(445 days)
(1) The Elecsys Rubella IgG immunoassay is for the in vitro quantitative determination of IgG antibodies to rubella virus in human serum and Li-heparin, K3-EDTA and sodium citrate plasma.
This assay may be used as an aid in the assessment of immune status to rubella in individuals including women of childbearing age.
The electrochemiluminescence immunoassay "ECLIA" is intended for use or Elecsys and cobas e immunoassay analyzers.
(2) Elecsys PreciControl Rubella IgG is used for quality control of the Elecsys Rubella IgG immunoassay on the Elecsys and cobas e immunoassay analyzers.
(1) The Elecsys Rubella IgG Immunoassay is a two-step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. The Rubella IgG assay contains: a biotin labeled monoclonal antibody against human IgG, a ruthenium-labeled anti-Rubella antibody fragment , biotin- and ruthenium-labeled Rubella-antigens and a Rubella-like particle. A relationship exists between the concentration of the IgG antibody targets present in a patient sample and the level of signal count detected by the system. The IgG assay is quantitative and is standardized against WHO materials. Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve provided with the reagent bar code. The test kit contains the human serum-based calibrators intended for use with the system.
(2) The Elecsys Precicontrol Rubella IgG contains two levels of human serum with Rubella IgG antibodies.
Here's an analysis of the acceptance criteria and supporting studies for the Elecsys Rubella IgG Immunoassay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary primarily focuses on demonstrating substantial equivalence to a predicate device, rather than explicit pre-defined acceptance criteria in terms of numerical thresholds for performance metrics. However, we can infer performance goals based on the presented data and the comparison to the predicate device.
| Performance Metric | Acceptance Criteria (Implied/Achieved for Substantial Equivalence) | Reported Device Performance (Elecsys Rubella IgG Immunoassay) |
|---|---|---|
| Method Comparison (vs Predicate: Zeus Scientific Rubella IgG ELISA Test System) | Agreement with predicate device demonstrating similar clinical utility. | See detailed breakdown below in "Study Details". |
| Limit of Blank (LoB) | As low as possible to ensure accurate negative results. | < 0.17 IU/mL |
| Limit of Detection (LoD) | As low as possible to ensure detection of low positive results. | < 0.21 IU/mL |
| Measuring Range | Sufficiently broad to cover clinically relevant concentrations. | 0.21 - 500 IU/mL |
| Precision (Intra-assay) | Low variability within a single assay run. | Low Control: SD 0.075-0.176 IU/mL; High Control: CV 1.20-6.79 %; Plasma Samples < 5 IU/mL: SD 0.059-0.399 IU/mL; Plasma Samples > 5 IU/mL: CV 1.64–8.21% |
| Precision (Inter-assay) | Low variability across different assay runs. | Low Control: SD 0.118-0.319 IU/mL; High Control: CV 3.35-7.69 %; Plasma Samples < 5 IU/mL: SD 0.076-0.428 IU/mL; Plasma Samples > 5 IU/mL: CV 2.08–9.54% |
| Analytical Specificity | High agreement in the presence of various disease states. | 96.6 % agreement with predicate for 60 specimens representing a variety of disease states. |
| Interferences | Recovery of positive samples within ± 20% of initial value. Assayed for icterus, hemolysis, lipemia, Immunoglobulin A, biotin, rheumatoid factors, and Rubella-specific Immunoglobulin M. | Unaffected by icterus (< 513 µmol/L), hemolysis (< 3.47 mmol/L), lipemia (< 1500 mg/dL), Immunoglobulin A (up to 1440 mg/dL), biotin (< 123 nmol/L). No interference from rheumatoid factors (up to 6210 IU/mL). Elevated levels of Immunoglobulin G and Rubella-specific Immunoglobulin M may cause interference. No high dose hook effect. |
| Expected Values/Prevalence | Consistent with known epidemiology for Rubella IgG antibodies. | Studies indicate 80-90% of adult population have detectable antibodies; 95% prevalence in a US reference laboratory study, 94.7% among women of childbearing age with values ≥ 10 IU/mL. |
2. Sample Size Used for the Test Set and Data Provenance
The 510(k) describes several test sets used for method comparison:
- US Routine Clinical Specimens and Acute/Recent Infection: 500 samples (25 negative, 475 positive). Data provenance is "US Routine Clinical Specimens."
