ELECSYS VITAMIN B12 ASSAY

K973702 · Boehringer Mannheim Corp. · CDD · Nov 13, 1997 · Clinical Chemistry

Device Facts

• Record ID: K973702
• Device Name: ELECSYS VITAMIN B12 ASSAY
• Applicant: Boehringer Mannheim Corp.
• Product Code: CDD · Clinical Chemistry
• Decision Date: Nov 13, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1810
• Device Class: Class 2

Intended Use

A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.

Device Story

Elecsys Vitamin B12 Assay is an in vitro diagnostic immunoassay for quantitative Vitamin B12 measurement. It utilizes an electrochemiluminescent (ECL) competition principle. Sample is pretreated to liberate bound Vitamin B12; then incubated with ruthenylated intrinsic factor and biotinylated Vitamin B12. The complex binds to streptavidin-coated microparticles. The reaction mixture is aspirated into a measuring cell where microparticles are captured on an electrode surface. Application of voltage induces chemiluminescent emission, measured by a photomultiplier. Results are calculated via a master calibration curve provided by reagent bar code. Used in clinical laboratories on the Elecsys 2010 instrument. Provides clinicians with quantitative B12 levels to assist in diagnosing and managing gastrointestinal malabsorption-related anemias.

Clinical Evidence

Bench testing only. Performance characteristics compared to BioRad Quantaphase II radioassay. Precision studies (N=60 per pool) showed %CVs ranging from 2.75% to 7.58%. Linearity established from 30-2000 pg/mL. Method comparison (N=346) yielded a correlation coefficient (r) of 0.9751 with a Passing Bablock regression of y=1.06X - 9.5. Interference testing demonstrated no significant interference from bilirubin, hemoglobin, lipemia, rheumatoid factor, dysproteinemia, or biotin at specified concentrations.

Technological Characteristics

Electrochemiluminescent immunoassay. Uses ruthenylated intrinsic factor and biotinylated Vitamin B12. Solid phase: streptavidin-coated microparticles. Detection: photomultiplier tube measuring chemiluminescence induced by electrode voltage. Instrument: Elecsys 2010. Calibration: master curve via reagent bar code. Assay duration: 18 minutes at 37°C. Sample types: serum, plasma, urine.

Indications for Use

Indicated for the quantitative determination of Vitamin B12 in human serum, plasma, and urine to aid in the diagnosis and treatment of anemias of gastrointestinal malabsorption.

Regulatory Classification

Identification

A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.

Predicate Devices

• BioRad Quantaphase II B12/Folate Assay (K935286)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows a sequence of handwritten digits. The digits appear to be '4973702'. The numbers are written in black ink on a white background. The handwriting is somewhat stylized, with some numbers appearing more rounded than others.

NOV 1 3 1997

| | 510(k) Summary |
|-------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Introduction | According to the requirements of 21 CFR 807.92, the following information<br>provides sufficient detail to understand the basis for a determination of<br>substantial equivalence. |
| 1.<br>Submitter<br>name,<br>address,<br>contact | Boehringer Mannheim Corporation<br>4300 Hacienda Drive<br>Pleasanton, CA 94588-2722<br>(510) 730 - 8413<br>Contact Person: Yvette Lloyd<br>Date Prepared: September 24, 1997 |
| 2. Device name | Proprietary name: Elecsys Vitamin B12 Assay<br>Common name: Electrochemiluminescent immunoassay for the determination<br>of Vitamin B12.<br>Classification name: System, Test, Vitamin B12 |
| 3. Predicate<br>device | The Boehringer Mannheim Elecsys Vitamin B12 is substantially equivalent to<br>other products in commercial distribution intended for similar use. Most<br>notably it is substantially equivalent to the currently marketed BioRad<br>Quantaphase II B12/Folate Assay (K935286). |

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# 10(k) Summary, Continued

l

4. Device Description Competition principle. Total duration of assay: 18 minutes, 37*C. Competition principic. Total adalabating the sample (15 mL) with the •] * incubation (9 immutes). By metreatment 2 (15 mL), bound Vitamin B12 is liberated into the serum.

