BERICHROM HEPARIN UF CALIBRATOR, BERICHROM HEPARIN UF CONTROL 1, AND BERICHROM HEPARIN UF CONTROL 2

K083175 · Siemens Healthcare Diagnostics · JPA · Jan 26, 2009 · Hematology

Device Facts

• Record ID: K083175
• Device Name: BERICHROM HEPARIN UF CALIBRATOR, BERICHROM HEPARIN UF CONTROL 1, AND BERICHROM HEPARIN UF CONTROL 2
• Applicant: Siemens Healthcare Diagnostics
• Product Code: JPA · Hematology
• Decision Date: Jan 26, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5425
• Device Class: Class 2

Indications for Use

Berichrom Heparin UF Calibrator is an in vitro diagnostic product used for the calibration of the Berichrom Heparin assay for measurement of unfractionated (UF) heparin. Berichrom Heparin UF Control 1 is an assayed, low level, quality control material for assessment of precision and analytical bias in the quantitative determination of unfractionated (UF) heparin with the Berichrom Heparin assay. Berichrom Heparin UF Control 2 is an assayed, high level, quality control material for assessment of precision and analytical bias in the quantitative determination of unfractionated (UF) heparin with the Berichrom Heparin assay.

Device Story

Lyophilized calibrator and assayed controls for unfractionated (UF) heparin measurement; contains porcine-derived UF heparin and buffered human plasma. Used in clinical laboratory settings to calibrate Berichrom Heparin assays and monitor assay performance via low and high-level controls. Requires reconstitution with distilled or deionized water. Assigned values are traceable to WHO International Standard for unfractionated heparin. Provides quality control for quantitative heparin measurement, assisting clinicians in monitoring anticoagulant therapy.

Clinical Evidence

No clinical data. Bench testing only. Stability studies performed over 24 months (plus 1 month) at various storage conditions (+2 to +8°C, +15 to +25°C, ≤-18°C) to validate shelf life and reconstituted stability. Acceptance criteria based on deviation from Day 0 or freshly reconstituted values (±0.05 IU/mL for Control 1; ±20% for Calibrator and Control 2).

Technological Characteristics

Lyophilized product; porcine-derived unfractionated heparin in buffered human plasma. Reconstitution required (1.0 mL distilled/deionized water). Traceable to 5th WHO International Standard for unfractionated heparin. Storage: +2 to +8°C (closed).

Indications for Use

Indicated for use as a calibrator and quality control materials (low and high levels) for the quantitative measurement of unfractionated (UF) heparin in human plasma using the Berichrom Heparin assay. Intended for professional in vitro diagnostic use.

Regulatory Classification

Identification

A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.

Special Controls

*Classification.* Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.

Predicate Devices

• Dade Behring Heparin Calibrator and Controls (K042941)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k083175

B. Purpose for Submission:
Bundled submission for the clearance of new devices

C. Measurand:
Low molecular weight heparin

D. Type of Test:
Control/Calibrator

E. Applicant:
SIEMENS HEALTHCARE DIAGNOSTICS

F. Proprietary and Established Names:
Berichrom Heparin UF Calibrator
Berichrom Heparin UF Control 1
Berichrom Heparin UF Control 2

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| JPA | II | 21 CFR 864.5425 | 81 HEMATOLOGY |
| GIZ | II | 21 CFR 864.5425 | 81 HEMATOLOGY |
| GGC | II | 21 CFR 864.5425 | 81 HEMATOLOGY |

H. Intended Use:

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1. Intended use(s):

Berichrom Heparin UF Calibrator

For the calibration of the Berichrom Heparin assay for measurement of unfractionated (UF) heparin.

Berichrom Heparin UF Control 1

For use as a low level assayed control for the quantitative measurement of unfractionated (UF) heparin with the Berichrom Heparin assay.

Berichrom Heparin UF Control 2

For use as a high level assayed control for the quantitative measurement of unfractionated (UF) heparin with the Berichrom Heparin assay.

2. Indication(s) for use:

3. Special conditions for use statement(s):

4. Special instrument requirements:

I. Device Description:

Berichrom Heparin UF Calibrator

Berichrom Heparin UF Calibrator is a lyophilized product containing unfractionated (UF) heparin from porcine intestine and buffered human plasma. Each package contains 6 vials; each vial requires reconstitution with 1.0 mL distilled or deionized water.

Berichrom Heparin UF Control 1

Berichrom Heparin UF Control 1 is a lyophilized, low level, assayed control containing unfractionated (UF) heparin from porcine intestine and buffered human plasma. Each package contains 6 vials; each vial requires reconstitution with 1.0 mL distilled or

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deionized water.

## Berichrom Heparin UF Control 2

Berichrom Heparin UF Control 2 is a lyophilized, high level, assayed control containing unfractionated (UF) heparin from porcine intestine and buffered human plasma. Each package contains 6 vials; each vial requires reconstitution with 1.0 mL distilled or deionized water.

