K Number

Device Name

1,25-DIHYDROXYVITAMIN D125I RIA

Manufacturer

DIASORIN, INC.

Date Cleared

2002-03-26

(110 days)

Product Code

MRG

Regulation Number

862.1825

Intended Use

The 1,25-Dihydroxyvitamin D 1251 RIA is a competitive equilibrium radioimmunoassay intended for the quantitative determination of 1,25 dihydroxyvitamin D (1,25-(OH)2-D) in human serum or EDTA plasma to be used to assess 1,25-(OH)2-D deficiency associated with renal disease. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions in adult populations.

Device Description

The 1,25-Dihydroxyvitamin D 1251 RIA is a competitive radioimmunoassay intended for the quantitative determination of 1,25 Dihydroxyvitamin D (1,25-(OH)2-D) in human serum or EDTA plasma. The assay consists of a two-step procedure. Serum or plasma patient samples as well as standards and kit controls are first extracted with acetonitrile to free the 1,25-(OH)2 vitamin D2 and D3 from their vitamin D binding protein, and remove lipids that might interfere with the assay. The metabolites are then extracted by column chromatography on C18OH silica cartridges using a series of organic solvent washes. Following the extraction, the treated samples are assayed using a competitive radioimmunassay procedure. The primary antibody (rabbit anti-1,25-(OH)2 vitamin D) is highly specific for both 1,25(OH)2 vitamin D3 and 1,25(OH)2.vitamin D2. Vitamin D) is inghty specific for both 1,25(011)2 (011)2 vitamin D tracer Daring the binding sites on the primary antibody. Separation of bound and unbound vitamin D2 or D3 is accomplished using a goat anti-rabbit (GAR) polyethylene glycol precipitating complex. After an incubation and centrifugation, sample precipitates are proofitaing complex. The amount of radioactivity in the precipitate is inversely proportional to the concentration of 1,25-(OH)2 vitamin D in the sample. Values are proportional to the coma standard curve of known calibrators and expressed as pg/ml.

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Type

Center

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Date Received

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Applicant Name (Manufacturer)

Device Name

Decision

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ZIP

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Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

DiaSorin 25-Hydroxyvitamin D 1251 RIA

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a radioimmunoassay procedure involving chemical extraction, competitive binding, and radioactivity measurement. There is no mention of AI or ML in the intended use, device description, or performance studies.

Therapeutic

No.
The device is a diagnostic assay used to measure a substance in the body to assess a deficiency, and the results are used in conjunction with other clinical data for diagnosis and management decisions, not for direct therapeutic treatment.

Diagnostic

Yes

The device is intended for the quantitative determination of 1,25 dihydroxyvitamin D to assess 1,25-(OH)2-D deficiency associated with renal disease and to assist clinicians in patient management decisions, which falls under the definition of a diagnostic device.

SaMD (Software as a Medical Device)

The device description details a radioimmunoassay procedure involving physical components like reagents, columns, and a precipitating complex, indicating it is a hardware-based assay kit, not software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's for the "quantitative determination of 1,25 dihydroxyvitamin D (1,25-(OH)2-D) in human serum or EDTA plasma". This indicates it's used to test human samples in vitro (outside the body).
Device Description: The description details a laboratory procedure involving "human serum or EDTA plasma patient samples" and various chemical and immunological steps to measure a substance within those samples. This is characteristic of an in vitro diagnostic test.
Performance Studies: The performance studies describe collecting "Serum values" from human populations and evaluating the assay's ability to discriminate between different patient groups based on those serum values. This further confirms its use in analyzing human biological samples.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes

MRG

Device Description

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

adult populations

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

A clinical trial was conducted at three independent clinical laboratories. Serum values for 1,25(OH)2-vitamin D were collected from two distinct populations: apparently healthy normal donors, and patients with end-stage renal disease (ESRD). Reference ranges established in the trial are summarized below.

All Sites

Population	n	Mean	2 SD	Range
Normals	123	43.9	24.1	19.8-68.0
ESRD's	87			1.6-17.3

The equivalency of assay samples as either fresh serum or serum that has been frozen and The equivalely of about bangles mory table with 95% ANOVA determined P-values is presented below.

	Normals		ESRD's
	Frozen	Fresh	Frozen	Fresh
N	72	51	70	17
Mean	43.2	44.8	6.1	5.3
ANOVA	0.49		0.29

Reproducibility was established both at DiaSorin and during the clinical trial. Three human serum-based samples with 1,25-(OH)2-D concentrations distributed across the numan berain based calliples with 5 assay days at DiaSorin, spanning more than 60 Multiple technicians, as well as multiple lot numbers for all operating days. operaing were included. The combined results were evaluated by analysis of variance (ANOVA) and are summarized in the following table.

