(289 days)
For In Vitro Diagnostic Use Only.
The Risk of Ovarian Malignancy Algorithm (ROMA™) is a qualitative serum test that combines the results of HE4 EIA, ARCHITECT CA 125 II™ and menopausal status into a numerical score.
ROMA is intended to aid in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. ROMA is indicated for women who meet the following criteria: over age 18; ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. ROMA must be interpreted in conjunction with an independent clinical and radiological assessment. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: ROMA (HE4 EIA + ARCHITECT CA 125 II) should not be used without an independent clinical fradiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of ROMA (HE4 EIA + ARCHITECT CA 125 II) carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
The Risk of Ovarian Malignancy Algorithm (ROMATM) is a qualitative serum test in the form of a mathematical function combining the results of HE4 EIA, ARCHITECT CA 125 II™ and menopausal status into a numerical score.
ROMA was developed in a training set using separate logistic regression equations for premenopausal and postmenopausal women:
Premenopausal woman: Predictive Index (PI) = -12.0 + 2.38LN[HE4] + 0.0626LN[CA 125] Postmenopausal woman: Predictive Index (PI) = -8.09 + 1.04LNIHE4] + 0.732LNJCA 125J ROMA = exp(PI) / [1 + exp(PI)] *10
ROMA is used to stratify women into likelihood groups for finding cancer on surgery. In order to provide a specificity level of 75%, a cut point of ≥ 1.31 was used for premenopausal women and ≥ 2.77 was used for postmenopausal women who present with an ovarian adnexal mass. Women with ROMA results above these cut points is at high likelihood of finding malignancy on surgery.
The test system consists of the assays, reagents, software and instrument used to obtain the ROMA result. The ROMA instructions for use are provided with the HE4 EIA Kit. The HE4 EIA and ARCHITECT CA 125 II are performed according to the manufacturers' directions detailed in each product insert. The immunoassays used in ROMA are:
HE4 EIA: The HE4 EIA is an enzyme immunometric assay for the quantitative determination of HE4 in human serum.
ARCHITECT CA 125 II: The ARCHITECT CA 125 II assay is a Chemiluminescent Microparticle Immunoassay (CMIA) for the quantitative determination of OC 125 defined antigen in human serum and plasma on the ARCHITECT i System.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" percentages. However, it does present performance metrics as a demonstration of the device's effectiveness at specific cut-points. The key performance metrics are Sensitivity and Specificity for Epithelial Ovarian Cancer (EOC) stratification, and Negative Predictive Value (NPV) for the adjunctive use of ROMA with Initial Cancer Risk Assessment (ICRA).
Here's a table based on the provided performance data for Epithelial Ovarian Cancer (EOC) only and Adjunctive Use (All cancers & LMP Tumors):
ROMA Performance for Stratification of Epithelial Ovarian Cancer (EOC) Only
| Metric | Premenopausal (95% CI) | Postmenopausal (95% CI) |
|---|---|---|
| Sensitivity | 100.0% (66.4% - 100%) | 92.3% (79.1% - 98.4%) |
| Specificity | 74.5% (68.3% - 80.2%) | 76.8% (69.3% - 83.2%) |
Adjunctive Use of ROMA with ICRA (All Malignancies)
| Metric | ICRA Only (95% CI) | ROMA Only (95% CI) | Adjunctive (ROMA + ICRA) (95% CI) |
|---|---|---|---|
| Sensitivity | 73.3% (63.1% - 81.4%) | 82.6% (73.2% - 89.1%) | 88.4% (79.9% - 93.5%) |
| Specificity | 84.3% (80.2% - 87.6%) | 75.5% (70.9% - 79.5%) | 67.2% (62.3% - 71.8%) |
| Negative Predictive Value | 93.2% (90.0% - 95.4%) | 95.0% (91.9% - 96.9%) | 96.2% (93.1% - 97.9%) |
The document specifies ROMA cut-points to achieve a specificity level of 75%:
- Premenopausal women: ROMA value ≥ 1.31 for high likelihood of finding malignancy (specificity 74.5% reported).