J. Substantial Equivalence Information:

| Predicate | Item | Similarities | Differences |
| --- | --- | --- | --- |
| Berichrom Heparin UF Calibrator | | | |
| Dade Behring Calibrator and Controls-K042941 | Intended Use | For the calibration of heparin assay | |
| | Form | Lyophilized | |
| | Matrix | Plasma | |
| | Traceability | WHO Standard | |
| | Levels | One level | |
| | | | |
| Berichrom Heparin UF Control 1/2 | | | |
| Dade Behring Calibrator and Controls K042941 | Intended Use | Assayed control for the measurement of low molecular control | |
| | Form | Lyophilized | |
| | Analyte | Low molecular weight | |
| | Matrix | Plasma | |
| | Levels | Low and high control | 1 of each Control, sold separately, predicate 2 levels sold as a kit |

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

| STANDARDS |
| --- |
| Title and Reference Number |
| |

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Other Standards

| GUIDANCE | | |
| --- | --- | --- |
| Document Title | Office Division | Web Page |
| Guidance for Industry and FDA Staff: Bundling Multiple Devices or Multiple Indications in a Single Submission | OIVD | http://www.fda.gov/cdrh/mdufma/guidance/1215.html |
| Guidance for Industry and FDA Staff - Assayed and Unassayed Quality Control Material | OIVD | http://www.fda.gov/cdrh/oivd/guidance/2231.html |

L. Test Principle:

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:
n/a

b. Linearity/assay reportable range:
n/a

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The assigned values for Berichrom Heparin UF Calibrator, Berichrom Heparin UF Control 1 and Berichrom Heparin UF Control 2 are traceable to the 5th World Health Organization (WHO) International Standard for unfractionated heparin. Assigned values are obtained from multiple determinations, on multiple coagulation instruments and Berichrom Heparin

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lots. A typical assigned value for the calibrator is 1.20 IU/mL. Typical control values are 0.20 IU/mL for Control 1 and 0.60 IU/mL for Control 2.

## Stability Testing

## Shelf life (Closed)

## Study Duration

24 month shelf life; studies performed for 1 month past labeled shelf life.

## Testing Frequency

Day 0; 6, 9, 12, 18, 19, 24 and 25 months

## Storage

+2 to +8°C

## Replicates

Calibrator: Three six-point calibrator curves are generated from three vials of calibrator; a mean calibration curve is established from the three curves. At each time point, a vial is tested in duplicate.

Controls: At each time point, a vial is tested in duplicate.

## Acceptance Criteria

Control 1: Results obtained must not deviate more than ±0.05 IU/mL compared to Day 0 results

Calibrator & Control 2: Results obtained must not deviate more than ±20% compared to Day 0 results

The mean value at each time point is compared to the Day 0 value. Results obtained must meet the acceptance criteria. Shelf-life (expiration) dating assignment at commercialization reflects the real-time data on file at Siemens Healthcare Diagnostics Inc.

## Reconstituted (Open)

## Study Duration

24 month shelf life; studies performed for 1 month past labeled shelf life.

## Testing Frequency

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Day 0; 6, 9, 12, 18, 19, 24 and 25 months

## Storage

+15 to +25°C; tested after reconstitution at various time points up to 25 hours
+2 to +8°C; tested after reconstitution at various time points up to 49 hours
≤-18°C; tested after reconstitution at various time points up to 5 weeks

## Replicates

Calibrator: Three six-point calibration curves are generated from three vials of calibrator; a mean calibration curve is established from the three curves. At each time point, a vial is tested in duplicate.

Controls: At each time point, a vial is tested in duplicate.

## Acceptance Criteria

Control 1: Results obtained must not deviate more than ±0.05 IU/mL compared to the freshly reconstituted vial results.

Calibrator & Control 2: Results must not deviate more than ±20% compared to the freshly reconstituted vial results.

The mean value at each time point is compared to the value obtained from a freshly reconstituted vial. Results obtained must meet the acceptance criteria.

## Stability Testing

### Shelf life (Closed)

#### Study Duration

24 month shelf life; studies performed for 1 month past labeled shelf life.

#### Testing Frequency

Day 0; 6, 9, 12, 18, 19, 24 and 25 months

#### Storage

+2 to +8°C

#### Replicates

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Calibrator: Three six-point calibration curves are generated from three vials of calibrator; a mean calibration curve is established from the three curves. At each time point, a vial is tested in duplicate.

Controls: At each time point, a vial is tested in duplicate.

## Acceptance Criteria

Calibrator & Controls: Results obtained must not deviate more than $\pm 20\%$ compared to Day 0 results.

The mean value at each time point is compared to the Day 0 is value. Results obtained must meet the acceptance criteria. Shelf-life (expiration) dating assignment at commercialization reflects the real-time data on file at Siemens Healthcare Diagnostics Inc.

## Reconstituted (Open)

### Study Duration

24 month shelf life; studies performed for 1 month past labeled shelf life

### Testing Frequency

Day 0; 6, 9, 12, 18, 19, 24 and 25 months

### Storage

+15 to +25°C; tested after reconstitution at various time points up to 25 hours
+2 to +8°C; tested after reconstitution at various time points up to 49 hours
$\leq -18^{\circ}\mathrm{C}$; tested after reconstitution at various time points up to 5 weeks

### Replicates

Calibrator: Three six-point calibration curves are generated from three vials of calibrator; a mean calibration curve is established from the three curves. At each time point, a vial is tested in duplicate.

Controls: At each time point, a vial is tested in duplicate.

## Acceptance Criteria

Results obtained must not deviate more than $\pm 20\%$ compared to the freshly reconstituted vial results.

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The mean value at each time point is compared to the value obtained from a freshly reconstituted vial. Results obtained must meet the acceptance criteria.

d. Detection limit:
n/a

e. Analytical specificity:
n/a

f. Assay cut-off:
n/a

2. Comparison studies:
a. Method comparison with predicate device:
n/a
b. Matrix comparison:
n/a

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

4. Clinical cut-off:
n/a

5. Expected values/Reference range:
Values are determined using six reference curves derived on six coagulometer

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instruments with multiple reagent lots. 4 vials of control, 2 replicates per vial tested on each curve for a total of 48 values. The assigned value is the mean of the 48 values.

**N. Proposed Labeling:**

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

**O. Conclusion:**

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

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