(70 days)
- 1 . For in vitro diagnostic use only.
-
- For the qualitative and semi-quantitative detection of IgG antibodies to Sm/RNP in human serum by enzyme immunoassay.
- For use as an aid in the diagnosis of systemic rheumatic disease, particularly 3. mixed connective tissue disease (MCTD).
- For manual use, or for use with the HyPrep System Plus semi-automated fluid 4. handler.
The SeraQuest® Anti-Sm/RNP test is a solid-phase enzyme immunoassay (EIA), which is performed in microwells, at room temperature, in three thirty minute incubations. It has been developed to detect IgG antibodies which are directed against Sm/RNP nuclear antigen (Anti-Sm/RNP), in human serum.
The Calibrators in the SeraQuest Anti-Sm/RNP test set have been assigned Index values based on an in-house standard. Test results are reported as Index values.
Here's an analysis of the provided text regarding the SeraQuest® Anti-Sm/RNP device's acceptance criteria and studies:
Key Takeaways Before Diving In:
- This is a 510(k) summary, which means the device is being compared to a legally marketed predicate device for "substantial equivalence."
- The study described is a clinical comparison between the new device (SeraQuest) and the predicate device (Shield Diastat). It's not a standalone performance study against a definitive gold standard like pathology in the typical sense for a diagnostic assay, but rather a comparison to an established, similar diagnostic.
- The acceptance criteria are implied by the reported performance (specifically the relative sensitivity and specificity compared to the predicate). There aren't explicitly stated "acceptance criteria" values the new device had to meet, but rather the performance it achieved relative to the predicate.
1. Table of Acceptance Criteria and Reported Device Performance
| Metric | Acceptance Criteria (Implied by Predicate Comparison) | Reported Device Performance (SeraQuest Anti-Sm/RNP) |
|---|---|---|
| Relative Sensitivity* | High, comparable to predicate device | 100% (95% CI: 99.9% to 100%) |
| Relative Specificity* | High, comparable to predicate device | 90.4% (95% CI: 86.4% to 94.4%) |
| Overall Agreement* | High, comparable to predicate device | 95.4% (95% CI: 88.6% to 95.3%) |
*Note: All percentages are relative to the Shield Diastat Anti-Sm/RNP test (the predicate device). The confidence intervals (CI) are important indicators of the precision of these estimates. The "acceptance criteria" are implied because the purpose of a 510(k) is to demonstrate substantial equivalence, meaning the new device performs comparably to the predicate. No explicit numerical targets for sensitivity, specificity, or agreement are stated.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 252 specimens.
- Data Provenance: Not explicitly stated (e.g., country of origin). The study design appears to be retrospective, as it involves testing a collection of "specimens" against two existing assays, one of which is a predicate. There's no indication of prospective patient enrollment based on the provided text.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
-
Number of Experts: Not applicable in the traditional sense.
-
Qualifications of Experts: Not applicable.
Explanation: The "ground truth" for the test set in this study was established using the predicate device's results (Shield Diastat Anti-Sm/RNP test). The study is a comparison of the new device to the predicate, not an evaluation against an independent "expert consensus" or definitive clinical outcome. Therefore, there were no human experts establishing a distinct ground truth for the test set beyond the performance of the predicate device itself.
4. Adjudication Method for the Test Set
-
Adjudication Method: Not applicable.
Explanation: Since the "ground truth" was based on the predicate device's results, there was no need for human adjudication of discrepancies between expert opinions or between an expert and the device. The comparison involved the new device's results directly against the predicate device's results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
-
MRMC Study Done: No.
Explanation: This study is an in vitro diagnostic assay comparison, not an imaging or interpretation study involving human readers. Therefore, an MRMC study is not relevant to this type of device.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
-
Standalone Performance Done: Yes, in a way.
Explanation: The SeraQuest Anti-Sm/RNP test is an enzyme immunoassay (EIA). Such assays, once performed, produce a quantitative result (Index value) that is then interpreted. The clinical testing described, comparing its results directly to the predicate device's results, represents its "standalone" performance for detecting antibodies. There's no human "interpretation" component of the device's output described that would require a human-in-the-loop study; the output itself is the diagnostic result.
