ENHANCED ESTRADIOL (EE2) MASTER CURVE MATERIAL

K102904 · Siemens Healthcare Diagnostics · JJX · Nov 23, 2010 · Clinical Chemistry

Device Facts

• Record ID: K102904
• Device Name: ENHANCED ESTRADIOL (EE2) MASTER CURVE MATERIAL
• Applicant: Siemens Healthcare Diagnostics
• Product Code: JJX · Clinical Chemistry
• Decision Date: Nov 23, 2010
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 862.1660
• Device Class: Class 1

Indications for Use

The ADVIA Centaur® Enhanced Estradiol Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range in the ADVIA Centaur® Enhanced Estradiol (eE2) assay,

Device Story

ADVIA Centaur Enhanced Estradiol (eE2) Master Curve Material serves as a quality control tool for laboratory verification of calibration and reportable range for the ADVIA Centaur eE2 assay. The device consists of six levels of lyophilized material containing USP-grade estradiol in a human serum matrix with preservatives. Level 1 is a buffer with bovine serum albumin; levels 2-6 contain varying concentrations of estradiol (0, 60, 175, 450, 1500, and 2700 pg/mL). Used in clinical laboratory settings by technicians to ensure assay accuracy. The material is reconstituted and processed on the ADVIA Centaur system. Results from the material are compared against expected lot-specific values to confirm the system's performance within the reportable range, supporting clinical decision-making by ensuring reliable estradiol measurements for patient diagnosis and monitoring.

Clinical Evidence

No clinical data. Performance was established through bench testing, including validation of traceability, value assignment, and stability of the master curve materials.

Technological Characteristics

Lyophilized human serum matrix; contains bovine serum albumin, sodium azide (0.1% post-reconstitution), and preservatives. Six levels with specific estradiol concentrations (0-2700 pg/mL). Storage at 2-8°C. Reconstituted for use. No software or electronic components.

Indications for Use

Indicated for in vitro diagnostic use to verify calibration and reportable range of the ADVIA Centaur Enhanced Estradiol (eE2) assay. No specific patient population, age, or gender restrictions are defined as this is a laboratory quality control material.

Regulatory Classification

Identification

A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.

Predicate Devices

• VALIDATE Thyroid Calibration Verification Test Set (K062501)

Submission Summary (Full Text)

{0}

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

A. 510(k) Number:
k102904

B. Purpose for Submission:
New device

C. Measurand:
Control for Estradiol (eE2) analytes

D. Type of Test:
Not Applicable

E. Applicant:
Siemens Healthcare Diagnostics

F. Proprietary and Established Names:
ADVIA Centaur® Enhanced Estradiol (eE2) Master Curve Material

G. Regulatory Information:
1. Regulation section:
21 CFR §862.1660, Quality Control Material (Assayed and Unassayed)
2. Classification:
Class I, Reserved
3. Product code:
JJX – Single (Specified) Analyte Controls (Assayed and Unassayed))
4. Panel:
Clinical Chemistry (75)

{1}

Page 2 of 6

## H. Intended Use:

1. Intended use(s):

See Indications for Use below.

2. Indications(s) for use:

The ADVIA Centaur® Enhanced Estradiol (eE2) Master Curve Material is for *in vitro* diagnostic use in the verification of calibration and reportable range in the ADVIA Centaur® Enhanced Estradiol (eE2) assay

3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

The ADVIA Centaur® Enhanced Estradiol (eE2) Master Curve Material is to be used with ADVIA Centaur XP systems.

## I. Device Description:

ADVIA Centaur Master Curve Material (MCM) is a single-analyte, lyophilized product containing various levels of USP-Grade estradiol in human serum. The kit consists of 1 vial each of 6 levels. Estradiol levels are value assigned for ADVIA Centaur systems. MCM are for in vitro diagnostic use in the verification of calibration and reportable range in ADVIA Centaur Enhanced Estradiol assay. MCM are not intended for use as routine quality control material.

MCM levels 2 though 6 are manufactured using normal male human serum spiked with USP grade estradiol stock to target values of 60, 175, 400, 1500, and 2700 pg/mL. The eE2 MCM1 is manufactured using the eE2 buffer basepool with a target of 0 pg/mL.

The eE2 MCMs are filled at 1 mL into 5 mL amber vials and then lyophilized. The lyophilized material is stored at 2-8°C.

The eE2 MCM’s contain human source material. Each human serum or plasma donor unit used in the manufacture of this product was tested by FDA approved methods and found nonreactive for hepatitis B surface antigen (HBsAg), antibody to hepatitis C (HCV), and antibody to HIV-1/2. However, all products manufactured using human source material should be handled as potentially infectious. Because no test method can offer complete assurance that hepatitis B or C viruses, HIV, or other infectious agents are absent, these products should be handled according to established good laboratory practices.

