(490 days)
IMMULITE CMV IgG is designed for the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to CMV
IMMULITE® CMV IgG is a solid-phase, two-step, chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a CMV antigen.
The Diagnostic Products Corporation IMMULITE® CMV IgG is a device for the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human serum, intended for in vitro diagnostic use to determine serological status to CMV.
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria (Implicit) | IMMULITE vs. CDC | IMMULITE vs. CYTOMEGELISA II IgG | IMMULITE vs. IMx CMV IgG |
|---|---|---|---|
| Agreement | 100.0% | 98.5% | 99.5% |
| Sensitivity | 100.0% | 97.9% | 100.0% |
| Specificity | 100.0% | 100.0% | 98.7% |
Note: The document implicitly defines acceptance criteria through the comparison of the IMMULITE® CMV IgG with established predicate devices and a proficiency panel from the CDC. The reported performance demonstrates high agreement, sensitivity, and specificity across all comparisons.
2. Sample Size Used for the Test Set and Data Provenance:
- IMMULITE vs. CDC: n = 100
- IMMULITE vs. CYTOMEGELISA II IgG: n = 202
- IMMULITE vs. IMx CMV IgG: n = 200
The document does not explicitly state the country of origin for all data or whether the studies were retrospective or prospective. However, the use of a "CMV proficiency panel obtained from the United States Centers for Disease Control and Prevention (CDC)" suggests data provenance from the United States for that specific comparison. For the other comparisons with commercial assays, the provenance of the samples is not specified.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts:
This information is not provided in the document. The ground truth for comparative studies was established by either:
- The results of the "CMV proficiency panel obtained from the United States Centers for Disease Control and Prevention (CDC)".
- The results from the predicate devices: BioWhittaker CYTOMEGELISA II IgG and Abbott Laboratories' IMx* CMV IgG.
The process of how the CDC panel established its ground truth or how the predicate devices' ground truths were validated is not detailed.
4. Adjudication Method for the Test Set:
The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for resolving discrepancies or establishing ground truth within the context of these comparative studies. The comparisons directly used the results from the CDC panel or the predicate devices as reference.
5. 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:
This information is not applicable. The device described, IMMULITE® CMV IgG, is an automated immunoassay for antibody detection, not an AI-assisted diagnostic tool that would involve human readers interpreting results. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed or reported.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Yes, a standalone performance assessment was effectively conducted. The reported "Agreement," "Sensitivity," and "Specificity" for the IMMULITE® CMV IgG assay were determined by comparing its automated results against established reference standards (the CDC panel and predicate devices). This represents the performance of the algorithm/device itself without human intervention in the interpretation of the primary quantitative signal from the immunoassay to generate the qualitative result.
7. The Type of Ground Truth Used:
The ground truth used for these studies was based on:
- Proficiency Panel Data: From the United States Centers for Disease Control and Prevention (CDC), which likely represents a highly validated reference standard for CMV serology.
- Reference Assay Results: The results obtained from the BioWhittaker CYTOMEGELISA II IgG and Abbott Laboratories' IMx* CMV IgG assays, which are commercially marketed and presumably well-validated devices for CMV IgG detection.
These can be categorized as a form of reference standard comparison or external validation using established methods.
8. The Sample Size for the Training Set:
This information is not provided in the document. The document describes the performance of the product in a clinical comparison rather than detailing the development and training of a machine learning algorithm. As an immunoassay, the concept of a "training set" in the context of AI is not directly applicable. The assay's parameters would have been optimized during its development, but this process is not explicitly detailed as "training" in the AI sense.
9. How the Ground Truth for the Training Set Was Established:
This information is not provided because the IMMULITE® CMV IgG is an immunoassay, not an AI/machine learning model, therefore, the concept of a "training set" and its associated ground truth establishment does not apply in the context of this device and document.
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Diagnostic Products Corporation IMMULITE® CMV IgG
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K95.0672
JUN 17 1996
Attachment 9
510 (k) Summary
Safety and Effectiveness
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Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045 Tel: (213) 776-0180 Fax: (213) 776-0204
Image /page/1/Picture/1 description: The image shows a logo with the letters "DPC" in a bold, sans-serif font. The letters are connected and have a slightly rounded appearance. There is a small circle with a dot inside it, located to the upper right of the letter "C". The logo is black and the background is white.
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510 (k) Summary Safety and Effectiveness
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.
| Name: | Diagnostic Products Corporation |
|---|---|
| Address: | 5700 West 96th StreetLos Angeles, California 90045 |
| Telephone Number: | (213) 776-0180 |
| Contact Person: | Kenneth B. Asarch, Pharm.D., Ph.D. |
| Date of Preparation: | February 10, 1995 |
| Device Name: | IMMULITE ® CMV IgG |
| Trade: | LKCVZ (50 tests); LKCV2 (200 tests) |
| Catalog Number: | Reagent system for the determination of cytomegalovirus IgG antibodies in human serum. |
| Common: | |
| Classification: | Class II device (866.3175) |
| Manufacturer: | Diagnostic Products Corporation5700 West 96th StreetLos Angeles, California 90045 |
| Establishment Registration #: | DPC's Registration # is 2017183 |
| Substantially Equivalent Predicate Device: | BioWhittaker CYTOMEGELISA II IgGAbbott Laboratories' IMx* CMV IgG |
| Description of Device: | IMMULITE CMV IgG is a clinical device for use with the IMMULITE Automated Immunoassay Analyzer. |
| Intended Use of the Device: | IMMULITE CMV IgG is designed for the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to CMV |
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Summary and Explanation of the Test:
में बाद में स्थान के साथ में बाद में सबसे बाद में बाद में बाद में बाद में सबसे बाद में बाद में बाद में कि में बाद में कि में बाद में कि में कि में कि में कि में कि में कि मे
Cytomegalovirus (CMV), a member of the Herpesvirus group is found throughout the world. Humans of all ages are susceptible and infection is spread through sexual contact, direct exposure to infected body fluids, blood transfusions and organ transplants. Infection can be severe in patients with congenital or acquired cellular immune defects, including cancer patients, organ recipients and AIDS patients. The majority of infections are asymptomatic, however, CMV infections can be severe in neonates and immunocompromised individuals.
