ACCESS OSTASE IMMUNOENZYMETRIC ASSAY

K994278 · Beckman Coulter, Inc. · CIN · Mar 28, 2000 · Clinical Chemistry

Device Facts

• Record ID: K994278
• Device Name: ACCESS OSTASE IMMUNOENZYMETRIC ASSAY
• Applicant: Beckman Coulter, Inc.
• Product Code: CIN · Clinical Chemistry
• Decision Date: Mar 28, 2000
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1050
• Device Class: Class 2

Intended Use

This device is intended to be used as an aid in the management of postmenopausal osteoporosis and Paget's disease.

Device Story

Access Ostase Assay is a paramagnetic particle, chemiluminescent immunoassay used with the Access Immunoassay System. It measures bone alkaline phosphatase (BAP) in human serum and plasma samples. The device utilizes a monoclonal antibody to BAP on magnetic particles; the assay signal is generated via an automated luminometer. The system is intended for clinical laboratory use to assist physicians in managing postmenopausal osteoporosis and Paget's disease by providing quantitative data on osteoblastic activity. The automated process replaces manual radiometric methods, offering improved workflow efficiency for laboratory technicians. Results are provided to clinicians to inform patient management decisions.

Clinical Evidence

Bench testing only. Method comparison study (N=172) between Access Ostase and Tandem-R Ostase showed a slope of 0.9756, intercept of -0.5987, and r=0.9895. Mean percentage differences were -5.96% for osteoporosis patients and -7.01% for Paget's disease patients. Imprecision studies showed total %CV ranging from 3.6% to 6.4%. Spike and recovery averaged 92.4%; dilution recovery averaged 92.2%. No significant interference was observed for tested substances including acetaminophen, aspirin, and various bone-related medications.

Technological Characteristics

Paramagnetic particle, chemiluminescent immunoassay. Solid phase: magnetic particles. Detection: luminometer. Analyte: bone alkaline phosphatase. Specimen matrix: human serum and plasma. Automated system. Software-controlled assay processing.

Indications for Use

Indicated for the quantitative measurement of bone alkaline phosphatase (BAP) in human serum and plasma as an aid in the management of postmenopausal osteoporosis and Paget's disease.

Regulatory Classification

Identification

An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Predicate Devices

• Tandem®-R Ostase® Assay (K961573)

Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS

#### 1.0 SUBMITTED BY:

Jill Kull, RAC, Staff Regulatory Specialist Beckman Coulter Inc., 7330 Carroll Rd. / P.O. Box 269006, San Diego, CA 92196-9006 Telephone: [phone] FAX: [phone] e-mail: [e-mail]

#### 2.0 DATE SUBMITTED:

March 14, 2000

#### DEVICE NAME(S) 3.0

- 3.1 Proprietary Names Access® Ostase® Assay on the Access Immunoassay Analyzer 3.2
- Classification Names Bone alkaline phosphatase (BAP) test system.

#### PREDICATE DEVICE 4.0

| Beckman Coulter<br>Product | Predicate | Predicate Company | Docket<br>Number |
|----------------------------|----------------------------|-----------------------|------------------|
| Access® Ostase®<br>Assay | Tandem®-R<br>Ostase® Assay | Beckman Coulter, Inc. | K961573 |

#### 5.0 DESCRIPTION OF THE DEVICE

The Access Ostase Assay is a paramagnetic particle, chemiluminescent immunoassay for use with the Access Immunoassay System for the quantitative measurement of bone alkaline phosphatase (BAP), an indicator of osteoblastic activity, in human serum and plasma.

Beckman Coulter Inc., Section 510(k) Notification Access® Ostase® Assay - K994278 Additional Information

Page 26

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### 6.0 INTENDED USE OF THE DEVICE

This device is intended to be used as an aid in the management of postmenopausal osteoporosis and Paget's disease.

### 7.0 COMPARISON TO THE PREDICATE

| Technological<br>Characteristic | Access Ostase | Tandem-R<br>Ostase<br>(Predicate) |
|---------------------------------|--------------------------------------------------------------------------------|-----------------------------------|
| Analyte<br>Measured | Human bone alkaline phosphatase | Same |
| Intended Use | Aid in the management of<br>postmenopausal osteoporosis and<br>Paget's disease | Same |
| Solid Phase<br>Antibody | Monoclonal antibody to BAP | Same |
| Specimen Matrix | Human serum and plasma | Human serum |
| Assay Signal | Enzymetric/<br>Luminometer | Radiometric/<br>Gamma Counter |
| Assay Solid<br>Phase | Magnetic particles | Bead |
| System Method | Automated | Manual |

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### 8.0 SUMMARY OF PERFORMANCE DATA