## J. Substantial Equivalence Information:

1. Predicate device name(s):

{2}

Page 3 of 6

Thyroid Calibration Verification Test System

2. Predicate 510(k) number(s):

k062501

3. Comparison with predicate:

| Reagent Similarities and Differences | | |
| --- | --- | --- |
| | Candidate Device
ADVIA Centaur Master Curve
Material (k102904) | Predicate Device
Maine Standards Company
VALIDATE Thyroid Calibration
Verification Test Set (k062501) |
| Intended/Indications for Use | is for in vitro diagnostic use in the verification of calibration and reportable range | Same |
| Specimen Matrix | Human serum | Human serum |
| Form | Lyophilized | Liquid |
| Analytes | Enhanced Estradiol Only | Multiple analytes, including: Triiodothyronine (Ta), Thyroxine (ff4), human Thyroid Stimulating Hormone (TSH) and Cortisol |
| Storage | 2 to 8°C | -10 to -20 °C |
| Stability | Unopened-until expiration date on the vial label
Reconstituted- 14 days or Onboard-6 hours | Unopened-until expiration date on storage container when stored as directed |

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

- Evaluation of Matrix Effects; Approved Guideline - (CLSI EP14-A).

L. Test Principle:

Not Applicable

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Not Applicable

b. Linearity/assay reportable range:

Not Applicable

{3}

Page 4 of 6

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

Traceability:
The ADVIA Centaur eE2 assay and the Master Curve Materials are traceable to ID-GC/MS values.

Stability:
Real time (2-8 °C) and accelerated (25°C and 37°C) stability studies are being conducted on at least two lots of ADVIA Centaur Enhanced Estradiol Master Curve Material. The control material is stored at < -40°C, which was determined to be appropriate by comparison of the control material stored at -40°C to a master set stored at -80°C or standards that are stored at -80°C. The acceptance criteria states that the percent difference in material must be within 10% of the -40°C daily dose or the 2-8°C day zero dose with no adverse trends.

Open vial studies are being performed for 42 days at 2-8°C. Vials are opened at day zero and at each time point, the open vial, a frozen vial (that was placed in aliquots after reconstitution), and a fresh vial are tested. Percent recovery is calculated using the average dose from triplicate results and the acceptance criteria is that the open vial must be within 10% or two standard deviations from the frozen material. The sponsor will claim that it is stable for 14 day once reconstituted and stored at 2-8 °C.

On-system stability is being measured by using at least two lots of material for 24 hours at room temp in uncapped centaur tubes. 15 sets of material are reconstituted and pooled in 50 mL polypropylene tubes. The material is then distributed at 1 mL in sample cups. Five cups are capped and stored at 2-8°C, and the other five cups are left uncapped at room temperature. Tubes are capped at 0, 2, 4, 8, and 24 hours and then the percent recovery is measured using the average dose from triplicate results against the 2-8°C material. The acceptance criteria require that the percent recovery must be within 10% or two standard deviations of the 2-8°C stored material. The sponsor will claim that it is stable for 6 hours once reconstituted and placed on the system.

Value Assignment
Estradiol Master Curve Material is value assigned using an internal estradiol "gold standard" set that uses a panel of real serum samples and was value assigned by Gas Chromatography Mass Specification. The MCM and Gold standards are tested on three different ADVIA Centaur XP systems and MCM values are calculated for each system independently. The assigned value for each MCM is the average analyte recovered and must quality controls are calculated by the recovery of controls using calibrator values and must fall within set specifications. The target specifications for production lots are:

{4}

Page 5 of 6

| | | | Dose | |
| --- | --- | --- | --- | --- |
| | UOM | TARGET | RANGE LOW | RANGE HIGH |
| MCM1 | pg/mL | 0 | NA | ≤11.8 |
| MCM2 | pg/mL | 60 | 53 | 67 |
| MCM3 | pg/mL | 175 | 154 | 196 |
| MCM4 | pg/mL | 450 | 396 | 504 |
| MCM5 | pg/mL | 1500 | 1320 | 1680 |
| MCM6 | pg/mL | 2700 | 2430 | 2970 |

The customer ranges for the product insert are then determined by the following equations:

Upper Limit Customer Range = Assigned Target + Assigned Target x % interval
Lower Limit Customer Range = Assigned Target – Assigned Target x % interval
The percent intervals are ± 25% for MCM2-MCM6.

## Matrix Effects

The sponsor performed spiking recovery of MCM2-6 to determine matrix effects. A stock solution of USP-Grade estradiol was added to the sample and the material was recovered. The acceptance criteria were that the recoveries across all 6 samples had to be within ±10% and no individual recovery could be more than ±15%. All of their samples met the acceptance criteria and show that there is no significant matrix effect from using pooled human serum with sodium azide as the base matrix for eE2 MCM's.

d. Detection limit:

Not applicable

e. Analytical specificity:

Not Applicable

f. Assay cut-off:

Not Applicable

2. Comparison studies:

a. Method comparison with predicate device:

Not Applicable

b. Matrix comparison:

Not applicable.

5

{5}

Page 6 of 6

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

4. Clinical cut-off:
Not Applicable

5. Expected values/Reference range
The expected values are provided in the eE2MCM lot-specific value sheet. The assigned values were established using the ADVIA Centaur eE2 assay.

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.

6