(837 days)
CD4 (Leu-3a) FITC
Not Found
No
The device is a monoclonal antibody conjugate used for flow cytometry, a standard laboratory technique. There is no mention of AI/ML in the description, intended use, or performance studies. The analysis involves calculating percentages and ratios based on flow cytometry data, which is a deterministic process, not AI/ML.
No
This device is an in-vitro diagnostic (IVD) tool used for identifying and enumerating cells, which aids in diagnosis and prognosis, but does not provide therapy or treatment.
Yes
The device is used to identify and enumerate CD4+ human T lymphocytes in whole blood, which is clinically significant in the prognosis of secondary immunodeficiency diseases, such as AIDS. This measurement provides information for diagnosis and monitoring of disease progression.
No
The device is a monoclonal antibody conjugate, which is a biological reagent used in flow cytometry, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use clearly states that the device is used to "identify and enumerate the percentage of CD4+ human T lymphocytes in whole blood by flow cytometry." This is a diagnostic purpose, providing information about a patient's health status.
- Clinical Significance: The document explicitly links the identification and enumeration of CD4+ lymphocytes to the "prognosis of secondary immunodeficiency diseases (acquired immunodeficiency syndrome [AIDS])" and the "progression of AIDS." This demonstrates the clinical utility of the test results in diagnosing and managing a disease.
- Sample Type: The device is used with "whole blood," which is a biological specimen taken from the human body.
- Method: Flow cytometry is a laboratory technique used to analyze characteristics of cells in a fluid. This is a common method used in in vitro diagnostics.
The information provided aligns with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to monitor therapeutic measures.
N/A
Intended Use / Indications for Use
Ortho-mune OKT4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate is used to identify and enumerate the percentage of CD4+ human T lymphocytes in whole blood by flow cytometry.
Identification and enumeration of abnormal levels of CD4lymphocytes may be clinically significant in the prognosis of secondary immunodeficiency diseases (acquired immunodeficiency syndrome [AIDS]).
AIDS is characterized by a severe reduction in T helper (CD3+CD4+) lymphocytes and a decrease in the CD4:CD8 ratio. The CD4:CD8 ratio has been used as a predictor of time to the development of AIDS. CD4 counts should also be determined using a CD3/CD4 combination reagent to eliminate monocyte contamination (CD3-CD4+dim). CD4+lymphocytes (expressed as an absolute number, a percentage of lymphocytes or as a ratio of CD4+ to CD8+ T lymphocytes) represents the best single predictor of the progression of AIDS. CD4+ lymphocyte numbers usually start to decline relatively soon after human immunodeficiency virus (HIV) infection.
Product codes
GKZ
Device Description
Ortho-mune OKT4A Monoclonal Antibody (Murine) FITC Conjugate contains the purified monoclonal antibody OKT4A conjugated to the fluorochrome fluorescein isothiocyanate.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Flow cytometry
Anatomical Site
Whole blood
Indicated Patient Age Range
Not Found
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
Performance of Ortho-mune OKT4A Monoclonal Antibody (Murine) FITC Conjugate was compared with that of CD4 (Leu-3a) FITC at three external, geographically distinct sites. Whole blood specimens from 206 normal donors, and 88 AIDS/ARC patients were stained and analyzed using the ORTHO CYTORONABSOLUTE™ flow cytometer, Ortho Diagnostic Systems Inc.
For each specimen, the percentage of gated cells which showed positive by each marker was calculated.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Performance Comparison Study:
- Study type: Comparison of Ortho-mune OKT4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate with predicate device CD4 (Leu-3a) FITC.
- Sample size: 206 normal donors and 88 AIDS/ARC patients.
- Key results:
- Normal Donors (N=206):
- Ortho-mune OKT4A (CD4)+: Mean % = 47.0, Range % = 12.4 - 68.7
- LEU-3a (CD4)+: Mean % = 45.1, Range % = 14.6 - 64.6
- AIDS/ARC Patients (N=88):
- Ortho-mune OKT4A (CD4)+: Mean % = 18.3, Range % = 1.0 - 55.1
- LEU-3A (CD4)+: Mean % = 17.2, Range % = 0.6 - 51.6
- Linear regression analysis (combined normal and AIDS/ARC populations): Y = 0.969 + 1.019(X), R-value = 0.985.