- Banked Samples: 345 samples (145 negative, 200 positive). Data provenance is not explicitly stated but implies collected and stored samples for research or clinical use.
- Samples Collected During a Rubella Outbreak: 71 samples (10 negative, 61 positive). Data provenance is "Rubella Outbreak."
- Pregnant Women: 150 serum samples. Data provenance is "US."
- Vaccinated Individuals: 15 samples from 13 subjects (commercially available vaccination follow-up panels). Data provenance is commercially available panels.
- Low Positive Samples: 84 serum samples. Data provenance is not explicitly stated, but these were samples that gave low positive on the reference assay.
All mentioned samples appear to be retrospective as they were collected and then tested.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the "number of experts" or their "qualifications" used to establish the ground truth for the test sets. For immunoassay devices like this, the "ground truth" is typically established by the results of a reference assay (often a well-established, previously cleared or gold-standard laboratory method) or clinical correlation (e.g., confirmed infection during an outbreak).
In this case, the predicate device, Zeus Scientific Rubella IgG ELISA Test System (K984180), serves as the primary comparator for establishing agreement, and its results are implicitly treated as the ground truth or reference standard for comparison. The performance of the predicate device would have been established through its own clinical trials and regulatory clearance.
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
The document does not describe an adjudication method with multiple readers or experts to resolve discrepancies for the test set. Instead, it directly compares the Elecsys Rubella IgG Immunoassay results against the predicate device's results. Any discrepancies are reported as part of the agreement percentages.
5. 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, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an automated in vitro diagnostic immunoassay, not an AI-assisted diagnostic imaging or pathology tool involving human "readers" interpreting results. Its performance is evaluated biochemically against a reference method.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance studies described are for the Elecsys Rubella IgG Immunoassay in a standalone fashion. The assay automatically processes samples and provides quantitative results (IU/mL) without direct human intervention in the result determination process once the sample is loaded and the assay run begins. The results are then interpreted by a healthcare professional in a clinical context.
7. The Type of Ground Truth Used
The primary "ground truth" used for performance evaluation is the results obtained from the legally marketed predicate device, the Zeus Scientific Rubella IgG ELISA Test System (K984180).
Additionally, for specific study cohorts:
- For "US Routine Clinical Specimens and Acute/Recent Infection," the classification might be based on clinical diagnosis (acute/recent infection) or general population screening.
- For "Rubella Outbreak," the classification of samples as negative/positive would likely be based on epidemiological and/or confirmatory testing methods during the outbreak.
- For "Vaccinated Individuals," the expected positive status is derived from the history of vaccination.
8. The Sample Size for the Training Set
The 510(k) summary does not specify a separate "training set" in the context of machine learning or AI models. For an immunoassay, the equivalent of a "training set" would be the samples used during product development and optimization (e.g., to establish calibration curves, optimize reagent concentrations, and define cut-offs). This information is typically proprietary and not detailed in a 510(k) summary, which focuses on validation data demonstrating substantial equivalence to a predicate. The document mentions a master curve provided with the reagent bar code, implying an internal standardization process.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" with ground truth in the AI sense is not applicable. For general immunoassay development and standardization, the "ground truth" for calibrators and controls is typically established through:
- Traceability to International Reference Standards: The Elecsys Rubella IgG Immunoassay explicitly states traceability to the "1st International Standard for Anti-Rubella Immunoglobulin, human, NIBSC RUBI-1-94; formerly referred to as proposed 3rd WHO Reference Standard Preparation." This WHO standard serves as the ultimate ground truth for quantitative accuracy.
