AXSYM INTACT PTH, MODEL 2G06

{0}------------------------------------------------ # SUMMARY OF SAFETY AND EFFECTIVENESS 4.0 Diagnostic Systems Laboratories, Inc. Submitter: 445 Medical Center Boulevard Webster, Texas 77598 Phone: 281-332-9678 FDA Registration # 1628193 Contact: Carroll Potts Manager of Regulatory Affairs Office: (281) 332-9678 Fax: (281) 338-1895 cpotts@dslabs.com | Date of Summary: | May 22, 2002 | |------------------------|---------------------------------------| | Device Trade Name: | AxSYM Intact PTH | | Regulation Cite: | 21CFR862.1545 | | Classification Name: | Parathyroid Hormone | | Analyte Code and Name: | (CEW) Parathyroid Hormone Test System | | Regulatory Class: | II | This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92 to provide sufficient detail to understand the basis for a determination of substantial equivalence. 8020945 The assigned 510(k) number is:________________________________________________________________________________________________________________________________________________ #### Test Description: 4.1 Parathyroid hormone (PTH, parathyrin) is synthesized as a pre-pro hormone 4.1.1 by the chief cells of the parathyroid glands [1,2]. In normal physiology, PTH levels increase in response to decreased serum calcium and decrease in response to increased serum calcium resulting in a close inverse relationship between PTH and calcium concentrations [1,6]. Abnormal PTH levels can thus be detected by examining this interrelationship. Concurrent increases in PTH and calcium occur in the various forms of hyperparathyroidism, including multiple endocrine neoplasia (MEN) types I and II, parathyroid turnors, and idiopathic hyperparathyroidism [6,7]. Concurrent declines in calcium and PTH occur in the various forms of primary hypoparathyroidism and in disorders affecting PTH secretion, such as hypo- or hyper-magnesemia [8]. Abnormally low calcium levels in the presence of extremely elevated PTH levels can occur in a group of genetic disorders called pseudohypoparathyroidism [9]. Abnormally high calcium levels in the presence of low or normal PTH levels are characteristic of malignancy-associated hypercalcemia secondary to PTH-related peptide (PTHrP) production [10]. Abnormal concentrations and/or actions of PTH with essentially normal serum calcium levels may also occur, e.g. in renal osteodystrophy [11]. NOTE: The bibliography notations used make reference to the Bibliography Section at the end of the AxSYM I PTH Package Insert. {1}------------------------------------------------ Immunoassays for I-PTH and its two major metabolic fragments have been 4.1.2 developed. Clinical investigations indicate that the diagnostic sensitivities of the Nterminal and C-terminal assays are limited, possibly due in part to variable concentrations of minor fragments and the performance characteristics of the assays [1,4]. Selective measurement of mainly I PTH has theoretical advantages since it may be more reflective of biologically active PTH production and action. The AxSYM® I PTH assay uses paired monoclonal and polyclonal 4.1.3 antibodies, each reactive with epitopes in the N-terminal portion of intact human PTH (1-84). The polyclonal antibody is biotin labeled. I PTH in the sample serves to bridge the two antibodies. #### 4.2 Principle Of The Test: AxSYM I PTH is based on the Microparticle Enzyme Immunoassay 4.2.1 (MEIA) technology. The AxSYM I PTH reagents and sample are pipetted in the following sequence: #### 4.2.2 SAMPLING - Sample and all AxSYM® I PTH Reagents required for one test are pipetted by . the sampling probe into various wells of a Reaction Vessel (RV). The RV is immediately transferred into the Processing enter. Further pipetting is done in the Processing Center by the Processing Probe. #### PROCESSING 4.2.3 - An aliquot of the reaction mixture containing the antibody-antigen complex . bound to the microparticles is transferred to the matrix cell. The microparticles bind irreversibly to the glass fiber matrix.. - The matrix cell is washed with the TRIS Wash Buffer. ● - The Anti-PTH: Biotin Conjugate is dispensed onto the matrix cell and binds . with the antibody-antigen complex. - The matrix cell is washed to remove unbound materials. . - The Anti-Biotin: Alkaline