& 2. The VITROS Immunodiagnostic Products Folate Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3 - for the in vitro quantitative measurement of folate in human serum and plasma (heparin) and whole blood (red cell folate), to aid in the differential diagnosis of anemia.
The VITROS Immunodiagnostic Products Folate Calibrators - for in vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of folate in human serum and plasma (heparin).
The VITROS Immunodiagnostic Products Red Cell Folate Pack - for whole blood sample preparation, to allow the in vitro quantitative measurement of red cell folate using the VITROS Immunodiagnostic System.

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 Folate Reagent Pack, VITROS Immunodiagnostic Products Folate Calibrators and the VITROS Immunodiagnostic System. The VITROS Folate Reagent Pack consists of: The VITROS Immunodiagnostic Products Folate Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3
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 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.

AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and the study proving the device meets them. It's important to note that the document is a 510(k) summary, which often
focuses on substantial equivalence to a predicate device rather than exhaustive performance studies with strict "acceptance criteria" as might be defined for a novel device. The "acceptance
criteria" here are primarily implied by the demonstration of substantial equivalence and correlation to the predicate.

Acceptance Criteria and Performance Comparison

The document describes two devices:

(a) VITROS Folate assay (for serum and plasma folate)
(b) VITROS Red Cell Folate Pack (for red cell folate)

Both are compared to the Bio-Rad Quantaphase II Folate Radioassay (K935286) as the predicate device. The primary "acceptance criterion" appears to be demonstrating substantial equivalence
to this predicate device by showing a good correlation and acceptable bias in measurements.

Table of Acceptance Criteria (Implied) and Reported Device Performance

Criterion Type	Specific Criterion (Implied/Predicate Performance)	VITROS Folate Assay (Serum/Plasma) Performance	VITROS Red Cell Folate Pack Performance
Substantial Equivalence	Demonstrated by strong correlation and acceptable bias to predicate.	Relationship: VITROS = 0.999 x Bio-Rad + 0.676 ng/mL	Relationship: VITROS = 1.17 x Bio-Rad + 4.0 ng/mLCorrelation (r): 0.979Bias: 17% overall positive bias. (Acknowledged as "true numerical differences")
Calibration Range	0 – 20 ng/mL (matches predicate)	0 – 20 ng/mL	0 – 20 ng/mL
Basic Principle	To be consistent with predicate method or clinically acceptable alternative.	Solid phase assay (different from predicate's radioassay, but deemed acceptable)	Solid phase assay (different from predicate's radioassay, but deemed acceptable)
Tracer	To be consistent with predicate method or clinically acceptable alternative.	Enzyme labeled (different from predicate's 125Iodine, but deemed acceptable)	Enzyme labeled (different from predicate's 125I, but deemed acceptable)
Instrumentation	To be consistent with predicate method or clinically acceptable alternative.	VITROS Immunodiagnostic System (different from predicate's Gamma Counter, but deemed acceptable)	VITROS Immunodiagnostic System (different from predicate's Gamma Counter, but deemed acceptable)
Sample Type	Serum or plasma (EDTA)	Serum, plasma (heparin) (Broader than predicate, includes heparin plasma)	Whole blood (EDTA or heparin) (Broader than predicate, includes heparin)
Binding protein	Folate binding protein	Folate binding protein, purified from bovine milk (More specific description, but functionally equivalent)	Folate binding protein
Sample volume	200 µL	53 µL (Significantly lower than predicate)	53 µL (Significantly lower than predicate)
Incubation time/temp	1 hour at room temperature.	73 mins at 37 °C (Different from predicate, but within acceptable limits for a new method)	Whole blood prep: 90 mins room temp; Folate assay: 73 mins at 37°C (Different from predicate, but deemed acceptable)
Analytical Sensitivity	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Not explicitly mentioned for Red Cell Folate.
Specificity	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Not explicitly mentioned for Red Cell Folate.
Precision	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Tested, results referred to package insert.
Dilution (Linearity)	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Tested, results referred to package insert.
Expected Values	Implied to be established.	Tested, results referred to package insert.	Tested, results referred to package insert.

Study Details

The studies performed for both the VITROS Folate assay and the VITROS Red Cell Folate Pack
are primarily comparative effectiveness studies against the predicate device.

