(126 days)
ZYMUTEST HIA IgG and IgGAM kits are designed as a solid phase enzyme- linked immunosorbent assay (ELISA). These products are intended to be used as an in vitro diagnostics kit by Hematology, coagulation or other pathology laboratories to assist in screening patients samples for the presence of heparin- associated antibodies commonly found in patients with heparin induced thrombocytopenia or thrombosis (HIT).
The ZYMUTEST HIA is solid phase enzyme linked immunosorbent assay (ELISA) designed to detect antibodies. These antibodies are found in some patients undergoing heparin therapy.
The provided 510(k) summary describes the ZYMUTEST HIA IgG and ZYMUTEST HIA IgGAM devices, which are ELISA kits designed to detect heparin-associated antibodies related to Heparin Induced Thrombocytopenia (HIT). The submission establishes substantial equivalence to existing predicate devices (ASSERACHROM ®HPIA Test Kit and PF4 ENHANCED Solid Phase ELISA).
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly based on establishing substantial equivalence with the predicate devices. The primary performance metrics reported are agreement, co-positivity, and co-negativity with the predicate devices, along with intra- and inter-assay reproducibility. Specific numerical acceptance criteria are not explicitly stated as target percentages for agreement, co-positivity, or co-negativity, but the general conclusion implies that the observed values meet the FDA's criteria for substantial equivalence.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Agreement (vs. Predicate) | Sufficient agreement to demonstrate substantial equivalence | Zymutest IgGAM vs. Asserachrom (n=243): 76% |
| Zymutest IgGAM vs. GTI PF4 Enhanced (n=345): 74% | ||
| Zymutest IgG vs. Asserachrom (n=243): 76% | ||
| Co-positivity (vs. Predicate) | Sufficient co-positivity to demonstrate substantial equivalence | Zymutest IgGAM vs. Asserachrom (n=243): 64% |
| Zymutest IgGAM vs. GTI PF4 Enhanced (n=345): 58% | ||
| Zymutest IgG vs. Asserachrom (n=243): 44% | ||
| Co-negativity (vs. Predicate) | Sufficient co-negativity to demonstrate substantial equivalence | Zymutest IgGAM vs. Asserachrom (n=243): 81% |
| Zymutest IgGAM vs. GTI PF4 Enhanced (n=345): 90% | ||
| Zymutest IgG vs. Asserachrom (n=243): 90% | ||
| Intra-assay Reproducibility | CV below 10% | CVs below 10% (for positive control) |
| Inter-assay Reproducibility | CV below 10% | CVs below 10% (for positive control) |
2. Sample Size for the Test Set and Data Provenance
- Zymutest IgGAM vs. Asserachrom (internal study): 44 plasma samples. Provenance not specified, but stated as an "internal study," suggesting it was conducted by Hyphen BioMed. Retrospective or prospective nature is not specified.
- Zymutest IgGAM vs. Asserachrom (clinical studies): 243 plasma samples. Provenance from "Combined Site 1 & 2." Specific country of origin or whether retrospective/prospective is not specified.
- Zymutest IgGAM vs. GTI PF4 Enhanced (clinical studies): 345 plasma samples. Provenance from "Combined Sites 1,2,3." Specific country of origin or whether retrospective/prospective is not specified.
- Zymutest IgG vs. Serotonin Release Assay (SRA) (clinical studies): 174 samples. Provenance not specified. This appears to be a reference method rather than a predicate.
- Zymutest IgG vs. Asserachrom (clinical studies): 243 samples. Provenance from "Combined Sites 1 & 2." Specific country of origin or whether retrospective/prospective is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The ground truth for the comparison studies was established by the predicate devices (ASSERACHROM ®HPIA and PF4 ENHANCED) and the Serotonin Release Assay (SRA). There is no mention of human experts being used to establish ground truth for the test set; instead, the results of existing, legally marketed diagnostic tests are used as the reference.
4. Adjudication Method for the Test Set
Not applicable. The comparisons are directly against the results of the predicate devices or the SRA, not against expert consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is an in vitro diagnostic device, and the evaluation focuses on its performance compared to other diagnostic assays, not on human reader performance with or without AI assistance.