- Internal Reference Methods and Protocols: Manufacturers use their own established reference methods and rigorous internal studies to characterize and assign values to calibrators and controls, ensuring lot-to-lot consistency and accuracy traceable to international standards.
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510(k) Summary
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
| Submitter name, address, contact | Roche Diagnostics9115 Hague RoadIndianapolis, IN 46250(317) 521 - 3723Contact Person: Theresa A. BushDate Prepared: November 21, 2008 |
|---|---|
| Device Name | Proprietary name: (1) Elecsys Rubella IgG Immunoassay(2) Elecsys Rubella IgG PreciControlCommon name: (1) Rubella IgG Immunoassay(2) Rubella IgG PreciControl |
| Device Description | Classification name: (1) Rubella Virus serological reagents(2) Single (specified) analyte controls (assayed and unassayed)(1) The Elecsys Rubella IgG Immunoassay is a two-step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. The Rubella IgG assay contains: a biotin labeled monoclonal antibody against human IgG, a ruthenium-labeled anti-Rubella antibody fragment , biotin- and ruthenium-labeled Rubella-antigens and a Rubella-like particle. A relationship exists between the concentration of the IgG antibody targets present in a patient sample and the level of signal count detected by the system. The IgG assay is quantitative and is standardized against WHO materials. Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve provided with the reagent bar code. The test kit contains the human serum-based calibrators intended for use with the system.(2) The Elecsys Precicontrol Rubella IgG contains two levels of human serum with Rubella IgG antibodies. |
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| Intended use | (1) The Elecsys Rubella IgG immunoassay is for the in vitro quantitativedetermination of IgG antibodies to rubella virus in human serum and Li-heparin, K3-EDTA and sodium citrate plasma.This assay may be used as an aid in the assessment of immune status torubella in individuals including women of childbearing age.The electrochemiluminescence immunoassay "ECLIA" is intended for use orElecsys and cobas e immunoassay analyzers.(2) Elecsys PreciControl Rubella IgG is used for quality control of theElecsys Rubella IgG immunoassay on the Elecsys and cobas e immunoassayanalyzers. |
|---|---|
| Indications forUse | The Elecsys Rubella IgG assay may be used as an aid in the assessment ofimmune status to rubella in individuals including women of childbearing age. |
| Substantialequivalence | The Elecsys Rubella IgG Test System is substantially equivalent to otherdevices legally marketed in the United States.Elecsys Rubella IgG Immunoassay is equivalent to the Zeus ScientificRubella IgG ELISA Test System cleared in K983805 |
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510(k) Summary, Continued
Substantial equivalence – similarities
| (1) Rubella IgG Immunoassay Comparison | ||
|---|---|---|
| Feature | Elecsys Rubella IgGImmunoassay | Predicate Device: Zeus ScientificRubella IgG ELISA Test System(K984180) |
| Intended Use | The Elecsys Rubella IgGimmunoassay is for the in vitroquantitative determination of IgGantibodies to rubella virus in humanserum and Li-heparin, K3-EDTAand sodium citrate plasma.This assay may be used as an aid inthe assessment of immune status torubella in individuals includingwomen of childbearing age.The electrochemiluminescenceimmunoassay "ECLIA" is intendedfor use on Elecsys and cobas eimmunoassay analyzers. | The Zeus Scientific, Inc. LaboratoriesRubella IgG ELISA Test System isdesigned for the qualitative and/orquantitative detection of IgG antibodiesto rubella virus in human serum. Thetest system is intended to be used toevaluate single sera for immune statusor paired sera to demonstrateseroconversion, and is for in vitrodiagnostic use. |