Sample size for the test set and data provenance:
- Test Set Sample Size: Not explicitly stated as a number of samples. The document mentions "samples from a variety of clinical categories" and "patient specimens covering a variety
  of clinical categories." This suggests a diverse patient population was used, but the exact count is not provided.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the use of "patient specimens" and "currently commercially available reagents"
  implies real-world samples from a clinical setting. It's likely a retrospective collection as is common for these types of studies comparing new assays to established ones.
Number of experts used to establish the ground truth for the test set and their qualifications:
- Not Applicable. For an in vitro diagnostic (IVD) quantitative assay, the "ground truth" is typically defined by the measurement results from a recognized reference method or a
  well-established predicate device, not by expert interpretation. In this case, the predicate device (Bio-Rad Quantaphase II Folate Radioassay) serves as the de facto "ground truth"
  for comparison purposes.
Adjudication method for the test set:
- Not Applicable. As per the point above, adjudication by multiple experts is not relevant for establishing ground truth for a quantitative chemical assay. The comparison is made
  between the new device's readings and the predicate device's readings.
If a multi reader multi case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance:
- Not Applicable. This is an in vitro diagnostic device (quantitative assay), not an AI-assisted diagnostic imaging or interpretation system. Therefore, MRMC studies and human reader
  improvement with AI assistance are not relevant.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The VITROS Folate assay and Red Cell Folate Pack are standalone automated IVD systems. Their performance metrics (correlation, bias, analytical characteristics)
  are measured inherently without human interpretation of the result itself. Human involvement is in sample preparation, loading, and reviewing the reported numerical values, but the
  measurement process is automated.
The type of ground truth used:
- Predicate Device Measurements: The ground truth for this substantial equivalence argument is the measurement results obtained from the Bio-Rad Quantaphase II Folate Radioassay
  (K935286).
- Analytical Performance: Additional "ground truths" are established internally for analytical performance characteristics (precision, linearity, expected values) using laboratory
  standards and methods, but the primary comparison is to the predicate.
The sample size for the training set:
- Not Applicable/Not Provided. For an IVD assay, there isn't typically a "training set" in the machine learning sense. The assay is developed using analytical chemistry principles,
  reagent formulation, and instrument calibration. The studies described are performance verification or validation tests rather than model training.
How the ground truth for the training set was established:
- Not Applicable. As there's no "training set" in the machine learning context, this question is not relevant. The development of the assay relies on established scientific principles
  and internal validation of reagents and methods.

Summary

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510(k) Summary

(a) VITROS Folate assay

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: طبط / 1 / 984 / 1

1. 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 18th, 1998

2. Device Name

(a) Folate assay

Trade or Proprietary Name: VITROS Immunodiagnostic Products Folate assay Common Name: Serum folate assay Classification Name: Folate assay for the in vitro quantitative measurement of folate in human serum and plasma (heparin).

3. Predicate Device

The VITROS Immunodiagnostic Products Folate assay is substantially equivalent to Bio-Rad Quantaphase II Folate Radioassay (K935286).

4. Device Description

VITROS Immunodiagnotic Products Folate Assay and Red Cell Folate Pack

{1}------------------------------------------------

The system is comprised of three main elements:

1. The VITROS Immunodiagnostic Products range of products, in this case VITROS Immunodiagnostic Products Folate Reagent Pack, VITROS Immunodiagnostic Products Folate Calibrators and the VITROS Immunodiagnostic System. The VITROS Folate Reagent Pack consists of: The VITROS Immunodiagnostic Products Folate Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3
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).
1. Common reagents used by the VITROS System in each assay. The VITROS 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 Folate assay is intended for the in vitro quantitative measurement of folate in human serum and plasma (heparin) and whole blood (red cell folate), to aid in the differential diagnosis of anemia.

6. Comparison to Predicate Device

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

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

VITROS Folate assay =0.999 x Bio-Rad Quantaphase II Folate Radioassay + 0.676 ng/mL Comparisons of the VITROS Folate assay and the predicate device were performed with samples from a variety of clinical categories.

{2}------------------------------------------------

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

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

DeviceCharacteristic	VITROS Folate assay	PredicateDevice
Calibration range	0 – 20 ng/ml	0-20 ng/mL
Basic principle	Solid phase assay	Radioassay
Tracer	Enzyme labeled	125Iodine
Instrumentation	VITROSImmunodiagnostic System	Gamma Counter
Sample type	Serum, plasma (heparin)	Serum or plasma (EDTA)
Binding protein	Folate binding protein,purified from bovine milk.	Folate binding protein
Sample volume	53 µL	200 µL
Incubation time andtemperature	73 mins 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 Folate assay performs substantially equivalent to the predicate device, that 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 Folate assay is safe and effective for the stated intended use.

{3}------------------------------------------------

(b) VITROS Red Cell Folate Pack

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: __________________

1. 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 18th, 1998

2. Device Name

Trade or Proprietary Name: VITROS Immunodiagnostic Products Red Cell Folate Pack (performed using the Vitros Folate Reagent Pack 1/2, VITROS Vitamin B12/Folate Reagent Pack 3 and the VITROS Red Cell Folate Pack)

Common Name: Red cell folate assay.

Classification Name: Red cell folate assay for the in vitro quantification of folate in human whole blood.

3. Predicate Device

The VITROS Immunodiagnostic Products Red Cell Folate assay, is substantially equivalent to Bio-Rad Quantaphase II Folate Radioassay used with the Bio-Rad Red Cell Folate Reagent Pack (K935286).