6. Standalone Performance Study
Yes, the studies presented are standalone performance studies of the ZYMUTEST HIA IgG and IgGAM devices, comparing their results directly with established predicate devices and a reference method (SRA). The performance metrics (agreement, co-positivity, co-negativity, reproducibility) characterize the algorithm's (device's) performance.
7. Type of Ground Truth Used
The ground truth used for the comparison studies was the results obtained from legally marketed predicate in vitro diagnostic devices (ASSERACHROM ®HPIA and PF4 ENHANCED) and a reference assay (Serotonin Release Assay - SRA). This falls under the category of using established, validated diagnostic tests as the reference standard.
8. Sample Size for the Training Set
The document does not provide information about a "training set" in the context of machine learning or AI. This device is an ELISA kit, not an AI-powered diagnostic system. The validation studies instead compare the device's performance against existing methods.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no mention of a training set for machine learning or AI in this 510(k) submission.
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510(k) #K071255
510(k) Summary
SEP - 7 2007
Submitted by:
Hyphen BioMed 95000 Neuville sur oise, France Phone # 01 34 40 65 10 Fax# 301 34 48 72 36
| Contact Person: | Dr. Jean Amiral, President & Scientific Director | |
|---|---|---|
| Summary prepared by: | April 30th 2007 | |
| Name of the Device: | ZYMUTEST HIA IgG and ZYMUTEST HIA IgGAM | |
| Classification Name: | Anti-Platelet Factor IV Complex Antibodies | |
| Regulation #: | 864.7695 | |
| Product Code: | LCO/0545 |
ldentification of Predicate device:
- ASSERACHROM ® HPIA Test Kit (Stago)
-
- PF4 ENHANCED Solid Phase ELISA (GTI)
Predicate device 510 (k) number:
Description of the Device:
The ZYMUTEST HIA is solid phase enzyme linked immunosorbent assay (ELISA) designed to detect antibodies. These antibodies are found in some patients undergoing heparin therapy.
Indication for use:
ZYMUTEST HIA IgG and IgGAM kits are designed as a solid phase enzymelinked immunosorbent assay (ELISA). These products are intended to be used as an in vitro diagnostics kit by Hematology, coagulation or other pathology laboratories to assist in screening patients samples for the presence of heparinassociated antibodies commonly found in patients with heparin induced thrombocytopenia or thrombosis (HIT).
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Substantial equivalence is based on comparison of characteristics to the predicate devices.
ZYMUTEST HIA test kit uses the same principle as the predicate devices ASSERACHROM ®HPIA test kit and PF4 ENHANCED which are substantially equivalent in performance, intended use and technical principle.
| Item | Device (ZYMUTESTHIA IgG and IgGAM) | Predicate(ASSERACHROM®HPIA) | Predicate(PF4Enhanced) |
|---|---|---|---|
| Intended Use | Determination of anti-heparin Platelet factor 4 | Same | Same |
| SampleRequirement | Citrated human plasmaor Serum | Same | Same |
| Design | Sandwich technique ofenzyme-linkedimmunosorbent assay(ELISA) | Same | Same |
In addition, these products have the same indication for use and same scientific technology.
Summary of performance Data:
Inter-lot reproducibility and comparison with predicate device
- Zymutest IgGAM was compared with Asserachrom (predicate device). Total . of 44 plasma samples were analyzed. This was an internal study.
| Asserachrom | ZymutestIgGAM | %Agreement | |
|---|---|---|---|
| Positive | 28 | 30 | 93% |
| Negative | 16 | 14 | 88% |
- In clinical studies, Zymutest IgGAM was compared with Asserachrom for . n=243 plasma samples.
| CombinedSite 1 & 2 | AsserachromPositive | AsserachromNegative | |
|---|---|---|---|
| ZymutestPositive | 48 | 32 | |
| IgGAMNegative | 27 | 136 | |
| Agreement | 76% | ||
| Co-positivity | 64% | ||
| Co-negativity | 81% | ||
| Sample Size | 243 |
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- . In clinical studies, Zymutest IgGAM was compared with GTI PF4 Enhanced for n=345 plasma samples.