| Indication forUse | This assay may be used as an aid inthe assessment of immune status torubella in individuals includingwomen of childbearing age. | The test system is intended to be usedto evaluate single sera for immunestatus or paired sera to demonstrateseroconversion, and is for in vitrodiagnostic use. |
| Assay Protocol | ElectrochemiluminescentImmunoassay | ELISA |
| Sample Type | Human serum, lithium heparinplasma, potassium EDTA plasmaand sodium citrate plasma | Serum |
| InstrumentPlatform | Roche Elecsys 2010/ cobas e 411and MODULAR ANALYTICSE170 (Elecsys module)/ cobas e601 analyzers. | No automated instrument platform.ELISA equipment/ microwell platereader needed. No specific modelrequired. |
| Calibrator | Included in kit | Included in kit |
| Calibrator levels | Two | One |
| Format | Human serum | Human serum |
| CalibratorStability | After opening at 2-8°C: 8 weeksOn Elecsys 2010/ cobas e 411: upto 5 hoursOn E170/ cobas e 601: use onlyonce | Store between 2-8 °C. |
| Calibrationfrequency | Once per reagent lot and• After 1 month when usingsame reagent lot• After 7 days when usingsame reagent kit• As required per QC findingsor pertinent regulations | Each time the assay is run. |
| Controls | PreciControl Rubella IgG (soldseparately) | Positive and negative control includedin kit. |
| Traceability | 1st International Standard for Anti-Rubella Immunoglobulin, human,NIBSC RUBI-1-94; formerlyreferred to as proposed 3rd WHOReference Standard Preparation | Recovery of WHO Reference Standardis shown. |
| Reagent Stability | Unopened 2-8°C - up to expirationOpened 2-8°C - 12 weeksOnboard- 2 weeks or 12 weeks(stored alternately in refrigeratorand on the analyzer- ambienttemperature 20-25°C; up to 84 hoursopened in total.) | Unopened kit: Store at 2-8°C.Coated microwell strips: 2-8°C shouldbe immediately resealed withdessicant, stable 60 days providedindicator on dessicant pouch remainsblue.Conjugate, Control, Calibrator, TMB,and Diluent: 2-8°CWash buffer and Stop Solution: 2-25°CDiluted wash buffer: stable at roomtemperature 7 days or 30 days at 2-8°C |
| Measuring | 0.21 - 500 IU/mL | 0-20 IU/mL |
| Precision | ||
| Intrassay: (range of values)Low Control: SD 0.075-0.176 IU/mLHigh Control: CV 1.20-6.79 %Plasma Samples < 5 IU/mL:SD 0.059 - 0.3.99 IU/mLPlasma Samples > 5 IU/mL:CV 1.64 – 8.21%Inter-assay:Low Control: SD 0.118-0.319 IU/mLHigh Control: CV 3.35 - 7.69%Plasma Samples < 5 IU/mL:SD 0.076 - 0.428 IU/mLPlasma Samples > 5 IU/mL:CV 2.08 – 9.54% | Intraassay:Low: 5.1-6.2%Medium: 6.8-13.2%High: 4.4-8.96%Inter-assay:Low:6.3 %Medium:5.8%High:8.7% | |
| Limit of Blank | < 0.17 IU/mL | Not stated. |
| Limit ofDetection | < 0.21 IU/mL | Not stated. |
| AnalyticalSpecificity | 96.6 % agreement with predicate for60 specimens representing a varietyof disease states. | Not stated. |
| Interferences | The assay is unaffected by icterus(bilirubin < 513 µmol/L or < 30mg/dL), hemolysis (Hb < 3.47mmol/L or < 5.6 g/dL), lipemia(Intralipid < 1500 mg/dL),Immunoglobulin A up to 1440mg/dL, and biotin < 123 nmol/L or< 30 ng/mL.Criterion: Recovery of positivesamples within ± 20% of initialvalue.No interference was observed fromrheumatoid factors up to aconcentration of 6210 IU/mL.Rubella-specific Immunoglobulin Mmay cause interference. Elevatedlevels of Immunoglobulin G maycause interference. There is no highdose hook effect within the assaymeasuring range. | No anticoagulants or preservativesshould be added; avoid usinghemolyzed, lipemic, or bacteriallycontaminated samples. |
| Expected Values | 80-90% of adult population has detectable antibodies to rubella. | |