4. 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:

1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products Red Cell Folate Pack, VITROS Immunodiagnostic Products Folate Pack 1/2, VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3, VITROS Immunodiagnostic Products Folate Calibrators, which are combined by the VITROS Immunodiagnostic System to perform the VITROS Red Cell Folate assay).
  VITROS Immunodiagnotic Products Folate Assay and Red Cell Folate Pack

{4}------------------------------------------------

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).
1. Common reagents used by the VITROS System in each assay. The VITROS 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 Red Cell Folate Pack is intended for use in whole blood sample preparation to allow the in vitro quantitative measurement of red cell folate using the VITROS Immunodiagnostic System.

6. Comparison to Predicate Device

The VITROS Immunodiagnostic Products Red Cell Folate assay, is substantially equivalent to Bio-Rad Quantaphase II Folate Radioassay (predicate device), used with the Bio-Rad Red Cell Folate Reagent Pack, that was cleared by FDA (K935286) for IVD use.

The relationship between the VITROS Red Cell Folate assay and the predicate device, determined by Deming's Regression, is:

VITROS Red Cell Folate assay =1.17 x Bio-Rad Ouantaphase II Folate assay (used with the Bio-Rad Red Cell Folate Reagent Pack ) + 4.0 (ng/mL)

Comparisons of the VITROS Red Cell Folate assay and the predicate device were performed with samples from a variety of clinical categories.

Although there was a good correlation between the assays (r = 0.979), the VITROS assay showed an overall 17% positive bias. The results reflect true numerical differences for red cell folate measurement between the VITROS and Bio-Rad Quantaphase II assays.

In addition to the studies mentioned above, tests were performed to obtain precision, linearity and expected values. Refer to the VITROS Red Cell Folate Pack package insert for VITROS Red Cell Folate assay results.

Table 1 lists the similarities and differences of the device characteristics between the VITROS Red Cell Folate assay with the predicate device, Bio-Rad Quantaphase II Folate assay (used with the Bio-Rad Red Cell Folate Reagent Pack ).

{5}------------------------------------------------

							Table 1 List of the assay characteristics
--	--	--	--	--	--	--	-------------------------------------------

DeviceCharacteristic	VITROS Red Cell Folateassay	PredicateDevice
Calibration range	0 - 20 ng/ml	0 - 20 ng/ml
Basic principle	Solid phase assay	Radioassay
Tracer	Enzyme labeled	125I
Instrumentation	VITROSImmunodiagnostic System	Gamma Counter
Sample type	Whole blood (EDTA orheparin)	Whole blood (EDTA)
Binding Protein	Folate binding protein	Folate binding protein
Sample volume	53 µL	200 µL
Incubation time andtemperature	90 minutes at roomtemperature (whole bloodpreparation); 73 minutes at37° C (folate assay)	90 minutes at roomtemperature (whole bloodpreparation); 60 minutesat room temperature(folate assay).

7. Conclusions

The data presented in the pre-market notification demonstrate that the VITROS Red Cell Folate assay performs substantially equivalent to the predicate, that 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 Red Cell Folate assay is safe and effective for the stated intended use.

{6}------------------------------------------------

Image /page/6/Picture/10 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles a human figure in profile, with three overlapping heads or faces.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 5 1999

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

Re: K984166 Trade Name: VITROS Immunodiagnostic Products Folate Assay Product Code: CGN Regulatory Class: II 118 II Dated: January 6, 1999 Received: January 7, 1999

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.

{7}------------------------------------------------

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 vours.

Steven Autman

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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Chapter 1 - Summary Information

Indications for Use Statement

Page 1 of 1

510(k) Number (if known)

{

Device Name:	1. VITROS Immunodiagnostic Products Folate Reagent Pack 1/22. VITROS Immunodiagnostic Products Vitamin B12/Folate ReagentPack 33. VITROS Immunodiagnostic Products Folate Calibrators
	4. VITROS Immunodiagnostic Products Red Cell Folate Pack
Indications for Use:	1. & 2. The VITROS Immunodiagnostic Products Folate Reagent Pack1/2 and the VITROS Immunodiagnostic Products Vitamin B12/FolateReagent Pack 3 - for the in vitro quantitative measurement of folate inhuman serum and plasma (heparin) and whole blood (red cell folate), toaid in the differential diagnosis of anemia.
	3. The VITROS Immunodiagnostic Products Folate Calibrators - for in vitro use in the calibration of the VITROS Immunodiagnostic Systemfor the quantitative measurement of folate in human serum and plasma(heparin).
	4. The VITROS Immunodiagnostic Products Red Cell Folate Pack - forwhole blood sample preparation, to allow the in vitro quantitativemeasurement of red cell folate using the VITROS ImmunodiagnosticSystem.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sean Cooper

(Division Sign-Off)

Division of Clinical Laboratory Devices

510(k) Number	K 984166
---------------	----------

Prescription Use (Per 21 CFR 801.109)	OR	Over-The-Counter Use
---------------------------------------	----	----------------------

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1295 Folic acid test system.

(a)
Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.(b)
Classification. Class II.