CMV is the most common congenital infection, infecting between 0.5 and 2.5 percent of newborn infants. Five percent of these will develop classic cyromegalic inclusion disease with jaundice, pneumonia and central nervous system disorder. Infected infants may be asymptomatic at birth, but can develop neurological problems later in life.
Between 40 and 100 percent of people have detectable antibody, with the prevalance highest in developing countries. Serological screening of blood used for transfusion cna limit the transmission of infection. In addition, transplantation of organs from donors seronegative for CMV antibodies appears to limit the incidence of acute infection in the recipient.
Summary and Explanation of the Device:
IMMULITE® CMV IgG is a solid-phase, two-step, chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a CMV antigen.
Prediluted patient sample (1-in-21 dilution) and a protein-based buffer are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37℃ with intermittent agitation. During this time, CMV IgG in the sample binds to the CMV antigen-coated bead. Unbound serum is then removed by a centrifugal wash.
An alkaline phosphatase-labeled anti-human IgG antibody is introduced, and the Test Unit is incubated for another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added. and the Test Unit is incubated for an additional 10 minutes.
The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple reading. The bound complex - and thus the photon output, as measured by the luminometer - is directly related to the presence of CMV IgG in the sample. A qualitative result is then obtained by comparing the patient result to a stored Master Cutoff
Performance Equivalence - Technology Comparison:
Diagnostic Products Corporation (DPC) asserts that IMMULITE® CMV IgG is substantially equivalent to the CYTOMEGELISA II IgG kit marketed by BioWhittaker Inc. (Walkersville, MD), and the IMx® CMV IgG kit marketed by Abbott Laboratories (Abbott Park, IL).
Each product is designed for the detection of IgG antibodies to cytomegalovirus (CMV) in human serum. Each product is intended strictly for in vitro diagnostic use as an aid in the determination of serological status to CMV.
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Performance Equivalence - Technology Comparison (continued):
IMMULITE® CMV IgG is a chemiluminescent enzyme immunoassay, CYTOMEGELISA II IgG is an enzyme-linked immunosorbent assay (ELISA), and IMx CMV IgG is a microparticle enzyme immunoassay (MEIA). The technology in DPC's IMMULITE CMV IgG is identical to technology used in previously cleared and commercially marketed IMMULITE® products.
In the CYTOMEGELISA II IgG assay, purified CMV antigen is attached to the surface of microplate wells. Diluted patient serum is added to the wells, and the CMV IgG specific antibody, if present, binds to the antigen. All unbound antibody is washed away and enyzme-sonjugated anti-human IgG is added. The enzyme conjugate binds to the antibody-antigen complex. Excess enzyme conjugate begins a hydrolytic reaction. After a specified time, the enzyme reaction is stopped. The intensity of the color generated is proportional to the amount of CMV IgG specific antibody in the sample. The results are read by a spectrophotometer, producing an indirect measurement of the CMV IgG specific antibody in the serum.
In the IMx CMV IgG assay, the patient sample and diluent buffer are added to predilution well of a reaction cell. CMV coated microparticles and the diluted sample are added to an incubation well. The CMV antibody binds to the CMV coated microparticles, forming an antigen-antibody complex. Diluent buffer is added to the reaction mixture and an aliquot of the antigen-antibody complex is transferred to the glass fiber matrix. The microparticles bind irreversibly to the glass fiber matrix is washed to remove unbound materials. The anti-human IgG/alkaline phosphatase conjugate is dispensed onto the matrix and binds to the antigen-antibody complex. Finally, the matrix is washed to remove unbound materials, the substrate, 4-Methylumbelliferyl Phosphate, is added to the matrix, and the fluorescent product is measured by the optical assembly.
Performance Equivalence - Method Comparison:
The clinical performance of the IMMULITE CMV IgG procedure was compared to a CMV proficiency panel obtained from the United States Centers for Disease Control and Prevention (CDC), the CYTOMEGELISA II IgG assay, and the IMx CMV IgG assay. A summary of the results is shown in the table below.
| IMMULITE vs.CDC | IMMULITE vs.CYTOMEGELISA II IgG | IMMULITE vs.IMx CMV IgG | |
|---|---|---|---|
| Agreement | 100.0% | 98.5% | 99.5% |
| Sensitivity | 100.0% | 97.9% | 100.0% |
| Specificity | 100.0% | 100.0% | 98.7% |
| n= | 100 | 202 | 200 |
Conclusion:
The conclusions drawn from the clinical and nonclinical studies demonstrate that the device is safe, effective, and performs as well as, or better, than the current legally marketed devices.
Kenneth B. Gooch
Kenneth B. Asarch, Pharm.D., Ph.D. Director of Regulatory Affairs
2/10/95
Date
'Date
§ 866.3175 Cytomegalovirus serological reagents.
(a)
Identification. Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.(b)
Classification. Class II (performance standards).