(35 days)
The MESACUP-2 Test CENP-B is a semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of anti-CENP-B antibodies in human serum. The MESACUP-2 Test CENP-B is intended for in vitro diagnostic use as an aid in the diagnosis of CREST syndrome and related connective tissue diseases.
The MESACUP-2 Test CENP-B is an enzyme-linked immunosorbent assay (ELISA), utilizing the 96microwell plate format, similar to the predicate device. Diluted serum samples, calibrator sera, and controls are incubated in microwells coated with CENP-B antigen. Incubation allows the anti-CENP-B antibodies present in the samples to react with the immobilized antigen. After the removal of unbound serum proteins by washing, antibodies specific for human immunoglobulins (IgG, IgM and IgA), labeled with horseradish peroxidase (HRP), are added forming complexes with the CENP-B bound antibodies. Following another washing step, the bound enzyme-antibody conjugate is assayed by the addition of a single solution containing tetramethlybenzidine (TMB) and hydrogen peroxide (H2O2) as the chromogenic substrate. The intensity of the color generated is proportional to the serum concentration of anti-Jo-1 antibodies. Optical density is read spectrophotometrically at 450nm. The total incubation time (at room temperature) of the assay is 150 minutes. The assay makes use of two calibrators to measure the amount of anti-CENP-B antibody in patient samples.
The MESACUP-2 Test CENP-B is an in vitro diagnostic device intended to detect anti-CENP-B antibodies in human serum.
Here's an analysis of its acceptance criteria and the supporting study:
1. Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance (%) |
|---|---|
| Specificity (healthy donors) | 95% (MESACUP-2 Test) |
| Specificity (healthy donors) | 100% (Predicate Device) |
| Sensitivity (CREST Syndrome) | 90% (MESACUP-2 Test) |
| Sensitivity (CREST Syndrome) | 95% (Predicate Device) |
| Relative Agreement | 95% (between MESACUP-2 and Predicate) |
Note: The document implies that the performance of the MESACUP-2 Test CENP-B is considered equivalent to the predicate device, thereby meeting the acceptance criteria for market clearance. The specific numerical thresholds for "acceptance" beyond establishing equivalence are not explicitly stated as strict cut-offs, but rather demonstrated through comparable performance.
2. Sample Size Used for the Test Set and Data Provenance
The document states that in-house studies were conducted.
- Healthy Donor Population: The sample size for healthy donors is not specified.
- CREST Syndrome Population: The sample size for the CREST Syndrome population is not specified.
- Data Provenance: The studies were "in-house," suggesting the data was collected and analyzed by the manufacturer. The country of origin is not specified, but the submission is to the U.S. FDA, implying relevance to a U.S. context. The studies appear to be retrospective as they are described as "in-house studies" and "additional studies" rather than a prospective clinical trial.
3. Number of Experts and Qualifications for Ground Truth
The document does not provide information on the number of experts used or their qualifications for establishing the ground truth for the test sets.
4. Adjudication Method for the Test Set
The document does not describe any adjudication method used for the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was mentioned. The device is an ELISA assay; therefore, a human-in-the-loop scenario, as typically seen in image interpretation or diagnostic aid, does not apply in the same way. The comparison is between two analytical methods (the MESACUP-2 Test and the predicate device).
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The "in-house studies" and "additional studies" of the MESACUP-2 Test CENP-B's specificity and sensitivity directly report the algorithm's (or device's) performance without human intervention in the interpretation of the output. The MESACUP-2 Test CENP-B is a laboratory assay that produces a quantitative result (optical density) which is then interpreted against established cut-offs by the device's design, not by a human reader's subjective assessment.
7. Type of Ground Truth Used
- For Specificity (Healthy Donor Population): The ground truth was based on a "healthy donor serum population," implying that these individuals were confirmed not to have anti-CENP-B antibodies or the associated conditions.
- For Sensitivity (CREST Syndrome Population): The ground truth was established using a "CREST Syndrome population on both assay respectively for anti-CENP-B antibodies previously also found positive by double immunodiffusion (DID)." This indicates that Double Immunodiffusion (DID) was used as the reference standard (ground truth) to independently confirm the presence of anti-CENP-B antibodies in the CREST Syndrome patients.
8. Sample Size for the Training Set
The document does not provide information about a separate training set or its sample size. For an ELISA assay, the "training" equivalent might involve optimizing assay parameters and cut-offs using a set of known samples, but this is not explicitly detailed.