- Postmenopausal women: ROMA value ≥ 2.77 for high likelihood of finding malignancy (specificity 76.8% reported).
2. Sample Size and Data Provenance
- Test set sample size: 461 women were evaluable in the study. This was broken down into 240 premenopausal women and 221 postmenopausal women.
- Data provenance: The data was obtained from a "prospective, multi-center, blinded clinical trial". The country of origin is not explicitly stated, but clinical trials for FDA submissions typically involve sites in the US or internationally recognized centers. The study is described as prospective.
3. Number of Experts and Qualifications for Ground Truth
The document mentions an "Initial cancer risk assessment (ICRA) was completed by a non-gynecological oncologist". It does not specify the number of non-gynecological oncologists, their years of experience, or their exact qualifications beyond their specialty.
4. Adjudication Method for the Test Set
The primary ground truth for malignancy was based on histopathology reports collected after surgery. There is no explicit mention of an adjudication method among multiple readers for the histopathology, implying a single official report was used.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC study is explicitly presented in the provided text. The document compares ROMA's performance to an "Initial Cancer Risk Assessment (ICRA)" but does not describe ICRA as a multi-reader assessment or compare human readers with and without AI assistance. It evaluates the "adjunctive use of ROMA with ICRA" as a combined approach versus ICRA alone and ROMA alone.
Effect size of human readers improving with AI vs. without AI: Not directly applicable as an MRMC study was not described. However, the NPV for classifying benign patients into the low likelihood group increased from 93.2% (ICRA only) to 96.2% (Adjunctive use with ROMA + ICRA), implying an improvement in ruling out cancer with the addition of ROMA. This is an improvement of 3.0 percentage points in NPV.
6. Standalone Performance
Yes, standalone performance for ROMA was done and is reported.
- The "Use of ROMA for stratification into low likelihood and high likelihood groups for finding malignancy on surgery" section provides standalone performance metrics for ROMA (Sensitivity, Specificity, etc.) for premenopausal and postmenopausal women.
- The "Adjunctive use of ROMA with Initial Cancer Risk Assessment (ICRA)" section also includes "ROMA" column which can be interpreted as standalone ROMA performance for comparison.
7. Type of Ground Truth Used
The ground truth used was histopathology reports collected after surgery. This is considered a definitive diagnostic method for determining malignancy.
8. Sample Size for the Training Set
ROMA's development is mentioned to have used a "training set" for separate logistic regression equations. However, the sample size for this training set is not provided in the document.
9. How the Ground Truth for the Training Set Was Established
The document states ROMA "was developed in a training set using separate logistic regression equations". While it implies the training set would also have used histopathology as ground truth, similar to the test set, the method for establishing ground truth for the training set is not explicitly detailed.
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510(k) SUMMARY
SEP = 1 2011
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.
Fujirebio Diagnostics, Inc.
The assigned 510(k) number is: K103358
Submitter Information
Address:
| 201 Great Valley ParkwayMalvern, PA 19355 | |
|---|---|
| Contact person: | Diana L. Dicksondicksond@fdi.com |
| Summary preparation date: | August 31, 2011 |
| Name of Device | |
| Trade/Proprietary Name: | ROMATM (HE4 EIA + ARCHITECT CA 125 IITM) |
| Common/Usual Name: | ROMA(Risk of Ovarian Malignancy Algorithm)using HE4 EIA and ARCHITECT CA 125 II |
| Regulation Number: | 21 CFR 866.6050 |
| Regulatory Class: | Class II |
| Product Code: | ONX |
Predicate Device
OVA1™ Test (K081754)
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Intended Use
For In Vitro Diagnostic Use Only.
The Risk of Ovarian Malignancy Algorithm (ROMA™) is a qualitative serum test that combines the results of HE4 EIA, ARCHITECT CA 125 II™ and menopausal status into a numerical score.