#### 8.1 Method Comparison Study Results

### Access Ostase vs. Tandem-R Ostase

| Slope | Intercept | r | N |
|--------|-----------|--------|-----|
| 0.9756 | -0.5987 | 0.9895 | 172 |

### Mean % Differences Between Access Ostase and Tandem-R Ostase

| Populations | N<br>(# pairs) | Mean<br>%Difference* | Standard<br>Deviation |
|--------------|----------------|----------------------|-----------------------|
| Osteoporosis | 88 | -5.96% | 12.37% |
| Paget's | 84 | -7.01% | 14.25% |

* Mean % Difference = [(Access -Tandem )/(Access+ Tandem/2)) X 100

#### 8.2 Imprecision Summary

The between-run %CV observed across the concentrations tested ranged from 3.3% to 5.9%. The within-run %CV observed across the concentrations tested ranged from 1.5% to 2.6%. The total %CV observed across the concentrations tested ranged from 3.6% to 6.4%.

#### 8.3 Recovery and Specimen Dilution

The results of spike and recovery across 15 samples ranged from 89.9% to 95.3% with an average recovery of 92.4%.

The results for ten (10) samples in the dilution study ranged from 78.1% to 106.1% with an average recovery of 92.2%. Regression analysis of these data yielded slopes ranging from 0.9280 to 1.0075 with an overall average slope of 0.9682. Correlation coefficients (r) ranged from 0.9999 to 0.9983 with an overall average correlation coefficient of 0.9994.

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### 8.4 Interfering Substances

The following substances and concentrations were evaluated for interference in the Access Ostase Assay. There is no significant interference from any of the substances tested at these concentrations.

| Substance | Concentration<br>Tested | Substance | Concentration<br>Tested |
|-------------------------------------------|-------------------------|---------------|-------------------------|
| Acetaminophen | 35 mg/dL | Ibuprofen | 40 mg/dL |
| alendronate | 8 mg/dL | Pamidronate | 18 mg/dL |
| Aspirin | 50 mg/dL | progesterone | 25 mg/dL |
| bilirubin –<br>unconjugated<br>conjugated | 40 mg/dL<br>20 mg/dL | protein | 3.8 and<br>15.6 g/dL |
| calcitonin-salmon | 112 IU/dL | raloxifene | 12 mg/dL |
| Calcium | 40 mg/dL | risedronate | 6 mg/dL |
| estrogen | 10 mg/dL | triglycerides | 2000 mg/dL |
| etidronate | 105 mg/dL | vitamin D | 80,500 IU/dL |
| hemoglobin | 500 mg/dL | | |

In summary, there is no significant interference from any of the substances tested at the concentrations listed above.

- 8.5 Reactivity with Intestinal, Placental and Liver Alkaline Phosphatase lsoenzymes
In these studies, 100 U/L of intestinal alkaline phosphatase yielded a result of 1.8 µg/L in the Access Ostase Assay. 100 U/L of placental alkaline phosphatase activity yielded a result of 0.3 µg/L in the Access Ostase Assay.

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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- Question 4. Please add a statement at the beginning of the clinical trial section indicating that all the clinical trials were performed with the Tandem-R.
- The following statement was added to page 5 (page 95 of the original Answer: submission) of the directional insert.

# CLINICAL STUDIES

In the following section the studies were generated using the Tandem-R Ostase Assay.

Question 5: Please send a copy of the revised labeling for the File.

Answer: A copy of the revised directional insert is attached.

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Image /page/5/Picture/2 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the seal is a stylized image of three birds in flight, arranged in a row.

MAR 28 2000

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Ms. Jill Kull, RAC Staff Regulatory Specialist Beckman Coulter, Inc. 7330 Carroll Road P.O. Box 269006 San Diego, California 92196-9006

K994278 Re: Trade Name: Access® Ostase® Assay Regulatory Class: II Product Code: CIN, JIS Dated: March 14, 2000 Received: March 15, 2000

Dear Ms. Kull:

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 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). 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 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, 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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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" (21CFR 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 [phone] or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

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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# INDICATIONS FOR USE STATEMENTS

510(k) Number (if known): Not yot assigned

Access® Ostase® Assay Device Name:

Indications for Use:

Beckman Coulter, Inc's Access Ostase Assay is a paramagnetic particle, chemiluminescent immunoassay for use with the Access Immunoassay System for the quantitative measurement of bone alkaline phosphatase (BAP), an indicator of osteoblastic activity, in human serum and plasma. This device is intended to be used as an aid in the management of postmenopausal osteoporosis and Paget's disease.

# 21 CFR 862.1050 Alkaline Phosphatase or isoenzymes test system

- (a) Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
(b) *Classification*. Class II.

Division of Clinical Laboratory Devices

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

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

Beckman Coulter Inc., Section 510(k) Notification Access® Ostase® Assay AccessOstase\Section_1.doc

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