- Conclusion: The study demonstrates that the performance of Ortho-mune OKT4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate is equivalent to CD4 (Leu-38) FITC reagent in identification and enumeration CD4+ human lymphocytes in whole blood by flow cytometry.
- Normal Donors (N=206):
Within-Laboratory Reproducibility Study:
- Study type: Reproducibility within laboratories.
- Sample size: Ten normal donors.
- Data processing: Samples were processed using antibody-coated magnetic microbeads to produce low, normal, and high percent positive CD4 populations. Samples were stained with Ortho-mune OKT4A (CD4) FITC Conjugate and run on the ORTHO CYTORONABSOLUTE. All samples were analyzed in replicates of ten.
- Key results: Coefficients of variation (CV) calculated from the standard deviation between replicates demonstrated excellent within-laboratory reproducibility at all concentrations tested.
- Low CD4 Level: Site 1 CV = 7.60, Site 2 CV = 6.12, Site 3 CV = 5.47
- Normal CD4 Level: Site 1 CV = 2.33, Site 2 CV = 2.00, Site 3 CV = 2.21
- High CD4 Level: Site 1 CV = 1.93, Site 2 CV = 1.79, Site 3 CV = 2.09
Between-Laboratory Reproducibility Study:
- Study type: Reproducibility between independent laboratories.
- Sample size: Ten normal donor samples.
- Data processing: Samples were processed using antibody-coated magnetic microbeads to produce low, normal, and high percent positive CD4 populations. Samples were stained with Ortho-mune OKT4A (CD4) FITC Conjugate and run on the ORTHO CYTORONABSOLUTE. All samples were analyzed in replicates of ten.
- Key results: Data showed excellent between-laboratory reproducibility.
- Mean Percent Positive: Low = 9.25, Normal = 47.70, High = 5.15 (Typo in original table, likely 55.15 or similar)
- CV: Low = 4.09, Normal = 1.53, High = 0-60 (Typo in original table, likely a single value)
Linearity Study:
- Study type: Linearity of performance across a range of lymphocyte counts.
- Sample size: Specimens from four normal donors.
- Data processing: Whole blood specimens were concentrated and then diluted to produce samples of high, normal, and low numbers of lymphocyte subsets. A portion of each sample was stained in triplicate using Ortho-mune OKT4A (CD4) FITC Conjugate and analyzed using the CYTORONABSOLUTE. Total lymphocyte count obtained using an automated hematology analyzer.
- Key results: Regent demonstrated linear performance for total CD4+ lymphocyte subsets across a lymphocyte count range of 20 cells/uL to 9000 cells/uL. Slopes were indistinguishable from 1 and R values were 1.000 for all donors and for the combined data.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Mean % CD4+ cells
- Range % CD4+ cells
- Coefficients of Variation (CV)
- 95% Confidence Intervals
- Slope (from linear regression)
- Intercept (from linear regression)
- R-value (from linear regression)
Predicate Device(s)
CD4(Leu™-3a) FITC
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 864.5220 Automated differential cell counter.
(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”
0
Ortho-munç OKT4A (CD4) FITC Conjugatc
Ref. No. K951459 - Submitted July, 1997
510(k) Summarv
JUL 1 4 1997
SUBMITTER: Ortho Diagnostic Systems Inc. 1001 U.S. Highway 202 Raritan, NJ 08869-0606
CONTACT: Gail Kromer Tcl: (908) 218-8179 Fax: (908) 218-8168
DEVICE NAME: Ortho-mune™OKT™4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate
PREDICATE: CD4(Leu™-3a) FITC
DATE: July 8, 1997
DEVICE DESCRIPTION
Ortho-mune OKT4A Monoclonal Antibody (Murine) FITC Conjugate contains the purified monoclonal antibody OKT4A conjugated to the fluorochrome fluorescein isothiocyanate.