·2nd incubation (9 minutes): By incubating the pretreated sample with the •2nd incubation (9 innutes): Dy most, and immunocomplex is formed, the ruthenylated" * " intrilisic Tactor (70 this), " = " = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = · 3rd incubation (9 minutes): After addition of of streptaviding of a streptaviding of the still, •3rd incubation (9 mL) and Vitamin B12 labeled with biotin (60 mL), the still-

microparticles (30 mL) and Vitalini Dr.2 recorder become occupied, with the vacant sites of the ruthenylated Intrinst For and B12 biotin complex.
formation of an ruthenylated Intrinsic Factor-Viraming of biotin formation of an rutherrylated markisto i actor-phase via interaction of biotin.
The entire complex becomes bound to the solid phase via interaction of biotin. and streptavidin.

·The reaction mixture is aspirated into the measuring cell where the · I he reaction inixture is aspirated onto the surface of the electrode. microparticles are then removed with Procell. Application of a voltage Unbound substances are then removed was a secure in which is measured
to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).

·Results are determined via a calibration curve which is instrument-· Results are 'delemined ' via- a 'culturation and a master curve provided via the reagent bar code.

**Tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy)**3)

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| | 510(k) Summary, Continued |
|--------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 5.<br>Intended use | Assay for the in vitro quantitative determination of Vitamin B12 in human serum and plasma. |
| 6.<br>Comparison to predicate device | The Boehringer Mannheim Elecsys Vitamin B12 Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed BioRad Quantaphase II B12/Folate Assay (K935286). |
| | The following table compares the Elecsys Vitamin B12 Assay with the predicate device, BioRad Quantaphase II B12/Folate Assay. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device is provided in attachment 6. |
| | <b>Similarities:</b> |
| | <ul><li>Intended Use: Assay for the in vitro quantitative determination of Vitamin B12</li><li>Sample type: Serum and plasma</li><li>Assay range: 0- 2000 pg/mL</li><li>Same binding protein: Porcine Intrinsic Factor</li></ul> |

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## 10(k) Summary, Continued

1 1 1 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4

6.

Comparison to predicate device cont.

#### Differences:

| Feature | Elecsys<br>Vitamin B12 | Biorad Quantaphase II<br>B12/Folate radioassay |
|----------------------------|--------------------------|------------------------------------------------|
| Reaction test<br>principle | Electrochemiluminescence | Radiobinding assay using<br>57Co |
| Instrument<br>required | Elecsys 2010 | Gamma Counter |

#### Performance Characteristics:

| Feature | Elecsys Vitamin B12<br>Modified NCCLS (pg/ml): | BioRad Quantaphase II<br>B12/Folate Radioassay<br>Within-Run and Total Precision<br>(pg/ml): |
|--------------------|------------------------------------------------|----------------------------------------------------------------------------------------------|
| Precision<br>Level | Pool 1 | I |
| | Pool 2 | II |
| | Pool 3 | III |
| | | IV |
| N | 60 | 40 |
| | 60 | 40 |
| | 60 | 40 |
| | | 40 |
| Mean | 203.27 | 127 |
| | 481.02 | 273 |
| | 1499.36 | 622 |
| | | 1325 |
| Within run SD | 14.11 | 8.9 |
| | 20.38 | 15.7 |
| | 41.23 | 51.7 |
| | | 52.8 |
| %CV | 6.94 | 4.10 |
| | 4.24 | 4.1 |
| | 2.75 | 5.9 |
| | | 4.0 |
| Mean | 203.27 | 127 |
| | 481.02 | 429 |
| | 1499.36 | 807 |
| | | 1314 |
| Total SD | 15.41 | 8.6 |
| | 21.08 | 29.3 |
| | 47.78 | 36.2 |
| | | 75.3 |
| %CV | 7.58 | 6.8 |
| | 4.38 | 6.8 |
| | 3.19 | 4.5 |
| | | 5.7 |
| Level | Level 1 | |
| | Level 2 | |
| N | 60 | |
| | 60 | |
| Mean | 1119.49 | |
| | 471.30 | |
| Within run | 31.28 | |
| | 25.84 | |
| %CV | 2.79 | |
| | 5.48 | |
| Mean | 1119.49 | |
| | 471.30 | |
| Total | 36.20 | |
| | 26.77 | |
| %CV | 3.23 | |
| | 5.68 | |