ROMA is intended to aid in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. ROMA is indicated for women who meet the following criteria: over age 18; ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. ROMA must be interpreted in conjunction with an independent clinical and radiological assessment. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: ROMA (HE4 EIA + ARCHITECT CA 125 II) should not be used without an independent clinical fradiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of ROMA (HE4 EIA + ARCHITECT CA 125 II) carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
Device Description
The Risk of Ovarian Malignancy Algorithm (ROMATM) is a qualitative serum test in the form of a mathematical function combining the results of HE4 EIA, ARCHITECT CA 125 II™ and menopausal status into a numerical score.
ROMA was developed in a training set using separate logistic regression equations for premenopausal and postmenopausal women:
Premenopausal woman: Predictive Index (PI) = -12.0 + 2.38LN[HE4] + 0.0626LN[CA 125] Postmenopausal woman: Predictive Index (PI) = -8.09 + 1.04LNIHE4] + 0.732LNJCA 125J ROMA = exp(PI) / [1 + exp(PI)] *10
ROMA is used to stratify women into likelihood groups for finding cancer on surgery. In order to provide a specificity level of 75%, a cut point of ≥ 1.31 was used for premenopausal women and ≥ 2.77 was used for postmenopausal women who present with an ovarian adnexal mass. Women with ROMA results above these cut points is at high likelihood of finding malignancy on surgery.
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The test system consists of the assays, reagents, software and instrument used to obtain the ROMA result. The ROMA instructions for use are provided with the HE4 EIA Kit. The HE4 EIA and ARCHITECT CA 125 II are performed according to the manufacturers' directions detailed in each product insert. The immunoassays used in ROMA are:
| HE4 EIA | The HE4 EIA is an enzyme immunometric assay for the quantitativedetermination of HE4 in human serum. |
|---|---|
| ARCHITECT CA 125 II | The ARCHITECT CA 125 II assay is a ChemiluminescentMicroparticle Immunoassay (CMIA) for the quantitative determinationof OC 125 defined antigen in human serum and plasma on theARCHITECT i System. |
Substantial Equivalence
. '
| Similarities | ||
|---|---|---|
| ROMA(HE4 EIA +ARCHITECT CA 125 II)(Proposed Device) | OVA1™ Test(Predicate Device)K081754 | |
| Device Type | In vitro diagnostic | In vitro diagnostic |
| Classification | Class II | Class II |
| Regulation Number | 21 CFR 866.6050 | 21 CFR 866.6050 |
| Product Usage | Ovarian adnexal massassessment score test systemClinical and Hospital laboratories | Ovarian adnexal massassessment score test systemClinical and Hospital laboratories |
| Product Code | ONXSerum, algorithm, ovarian cancerassessment test | ONXSerum, algorithm, ovarian cancerassessment test |
| Panel | Immunology (82) | Immunology (82) |
| Serum Analyte | CA 125 | CA 125 |
| Use | The information provided by theROMA Test should be used by thephysician only as an adjunctivetest to complement, not replace,other diagnostic and clinicalprocedures. | The information provided by theOVA1 Test should be used by thephysician only as an adjunctivetest to complement, not replace,other diagnostic and clinicalprocedures. |
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Premarket Notification (510(k)) ROMA (HE4 EIA + ARCHITECT CA 125 II)
Image /page/3/Picture/1 description: The image shows the logo for FUJIREBIO Diagnostics, Inc. The logo consists of a stylized graphic on the left and the company name on the right. The graphic is a black and white abstract shape. The text "FUJIREBIO" is in bold, black letters, and "Diagnostics, Inc." is in a smaller font size below it.