| CombinedSites | GTI PF4-Enhanced | ||
|---|---|---|---|
| 1,2,3 | Positive | Negative | |
| ZymutestIgGAM | Positive | 101 | 17 |
| Negative | 74 | 153 | |
| Agreement | 74% | ||
| Co-positivity | 58% | ||
| Co-negativity | 90% | ||
| Sample Size | 345 |
- In clinical studies, Zymutest IgG was compared with Seritonin Release Assay . (SRA) for n=174 samples. Matches indicate that both were positive or both were negative.
| ﺍﻟﻤﺴﺎﻋﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘMate1nes0 | |
|---|---|
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | 00 |
| % Matching | Button & AMER LOUI |
- In clinical studies, Zymutest IgG was compared with Asserachrom for n=243 . samples.
| CombinedSites 1 &2 | Asserachrom | |
|---|---|---|
| Positive | Negative | |
| ZymutestIgG | 33 | 17 |
| 42 | 151 | |
| Agreement | 76% | |
| Co-positivity | 44% | |
| Co-negativity | 90% | |
| Sample Size | 243 |
Reproducibility
Intra-assay: ZYMUTEST HIA Ig G and ZYMUTEST Ig GAM were tested on vials of positive control, in duplicate, taken at random from the lot.
| Positive control | |||
|---|---|---|---|
| Anti P | A BR CONSUL COLLEGIAN A | Carolina Art | |
| na 1947 11Anti I | |||
| Anti PF.12404------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
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The reproducibility for Intra assay precision for the positive control was performed. The CVs are below 10%, in compliance with the specifications, and confirm an excellent homogeneity for the intra assay.
Inter assay : Tested on one vial of positive control :
| i Positive control----------- | AL FOL | |
|---|---|---|
| Int 0610270. In T. | AND AND OF COLLECTION COLLEGION COLLEGION | |
| GAM Int 061027Gread for the | ANNO AND OLDING & AND1But Miller Councille of the career of the comparis of the comparis of the comparisms of the |
The inter assay for all of the positive control results are in compliance with the specifications (CV below 10%).
Conclusion
Based on comparison with the legally marketed PF 4 Enhanced and Asserachrom devices, the data demonstrates that ZYMUTEST HIA Ig G and ZYMUTEST HIA Ig GAM devices perform as well as the predicate device and they do not present new issues of safety and effectiveness. The Intra and inter assay reproducibility of the devices (ZYMUTEST HIA Ig G and ZYMUTEST HIA Ig GAM) is within 10 % CV.
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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion around the eagle. The logo is black and white.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Hyphen BioMed C/O Ola Anderson Aniara Corporation 6560 Gove Court Mason, Ohio 45040
SEP - 7 2007
Re: K071255 Trade/Device Name: Zymutest HIA IgG and Zymutest HIA IgGAM Regulation Number: 21 CFR 864.7695 Regulation Name: Platelet Factor 4 Radioimmunoassay Regulatory Class: Class II Product Code: LCO Dated: April 30, 2007 Received: May 10, 2007
Dear Mr. Anderson:
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 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 requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter
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Page 2 - Ola Anderson
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,
Robert A. Becker
Robert L. Becker, M.D., Ph.D. 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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Indication for Use Statement
510(k) Number: 071255
ZYMUTEST HIA IgG and IgGAM Device Name:
Indications for use:
ZYMUTEST HIA IgG and IgGAM kits are designed as a solid phase enzyme- linked immunosorbent assay (ELISA). These products are intended to be used as an in vitro diagnostics kit by Hematology, coagulation or other pathology laboratories to assist in screening patients samples for the presence of heparin- associated antibodies commonly found in patients with heparin induced thrombocytopenia or thrombosis (HIT).
Prescription Use × (Part 21 CFR 801 Subpart D)
Over-The-Counter Use AND/OR (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Jayline Bautista
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safe
510(k) K071255
Page 1 of 1
§ 864.7695 Platelet factor 4 radioimmunoassay.
(a)
Identification. A platelet factor 4 radioimmunoassay is a device used to measure the level of platelet factor 4, a protein released during platelet activation by radioimmunoassay. This device measures platelet activiation, which may indicate a coagulation disorder, such as myocardial infarction or coronary artery disease.(b)
Classification. Class II (performance standards).