(76 days)
The UniMark™ Midstream Pregnancy Test Stick is intended for the qualitative measurement of human chorionic gonadotropin (hCG) in urine as a home use screening test for pregnancy.
The UniMark™ Midstream Pregnancy Test Stick is a home use, rapid, visual, one step screening test for pregnancy. UniMark™ is a colored solid-phase immunoassay for qualitative detection of elevated levels of hCG in urine for the early pregnancy diagnosis. It is based on a two-site sandwich immunometric assay which utilizes a unique combination of monoclonal and polyclonal antibodies to selectively identify hCG with a high degree of sensitivity. UniMark™ contains a strip with a sample pad and a membrane area. The former contains mouse anti-hCG monoclonal antibody conjugated with colloid gold. The latter is coated with goat anti-mouse IgG at the control zone and goat anti-hCG antibody at the test zone. During the test, the urine is sucked up through sample pad by capillary action, and hCG in the urine sample binds to the gold conjugate, moving chromatographically toward the membrane. The immobilized goat anti-hCG antibody at the test zone catches the resulting complexes, forming an antibody-hCG-gold conjugate complex. The appearance of a purple band in the test window resulted from the complex shows a positive result, which indicates presence of hCG and suggests a pregnancy. Absence of this band, on the other hand, displays a negative result, i.e. no detectable hCG in the urine sample. The appearing of a purple band in the control window demonstrates proper performance and validity of the reactive reagent.
Here's an analysis of the provided text regarding the UniMark™ Midstream Pregnancy Test Stick, structured to address your specific questions:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance (UniMark™) |
|---|---|
| Sensitivity | 25 mIU/ml or greater |
| Accuracy | >99% |
| Specificity | No interferences (from hLH, hFSH, hTSH) |
Detailed Performance Breakdown:
Non-Clinical Tests:
- Sensitivity:
- 0 mIU/ml hCG: 100% negative (3 lots tested)
- 20 mIU/ml hCG: 95% negative, 5% positive (3 lots tested) - Note: This indicates some border-line detection at 20 mIU/ml, but full positive detection is at 25 mIU/ml.
- 25 mIU/ml hCG: 100% positive (3 lots tested)
- 50 mIU/ml hCG: 100% positive (3 lots tested)
- 100 mIU/ml hCG: 100% positive (3 lots tested)
- Specificity (Interference Studies):
- hLH: No interference observed at 10, 100, 200 mIU/ml hLH. The device remained positive when 25 mIU/ml hCG was added to these hLH concentrations.
- hFSH: No interference observed at 1000 mIU/ml hFSH. The device remained positive when 25 mIU/ml hCG was added.
- hTSH: No interference observed at 1000 uIU/ml hTSH. The device remained positive when 25 mIU/ml hCG was added.
Clinical Tests:
- Correlation with CIDA Professional Test (Reference Standard): 100% correlation with UniMark™ home user results.
- UniMark™ Positive / CIDA Positive: 119 cases
- UniMark™ Negative / CIDA Negative: 27 cases
- Total cases: 146
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Test Set): 146 home users.
- Data Provenance: Prospective, from a women's center in southern New Jersey, USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
- Number of Experts: At least two for the clinical portion:
- "The user test results were observed and verified by the lab assistant (to verify correct interpretation of positive or negative)."
- The "CIDA professional test results" imply a professional lab test was used as the ground truth, likely interpreted by qualified lab personnel, though their specific qualifications are not detailed beyond "professional test."
- Qualifications of Experts: The text states "lab assistant" and "CIDA professional test results." Specific qualifications (e.g., years of experience, certification) are not provided for either.
