Code | GGN | |
| | Classification Panel | Hematology (81) | |
| Predicate Device | K071255 (Zymutest HIA IgG from HYPHEN Biomed) | | |
4
| Indications for Use /
Intended Use | HemosIL AcuStar HIT-IgG(PF4-H) is a qualitative, fully automated, chemiluminescent
immunoassay (CIA) for the detection of IgG antibodies that react with Platelet Factor
4 (PF4) when complexed to heparin. The assay is for use in human 3.2% or 3.8%
citrated plasma and serum on the ACL AcuStar instrument in a laboratory setting.
The result provided by the assay should be interpreted as either positive or negative
based on the assay cut-off (1.00 U/mL). The positive or negative result aids in
determining the risk for heparin induced thrombocytopenia (HIT) when used in
conjunction with other laboratory and clinical findings.
Anti-PF4/Heparin antibodies are commonly found in patients with HIT. For use in adult
population suspected of HIT. Not for use in isolation to exclude HIT.
HemosIL AcuStar HIT Controls are for the quality control of the HemosIL AcuStar
HIT-IgG(PF4-H) assay as performed on the ACL AcuStar.
For prescription use. |
|--------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Description
Reagent Cartridges
with Calibrators | The HemosIL AcuStar HIT-IgG(PF4-H) assay is a chemiluminescent two-step
immunoassay consisting of magnetic particles coated with PF4 complexed to
polyvinyl sulfonate (PVS) which capture, if present, the PF4/Heparin antibodies from
the sample. After incubation, magnetic separation, and a wash step, a tracer
consisting of an isoluminol-labeled anti-human IgG antibody is added and may bind
with the captured PF4/Heparin IgG on the particles. After a second incubation,
magnetic separation, and a wash step, reagents that trigger the luminescent
reaction are added, and the emitted light is measured as relative light units (RLUs)
by the ACL AcuStar optical system. The RLUs are directly proportional to the
PF4/Heparin IgG concentration in the sample.
The HemosIL AcuStar HIT-IgG(PF4-H) kit consists of: |
| | R HIT-IgG(PF4-H) Cartridge for 25 determinations: Cartridge containing 1 vial of
magnetic particle suspension coated with PF4/PVS complex, 1 vial of assay
buffer, 1 vial of tracer consisting of an mAb anti-human IgG antibody labeled
with isoluminol, and 1 vial of sample diluent used for the regular predilution
of the sample. The reagents are in a phosphate or Tris buffer containing bovine
serum albumin, bovine fetal serum, PF4/PVS complex, mouse monoclonal IgG,
stabilizers, and preservative. |
| | C1 HIT-IgG(PF4-H) Calibrator 1: Barcoded tube of a solution with humanized mAb
anti-PF4-Heparin in Tris buffer containing bovine serum albumin, stabilizers
and preservative. |
| | C2 HIT-IgG(PF4-H) Calibrator 2: Barcoded tube of a solution with humanized mAb
anti-PF4-Heparin in Tris buffer containing bovine serum albumin, stabilizers,
and preservative. |
| | The calibrators are lot specific and they cannot be used with other lots of reagents. |
| Controls | The Low and High HIT Controls are prepared by means of a dedicated process and
contain different concentrations of humanized monoclonal anti-PF4-Heparin. |
| Low HIT Control: Control intended for the assessment of precision and accuracy of the
HemosIL AcuStar HIT-IgG(PF4-H) assay below the cut-off. | |
| | High HIT Control: Control intended for the assessment of precision and accuracy of
the HemosIL AcuStar HIT-IgG(PF4-H) assay above the cut-off. |
| | Use of both controls is recommended for a complete quality control program. |
5
| Comparison to Predicate | ||
|---|---|---|
| Item | Predicate | New Device |
| Trade Names | Zymutest HIA IgG | |
| (Kit Includes 2 Control Levels) | HemosIL AcuStar HIT-IgG(PF4-H) | |
| HemosIL AcuStar HIT Controls | ||
| Manufacturer | HYPHEN Biomed | Instrumentation Laboratory Co. |
| Similarities | ||
| Measurand | Anti-PF4/Heparin IgG Antibodies | Same |
| Assay Type | Qualitative | Same |
| Product Code | LCO | Same |
| Regulation Section | 864.7695 | Same |
| Classification | Class II | Same |
| Intended Use | The ZYMUTEST HIA, IgG ELISA kit, | |
| is a qualitative assay intended for | ||
| the detection of heparin- | ||
| dependent antibodies of the IgG | ||
| isotype, in human plasma, by | ||
| clinical laboratories. It is intended | ||
| for in vitro diagnostic use. | HemosIL AcuStar HIT-IgG(PF4-H) is a qualitative, fully | |
| automated, chemiluminescent immunoassay (CIA) | ||
| for the detection of IgG antibodies that react with | ||
| Platelet Factor 4 (PF4) when complexed to heparin. | ||
| The assay is for use in human 3.2% or 3.8% citrated | ||
| plasma and serum on the ACL AcuStar instrument | ||
| in a laboratory setting. | ||
| The result provided by the assay should be | ||
| interpreted as either positive or negative based on | ||
| the assay cut-off (1.00 U/mL). The positive or | ||
| negative result aids in determining the risk for | ||