| Differences | ||
|---|---|---|
| ROMA(HE4 EIA +ARCHITECT CA 125 II)(Proposed Device) | OVA1™ Test(Predicate Device)K081754 | |
| Intended Use | For In Vitro Diagnostic Use Only.The Risk of Ovarian MalignancyAlgorithm (ROMA™) is aqualitative serum test thatcombines the results of HE4 EIA,ARCHITECT CA 125 II™ andmenopausal status into anumerical score.ROMA is intended to aid inassessing whether apremenopausal orpostmenopausal woman whopresents with an ovarian adnexalmass is at high or low likelihood offinding malignancy on surgery.ROMA is indicated for women whomeet the following criteria: overage 18; ovarian adnexal masspresent for which surgery isplanned, and not yet referred to anoncologist. ROMA must beinterpreted in conjunction with anindependent clinical andradiological assessment. The testis not intended as a screening orstand-alone diagnostic assay. | The OVA1™ Test is a qualitativeserum test that combines theresults of five immunoassays intoa single numerical score. It isindicated for women who meet thefollowing criteria: over age 18;ovarian adnexal mass present forwhich surgery is planned, and notyet referred to an oncologist. TheOVA1 Test is an aid to furtherassess the likelihood thatmalignancy is present when thephysician's independent clinicaland radiological evaluation doesnot indicate malignancy. The testis not intended as a screening orstand-alone diagnostic assay. |
| Measurand | Score based on 2 analytes | Score based on 5 serum analytes |
| Type of Test | Software algorithm and 2immunoassays | Software algorithm and 5immunoassays |
| Serum Analyte | HE4 | Transthyretin, Apolipoprotein A-1,β2-microglobulin, Transferrin |
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Use of ROMA for the likelihood of malignancy assessment in women presenting with an adnexal mass who will undergo surqical intervention
ROMA takes into account the results of HE4 EIA and the results of ARCHITECT CA 125 II as well as the menopausal status of the woman. The ROMA value is used to aid in assessing whether a woman is at high or low likelihood of finding malignancy on surgery.
The effectiveness of ROMA was determined in a prospective, multi-center, blinded clinical trial for premenopausal and postmenopausal women presenting with an adnexal mass requiring surgical intervention.
A total of 461 women were evaluable in the study. For each patient, an initial cancer risk assessment (ICRA) was completed by a non-gynecological oncologist, providing the assessment of the patient's mass as benign (negative) or malignant (positive) based upon the information available to the non-gynecological oncologist during their work-up of the patient. The corresponding histopathology reports were collected after surgery.
Using a preoperatively collected serum sample, ROMA was determined and the patient was stratified into a low or a high likelihood group for finding malignancy on surgery.
The histopathological classifications of the 461 evaluable patients are summarized below:
| Histopathological classification | All | Premenopausal | Postmenopausal | |||
|---|---|---|---|---|---|---|
| N | % | N | % | N | % | |
| Benign Pathology | 375 | 81.3 | 220 | 91.7 | 155 | 70.1 |
| Low Malignant Potential (LMP) /Borderline | 18 | 3.9 | 7 | 2.9 | 11 | 5.0 |
| Epithelial Ovarian Cancer | 48 | 10.4 | 9 | 3.7 | 39 | 17.6 |
| Non-Epithelial Ovarian Cancer | 2 | 0.4 | 0 | 0.0 | 2 | 0.9 |
| Other Gynecological Cancer | 10 | 2.2 | 3 | 1.2 | 7 | 3.2 |
| Other Cancer | 7 | 1.5 | 1 | 0.4 | 6 | 2.7 |
| Metastatic Cancer | 1 | 0.2 | 0 | 0.0 | 1 | 0.5 |
| Total | 461 | 100.0 | 240 | 23.3 | 221 | 76.7 |
Histopathological classification of the multi-center study patients
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Use of ROMA for stratification into low likelihood and high likelihood groups for finding malignancy on surgery
The following cut-points were used in order to provide a specificity level of 75%: Premenopausal women
ROMA value ≥ 1.31 = High likelihood of finding malignancy
ROMA value < 1.31 = Low likelihood of finding malignancy
Postmenopausal women
ROMA value ≥ 2.77 = High likelihood of finding malignancy
ROMA value < 2.77 = Low likelihood of finding malignancy
The reported result should include both the premenopausal and postmenopausal likelihood result and associated ROMA score on a scale of 0-10.