4. Adjudication Method for the Test Set
- Clinical Test Set: The text indicates that the home user's interpretations were "observed and verified by the lab assistant." This suggests a form of 1:1 verification, where the lab assistant confirmed the user's reading. The "CIDA professional test" was then used as the definitive ground truth against which both the home user's interpretation and the lab assistant's verification would presumably align or be compared. It implies a direct comparison rather than a formal voting/adjudication process like 2+1 or 3+1 among multiple human readers of the device itself.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- MRMC Study: No, an MRMC comparative effectiveness study was not conducted. This device is a standalone home-use test, and the study evaluated its performance against a professional lab test, not the improvement of human readers with AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
- Standalone Performance: Yes, the entire study effectively evaluates the standalone performance of the UniMark™ device itself. Both the non-clinical (sensitivity, specificity) and clinical (correlation with CIDA) tests assess the device's ability to accurately detect hCG without human interpretive intervention beyond observing the colored bands. The "home user" aspect tests the device usability and interpretability by a layperson, but the underlying performance is that of the device.
7. The Type of Ground Truth Used
- Clinical Test Set: The primary ground truth for the clinical study was the CIDA professional test results. This represents a laboratory reference standard.
- Non-Clinical Test Set: The ground truth for sensitivity and specificity was known concentrations of hCG, hLH, hFSH, and hTSH (prepared according to WHO standards).
8. The Sample Size for the Training Set
- The document describes performance data for the UniMark™ device, which is a chemical/immunological test kit. It does not employ an AI algorithm or machine learning model, and therefore, there is no training set in the context of AI development. The device relies on pre-determined biochemical reactions.
9. How the Ground Truth for the Training Set Was Established
- As stated in point 8, there is no training set for this type of device.
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K96 0174
1991 - 1992 - 1992 APR - 1 1996
- 510(k) Summary of Information Respecting Safety and Effectiveness 8.
- Legally Marketed Device A.
Biotech Atlantic claims substantial equivalence to the UniStep™ HCG Pregnancy Test Device (K941090) currently in commercial distribution (outside the U.S.) by Biotech Atlantic. Inc.
- B. Device Description
The UniMark™ Midstream Pregnancy Test Stick is a home use, rapid, visual, one step screening test for pregnancy.
Human chorionic gonadotropin (hCG) is a glycoprotein hormone synthesized by the placenta and released in blood and urine soon after the implantation of a fertilized ovum in the chorionic tissue. The rapidly rising levels of hCG provide a stimulus to the corpus luteum (luteotrophic effect). Instead of involution in a non-pregnant menstrual cycle, the corpus luteum continues to grow and secretes increasing quantities of hormone progesterone which is needed to maintain pregnancy. Thus, hCG is the principal signal and specific marker of the pregnancy.
A number of variations were used for the next 30 years. They have been rapidly superseded in the 1960s because of their cost and inconvenience since immunoassays were introduced. Like other members of glycoprotein hormones, such as Luteinizing Hormone (hLH), Follicle Stimulating Hormone (hFSH), and Thyroid Stimulating Hormone (hTSH), hCG is composed of two subunits: an alpha-subunit, which is virtually identical in all four; and a beta-subunit, which is characteristic of the individual hormone, therefore determines the specificity of the action. Use of monoclonal antibodies to the beta-subunit of hCG is an important which provides the feasibility to manufacture new generations of immunoassays with consistent specificity and high sensitivity to detect hCG. Pregnancy test now reaches a level which is generally considered unlikely to be surpassed either by better test or alternative technology.
UniMark™ is a colored solid-phase immunoassay for qualitative detection of elevated levels of hCG in urine for the early pregnancy diagnosis. It is based on a two-site sandwich immunometric assay which utilizes a unique combination of monoclonal and polyclonal antibodies to selectively identify hCG with a high degree of sensitivity. UniMark™ contains a strip with a sample pad and a membrane area. The former contains mouse anti-hCG monoclonal antibody conjugated with colloid gold. The latter is coated with goat anti-mouse IgG at the control zone and goat anti-hCG antibody at the test zone. During the test, the urine is sucked up through sample pad by capillary action, and hCG in the urine sample binds to the gold conjugate, moving chromatographically toward the membrane. The immobilized goat anti-hCG antibody at the test zone catches the resulting complexes, forming an antibody-hCG-gold conjugate complex. The appearance of a purple band in the test window resulted from the complex shows a
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positive result, which indicates presence of hCG and suggests a pregnancy. Absence of this band, on the other hand, displays a negative result, i.e. no detectable hCG in the urine sample. The appearing of a purple band in the control window demonstrates proper performance and validity of the reactive reagent.