7. The Type of Ground Truth Used
-
Type of Ground Truth: The results of a legally marketed predicate device (Shield Diastat Anti-Sm/RNP test).
Explanation: The study establishes the performance of the SeraQuest device by comparing its categorization (positive, equivocal, negative) against that of the predicate device.
8. The Sample Size for the Training Set
-
Sample Size for Training Set: Not explicitly stated.
Explanation: The document describes the "Summary of Clinical Testing" as a single study involving 252 specimens. It does not separate this into distinct "training" and "test" sets as one might for a machine learning model. For a traditional immunoassay, development and calibration (which might use a "training set" of sorts) would occur during the assay's design phase, but this clinical study appears to be a final validation. The calibrators developed "based on an in-house standard" likely involved a separate set of samples during development, but their size is not provided here.
9. How the Ground Truth for the Training Set Was Established
-
How Ground Truth for Training Set Was Established: Not explicitly stated for a distinct training set in the context of this clinical evaluation.
Explanation: The document mentions that "The Calibrators in the SeraQuest Anti-Sm/RNP test set have been assigned Index values based on an in-house standard." This implies that internal standards and a reference method were used during the development and calibration of the assay. However, the details of these standards, the specific samples used, or how their "ground truth" was established are not provided in this 510(k) summary. This typically involves established reference samples or characterized patient samples for assay development, but it's distinct from the clinical comparison study described for regulatory submission.
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APPENDIX 3 (revised 4/24/98)
Quest International, Inc., 1938 N.E. 148th Terrace, N. Miami, FL 33181 Page No. 124
MAY 1 2 1998
510(k) SUMMARY
| Applicant: | Quest International, Inc.1938 N.E. 148th TerraceNorth Miami, FL 33181 |
|---|---|
| Registration No. | 1061839 |
| Contact Person: | Robert A. Cort, V.P., Quality Assurance |
| Telephone: | (305) 948-8788 |
| Telefax: | (305) 948-4876 |
| Manufacturing Site: | Same as above |
| Device: | SeraQuest® Anti-Sm/RNP |
| Device Name: | Antinuclear antibody immunological test system (21CFR § 866.5100)Device Classification: Class II (performance standards) |
>scription:
The SeraQuest Anti-Sm/RNP test is a solid-phase enzyme immunoassay (EIA), which is performed in microwells, at room temperature, in three thirty minute incubations. It has been developed to detect IgG antibodies which are directed against Sm/RNP nuclear antigen (Anti-Sm/RNP), in human serum.
The Calibrators in the SeraQuest Anti-Sm/RNP test set have been assigned Index values based on an in-house standard. Test results are reported as Index values.
Principle:
Diluted samples are incubated in wells coated with Sm/RNP antigen. Antibodies against Sm/RNP (if present) are immobilized in the wells. Residual sample is eliminated by washing and conjugate (enzyme-labeled antibodies to human IgG) is added and incubated. If IgG antibodies to Sm/RNP are present, the conjugate will be immobilized in the wells. Residual conjugate is eliminated by washing and draining, and the enzyme substrate is added and incubated. In the presence of the enzyme, the substrate is converted to a yellow end-product which is read photometrically at 405 nm.
Intended Use:
For the qualitative and semi-quantitative detection of human antibodies to Sm/RNP nuclear antigen human serum by enzyme immunoassay. For use as an aid in the diagnosis of systemic rheumatic
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APPENDIX 3 (revised 4/24/98)
sease, particularly mixed connective tissue disease. For manual use, or for use with the HyPrep رو. ystem Plus. For In Vitro Diagnostic Use Only.
Predicate Device:
The SeraQuest Anti-Sm/RNP test is substantially equivalent in intended use and performance, to the Shield Diastat Anti-Sm/RNP test, Shield Diagnostics, Dundee, U.K.