9. How Ground Truth for the Training Set Was Established
As no specific training set is mentioned, information on how its ground truth was established is not available in the provided text.
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MAR - 4 2004
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SUMMARY OF 510(K) SAFETY AND EFFECTIVENESS MESACUP-2 Test CENP-B January 27, 2004
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 MESACUP-2 Test CENP-B is compared to a legally marketed predicate device and a substantial File MEBA Core Claim made. The predicate device is Quanta Lite Centromere ELISA (K926562) currently equivalier cland marketed by Inova Diagnostics, Inc., 10180 Scripps Ranch Boulevard, San Diego, CA 92131.
The MESACUP-2 Test CENP-B is an enzyme-linked immunosorbent assay (ELISA), utilizing the 96microwell plate format, similar to the predicate device. Diluted serum samples, calibrator sera, and controls are incubated in microwells coated with CENP-B antigen. Incubation allows the anti-CENP-B antibodies present in the samples to react with the immobilized antigen. After the removal of unbound serum proteins by washing, antibodies specific for human immunoglobulins (IgG, IgM and IgA), labeled with horseradish peroxidase (HRP), are added forming complexes with the CENP-B bound antibodies. Following another washing step, the bound enzyme-antibody conjugate is assayed by the addition of a single solution containing tetramethlybenzidine (TMB) and hydrogen peroxide (H2O2) as the chromogenic substrate. The intensity of the color generated is proportional to the serum concentration of anti-Jo-1 antibodies. Optical density is read spectrophotometrically at 450nm. The total incubation time (at room temperature) of the assay is 150 minutes. The assay makes use of two calibrators to measure the amount of anti-CENP-B antibody in patient samples.
The intended use of the device is a semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of anti-CENP-B antibodies in human serum. The MESACUP-2 Test CENP-B is intended for in vitro diagnostic use as an aid in the determination of CREST syndrome and related connective tissue diseases ..
Performance indicates that MESACUP-2 Test CENP-B and the Quanta Lite Centromere ELISA are equivalent. In-house studies indical specificity of 95% and 100% for anti-CENP-B antibodies in a healthy donor serum population respectively. Additional studies resulted a sensitivity of 90% and 95% with a CREST Syndrome population on both assay respectively for anti-CENP-B antibodies previously also found positive by double immunodiffusion (DID). In general, the performance characteristics are comparable between the two methods (95% relative agreement).
Ylusk Robe
Yusuke Kobe Vice President, Sales and Marketing Department
1/28/2004
Date
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAR - 4 2004
Mr. Yusuke Kobe VP, Sales and Marketing Department Rhigene, Inc 455 State Street - Suite 104 Des Plaincs, IL 60016
K040200 Re:
Trade/Device Name: MESACUP-2 Test CENP-B Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LJM Dated: February 24, 2004 Received: February 25, 2004
Dear Mr. Kobe:
We have reviewed your 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 for assessment 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 rou may, chereferey misions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adultcration.
If your device is classified (sec above) into either class II (Special Controls) or class III (PMA), it If your device to such additional controls. Existing major regulations affecting your device can indy ve Saley 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 complics with other requirements of the Act that + + Federal statutes and regulations administered by other Federal agencies. You must or any I with all the Act's requirements, including, but not limited to: registration and listing (21 CHR Parts 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 510(k) I mis letter will and w yourse FITA finding of substantial equivalence of your device to a legally promaticated predicated in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or you dent openite and advertising of your device, please contact the Office of or questions on the presidention and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I va may obatin ourseturers, International and Consumer 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,
Joseph L. Hackett
Joseph L. Hackett, Ph.D. Acting Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use Statement
510(k) Number: K040200_
Device Name: MESACUP-2 Test CENP-B
Indications for Use:
The MESACUP-2 Test CENP-B is a semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of anti-CENP-B antibodies in human serum. The MESACUP-2 Test CENP-B is intended for in vitro diagnostic use as an aid in the diagnosis of CREST syndrome and related connective tissue diseases.
The MESACUP-2 Test CENP-B is intended to be used by clinical (hospital and reference) laboratories.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NECESSARY) Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (per 21 CFR 801.109) OR
Over-The-Couter Use
Optional Format 1-2-96)
Maria Chan
Division Sign-Off
Office of In Vitto Diagnostic Device Evaluation and
510(k) 340200
§ 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).