Phosphatase Conjugate is then dispensed onto the . matrix cell and binds with the biotinylated antibody-antigen complex. - The matrix cell is washed to remove unbound materials. . - The substrate, 4-Methylumbelliferyl Phosphate, is added to the matrix cell and . the fluorescent product is measured by the MEIA optical assembly. {2}------------------------------------------------ #### 4.3 Intended Use: AxSYM® Intact PTH is a Microparticle Enzyme Immunoassay (MEIA) for the in vitro quantitative determination of intact human parathyroid hormone (I PTH) in human serum or plasma on the AxSYM® system. The AxSYM® I PTH assay is intended for use as an aid in the differential diagnosis of hypercalcemia and hypocalcemia. #### 4.4 Substantial Equivalence: The AxSYM® Intact PTH assay is substantially equivalent to another 4.4.1 device marketed in the United States. We claim equivalence to the DSL-8000 ACTIVE™ Intact PTH IRMA (K896294). - To demonstrate substantial equivalence between the two assays, serum and 4.4.2 plasma samples were assayed using both methods. Method correlation between the AxSYM® I PTH and the predicate device was examined using 120 samples. The resulting regression equation was determined to be: [AxSYM® I PTH] = 0.99 [DSL ACTIVE™ I PTH IRMA] + 10.0 r = 0.97 p < 0.0001 The results of least squares regression analysis indicated very high correlation between the two methods (r = 0.97). The 95% confidence interval about the slope is [95% CI (0.95, 1.05)]. This correlation between the two methods is highly significant (p<0.0001). The 95% CI about the intercept is [95% CI (-11.72, 31.82)]. The intercept is not statistically significant (p<0.35). Specimen values ranged from 4 - 1961 pg/mL with the AxSYM® I PTH and 6 – 1836 pg/mL with the predicate device, DSL ACTIVE™ Intact PTH IRMA. {3}------------------------------------------------ Similarities: The following table compares the similarities between the AxSYM® I PTH assay with the predicate device: | Feature | AXSYM® I PTH | Predicate Device<br>(K896294) | |--------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------| | Assay Principle | Sandwich Assay | Sandwich Assay | | Intended Use | for the <i>in vitro</i> quantitative<br>determination of intact human<br>parathyroid hormone (I PTH)<br>in human serum or plasma on<br>the AxSYM® system | for the quantitative<br>measurement of Intact PTH (I-<br>PTH) in serum or plasma. | | Indication for Use | an aid in the differential<br>diagnosis of hypercalcemia and<br>hypocalcemia | None stated in package insert | | Sample type | Human serum or plasma | Human serum or plasma | | Sample required | 185 µL | 200 µL | | Dynamic Range | 0 - 2000 pg/mL | 0 - 2000 pg/mL | | Expected Values | 8 - 57.8 pg/mL | 9 - 55 pg/mL | | Traceability | Traceable to DSL I PTH<br>IRMA | Traceable to Nichols I PTH<br>Assay | The following table compares the differences between the AxSYM I PTH Differences: assay and the predicate device: | Feature | AxSYM I PTH | Predicate Device (K896294) | |------------------|-------------------------------------------------------------------------------------|-------------------------------------------------------------------------| | Assay Technology | Microparticle Enzyme<br>Immunoassay (MEIA)<br>employing the "sandwich"<br>principle | Immunoradiometric Assay<br>(IRMA) employing the<br>"sandwich" principle | | Instrument | AxSYM Immunoassay<br>Analyzer | Gamma Counter | {4}------------------------------------------------ # Performance Characteristics: The following table compares the assay performance characteristics between the | Characteristics | AxSYM® Intact PTH | Predicate Device (K896294) | |---------------------------|---------------------------------------------------------------|---------------------------------------------------------------| | Precision (Within<br>Run) | Level I (35.3 pg/mL): 5.9 % CV | Level I (13.0 pg/mL): 3.1 % CV | | | Level II (202.9 pg/mL): 6.2 % CV | Level II (23.0 pg/mL): 3.5 % CV | | | Level III (649.7 pg/mL): 6.5 % CV | Level III (476 pg/mL): 1.9 % CV | | Precision (Inter) | Level I (35.3 pg/mL): 9.4 % CV | Level I (13.0 pg/mL): 3.1 % CV | | | Level II (202.9 pg/mL): 8.1 % CV | Level II (23.0 pg/mL): 5.2 % CV | | | Level III (649.7 pg/mL): 8.8 % CV | Level