| Studies indicate that 80-90% of the adult population have detectable antibodies to rubella. According to the literature, in general, 90% of the U.S. population has either been vaccinated or exposed to rubella, with rubella IgG values greater than or equal to 10 IU/mL. In a study of 500 subjects from a United States reference laboratory, the prevalence of IgG antibodies to Rubella was shown to be 95%. Prevalence was 94.7% among women of childbearing age. | ||
| MethodComparison with95% CI(Elecsys® vsZeus ScientificRubella IgM): | US Routine Clinical Specimens and Acute/Recent Infection:Negative Agreement: 64.0% (16/25) 42.5 - 82.0%Positive Agreement: 98.1% (466/475) 96.4-99.1%Banked Samples:Negative Agreement: 96.6% (140/145) 92.1-98.9%Positive Agreement: 84.0% (168/200) 78.2-88.8%Samples Collected During a Rubella Outbreak:Negative Agreement: 100% (10/10) 69.1-100.0%Positive Agreement: 82.0% (50/61) 70.02-90.6%Pregnant WomenSerum samples were collected from 150 pregnant women in the US and tested on the Elecsys and the reference assay. The Elecsys Rubella IgG showed 100 % agreement (95% CI: 97.57- 100%), with 150/150 positive tests..Vaccinated Individuals:Commercially available vaccination follow-up panels comprising 15 samples from 13 subjects were also tested. The final specimen from each panel yielded 100 % agreement (95% CI: 75.29%~100%) between the methods, with 13/13 positive test results.Testing of Low Positive Samples84 serum samples that gave low positive (10-20 IU/mL) on the reference assay were tested with the Elecsys Rubella IgG assay. The positive agreement was 80/84 or 95.2%. (88.25 - 98.69%) |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows a circular logo for the Department of Health & Human Services USA. The logo features the department's name in a circular arrangement around a stylized eagle symbol. The eagle is depicted with three curved lines representing its body and wings.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Roche Diagnostics C/O Theresa A Bush, PhD, DABCC, RAC Regulatory Affairs Principal 9115 Hague Road Indianapolis, IN 46250
DEC 0 5 2008
Re: K072617
Trade/Device Name: Elecsys Rubella IgG immunoassay Elecsys Rubella IgG PreciControl Regulation Number: 21 CFR 866.3510 Regulation Name: ELISA, Rubella Regulatory Class: Class II Product Code: LFX, JJX Dated: November 13, 2008 Received: November 14, 2008
Dear Dr. Bush:
We have reviewed vour 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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 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), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Sally attigra
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Elecsys Rubella IgG and IgM Test Systems
Indications for Use
510(k) Number (if known):
Device Name: Elecsys Rubella IgG Immunoassay
Indications For Use:
The Elecsys Rubella IgG immunoassay is for the in vitro quantitative determination of IgG antibodies to rubella virus in human serum and Li-heparin, K3-EDTA and sodium citrate plasma.
This assay may be used as an aid in the assessment of immune status to rubella in individuals including women of childbearing age.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
Prescription Use XXX (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Wie Schif
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
K072617 510(k)
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Elecsys Rubella IgG and IgM Test Systems
Indications for Use
510(k) Number (if known): K072617
Device Name: Elecsys PreciControl Rubella IgG
Indications For Use:
Elecsys PreciControl Rubella IgG is used for quality control of the Elecsys Rubella IgG immunoassay on the Elecsys and cobas e immunoassay analyzers.
Prescription Use _ XXX (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
We Schuf
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K072617
§ 866.3510 Rubella virus serological reagents.
(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.