INTENDED USE:
Ortho-mune OKT4A FITC Conjugate is intended for use in identification and enumeration of CD4+ human T lymphocytes in whole blood by flow cytometry. The intended use is the same as the intended use of the predicate device, CD4 (Leu-3a) FITC commercially distributed by Becton Dickinson Immunocytometry Systems.
TECHNOLOGICAL CHARACTERISTICS
Both Ortho-mune OKT4A Monoclonal Antibody (Murine) FITC Conjugate and CD4 (Leu-3a) FITC utilize monoclonal antibodies specific for human helper/inducer T cells OKT4A/Leu-3a) respectively, conjugated to the same fluorochrome, fluorescein isothiocyanate.
1
PERFORMANCE CHARACTERISTICS
Performance of Ortho-mune OKT4A Monoclonal Antibody (Murine) FITC Conjugate was compared with that of CD4 (Leu-3a) FITC at three external, geographically distinct sites. Whole blood specimens from 206 normal donors, and 88 AIDS/ARC patients were stained and analyzed using the ORTHO CYTORONABSOLUTE™ flow cytometer, Ortho Diagnostic Systems Inc.
For each specimen, the percentage of gated cells which showed positive by each marker was calculated. The mean and range of the percent CD4+ cells for the normal donor and AIDS/ARC population are shown in Table I and Table 2 respectively.
| PERCENT POSITIVE STAINED CELLS IN NORMAL DONORS DETECTED BY
OKT4A AND LEU-3A ASSAYED ON THE CYTORONABSOLUTE
| N=206 | |||||
|---|---|---|---|---|---|
| Ortho-mune | |||||
| Reagent | Mean % | Range % | BD | ||
| Reagent | Mean % | Range % | |||
| OKT4A | |||||
| (CD4)+ | 47.0 | 12.4 - 68.7 | LEU-3a | ||
| (CD4)+ | 45.1 | 14.6 - 64.6 |
TABLE 1
TABLE 2
| Ortho-mune
Reagent | Mean % | Range % | BD
Reagent | Mean % | Range % |
|-----------------------|--------|------------|------------------|--------|------------|
| OKT4
(CD4)+ | 18.3 | 1.0 - 55.1 | LEU-3A
(CD4)+ | 17.2 | 0.6 - 51.6 |
2
Linear regression analysis of total percent CD4+ cells from the combined normal and AIDS/ARC populations is found in Chart 1.
CHART 1
Ortho-mune OKT4A (CD4) FITC vs CD4 (Leu-3a) FITC
Ortho-mune OKT4A(FITC)
Image /page/2/Figure/5 description: The image is a scatter plot comparing "Ortho-mune Reagent" and "Predicate Reagent". The x-axis represents "Predicate Reagent", and the y-axis represents "Ortho-mune Reagent", both ranging from 0 to 70. The scatter plot shows a strong positive correlation between the two reagents, with data points clustered closely around a regression line, which is defined by the equation Y = 0.969 + 1.019(X), and the R-value is 0.985.
This study demonstrates that the performance of Ortho-mune OKT4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate is equivalent to CD4 (Leu-38) FITC reagent in identification and enumeration CD4+ human lymphocytes in whole blood by flow cytometry.
c:\data\word\CD4
3
WITHIN-LABORATORY REPRODUCIBILITY
Ten normal donors were used in a within-laboratory reproducibility study at three independent laboratories. The samples were processed using antibody-coated magnetic microbeads to produce low, normal and high percent positive CD4 populations to simulate leukopenia and leukocytosis. The samples were stained with Ortho-mune OKT4A (CD4) FITC Conjugate and run on the ORTHO CYTORONABSOLUTE. All samples were analyzed in replicates of ten. The coefficients of variation, calculated from the standard deviation between replicates, were compared and demonstrated excellent within-laboratory reproducibility at all concentrations tested. The 95% confidence intervals were calculated from the standard error of the site mean which includes variance components from replicate and donor variability minimized by the number of donors (10). The comparison of normal, concentrated (high) and diluted (low) samples is contained in Table 3.