Summary of technological characteristics:
| Characteristic | SeraQuest Anti-Sm/RNP | Shield Diastat Anti-Sm/RNP |
|---|---|---|
| Description: | Enzyme Immunoassay | Enzyme Immunoassay |
| Intended Use: | The detection ofantibodies against Sm/RNPin human serum. | The detection ofantibodies against Sm/RNPin human serum. |
| Antigen Source: | Calf Thymus | Calf Thymus |
| Solid Phase: | Plastic Microwell | Plastic Microwell |
| Number of Incubation Periods: | Three | Three |
| Sample Dilution: | 1:50 | 1:500 |
| Sample IncubationDuration: | 30 minutes | 60 minutes |
| Incubation Temperature: | Room temperature | Room temperature |
| Enzyme-labeled Conjugate: | ||
| Antibody | Goat anti-human IgG | Goat anti-human IgG |
| Enzyme | Alkaline phosphatase | Alkaline phosphatase |
| Conjugate Volume: | 100 μl | 100 μl |
| Conjugate IncubationDuration: | 30 minutes | 30 minutes |
| Substrate: | p-Nitrophenylphosphate | phenolthaleinmonophosphate |
| Substrate Volume: | 100 μl | 100 μl |
| ubstrate Incubation | 30 minutes | 30 minutes |
| Stop Reagent: | 0.5 M Trisodiumphosphate | SodiumHydroxide |
| Stop Reagent Volume: | 100 µl | 100 µl |
| Readout: | Spectrophotometric405 nm | Spectrophotometric540-565 nm |
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Quest International, Inc., 1938 N.E. 148th Terrace, N. Miami, FL 33181 Page No. 126
Summary of Clinical Testing:
Of the 252 specimens tested, 40 were positive, and 189 were negative in both the SeraQuest and Shield tests (please see Table C-3). Of the remaining specimens, 23 specimens which were negative by the Shield test, 20 were positive and 3 equivocal by the SeraQuest test. Please see Table 1 below.
TABLE 1.
Sm/Anti-RNP SHIELD ASSAYS AND RESULTS OF SeraQuest Anti-Sm/RNP ASSAYS OF 252 SERUM SPECIMENS.
| SeraQuest Anti-Sm/RNP | |||||
|---|---|---|---|---|---|
| ShieldAnti-Sm/RNP | Positive | Equivocal | Negative | % | 95 % CIv |
| Positive | 4 0 | 0 | 0 | Relative sensitivity100 | 99.9 to 100 |
| Negative | 2 0 | 3 | 189 | Relative specificity*Overall agreement*90.495.4 | 86.4 to 94.488.6 to 95.3 |
· Excluding equivocal results.
- Calculated by the normal method.
Reference: Gardner, M.J. and Altman, D.G., Confidence Intervals Rather Than Hypothesis Testing. Brit. Med. J., 292: 746-750, 1986.
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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three heads facing to the right. The eagle is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAY | 2 1998
Robert A. Cort Vice President, Ouality Assurance QUEST INTERNATIONAL, INC. 1938 N.E. 148th Terrace North Miami, FL 33181
Re: K980811 Trade Name: SeraQuest® Anti-Sm/RNP Regulatory Class: II Product Code: LKP Dated: April 28, 1998 Received: April 28, 1998
Dear Mr. Cort:
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 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 -
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 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
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Quest International, Inc., 1938 N.E. 148th Terrace, N. Miami, FL 33181 Page No. 154
APPENDIX 8
Page _ 1 of _ し
510(k) Number (if known): K 980 & //
Device Name: SeraQuest Anti-Sm/RNP
Indications For Use:
- 1 . For in vitro diagnostic use only.
-
- For the qualitative and semi-quantitative detection of IgG antibodies to Sm/RNP in human serum by enzyme immunoassay.
- For use as an aid in the diagnosis of systemic rheumatic disease, particularly 3. mixed connective tissue disease (MCTD).
- For manual use, or for use with the HyPrep System Plus semi-automated fluid 4. handler.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
| (Division Sign-Off) | |
|---|---|
| Division of Clinical Laboratory Devices | |
| 510(k) Number | L990811 |
| Prescription Use | ✓ |
|---|---|
| (Per 21 CFR 801.109) |
OR
Over-The-Counter Use
(Optional Format 1-2-96)
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).