Sample	n	Mean (pg/mL)	Within-run S.D.	Within-run %C.V.	Between Day S.D.	Between Day %C.V.	Total S.D.	Total %C.V.
Low	25	25.8	1.76	6.8	3.8	14.6	4.0	15.3
Mid	25	41.3	3.16	7.7	4.6	11.1	5.1	12.3
High	25	105.2	11.86	11.3	11.8	11.2	14.4	13.7

These identical human serum-based controls were assayed during a clinical trial conducted at three different laboratories, over 16 different assays, spanning more than 110 days. The combined results from all three sites are summarized below.

Sample	n	Mean (pg/mL)	S.D.	%CV
Low	16	24.2	3.9	16.2
Mid	16	41.0	5.8	14.1
High	16	97.7	11.3	11.6

Similarly, kit controls included with each kit were included in each of the 16 assays The following table above, as prescribed in the package insert instructions. summarizes the precision of the controls over the course of the clinical trial.

		Site A	Site B	Site C	Total
Kit Control 1	n	7	4	8	19
	Mean	24.7	27.2	25.5	25.6
	SD	3.1	3.3	4.0	3.5
	%CV	12.5	12.2	15.8	13.7
Kit Control 2	n	7	4	7	18
	Mean	66.2	59.9	67.2	65.2
	SD	5.1	4.2	11.1	8.1
	%CV	7.8	7.1	16.6	12.4

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s)

DiaSorin 25-Hydroxyvitamin D 1251 RIA

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 862.1825 Vitamin D test system.

(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.

Summary

K014030

APPENDIX E

As required by 21 CFR 807.3, a summary of the 510(k) safety and effectiveness information contained in this submission is provided as Appendix E.

510(k) SUMMARY

SUBMITTED BY:

Diana Clive DiaSorin, Inc. 1951 Northwestern Ave. P.O. Box 285 Stillwater, MN 55082-0285 (651) 351-5582 voice (651) 351-5669 fax November 30, 2001

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.

NAME OF DEVICE: Trade Name:

1,25-Dihydroxyvitamin D 1251 RIA

Common Names/Descriptions:

the the Immunoassay for quantitative determination of 1,25 dihydroxyvitamin D (1,25-(OH)2-D)

Classification Name:

Vitamin D test system

PREDICATE DEVICE:

DiaSorin 25-Hydroxyvitamin D 1251 RIA

The 1,25-Dihydroxyvitamin D 1251 RIA assay is a competitive INTENDED USE: equilibrium radioimmunoassay intended for the quantitative determination of 1,25 dihydroxyvitamin D (1,25-(OH)2-D) in human serum or EDTA plasma to be used to assess 1,25-(OH)2-D deficiency associated with renal disease. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions in adult populations.

DEVICE DESCRIPTION: The 1,25-Dihydroxyvitamin D 1251 RIA is a competitive radioimmunoassay intended for the quantitative determination of 1,25 Dihydroxyvitamin D (1,25-(OH)2-D) in human serum or EDTA plasma. The assay consists of a two-step procedure. Serum or plasma patient samples as well as standards and kit controls are first extracted with acetonitrile to free the 1,25-(OH)2 vitamin D2 and D3 from their vitamin D binding protein, and remove lipids that might interfere with the assay. The metabolites are then extracted by column chromatography on C18OH silica cartridges using a series of organic solvent washes. Following the extraction, the treated samples are assayed using a

competitive radioimmunassay procedure. The primary antibody (rabbit anti-1,25-(OH)2 vitamin D) is highly specific for both 1,25(OH)2 vitamin D3 and 1,25(OH)2.vitamin D2. Vitamin D) is inghty specific for both 1,25(011)2 (011)2 vitamin D tracer Daring the binding sites on the primary antibody. Separation of bound and unbound vitamin D2 or D3 is accomplished using a goat anti-rabbit (GAR) polyethylene glycol precipitating complex. After an incubation and centrifugation, sample precipitates are proofitaing complex. The amount of radioactivity in the precipitate is inversely proportional to the concentration of 1,25-(OH)2 vitamin D in the sample. Values are proportional to the coma standard curve of known calibrators and expressed as pg/ml.

Feature	25-OH-D	1,25-(OH)2-D
Intended Use	FOR IN VITRO DIAGNOSTIC USE.
This kit is intended for the quantitative
determination of 25-hydroxyvitamin D
(25-OH-D) and other hydroxylated
vitamin D metabolites in human serum
or plasma to be used in the assessment
of vitamin D sufficiency. Assay
results should be used in conjunction
with other clinical and laboratory data
to assist the clinician in making
individual patient management
decisions in an adult population.	FOR IN VITRO DIAGNOSTIC USE.
This kit is intended for the quantitative
determination of 1,25-dihydroxy-
vitamin D (1,25-(OH)2-D) in human
serum or EDTA plasma to be used to
assess 1,25-(OH)2-D deficiency
associated with renal disease. Assay
results should be used in conjunction
with other clinical and laboratory data
to assist the clinician in making
individual patient management
decisions in adult populations.
Assay Type	RIA	RIA
Acetonitrile
Extraction	For isolation of 25-(OH)-D	For isolation of 1,25-(OH)2-D
Antiserum	Polyclonal specific for 25-(OH)-D2/D3	Polyclonal specific for 1,25-(OH)2-D2/D3
Tracer	125I radiolabeled 25-(OH)-D analog	125I radiolabeled 1,25-(OH)2-D3 analog
Precipitating
Complex	20 minute incubation at 20-25° C with
second antibody precipitating complex	20 minute incubation at 20-25° C with
second antibody precipitating complex
Kit Controls	Two levels, human serum based,
extracted identical to standards and
patient samples.	Two levels, human serum based,
extracted identical to standards and
patient samples.
Standards	Five levels, human serum based,
extracted identical to controls and
patient samples.	Five levels, human serum based,
extracted identical to controls and
patient samples.