TABLE 3: N = 10 WITHIN-LABORATORY REPRODUCIBILITY Ortho-mune OKT4A (CD4) FITC CONJUGATE PERCENT POSITIVE RESULTS
| CD4 Level | Low | Normal | High | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Subset: OKT4A (CD4) | Site 1 | Site 2 | Site 3 | Site 1 | Site 2 | Site 3 | Site 1 | Site 2 | Site 3 |
| Mean Percent Positive | 9.60 | 9.36 | 8.86 | 47.38 | 47.19 | 48.54 | 56.13 | 55.83 | 56.50 |
| CV | 7.60 | 6.12 | 5.47 | 2.33 | 2.00 | 2.21 | 1.93 | 1.79 | 2.09 |
| +/- 95% Confidence Interval | 4.18 | 3.53 | 3.45 | 3.74 | 3.84 | 4.22 | 4.93 | 4.91 | 5.15 |
4
BETWEEN-LABORATORY REPRODUCIBILITY
Ten normal donor samples were compared between three independent laboratories. The samples were processed using antibody-coated magnetic microbeads to produce low, normal and high percent positive CD4 populations. The samples were stained with Ortho-mune OKT4A (CD4) FITC Conjugate and run on the ORTHO CYTORONABSOLUTE. All samples were analyzed in replicates of ten. The betweenlaboratory coefficient of variation (CV) and the 95% confidence intervals were calculated from the standard deviation between site means. The data collected from all sites are shown in Table 4. The data show excellent between-laboratory reproducibility.
| TABLE 4: N = 10
BETWEEN-LABORATORY REPRODUCIBILITY
Ortho-mune OKT4A (CD4) FITC CONJUGATE
| PERCENT POSITIVE RESULTS | |||||||
|---|---|---|---|---|---|---|---|
| High | |||||||
| CD4 Level | |||||||
| Low | |||||||
| Normal | |||||||
| Mean Percent Positive | 9.25 | 47.70 | રહ. 15 | ||||
| CV | 4.09 | 1.53 | 0-60 | ||||
| +/- 95% Confidence | |||||||
| Interval | 1.63 | 3.14 | 1.46 |
Ortho-mune OKT4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate immunophenotyping reagent shows acceptable within and between laboratory reproducibility for determination of CD4+ lymphocyte percentages.
5
A linearity study was performed using an automated hematology analyzer to determine to tal lymphocyte count, and the CYTORONABSOLUTE flow cytometer to determine the percent positive CDx cells.
Specimens from four normal donors (whole blood, EDTA) were processed to produce samples with low, normal and high numbers of lymphocyte subsets. Each whole blood specimen was concentrated by harvesting the buffy coat to obtain a white blood cell count between 20,000 and 40,000 cells/ul and then diluting to produce samples of high, normal and low numbers of lymphocyte subsets. A portion of each sample was stained in triplicate using Ortho-mune OKT4A (CD4) FITC Conjugate immunophenotyping reagent and analyzed using the CYTORONABSOLUTE flow cytometer. The total lymphocyte count of the concentrated sample for each donor was obtained using an sutomated hematology analyzer.
Linear regression analyses were performed as follows. The expected (X axis ) values were calculated by multiplying the corresponding serial dilutions by the hematology analyzer derived buffy coat lymphocyte count and by the CYTORONABSOLUTE derived lymphocyte subser percent positive. The observed (Y axis) values were determined as the total lymphocyte count calculated from the hematology derived value of the concentrated sample times the CYTORONABSOLUTE derived lymphocyte subset percent positive at each dilution.
The Ortho-mune OKT4A (CD4) FITC Conjugate reagent demonstrated linear performance for total CD4+ lymphocyte subsets across a lymphocyte count range of 20 cells/uL to 9000 cells/uL as demonstrated with slopes indistinguishable from 1 and R values of 1,000.
Linear regression analyses of observed versus expected values for total percent CD4+ cells for each donor specimen are shown in. Regression analysis statistics are provided in Table 5.
