1 & 2. The VITROS Immunodiagnostic Products Vitamin B12 Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3 - for the in vitro quantitative measurement of vitamin B12 in human serum and plasma (EDTA or heparin) to aid in the differential diagnosis of anemia.

The VITROS Immunodiagnostic Products Vitamin B12 Calibrators - for in vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of vitamin B12 in human serum and plasma (EDTA or heparin).

Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma and urine. Coated microwells are used as the solid phase separation system.

The system is comprised of three main elements:

The VITROS Immunodiagnostic Products range of products, in this case VITROS Immunodiagnostic Products Vitamin B12 Reagent Pack 1/2, VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3, VITROS Immunodiagnostic Products Vitamin B12 Calibrators and the VITROS Immunodiagnostic System.
The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits.
Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent.

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

AI/ML Overview

The provided text describes the VITROS Immunodiagnostic Products Vitamin B12 assay, an in vitro diagnostic device for the quantitative measurement of vitamin B12. The data outlines a substantial equivalence study rather than a traditional clinical study with acceptance criteria often seen for imaging or AI devices.

Here's an analysis based on the provided text:

Acceptance Criteria and Device Performance:

The primary acceptance criterion is substantial equivalence to a predicate device. This is demonstrated by comparing key characteristics and performing a regression analysis.

Acceptance Criterion	Reported Device Performance (VITROS Vitamin B12 assay)
Substantial Equivalence to Predicate Device	Demonstrated through comparison of device characteristics and Deming's Regression analysis.
Calibration Range	0 - 2000 pg/mL (Matches predicate)
Basic Principle	Solid phase immunoassay (Different from predicate's radioassay, but equivalent for purpose)
Tracer	Enzyme labeled (Different from predicate's 57Co, but equivalent for purpose)
Instrumentation	VITROS Immunodiagnostic System (Different from predicate's Gamma Counter, but equivalent for purpose)
Sample Type	Serum, plasma (EDTA or heparin) (Broader than predicate's serum, plasma (EDTA))
Sample Volume	30 μL (Matches predicate)
Incubation Time & Temperature	58 minutes at 37° C (Different from predicate's 1 hour at room temperature, but equivalent for purpose)
Correlation with Predicate Device (Deming's Regression)	VITROS Vitamin B12 assay = 0.984 x Bio-Rad Quantaphase II B12 Radioassay + 9.59 (pg/mL)
Analytical Sensitivity	Performed (Specific value not provided in this summary)
Specificity	Performed (Specific value not provided in this summary)
Precision	Performed (Specific value not provided in this summary)
Dilution	Performed (Specific value not provided in this summary)
Expected Values	Performed (Specific value not provided in this summary)

Study Details:

The study conducted is a substantial equivalence study for an in vitro diagnostic (IVD) device, not a multi-reader multi-case (MRMC) comparative effectiveness study or a standalone algorithm performance study typical for AI/imaging devices.

Sample size used for the test set and the data provenance:
- The text states: "Comparisons of the VITROS Vitamin B12 assay and the predicate device were performed with samples from a variety of clinical categories."
- It also mentions: "Equivalence was demonstrated using currently commercially available reagents along with patient specimens covering a variety of clinical categories."
- Specific sample size is not provided in this summary.
- Data provenance: Not explicitly stated, but the reference to "patient specimens" suggests human biological samples. The geographical origin (country) and whether the data was retrospective or prospective are not mentioned.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is not applicable in the context of this type of IVD device study. The "ground truth" for an IVD assay like this is typically established by the predicate device's measurement, against which the new device is compared. There are no human "experts" establishing annotated ground truth for diagnosing B12 deficiency from images or clinical data in this document.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is not a study involving human readers' interpretations that require adjudication.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an AI or imaging device that assists human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The VITROS Immunodiagnostic System itself, which performs the assay, operates in a standalone manner for generating the quantitative B12 result. The performance data presented (calibration range, correlation with predicate, analytical sensitivity, etc.) are inherent to the assay and instrumentation, without human interpretation in the measurement process. However, this is not "standalone AI algorithm performance." It's standalone device performance.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The "ground truth" for comparison in this substantial equivalence study is the measurement obtained from the legally marketed predicate device (Bio-Rad Quantaphase II B12 Radioassay) for the same patient samples. The intent is to show the new device provides comparable quantitative results.
The sample size for the training set:
- This concept of a "training set" is not directly applicable to an IVD analytical performance study like this. The device itself (reagents, calibrators, and instrumentation) is developed and manufactured, and then its performance is validated. There isn't an "algorithm" being trained on a dataset in the way an AI model is.
How the ground truth for the training set was established:
- Not applicable as there is no "training set" in the context of AI model development for this type of IVD device. The reagents and assay method are developed based on scientific principles and validated through internal studies and often external clinical sample comparisons.