| heparin induced thrombocytopenia (HIT) when | ||
| used in conjunction with other laboratory and | ||
| clinical findings. | ||
| Anti-PF4/Heparin antibodies are commonly found | ||
| in patients with HIT. For use in adult population | ||
| suspected of HIT. Not for use in isolation to | ||
| exclude HIT. | ||
| HemosIL AcuStar HIT Controls are for the quality | ||
| control of the HemosIL AcuStar | ||
| HIT-IgG(PF4-H) assay as performed on the ACL | ||
| AcuStar. | ||
| Differences | ||
| Sample Type | Citrated Human Plasma | Citrated Human Plasma or Serum |
| Methodology | Enzyme-linked immunosorbent assay (ELISA) | Chemiluminescent immunoassay (CIA) |
| Instrumentation | Manual | Automated ACL AcuStar instrument |
| Reagents | Microtiter plate coated with unfractionated heparin | Cartridge containing magnetic particle suspension coated with PF4 complexed to polyvinyl sulfonate (PVS) |
| Antibodies | Goat antibodies specific for human IgG | Mouse monoclonal anti-human IgG antibody |
| Conjugate | Peroxidase conjugated anti-human IgG | Isoluminol conjugated anti-human IgG |
| Cut-off | When the assay is run at 20±1°C, the results are as follows: | |
| Positive: $A450 > 0.50$ Weakly Positive: $A450 > 0.30 to TP True Positives | ||
| - | FN | |
| FP False Positives | ||
| FN False Negatives |
| PPA | Positive Percent Agreement | $PPA = \frac{TP}{TP + FN}$ | $NPA = \frac{TN}{TN + FP}$ |
|---|---|---|---|
| NPA | Negative Percent Agreement |
$$PPV ,,,= \frac{TP}{TP + FP} ,,,\quad,, NPV ,,,= \frac{TN}{TN + FN} ,,,=$$
$$\begin{array}{cc} \textbf{Total Percent Agreenment} & & \ \end{array} \ \begin{array}{c} \textbf{TP} + \textbf{TN} \ \hline \textbf{TP} + \textbf{TN} + \textbf{FP} + \textbf{FN} \ \end{array}$$
Negative Predictive Value
Positive Predictive Value
NPV
PPV
TPA
13
Multicenter Method Comparison
A multicenter method comparison study was performed at three (3) hospitals, comparing the performance of HemosIL AcuStar HIT-IgG(PF4-H) with the predicate device, Zymutest HIA IgG (K071255) (n=802) and with the Serotonin Release Assay (SRA) (n=790).
The samples were from patients exposed to heparin that showed HIT related symptoms.
Samples were analyzed in singlicate, with no spiked samples used in this study.
HemosIL AcuStar HIT-IgG(PF4-H) vs. Predicate Device (Zymutest HIA IgG) .
The pooled results below are based on a cut-off of 1.00 U/mL for the HemosIL AcuStar HIT-IgG(PF4-H) assay and 0.5 OD cut-off value for Zymutest HIA IgG.
| Zymutest HIA IgG Results | ||||
|---|---|---|---|---|
| + | - | Total | ||
| + | 26 | 9 | 35 | |
| HemosIL AcuStar | ||||
| HIT IgG(PF4-H) Results | - | 48 | 719 | 767 |
| Total | 74 | 728 | 802 |
| HemosIL AcuStar HIT IgG(PF4-H) vs. Zymutest HIA IgG | Proportion | Wilson 95% CI | |
|---|---|---|---|
| PPA (Positive Percent Agreement) | 35% (26/74) | 25% | 47% |
| NPA (Negative Percent Agreement) | 99% (719/728) | 98% | 99% |
| Total Percent Agreement | 93% (745/802) | 91% | 94% |
14
HemosIL AcuStar HIT-IgG(pF4-H) Assay vs. SRA and Predicate vs. SRA
Patient samples in the multicenter study without a valid SRA result or with an indeterminate result (total N=12) were removed from calculations, bringing the final total to N = 790. The pooled results summarized below compare both HemosIL AcuStar HIT-lgG1p++) (cut-off of 1.00 U/mL) to the SRA test results and the Zymutest HIA IgG assay (cut-off of 0.5 OD) to the SRA test results.
- HemosIL AcuStar HIT-IgGipf4-н) Assay vs. SRA: ●
| SRA Results | HemosIL AcuStar HIT IgG(pF4-H) vs. SRA | Proportion | Wilson 95% Cl | |||||
|---|---|---|---|---|---|---|---|---|
| + | - | Total | PPV (Positive Predictive Value) | 76% (26/34) | 60% | 88% | ||
| HemosIL AcuStar | ||||||||
| HIT IgG(PF4-H) Results | + | 26 | 8 | 34 | NPV (Negative Predictive Value) | 98% (741/756) | 97% | ರಿಯ |
| - | 15 | 741 | 756 | Total Percent Agreement | 97% (767/790) | ರಿಕೆ% | 98% | |
| Total | 41 | 749 | 790 |
- Zymutest HIA IgG (Predicate) vs. SRA: ●
| SRA Results | ||||
|---|---|---|---|---|
| + | - | Total | ||
| Zymutest HIA IgG | ||||
| Results | + | 26 | 47 | 73 |
| - | 15 | 702 | 717 | |
| Total | 41 | 749 | 790 |
| Zymutest HIA IgG vs. SRA | Proportion | Wilson 95% CI | |
|---|---|---|---|
| PPV (Positive Predictive Value) | 36% (26/73) | 26% | 47% |
| NPV (Negative Predictive Value) | 98% (702/717) | 97% | 99% |
| Total Percent Agreement | 92% (728/790) | 90% | 94% |
- Conclusion for SRA testing: HemosIL AcuStar HIT-IgG(PF4-H) showed equivalent NPV and superior PPV performance to the predicate device when both assays were compared to the SRA method with the intended use adult population.
Conclusion:
The analytical and clinical study results demonstrate that the HemosIL AcuStar HIT-IgG(PF4-H) assay and HemosIL AcuStar HIT Controls are substantially equivalent to the predicate device, Zymutest HIA IgG (FDA cleared under K071255), and that the assay is safe and effective for its labeled intended use when compared to the SRA reference method.