6
-- · · · · · · ·
ု့
・・
. ' — ··· ··· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · CHART 2
Ortho - mune OKT4A(FITC)
:
.
Image /page/6/Figure/4 description: The figure is a scatter plot showing the relationship between expected CD4+ counts and observed CD4+ counts. The x-axis represents the expected CD4+ counts, ranging from 0 to 5000. The y-axis represents the observed CD4+ counts, ranging from 0 to 5000. A strong positive correlation is observed between the expected and observed CD4+ counts, with data points clustered tightly around a straight line.
DONOR ++ 81 ତ-ତ ପ ଅ ���� �� 在电子 时
.
!
7
. . . . . . . .
TABLE 5
| Ortho-mune | Donor | SLOPE | CI | INTERCEPT | CI | R |
|---|---|---|---|---|---|---|
| TOTAL CD4 | 1 | 0.999 | 0.003 | 6.099 | 5.242 | 1.000 |
| TOTAL CD4 | 2 | 1.000 | 0.001 | 0.395 | 2.226 | 1.000 |
| TOTAL CD4 | 3 | 0.999 | 0.003 | 4.449 | 4.176 | 1.000 |
| TOTAL CD4 | 4 | 1.000 | 0.001 | 0.285 | 1.316 | 1.000 |
| TOTAL CD4 | All | 0.999 | 0.001 | 2.777 | 1.655 | 1.000 |
CONCLUSION
Performance of Ortho-mune OKT4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate is substantially equivalent to CD4 (Leu-3a) FITC reagent in the identification and enumeration of CD4+ human T lymphocytes in whole blood by flow cytometry.
8
Image /page/8/Picture/1 description: The image is a black and white logo for the U.S. Department of Health and Human Services. The logo features the department's name in a circular arrangement around a stylized symbol. The symbol consists of three curved lines that resemble a stylized human figure.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Gail Kromer Manager, Regulatory Affairs 1 2000 1 4 1997 Ortho Diagnostic Systems, Inc. 1001 U.S. Hiqhway 202 Raritan, New Jersey 09969-0606
Re : K951459/S3 Trade Name: Ortho-mune™ OKT™4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate Requlatory Class: II Product Code: GKZ Dated: April 21, 1997 Received: April 23, 1997
Dear Ms. Kromer:
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 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 reqistration, listing of devices, good manufacturing practice, labelinq, 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 requirement, 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.
9
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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
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
10
Indications for Use Statement
Page 1 of 1
510(k) Number (if known) K951459
Ortho-mune™OKT™4A (CD4) Device Name: Monoclonal Antibody (Murine) FITC Conjugate
Indications for Use:
Ortho-mune OKT4A (CD4) Monoclonal Antibody (Murine) FITC Conjugate is used to identify and enumerate the percentage of CD4+ human T lymphocytes in whole blood by flow cytometry.
Identification and enumeration of abnormal levels of CD4lymphocytes may be clinically significant in the prognosis of secondary immunodeficiency diseases (acquired immunodeficiency syndrome [AIDS]).
AIDS is characterized by a severe reduction in T helper CD3+CD4+) lymphocytes and a decrease in the CD4:CD8 ratio. The CD4:CD8 ratio has been used as a predictor of time to the development of AIDS. CD4 counts should also be determined using a CD3/CD4 combination reagent to eliminate monocyte contamination (CD3-CD4+dim). CD4+lymphocytes (expressed as an absolute number, a percentage of lymphocytes or as a ratio of CD4+ to CD8+ T lymphocytes) represents the best single predictor of the progression of AIDS. CD4+ lymphocyte numbers usually start to decline relatively soon after human immunodeficiency virus (HIV) infection.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Retin E. Moti
Concurrence of CDRH, Office of Devicsider S Division of Clinics 510(k) Numb
Prescription Use
✓
(Per 21 CFR 801.109)
OR
Over-The-Counter-Use
(Optional Format 1-2-96)
Ortho Diagnostic Systems Inc. Ortho-mune ThoKT Tha (CD4) FITC Conjugate Ref. No. K951459 Additional Information - Submitted April, 1997 Page 1