The stratification of patients presenting with an adnexal mass into high likelihood of harboring malignant disease (epithelial ovarian cancer (EOC), borderline or low malignant potential (LMP) tumors and other gynecological or non-gynecological cancers) using ROMA results above the cutpoint ≥ 1.31 for premenopausal and ≥ 2.77 for postmenopausal women by histopathology is shown in the table below:
| Premenopausaln=240 | Postmenopausaln=221 | Alln=461 | |
|---|---|---|---|
| All EOC1 | 9/9 (100%) | 36/39 (92.3%) | 45/48 (93.8%) |
| EOC Stage I+II | 3/3 (100%) | 6/9 (66.7%) | 9/12 (75%) |
| EOC Stage III+IV | 5/5 (100%) | 29/29 (100%) | 34/34 (100%) |
| LMP Tumors | 4/7 (57.1%) | 9/11 (81.8%) | 13/18 (72.2%) |
| Other cancer2 | 2/4 (50%) | 11/16 (68.7%) | 13/20 (65.0%) |
| All cancer & LMP Tumors | 15/20 (75%) | 56/66 (84.8%) | 71/86 (82.6%) |
2 EOC patients were unstaged, 'non-epithelial ovarian cancer, other gynecologic, and non-gynecologic cancers.
The performance of ROMA for stratification into low likelihood and high likelihood groups for premenopausal and postmenopausal women with epithelial ovarian cancer (EOC) only is shown in the table below:
| Premenopausal (N = 229) | 95% CI | Postmenopausal (N = 194) | 95% CI | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Estimate | Estimate | ||||||||||
| Sensitivity | 100.0% (9/9) | 66.4% | 100% | 92.3% (36/39) | 79.1% | 98.4% | |||||
| Specificity | 74.5% (164/220) | 68.3% | 80.2% | 76.8% (119/155) | 69.3% | 83.2% | |||||
| TP - FP1 | 74.5% | 68.7% | 80.4% | 69.1% | 58.2% | 80.0% | |||||
| PPV2 | 13.8% (9/65) | 6.5% | 24.7% | 50.0% (36/72) | 38.0% | 62.0% | |||||
| NPV3 | 100.0% (164/164) | 97.8% | 100% | 97.5% (119/122) | 93.0% | 99.5% | |||||
| Prevalence | 3.9% (9/229) | 20.1% (39/194) |
TP-FP = True Positive rate - False Positive rate, "PPV = Positive Value, "NPV = Negative Predictive Value
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Adjunctive use of ROMA with Initial Cancer Risk Assessment (ICRA) for stratification into low likelihood and high likelihood groups of harboring malignancy
The performance for the adjunctive use of ROMA with ICRA (ROMA and/or ICRA being positive for high likelihood of finding malignancy on surgery) was evaluated by calculating sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value). Adding ROMA to ICRA produced a statistically significant improvement in the negative predictive value. The NPV for correctly classifying benign patients into the low likelihood group increased from 93.2 to 96.2%, making the adjunctive use of ROMA with ICRA effective in ruling out cancer.
| Total counts for premenopausal and postmenopausal women combined | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Malignancy by Pathology1 | No Malignancy by Pathology1 | ||||||||
| ICRA | ICRA | ||||||||
| Positive(HighLikelihood) | Negative(LowLikelihood) | Total | Positive(HighLikelihood) | Negative(LowLikelihood) | Total | ||||
| ROMA | Positive(HighLikelihood) | 58 | 13 | 71 | ROMA | Positive(HighLikelihood) | 28 | 64 | 92 |
| Negative(LowLikelihood) | 5 | 10 | 15 | Negative(LowLikelihood) | 31 | 252 | 283 | ||
| Total | 63 | 23 | 86 | Total | 59 | 316 | 375 |
Total counts for premenonausal and postmenonausal women combined
All malignancies found including EOC, LMP, non-epithelial ovarian cancer, other gynecologic, and non-gynecologic cancers
Performance for premenopausal and postmenopausal women combined with 95% Confidence Intervals (CI)
| ICRA | ROMA | Adjunctive | |||||
|---|---|---|---|---|---|---|---|
| Estimate | 95% CI | Estimate | 95% CI | Estimate | 95% CI | ||
| Sensitivity | 73.3% | 63.1% 81.4% | 82.6% | 73.2% 89.1% | 88.4% | 79.9% 93.5% | |
| Specificity | 84.3% | 80.2% 87.6% | 75.5% | 70.9% 79.5% | 67.2% | 62.3% 71.8% | |
| TP-FP1 | 57.5% | 47.3% 67.8% | 58.0% | 48.7% 67.3% | 55.6% | 47.1% 64.0% | |
| PPV2 | 51.6% | 42.9% 60.3% | 43.6% | 36.2% 51.2% | 38.2% | 31.7% 45.1% | |
| NPV3 | 93.2% | 90.0% 95.4% | 95.0% | 91.9% 96.9% | 96.2% | 93.1% 97.9% | |
| Prevalence | 18.7% |
TTP = True Positive rate - False Positive rate, "PPV = Positive Value, "NPV = Negative Predictive Value
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Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Fujirebio Diagnostics, Inc. c/o Ms. Diana L. Dickson Manager, Regulatory Affairs 201 Great Valley Parkway Malvern, PA 19355