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#### 10(k) Summary, Continued

Image /page/4/Picture/1 description: The image shows the logo for Boehringer Mannheim Corporation. The text is stacked on top of each other in a bold, sans-serif font. The words are all capitalized and in black.

Performance Characteristics:

6. Comparison
to predicate
device, (cont.)

**Performance Characteristics:**

| Feature | Elecsys Vitamin B12 | BioRad Quantaphase II<br>B12/Folate Radioassay |
|-----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------|
| Lower<br>Detection<br>Limit | 30 pg/ml | 20 pg/ml |
| Linearity | 30 - 2000 pg/ml | 20 - 2000 pg/ml |
| Method<br>Comparison | Vs BioRad Quantaphase II<br>B12/Folate Radioassay<br><br>Least Squares<br>$y =1.02X + 6.5$<br>$r=0.9751$<br>$N=346$<br><br>Passing Bablock:<br>$y=1.06X - 9.5$<br>$r=0.9751$<br>$N=346$ | Vs Commercially available<br>radioimmunoassay<br>$y =1.01x + 44$<br>$r=0.933$<br>$N=84$ |

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### 10(k) Summary, Continued RPORATIC

6.

o.
Comparison
to predicate
device, (cont.)

i

### Performance Characteristics:

| Feature | Elecsys Vitamin B12 | BioRad Quantaphase II<br>B12/Folate Radioassay |
|---------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------|
| Interfering<br>substances | No interference at:<br>(within 30 pg/ml at<br>Vitamin B12 level <300<br>pg/ml or within ±10% at<br>Vitamin B12 level > 300<br>pg/ml.) | No interference at: |
| Bilirubin | 80 mg/dL | 20 mg/dL unconjugated<br>20 mg/dL conjugated |
| Hemoglobin | 1800 mg/dL | 500 mg/dL |
| Lipemia | 2500 mg/dL | 3000 mg/dL |
| Rheumatoid Factor | 500 IU/mL | N/A |
| Dysproteinemia | 8.8 g/dL | N/A |
| Biotin | 50 pg/ml | N/A |
| Reference<br>Range<br>Vitamin B12,<br>pg/ml | Normal: 243 - 894<br>Indeterminant:<br>175 - 244<br>Deficient:<174 | Normal: 130 - 770<br><br>Deficient:<204 |
| | % Cross-reactivity | % Cross-reactivity |
| Cobinamide | 0.024 | 0.1 |

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Image /page/6/Picture/1 description: The image shows the words "Public Health Service" in bold, black font. The words are stacked on one line. The words are clearly legible and the image is simple.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Yvette Lloyd Boehringer Mannheim Corporation 4300 Hacienda Drive Pleasanton, California 94588-2722

NOV 1 3 1997

Re: K973702 Elecsys Vitamin B12 Assay Trade Name: Tier: II Requlatory Class: II Product Code: CDD Dated: September 24, 1997 September 26, 1997 Received:

Dear Ms. Lloyd:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 A substantially equivalent determination assumes compliance to 895. with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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10:38

510(k) Number (if known): N/A

Device Name: Elecsys Vitamin B12 Assay

Indications For Use:

A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.

Concurrence of CDRH, Office of Device Evaluation (ODE)

| Prescription Use | ✓ |
|----------------------|---|
| (Per 21 CFR 801.109) | |

OR

| Over-The-Counter Use | |
|--------------------------|--|
| (Optional Format 1-2-96) | |

(Division Sign-Off)
Division of Clinical Laboratory Devices.
510(k) Number K973702