HEALTHTEST HEPARIN/PLATELET FACTOR 4 ANTIBODY ASSAY

K040293 · Akers Laboratories, Inc. · LCO · May 28, 2004 · Hematology

Device Facts

• Record ID: K040293
• Device Name: HEALTHTEST HEPARIN/PLATELET FACTOR 4 ANTIBODY ASSAY
• Applicant: Akers Laboratories, Inc.
• Product Code: LCO · Hematology
• Decision Date: May 28, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7695
• Device Class: Class 2

Indications for Use

The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay is an in vitro diagnostic device designed for the detection of antibodies to Platelet Factor 4 complexed to polyanionic compounds such as polystyrene. These antibodies are found in some patients undergoing heparin therapy.

Device Story

HealthTEST® Heparin/Platelet Factor 4 Antibody Assay is a qualitative in vitro diagnostic test for detecting antibodies to PF-4/polyanionic complexes. The device consists of a mini-reactor with a membrane filtration system and a reagent dispenser. The user adds a patient serum or plasma sample to the reaction well, followed by reagents containing PF-4 coated dyed microparticles. If antibodies are present, particles agglutinate and are trapped by the membrane, preventing color migration past the results window line. If no antibodies are present, non-agglutinated particles pass through the membrane, allowing color to migrate past the line. The test is performed manually at the point of care. Results provide a qualitative assessment of antibody presence, aiding clinicians in the diagnosis of heparin-induced thrombocytopenia in patients receiving heparin therapy.

Clinical Evidence

Bench testing only. Two studies compared the device to a commercially available ELISA using fresh field samples. Study 1 (plasma, n=175): 90.1% specificity, 91.3% sensitivity, 90.3% overall agreement. Study 2 (serum, n=179): 98.1% specificity, 91.3% sensitivity, 97.2% overall agreement.

Technological Characteristics

Particulate immunofiltration assay (PIFA). Components: mini-reactor with membrane filtration and reagent dispenser. Reagents: dyed microparticles coated with purified PF-4 protein. Principle: visual signal based on particle agglutination and membrane filtration. Dimensions/form factor: manual, individual test format. Connectivity: none. Sterilization: not specified.

Indications for Use

Indicated for qualitative detection of heparin/PF-4 antibodies in serum or plasma of patients undergoing heparin therapy. Used to assist in screening for heparin-induced thrombocytopenia (HIT) or thrombosis in clinical settings requiring STAT results.

Regulatory Classification

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.

Predicate Devices

• Genetic Testing Institute PF4 ELISA Assay (K983379)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
K040293

B. Purpose for Submission:
New assay

C. Analyte:
Platelet Factor 4 Antibodies

D. Type of Test:
Qualitative Particulate ImmunoFiltration Assay (PIFA)

E. Applicant:
Akers Laboratory Inc

F. Proprietary and Established Names:
HealthTEST® Heparin/Platelet Factor 4 Antibody Assay

G. Regulatory Information:
1. Regulation section:
21 CFR 864.7695
2. Classification:
Class II
3. Product Code:
LCO
4. Panel:
81 Hematology

H. Intended Use:
1. Intended use(s):
The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay is a qualitative
in vitro diagnostic device designed for the detection of antibodies to Platelet
Factor 4 complexed to polyanionic compounds such as polystyrene.
2. Indication(s) for use:
The device is indicated for patients undergoing heparin therapy, who are at
risk for developing heparin induced thrombocytopenia.
3. Special condition for use statement(s):
4. Special instrument Requirements:

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# I. Device Description:

The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay consists of two components: a Mini-reactor device containing a membrane filtration system and a results window, and a dispenser containing reaction reagents.

The Mini-reactor contains a reaction well that allows the sample to react with the reagents. The sample is added to the reaction well followed by the reagents contained in the reagent dispenser. The reagents contain microparticles coated with purified PF-4 protein as well as additional enhancing agents designed to promote rapid agglutination of the particles in the presence of specific antibodies in the test sample.

