IMMULITE/IMMULITE 1000 CALCITONIN, MODEL LKCL AND IMMULITE 2000 CALCITONIN, MODEL L2KCL

K023304 · Diagnostic Products Corp. · JKR · Dec 9, 2002 · Clinical Chemistry

Device Facts

• Record ID: K023304
• Device Name: IMMULITE/IMMULITE 1000 CALCITONIN, MODEL LKCL AND IMMULITE 2000 CALCITONIN, MODEL L2KCL
• Applicant: Diagnostic Products Corp.
• Product Code: JKR · Clinical Chemistry
• Decision Date: Dec 9, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1140
• Device Class: Class 2

Indications for Use

IMMULITE/IMMULITE 1000 Calcitonin For in vitro diagnostic use with the IMMULITE/IMMULITE 1000 Analyzer - for the quantitativ measurement of calcitonin (thyrocalcitonin) in human serum, as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism IMMULITE 2000 Calcitonin For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the quantitative measurement of calcitonin (thyrocalcitonin) in human serum, as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.

Device Story

IMMULITE/IMMULITE 1000 and IMMULITE 2000 Calcitonin are automated, solid-phase, chemiluminescent enzyme immunoassays. Input: human serum sample. Process: sample incubated with alkaline phosphatase-conjugated polyclonal goat anti-calcitonin in a test unit/reaction tube containing a polystyrene bead coated with monoclonal murine anti-calcitonin; formation of antibody-sandwich complex; centrifugal wash removes unbound conjugate; addition of phosphate ester of adamantyl dioxetane substrate; hydrolysis by alkaline phosphatase produces unstable intermediate emitting light. Output: photon output measured by system luminometer, proportional to calcitonin concentration. Used in clinical laboratories; operated by trained laboratory personnel. Results used by physicians to aid diagnosis and management of thyroid/parathyroid conditions.

Clinical Evidence

Method comparison study performed on 53 patient samples for IMMULITE/IMMULITE 1000 and 67 patient samples for IMMULITE 2000, comparing results against the Nichols Advantage Calcitonin assay. Linear regression analysis for IMMULITE/IMMULITE 1000 yielded r=0.990; IMMULITE 2000 yielded r=0.982. No clinical prospective or retrospective diagnostic accuracy studies provided.

Technological Characteristics

Solid-phase, enzyme-labeled, two-site chemiluminescent immunometric assay. Solid-phase: polystyrene bead coated with monoclonal murine anti-calcitonin. Detection: alkaline phosphatase-conjugated polyclonal goat anti-calcitonin. Substrate: phosphate ester of adamantyl dioxetane. Energy source: automated luminometer. Connectivity: integrated with IMMULITE/IMMULITE 1000 or IMMULITE 2000 automated analyzers.

Indications for Use

Indicated for quantitative measurement of calcitonin in human serum to aid diagnosis and treatment of thyroid and parathyroid gland diseases, including carcinoma and hyperparathyroidism.

Regulatory Classification

Identification

A calcitonin test system is a device intended to measure the thyroid hormone calcitonin (thyrocalcitonin) levels in plasma and serum. Calcitonin measurements are used in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism (excessive activity of the parathyroid gland).

Predicate Devices

• Nichols Advantage™ Calcitonin (K964635)

Submission Summary (Full Text)

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IC23304

# DEC 0 9 2002

## 510 (k) Summary Safety and Effectiveness

This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.

| Name: | Diagnostic Products Corporation |
|---------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address: | 5700 West 96th Street<br>Los Angeles, CA 90045 |
| Telephone Number: | [phone] |
| Facsimile Number: | [phone] |
| Contact Person: | Edward M. Levine, Ph.D.<br>Director of Clinical Affairs |
| Date of Preparation: | October 1, 2002 |
| Device Name: | |
| Trade: | IMMULITE®/IMMULITE® 1000 Calcitonin<br>IMMULITE® 2000 Calcitonin |
| Catalog Number: | LKCL<br>L2KCL |
| CFR: | A calcitonin test system is a device intended to measure the<br>thyroid hormone calcitonin (thyrocalcitonin) levels in<br>plasma and serum. Calcitonin measurements are used in<br>the diagnosis and treatment of diseases involving the<br>thyroid and parathyroid glands, including carcinoma and<br>hyperparathyroidism (excessive activity of the parathyroid<br>gland). |
| Common: | Reagent system for the determination of calcitonin in<br>serum. |
| Classification: | Class II device, JKR (21 CFR 862.1140) |
| Panel: | Clinical Chemistry |
| CLIA Complexity Category: | We believe the category to be moderate, based on previous<br>classification of analogous tests. |
| Manufacturer: | Diagnostic Products Corporation (DPC)<br>5700 West 96th Street<br>Los Angeles, CA 90045-5597 |

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| Establishment<br>Registration #: | DPC's establishment Registration No. is 2017183 |
|-----------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Substantially Equivalent<br>Predicate Device: | Nichols Advantage™ Calcitonin (K964635) |
| Description of Device: | IMMULITE/IMMULITE 1000 Calcitonin and IMMULITE<br>2000 Calcitonin are solid-phase, chemiluminescent enzyme<br>immunoassays for use with their respective<br>IMMULITE/IMMULITE 1000 and IMMULITE 2000<br>Automated Analyzers. |
| Intended Use of the<br>Device: | IMMULITE/IMMULITE 1000 Calcitonin and IMMULITE<br>2000 Calcitonin are for <i>in vitro</i> diagnostic use for the<br>quantitative measurement of calcitonin in human serum, as<br>an aid in the diagnosis and treatment of diseases involving<br>the thyroid and parathyroid glands, including carcinoma<br>and hyperparathyroidism. |

### Technology:

This section does not contain any new information for a reviewer who is familiar with the DPC IMMULITE System based upon the review of previous IMMULITE and IMMULITE 2000 assay submissions.