III (472.0 pg/mL): 2.6 % CV | | Linearity (Mean ± SD) | 93.8 ± 8.9 % | 94.2 ± 10.5 % | | Recovery (Mean ± SD) | 95.3 ± 8.9 % | 97.7 ± 5.2 % | | Analytical Sensitivity | ≤ 2.0 pg/mL I PTH | 6.0 pg/mL I PTH | | Specificity | No detection of human PTH fragments<br>53-84, 44-68 and 39-84 | No detection of human PTH<br>fragments 53-84, 44-68 and 39-84 | | Interference | Bilirubin (20 mg/dL): < 10 % | ND | | | Triglycerides (1500 mg/dL): < 10 % | ND | | | Total Protein (3 mg/dL): < 10 % | ND | | | Hemoglobin (1000 mg/dL): < 10 % | ND | | | Red Blood Cells (0.2 % v/v): < 10 % | ND | | Limitations | No high dose effect up to 100K pg/mL | No high dose effect up to 300K pg/mL | | On-board Stability | 14 days @ 31°C | N/A | AxSYM® I PTH and the predicate device: N/A = Not Applicable ND = Not Determined #### Safety & Effectiveness: 4.5 - As explained in Section 4.1 of this submission, the I PTH levels are used in 4.5.1 conjunction with calcium levels as a clinical diagnostic tool to support the diagnosis of a disorder, as explained in the Summary and Explanation of the Test in the beginning of the AxSYM® I PTH Package Insert in Section 6.0. The I PTH assay is not used as a stand-alone test. Clinical interpretation requires simultaneous measurement of serum calcium levels. The levels of I PTH and calcium are repeated over a period of time for a diagnosis and during any type of treatment for effectiveness. - 4.5.2 The safety of use for both I PTH assays is substantially equivalent, but the AxSYM® I PTH assay has less risk associated with it due to the absence of radioactive materials. - Therefore, we conclude the safety and effectiveness of both assays are 4.5.3 substantially equivalent and favor the AxSYM® I PTH assay. {5}------------------------------------------------ ### Substantial Equivalence Conclusion 4.6 We conclude that the data and information supplied in this summary provide enough detail and support for our claim of substantial equivalence between the AxSYM® Intact PTH assay and the predicate device, DSL-8000 ACTIVE™ Intact PTH IRMA. {6}------------------------------------------------ Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird with three curved lines forming its body and wings. The bird is positioned within a circular border, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper portion of the circle. Food and Drug Administration 2098 Gaither Road Rockville MD 20850 MAY 3 1 2002 Mr. Carroll Potts, M.S. Manager of Regulatory Affairs Diagnostic Systems Laboratories, Inc. 445 Medical Center Blvd. Webster, TX 77598 k020945 Re: Trade/Device Name: AxSYM® Intact PTH Regulation Number: 21 CFR 862.1545; 21 CFR 862.1150; 21 CFR 862.1660 Regulation Name: Parathyroid hormone test system; Calibrator; Quality control material (assayed and unassayed) Regulatory Class: Class II Product Code: CEW; JIT; JIX Dated: March 22, 2002 Received: March 25, 2002 Dear Mr. Potts: 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, 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 (PMA), 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 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. {7}------------------------------------------------ Page 2 - 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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 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 {8}------------------------------------------------ ## INDICATIONS FOR USE 1.0 510 (k) Number (if known): Kozo945 Device Name: AxSYM® Intact PTH Indications for Use: AxSYM® Intact PTH is a Microparticle Enzyme Immunoassay (MEIA) for the in vitro quantitative determination of intact human parathyroid hormone (I PTH) in vitro quantiturre determination oxSYM® system. The AxSYM® I PTH assay is intended for use as an aid in the differential diagnosis of hypercalcemia and hypocalcemia. Jean Cooper (Division Sign-OB) Division of Clinical Laboratory Devices 510(k) Number K020945 (Please Do Not Write Below This Line. Continue On Another Page If Needed) Concurrence of CDRH, Office of Device Evaluation (ODE) ن Prescription Use (Per 21 CFR 801.109) OR Over-The Counter Use _________________________________________________________________________________________________________________________________________________________