Once the reagents have reacted with the sample in the reaction well, the reaction mixture automatically collects over the membrane filtration system. This system acts to filter agglutinated particles, while allowing non-agglutinated particles to pass through. Thus, as agglutinated, reactive sample will be trapped within the membrane. Since the dyed particles are trapped on this filter, no particles and hence no color, are able to migrate past the positive/negative line on the results window. Conversely, a non-agglutinated, non-reactive sample will pass through the membrane filter and into the wicking layers, and color will migrate past the positive/negative line.

# J. Substantial Equivalence Information:

1. Predicate device name(s): Genetic Testing Institute PF4 ELISA Assay
2. Predicate K number(s): K983379
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended use | Detects antibodies to the heparin/PF4 complex in patient’s circulation | Detects antibodies to the heparin?PF4 complex in patient’s circulation |
| Assay Type | Serology | Serology |
| Analyte Detected | Antibody to PF-4 complexed with polyanionic compounds | Antibody to PF-4 complexed with polyanionic compounds |
| Differences | | |
| Item | Device | Predicate |
| Sample matrix | Serum, plasma | Serum |
| Methodology | Immunoassay, Particulate ImmunoFiltration Assay (PIFA) | Immunoassay, Enzyme-linked Immunosorbent Assay (ELISA) |
| Throughput | Individual | Batch testing |

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# K. Standard/Guidance Document Referenced (if applicable):

## L. Test Principle:

The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay is based on the particulate immunofiltration principle. Dyed microparticles coated with purified platelet factor-4 (PF-4) protein derived from platelet-rich plasma provide the visual signal for the results of the assay. The ability of agglutinated or non-agglutinated particles to move through a filter medium is the measure of the reactivity/non-reactivity of the test sample.

## M. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

a. **Precision/Reproducibility:**
A study was performed using 5 replicates each of a positive and a negative patient control. The samples were tested daily for 4 consecutive days. Both serum and plasma was tested.

b. **Linearity/assay reportable range:**
n/a

c. **Traceability (controls, calibrators, or method):**
n/a

d. **Detection limit:**
n/a

e. **Analytical specificity:**

f. **Assay cut-off:**
The assay cut-off value was determined using patient samples tested on the predicate device. The cut-off value was designed to coincide with the cut-off of the predicate device (0.4).

The cut-off was validated by running a correlation study of 26 patient samples within the assay 20% cut-off range of 0.32 to 0.48. The specificity of this study was 92.3% and the sensitivity was 100%. A second evaluation was completed on 23 samples. Specificity of this study was 86.9%, and the sensitivity was 100.0%.

### 2. Comparison studies:

a. **Method comparison with predicate device:**
Study #1- Plasma

ELISA

| | | POS | NEG |
| --- | --- | --- | --- |
| HealthTEST | POS | 21 | 15 |
| | NEG | 2 | 137 |

$$
\text{Specificity} = 90.1\%
$$

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Sensitivity = 91.3%
Overall agreement = 90.3%

Study #2- Serum
ELISA

| | | POS | NEG |
| --- | --- | --- | --- |
| HealthTEST | POS | 21 | 3 |
| | NEG | 2 | 153 |

Specificity = 98.1%
Sensitivity = 91.3%
Overall agreement = 97.2%

b. Matrix comparison:
Fresh blood samples were drawn from 12 subjects is red top and EDTA purple to tubes and respectively processed into serum and plasma. Each pair of serum and plasma samples was evaluated with the HealthTEST® Heparin/Platelet Factor 4 Antibody Assay as directed by the package insert. Positive and negative patient controls were also ran.

Results demonstrated no difference between serum and plasma results.

3. Clinical studies:
a. Clinical sensitivity:
b. Clinical specificity:
c. Other clinical supportive data (when a and b are not applicable):

4. Clinical cut-off:

5. Expected values/Reference range:
Negative

N. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.