SEP 0 1 2011
Re: K103358
Trade/Device Name: ROMA™ (HE4 EIA +ARCHITECT CA 125 II™) Regulation Number: 21 CFR $866.6050 Regulation Name: Ovarian adnexal mass assessment score test system Regulatory Class: Class II Product Codes: ONX Dated: August 29, 2011 Received: August 30, 2011
Dear Ms. Dickson:
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). You may, therefore, market the device, subject to the general controls provisions of the Act and the limitations described below. 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.
The Office of In Vitro Diagnostic Device Evaluation and Safety has determined that there is a reasonable likelihood that this device will be used for an intended use not identified in the proposed labeling and that such use could cause harm. Therefore, in accordance with Section 513(i)(1)(E) of the Act, the following limitation must appear in the device's labeling:
PRECAUTION: ROMA (HE4 EIA + ARCHITECT CA 12.5 II) should not be used without an independent clinical /radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of ROMA (HE4 EIA + ARCHITECT CA 125 II) carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
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Page 2 - Ms. Diana L. Dickson
Please note that the above labeling limitations are required by Section 513(i)(1)(E) of the Act. Therefore, a new 510(k) is required before these limitations are modified in any way or removed from the device's labeling.
The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and permits your device to proceed to the market. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification if the limitation statement described above is added to your labeling.
If your device is classified (see above) into class II (Special Controls), 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).
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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 (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Alberto
Alberto Gutierrez, Ph. D.
Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known): K103358
Device Name: ROMA™ (HE4 EIA + ARCHITECT CA 125 IITM)
Indication For Use:
For In Vitro Diagnostic Use Only.
The Risk of Ovarian Malignancy Algorithm (ROMA™) is a qualitative serum test that combines the results of HE4 EIA, ARCHITECT CA 125 III''' and menopausal status into a numerical score.
ROMA is intended to aid in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. ROMA is indicated for women who meet the following criteria: over age 18; ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. ROMA must be interpreted in conjunction with an independent clinical and radiological assessment. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: ROMA (HE4 EIA + ARCHITECT CA 125 II) should not be used without an independent clinical /radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of ROMA (HE4 EIA + ARCHITECT CA 125 II) carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
Prescription Use _____________________________________________________________________________________________________________________________________________________________ (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)
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K103358
§ 866.6050 Ovarian adnexal mass assessment score test system.
(a)
Identification. An ovarian/adnexal mass assessment test system is a device that measures one or more proteins in serum or plasma. It yields a single result for the likelihood that an adnexal pelvic mass in a woman, for whom surgery is planned, is malignant. The test is for adjunctive use, in the context of a negative primary clinical and radiological evaluation, to augment the identification of patients whose gynecologic surgery requires oncology expertise and resources.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Ovarian Adnexal Mass Assessment Score Test System.” For the availability of this guidance document,see § 866.1(e).(c)
Black box warning. Under section 520(e) of the Federal Food, Drug, and Cosmetic Act these devices are subject to the following restriction: A warning statement must be placed in a black box and must appear in all advertising, labeling, and promotional material for these devices. That warning statement must read: