ROM PLUS

K110605 · Clinical Innovations, LLC · NQM · Nov 23, 2011 · Clinical Chemistry

Device Facts

• Record ID: K110605
• Device Name: ROM PLUS
• Applicant: Clinical Innovations, LLC
• Product Code: NQM · Clinical Chemistry
• Decision Date: Nov 23, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1550
• Device Class: Class 1

Intended Use

The Clinical Innovations ROM Plus fetal membrane rupture test is a rapid, qualitative immunochromatographic test for the in vitro detection of amniotic fluid in vaginal secretions of pregnant women with signs and symptoms of ROM. The test detects AFP (alpha-fetoprotein) and PP12 (placental protein 12 or insulin growth factor binding protein) from amniotic fluid in vaginal secretion. The test is for prescription use by health care professionals to aid in the detection of rupture of membranes (ROM) in pregnant women in conjunction with other signs and symptoms. The ROM Plus Quality Control Kit monitors the performance of the ROM Plus Fetal Membranes Rupture Test for the purposes of external quality control. The lyophilized human positive protein control is an assayed control material for qualitative testing.

Device Story

Rapid, qualitative lateral flow immunochromatographic test; detects AFP and PP12 (IGFBP-1) in vaginal secretions. Input: vaginal swab sample extracted in buffer; applied to cassette. Principle: antibodies (monoclonal mouse anti-human AFP/PP12; polyclonal sheep anti-PP12; goat anti-AFP) bind target proteins; visual test line appearance indicates positive result. Used in point-of-care settings by healthcare professionals. Output: visual qualitative result (test line presence). Assists clinicians in confirming ROM when used with other clinical evaluations (e.g., nitrazine, ferning, pooling). Benefits: rapid identification of amniotic fluid leakage; aids clinical decision-making regarding labor induction.

Clinical Evidence

Prospective clinical study at 3 US sites (n=264). Compared ROM Plus results against clinical assessment (visual leaking or 2/3 of ferning, pooling, nitrazine). Results: Sensitivity 0.99 (95% CI: 0.96-1.00), Specificity 0.75 (95% CI: 0.66-0.82). Subgroup analysis for gestational age ≤ 34 weeks (n=63) showed 100% positive percent agreement and 91% negative percent agreement.

Technological Characteristics

Lateral flow immunochromatographic assay. Components: sterile polyester swab, specimen extraction buffer, test cassette with integral timer. Analytes: AFP and PP12 (IGFBP-1). Detection: visual inspection. Settings: point-of-care and clinical laboratory. No electronic or software components.

Indications for Use

Indicated for pregnant women with signs and symptoms of fetal membrane rupture (ROM). For prescription use by healthcare professionals to aid in ROM detection in conjunction with other clinical signs/symptoms.

Regulatory Classification

Identification

A urinary pH (nonquantitative) test system is a device intended to estimate the pH of urine. Estimations of pH are used to evaluate the acidity or alkalinity of urine as it relates to numerous renal and metabolic disorders and in the monitoring of patients with certain diets.

Predicate Devices

• AmniSure™ ROM (Rupture Of fetal Membranes) Test (k081767)

Submission Summary (Full Text)

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K110605

NOV 2 3 2011

# 510(k) Summary for the Clinical Innovations, LLC ROMPlus

1. Applicant/Sponsor Clinical Innovations, LLC 747 W. 4170 S. Murray, Utah USA 84123 Contact Person: Wm. Dean Wallace, MD, PhD. Telephone: [phone] [e-mail] Date Prepared: November 7, 2011

### 2. Device Name

Proprietary Name: ROM Plus and ROM Plus Controls Common/Usual Name: Rupture Of Fetal Membranes (ROM) Rapid Diagnostic Test Classification Name: Urinary pH (Nonquantitative) Test System and Quality Control Material (Assayed and Unassayed)

## 3. Predicate Devices

AmniSure ROM (Rupture Of [fetal] Membranes) Test N-Dia, Inc .- k030849, k081767 Actim Prom and Controls Medix Biochemica -k061886 AmnioTest (pH swab) -k914419 AmniScreen (pH liner) - k071100

## 4. Device Description

The ROMPlus is a rapid test for detection of premature rupture of fetal membranes. The test principle is lateral flow immunochromatography. ROM Plus is available in packages of 5 tests. Each individual test pack contains a sterile polyester swab. specimen extraction buffer solution in a plastic vial and a cassette with integral timer containing the lateral flow strip packed in a foil pouch with desiccant.

The ROM Plus Controls contain one vial each of negative, and positive controls, with integral reconstitution solution.

Clinical Innovations, LLC 747 W. 4170 S. Murray, Utah USA 84123 5. Intended Use

The Clinical Innovations ROM Plus fetal membrane rupture test is a rapid, qualitative immunochromatographic test for the in vitro detection of amniotic fluid in vaginal secretions of pregnant women with signs and symptoms of ROM. The test detects AFP (alpha-fetoprotein) and PP12 (placental protein 12 or insulin growth factor binding protein) from amniotic fluid in vaginal secretion. The test is for prescription use by health care professionals to aid in the detection of rupture of membranes (ROM) in pregnant women in conjunction with other signs and symptoms.

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# 6. Technological Characteristics and Substantial Equivalence

The RQM Plus and the predicate devices cited above are both qualitative, lateral flow immunochromatographic assays intended to aid in detecting rupture of fetal membranes in pregnant women. Detection of results is by visual inspection. The analytes detected by ROM Plus and AmniSure and ActimPROM tests are similar amniotic fluid proteins. ROM Plus uses antibodies to PP12 (IGFBP-1) and AFP (alpha feto-protein). The specimen collection and extraction, test procedure, and reading and interpretation of results is similar between the three devices. All devices are intended for use in point-of-care and clinical laboratory settings. The differences between the ROM Plus and the predicate devices do not impact the safety or effectiveness of the proposed ROM Plus products for their intended uses.

# 7. Performance Testing

A series of nonclinical and clinical studies was conducted to assess the performance of the RQM Plus, These studies evaluated method comparison, repeatability, analytical sensitivity, analytical specificity and interfering substances.

- High Concentration ("High Dose Hook" effect) for the ROM Plus upper-detection . range, the PP12 and AFP were tested. Concentrations of PP12 were tested up to 400,000 ng/ml and AFP up to 200,000 ng/ml with positive visual results.
- For 100% of ROM Plus tests sampled, the lowest limit of detection (LOD) is 5 ne/ml for . PP12, and 150 ng/ml for AFP (these refer to concentrations in samples of vaginal secretions before dilution with the assay buffer).
- . Reproducibility was tested on different days at six levels of amniotic fluid spiked into a negative control. The assay was run on three lots of ROM Plus to determine the visual positive or negative results. Two low positives, two moderate positives and two high positives were run on three lots of ROM Plus on four different days. No difference in activity was observed.
- To determine interference and cross-reactivity of the assay, Tylenol, aspirin, and three . different bath products (Lever Soap, Noxzema cream, Pert Shampoo), were spiked into the low positive control at a final concentration of 0.1% without visual loss of activity. The same bath products were spiked into the negative-matrix control and shown to be negative. In addition, human semen, urine and blood were spiked into the low positive at a 10% final concentration without loss of activity. Human semen, urine and blood were also spiked into the negative-control matrix and shown to be negative. PP12 assay does not cross-react with IGFBP-2, IGFBP-3, and IGFBP-4 based on Western Blot results. ROM Plus was shown to be negative when tested with specimens that were positive for bacterial vaginosis and sexually transmitted diseases. All samples were pH>4.5.

A multi-center prospective observational study was performed. Clinicians performing ROM Plus testing were masked from the standard Clinical Assessment results. The clinical standard of either leaking from cervical os, or pooling/ferning/nitrazine were used.12,16 because these are commonly used in clinical hospital protocol to evaluate ROM. Corrections for ROM based on

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subsequent patient chart review was nos used in this study for the detection of ruptured membranes.

Results are shown below:

| Combined | Clin-Assess | positive | negative | ≥ 37 | Clin-Assess | positive | negative |
|------------|-------------|------------------|----------|------------|-------------|------------------|----------|
| ROM Plus | positive | 153 | 28 | ROM Plus | positive | 125 | 23 |
| | negative | 1 | 82 | | negative | 1 | 33 |
| Total: 264 | | | | Total: 182 | | | |
| Sens | 0.99 | CI: 0.96 to 1.00 | | Sens | 0.99 | CI: 0.96 to 1.00 | |
| Spec | 0.75 | CI: 0.66 to 0.82 | | Spec | 0.58 | CI: 0.46 to 0.71 | |
| PPV | 0.85 | CI: 0.79 to 0.90 | | PPV | 0.84 | CI: 0.78 to 0.89 | |
| NPV | 0.99 | CI: 0.94 to 1.00 | | NPV | 0.97 | CI: 0.85 to 0.99 | |
| 34-37 EGA | Clin-Assess | positive | negative | < 34 | Clin-Assess | positive | negative |
| ROM Plus | positive | 18 | 3 | ROM Plus | positive | 10 | 2 |
| | negative | 0 | 16 | | negative | 0 | 33 |
| Total: 37 | | | | Total: 45 | | | |
| Sens | 1.00 | CI: 0.82 to 1.00 | | Sens | 1.00 | CI: 0.72 to 1.00 | |
| Spec | 0.85 | CI: 0.64 to 0.95 | | Spec | 0.94 | CI: 0.81 to 0.98 | |
| PPV | 0.87 | CI: 0.65 to 0.95 | | PPV | 0.83 | CI: 0.55 to 0.95 | |

Table 1 : Clinical Study - ROM Plus vs. Clinical Assessment (pooling/ferning/nitrazine)

The results of all studies demonstrated that the ROM Plus Controls performed according to their specifications.

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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 consists of a circular arrangement of the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" surrounding a stylized image of an eagle or bird-like figure. The bird figure has outstretched wings and appears to be in flight or taking off.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Clinical Innovations c/o Dr. Wm. Dean Wallace 747 W 4170 South Murray, UT 84123

NOV 2 3 2011

k110605 Re:

Trade Name: ROM Plus Fetal Membranes Rupture Test Regulation Number: 21 CFR 862.1550 Regulation Name: Urinary pH Regulatory Class: Class I, reserved Product Codes: NQM, JJX Dated: November 14, 2011 Received: November 14, 2011

Dear Dr. Wallace:

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 forcrences above and in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device merslate conmise or proces that have been reclassified in accordance with the provisions of Amendinents, or to de rices that nations of the do not require approval of a premarket the Federal 7 000, Drag, and Coou may, therefore, market the device, subject to the general approvisions of the Act. The general controls provisions of the Act include controls pro ristions of 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 (1 Writ), it may of subject to water 21, Code of Federal Regulations (CFR), Parts 800 to 895. your device ban or load of to ther 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 moan that I DAT has mass statutes and regulations administered by other Federal agencies. of the Act of any I oderal statules and equirements, including, but not limited to: registration 1 ou must compty with an eas; labeling (21 CFR Parts 801 and 809); medical device alle fisting (21 OF N F art 807), as seen ( reporting (reporting of mounts as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Viro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 [phone]. 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 [phone] or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

jz

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# Indications for Use

#### k110605 510(k) Number:

#### Device Name: ROM Plus Fetal Membranes Rupture Test

### Indications for Use:

The Clinical Innovations ROM Plus fetal membrane rupture test is a rapid, qualitative immunochromatographic test for the in-vitro detection of amniotic fluid in vaginal secretions of pregnant women with signs and symptoms of ROM. The test detects AFP (alpha-fetoprotein) and PP12 (placental protein 12 or insulin growth factor binding protein) from amniotic fluid in vaginal secretion. The test is for prescription use by health care professionals to aid in the detection of rupture of membranes (ROM) in pregnant women in conjunction with other signs and symptoms.

The ROM Plus Quality Control Kit monitors the performance of the ROM Plus Fetal Membranes Rupture Test for the purposes of external quality control. The lyophilized human positive protein control is an assayed control material for qualitative testing.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (OIVD)

Signature

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) C-110605