IMMULITE/IMMULITE 1000 Calcitonin is a solid-phase, enzyme-labeled, two-site chemiluminescent immunometric assay. The solid-phase, a polystyrene bead enclosed within an IMMULITE/IMMULITE 1000 Test Unit, is coated with a monoclonal murine antibody specific for calcitonin.

While the patient serum sample and alkaline phosphatase-conjugated to polyclonal goat anti-calcitonin are incubated for approximately 30 minutes at 37℃ in the Test Unit with intermittent agitation, calcitonin in the sample is bound to form an antibody sandwich complex. Unbound enzyme conjugate is then removed by a centrifygal wash, after which substrate is added and the Test Unit is incubated for a further 10 minutes.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex and thus also the photon output, as measured by the luminometer - is proportional to the concentration of calcitonin in the sample.

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IMMULITE 2000 Calcitonin is a solid-phase, enzyme-labeled, two-site chemiluminescent immunometric assay. The solid-phase, a polystyrene bead, is coated with a monoclonal murine antibody specific for calcitonin.

While the patient serum sample and alkaline phosphatase-conjugated to polyclonal goat anti-calcitonin are incubated for approximately 30 minutes at 37℃ in the Reaction Tube with intermittent agitation, calcitonin in the sample is bound to form an antibody sandwich complex. Unbound enzyme conjugate is then removed by a centrifugal wash, after which substrate is added and the Reaction Tube is incubated for a further 5 minutes.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex and thus also the photon output, as measured by the luminometer - is proportional to the concentration of calcitonin in the sample.

Nichols Advantage Calcitonin assay is a two-site chemiluminescence immunoassay for the measurement of calcitonin in human serum. It utilizes two mouse monoclonal antibodies to human calcitonin. One of the mouse monoclonal antibodies is labeled with acridinium ester for detection, while a second mouse monoclonal antibody is coupled to biotin. Calcitonin is "sandwiched" between these antibodies.

The sample containing calcitonin is incubated simultaneously with both antibodies. The formation of a soluble sandwich complex occurs only in the presence of calcitonin molecules, which bridge the two antibodies. Therefore, only peptides that bridge these two antibodies can be quantitated.

After an initial incubation period, steptavidin coated magnetic particles are added to the reaction mixture and a second incubation follows. This allows for a highly specific and efficient means of binding the sandwich complex to the solid phase via the high affinity interaction between biotin and streptavidin. Free labeled antibody is separated from the labeled antibody bound to the magnetic particles by aspiration of the reaction mixture and subsequent washing. The wells containing the washed magnetic particles are transported into the system luminometer, which automatically injects Trigger 2, initiating the chemiluminescence reaction. The light is quantitated by the luminometer and expressed as RLU. The amount of bound labeled antibody is directly proportional to the concentration of calcitonin in the sample.

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### Performance Equivalence:

Diagnostic Products Corporation asserts that the IMMULITE/IMMULITE 1000 Calcitonin and IMMULITE 2000 Calcitonin produce substantially equivalent results to other commercially marketed Calcitonin assays, such as Nichols Advantage™ Calcitonin used with the Nichols Advantage™ Specialty System. Each product is designed for the quantitative measurement of calcitonin in human serum. Each product is intended strictly for in vitro diagnostic use as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.

### Method Comparison

The IMMULITE/IMMULITE 1000 Calcitonin procedure was compared to a commercially available assay (Nichols Advantage) on 53 patient samples, with calcitonin concentrations ranging up to approximately 1,200 pg/mL. Linear regression analysis vielded the following statistics.

| | (IMMULITE/IMMULITE 1000) = 0.71 (Nichols) + 4.2 pg/mL | r = 0.990 |
|--|-------------------------------------------------------|-----------|
| | Mean = 155 pg/mL (IMMULITE/IMMULITE 1000) | |

155 pg/mL (IMMULITE/IMMULITE 1000) Means: 212 pg/mL (Nichols)

The IMMULITE 2000 Calcitonin procedure was compared to a commercially available assay (Nichols Advantage) on 67 patient samples, with calcitonin concentrations ranging up to approximately 1,500 pg/mL. Linear regression analysis yielded the following statistics.

(IMMULITE 2000) = 0.81 (Nichols) - 0.4 pg/mL r = 0.982

Means: 193 pg/mL (IMMULITE 2000) 239 pg/mL (Nichols)

#### Conclusion:

The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® IMMULITE® 1000 Calcitonin and IMMULITE® 2000 Calcitonin.

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### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, consisting of a staff with two snakes coiled around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus. The seal is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

# DEC 0 9 2007

Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostics Products Corporation 5700 West 96th Street Los Angeles, CA 90045-5597

Re: k023304

.

Trade/Device Name: IMMULITE®/ IMMULITE® 1000 Calcitonin IMMULITE® 2000 Calcitonin Regulation Number: 21 CFR 862.1140 Regulation Name: Calcitonin test system Regulatory Class: Class II Product Code: JKR; JJY Dated: October 1, 2002 Received: October 3, 2002

Dear Dr. Levine

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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. Iisting 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 –

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer 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 Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# 510(k) Number (if known): Device Name: IMMULITE®/IMMULITE® 1000 Calcitonin IMMULITE® 2000 Calcitonin

Indications For Use:

### IMMULITE/IMMULITE 1000 Calcitonin

For in vitro diagnostic use with the IMMULITE/IMMULITE 1000 Analyzer - for the quantitativ measurement of calcitonin (thyrocalcitonin) in human serum, as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism

#### IMMULITE 2000 Calcitonin

For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the quantitative measurement of calcitonin (thyrocalcitonin) in human serum, as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.

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# 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)

22 n 002

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