Summary

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K984321

JAN 22 1999

Chapter 1 - Summary Information

510(k) Summary

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

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

Submitter name, address, contact Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 (716) 453-3607

Contact Person: Anne Zavertnik

Date 510(k) prepared: November 30th, 1998

2. Device Name

Vitamin B12 assay

Trade or Proprietary Name: VITROS Immunodiagnostic Products Vitamin B12 assay Common Name: Vitamin B12 assay

Classification Name: Vitamin B12 assay for the in vitro quantitative measurement of vitamin B12 in human serum and plasma (EDTA or heparin).

3. Predicate Device

The VITROS Immunodiagnostic Products Vitamin B12 assay is substantially equivalent to Bio-Rad Quantaphase II B12 Radioassay.

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510(k) Summary, continued

4. Device Description

The system is comprised of three main elements:

1. The VITROS Immunodiagnostic Products range of products, in this case VITROS Immunodiagnostic Products Vitamin B12 Reagent Pack 1/2, VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3, VITROS Immunodiagnostic Products Vitamin B12 Calibrators and the VITROS Immunodiagnostic System.
1. The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
Common reagents used by the VITROS System in each assay. The VITROS 3. Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K984310).

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

5. Device Intended Use

The VITROS Vitamin B12 assay is intended for the in vitro quantitative measurement of vitamin B12 in human serum and plasma (EDTA or heparin), to aid in the differential diagnosis of anemia.

6. Comparison to Predicate Device

The VITROS Immunodiagnostic Products Vitamin B12 assay is substantially equivalent to Bio-Rad Quantaphase II B12 Radioassay (predicate device), which was cleared by FDA (K935286) for IVD use.

The relationship between the VITROS Vitamin B12 assay and the predicate device, determined by Deming's Regression, is:

VITROS Vitamin B12 assay =0.984 x Bio-Rad Quantaphase II B12 Radioassay + 9.59 (pg/mL).

Comparisons of the VITROS Vitamin B12 assay and the predicate device were performed with samples from a variety of clinical categories.

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510(k) Summary, continued

In addition to the studies mentioned above, tests were performed to obtain analytical sensitivity, specificity, precision, dilution and expected values. Refer to the VITROS Vitamin B12 assay package insert for VITROS Vitamin B12 assay results.

Table 1 lists the similarities and differences of the device characteristics between the VITROS Vitamin B12 assay with the predicate device, Bio-Rad Quantaphase II B12 Radioassay.

Device	VITROS Vitamin B12	Predicate
Characteristic	assay	Device
Calibration range	0 - 2000 pg/mL	0 - 2000 pg/mL
Basic principle	Solid phase immunoassay	Radioassay
Tracer	Enzyme labeled	57Co
Instrumentation	VITROSImmunodiagnostic System	Gamma Counter
Sample type	Serum, plasma (EDTA orheparin)	Serum, plasma (EDTA)
	Sample volume	30 μL
Incubation time andtemperature	58 minutes at 37° C	1 hour at roomtemperature

Table 1 List of the assay characteristics

7. Conclusions

The data presented in the pre-market notification demonstrate that the VITROS Vitamin B12 assay performs substantially equivalent to the predicate device, which was cleared by FDA (K935286) for IVD use.

Equivalence was demonstrated using currently commercially available reagents along with patient specimens covering a variety of clinical categories.

The data presented in the premarket notification provide a reasonable assurance that the VITROS Vitamin B12 assay is safe and effective for the stated intended use.

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Public Health Service

JAN 22 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Anne Zavertnik Regulatory Affairs Associate Ortho-Clinical Diagnostics A•Johnson & Johnson Company 100 Indigo Creek Drive Rochester, New York 14626-5101

Re: K984321 Trade Name: VITROS Immunodiagnostic Products Vitamin B12 Assay Product Code: CDD Regulatory Class: II II IIS Dated: December 2, 1998 Received: December 3, 1998

Dear Ms. Zavertnik:

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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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 (770) 488-7655.

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"(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 (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

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Statement of Intended Use

510(k) Number (if known):	K984321
Page	1 of 1
Device Name:	1. VITROS Immunodiagnostic Products Vitamin B12 Reagent Pack 1/2 2. VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3 3. VITROS Immunodiagnostic Products Vitamin B12 Calibrators
Indications for Use:	1 & 2. The VITROS Immunodiagnostic Products Vitamin B12 Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3 - for the in vitro quantitative measurement of vitamin B12 in human serum and plasma (EDTA or heparin) to aid in the differential diagnosis of anemia.3. The VITROS Immunodiagnostic Products Vitamin B12 Calibrators - for in vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of vitamin B12 in human serum and plasma (EDTA or heparin).

and the same of the same of the same of the same of the states of the states and

(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)
(Division Sign-Off)
Division of Clinical Laboratory Devices

510(k) Number	K984321
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Regulation Number and Section

§ 862.1810 Vitamin B

12 test system.(a)
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.(b)
Classification. Class II.