TECHNOLOGICAL COMPARISON TO PREDICATE:

PERFORMANCE DATA: A clinical trial was conducted at three independent clinical laboratories. Serum values for 1,25(OH)2-vitamin D were collected from two distinct populations: apparently healthy normal donors, and patients with end-stage renal disease (ESRD). Reference ranges established in the trial are summarized below.

All Sites	1,25(OH)2D (pg/mL)
Population	n	Mean	2 SD	Range
Normals	123	43.9	24.1	19.8-68.0
ESRD's	87			1.6-17.3

The equivalency of assay samples as either fresh serum or serum that has been frozen and The equivalely of about bangles mory table with 95% ANOVA determined P-values is presented below.

	Normals		ESRD's
	Frozen	Fresh	Frozen	Fresh
N	72	51	70	17
Mean	43.2	44.8	6.1	5.3
ANOVA	0.49		0.29

			Within-run		Between Day		Total
Sample	n	Mean
(pg/mL)	S.D.	%C.V.	S.D.	%C.V.	S.D.	%C.V.
Low	25	25.8	1.76	6.8	3.8	14.6	4.0	15.3
Mid	25	41.3	3.16	7.7	4.6	11.1	5.1	12.3
High	25	105.2	11.86	11.3	11.8	11.2	14.4	13.7

| Sample | n | Mean
(pg/mL) | S.D. | %CV |
|--------|----|-----------------|------|------|
| Low | 16 | 24.2 | 3.9 | 16.2 |
| Mid | 16 | 41.0 | 5.8 | 14.1 |
| High | 16 | 97.7 | 11.3 | 11.6 |

		Site A	Site B	Site C	Total
Kit Control 1	n	7	4	8	19
	Mean	24.7	27.2	25.5	25.6
	SD	3.1	3.3	4.0	3.5
	%CV	12.5	12.2	15.8	13.7
Kit Control 2	n	7	4	7	18
	Mean	66.2	59.9	67.2	65.2
	SD	5.1	4.2	11.1	8.1
	%CV	7.8	7.1	16.6	12.4

The data collected during the clinical trial described above fully CONCLUSION: substantiates the intended use of the 1,25-Dihydroxyvitamin D 1251 RIA. Reference ranges established for both a healthy population and one with end stage renal disease are fully distinct. This indicates that the DiaSorin 1,25-Dihydroxvitamin D 131 RIA can effectively discriminate between the two populations based on 1,25-(OH)2-D serum values. Assay results can be used to assess 1,25-(OH)2-D deficiency associated with renal disease.

Image /page/4/Picture/2 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is a stylized symbol featuring three abstract shapes that resemble a person or a bird in flight. The shapes are layered on top of each other, creating a sense of movement and depth.

MAR 2 6 2002

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. David M. Ikeda Manager, Regulatory Affairs and Quality Systems DiaSorin Inc. 1990 Industrial Blvd. P.O. Box 285 Stillwater, MN 55082-0285

Re: K014030

Trade/Device Name: 1,25-Dihydroxyvitamin D 1251 RIA Kit Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: Class II Product Code: MRG Dated: February 18, 2002 Received: February 20, 2002

Dear Mr. Ikeda:

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.

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 1 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

INDICATIONS FOR USE

510(k) Number (if known):

Device Name:

1,25-Dihydroxyvitamin D 1251 RIA Kit

K014030

Indications For Use:

The 1,25-Dihydroxyvitamin D 1251 RIA is a competitive equilibrium radioimmunoassay intended for the quantitative determination of 1,25-dihydroxyvitamin D (1,25-(OH)2-D) in human serum or EDTA plasma to be used to assess 1,25-(OH)2-D deficiency associated with renal disease. Since hydroxylation of circulating 25-hydroxyvitamin D to the biologically active form 1,25-(OH)2-D occurs in the kidney, renal disease may result in reduced levels of 1,25-(OH)2-D and compromised calcium metabolic homeostasis. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions in adult populations.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Division Sign-Off

Carol C. Benson for Jean Cooper

vision of Clinical Laboratory D 510fki Number Prescription Use: the-Counter Use: (Per 21 CFR 801.109)