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C. Intended Use
The UniMark™ Midstream Pregnancy Test Stick is intended for the qualitative measurement of human chorionic gonadotropin (hCG) in urine as a home use screening test for pregnancy. -
D. Comparison with the Predicate Device
A summary comparison of the features of the UniMark™ and UniStep™ pregnancy tests is provided in Table 1 below.
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Table 1.
Feature Comparison of the UniMark™ and UniStep™ Pregnancy Tests
| UniMark™ | UniStep™ | |
|---|---|---|
| Intended Use | Qualitative measurementof hCGHome use | Qualitative measurementof hCGProfessional use |
| Reagents/Materials | Goat anti-hCGMouse anti-hCGMonoclonal conjugatePlastic device with splashguard and absorbent tip | Goat anti-hCGMouse anti-hCGMonoclonal conjugatePlastic device |
| Assay Method | Colored solid-phaseimmunoassayMidstream | Colored solid-phaseimmunoassayDrop application |
| Specimen | Urine | Urine |
| Time of Collection | Any time of day | First a.m. preferred |
| Storage | 2° to 30° C | 2° to 30° C |
| Reaction Time | 5 minutes | 5 minutes |
| Positive Result | Purple band in TestWindow | Purple band in TestWindow |
| Standardization | WHO 3rd IS 75/537 | WHO 3rd IS 75/537 |
| Sensitivity | 25mIU/ml or greater | 25mIU/ml or greater |
| Accuracy | >99% | >99% |
| Specificity | No interferences | No interferences |
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- E. Performance Data
Non-Clinical Tests
Sensitivity
| UniMark™Lot | HCG Concentration (mIU/ml), WHO 3rd IS 75/537) | ||||
|---|---|---|---|---|---|
| 0 | 20 | 25 | 50 | 100 | |
| 1 | -(100%) | -(95%)---+(5%) | +(100%) | ++(100%) | +++(100%) |
| 2 | -(100%) | -(95%)---+(5%) | +(100%) | ++(100%) | +++(100%) |
| 3 | -(100%) | -(95%)---+(5%) | +(100%) | ++(100%) | +++(100%) |
し
Specificity
hLH Study
| UniMark™Lot | hLH (mIU/ml) | hLH + hCG (MIU/ml) | |||||
|---|---|---|---|---|---|---|---|
| 0 | 10 | 100 | 200 | 10+25 | 100+25 | 200+25 | |
| 1 | - | - | - | - | + | + | + |
| 2 | - | - | - | - | + | + | + |
| 3 | - | - | - | - | + | + | + |
hFSH Study
| UniMark™Lot | hFSH (mIU/ml) | hFSH + hCG (mIU/ml) | |
|---|---|---|---|
| 0 | 1000 | 1000 + 25 | |
| 1 | - | - | + |
| 2 | - | - | + |
| 3 | - | - | + |
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| UniMark™Lot | hTSH (uIU/ml) | hTSH + hCG (uIU+ mIU/ml) | |
|---|---|---|---|
| 0 | 1000 | 1000 + 25 | |
| 1 | - | - | + |
| 2 | - | - | + |
| 3 | - | - | + |
Clinical Tests
The UniMark™ was evaluated in a consumer study of 146 home users selected on a random basis as they presented themselves at a women's center in southern New Jersey. The home users represented a diversity of age, background and education.
The study was explained to the home users by either the center's nurse or lab assistant. If the home user agreed to participate, written and verbal instructions on how to perform the test were provided. In addition to performing the midstream test procedure, the home users were asked to collect a sample of the same urine specimen. At the conclusion of the test, each home user was asked to complete a questionnaire to obtain feedback on the test. The user test results were observed and verified by the lab assistant (to verify correct interpretation of positive or negative).
There was 100% correlation between the UniMark™ home user and CIDA professional test results, as shown in Table 2 below.
| Table 2.CIDA | ||
|---|---|---|
| Positive | Negative | |
| UniMark™ | 119 | 27 |
| 0 | 0 |
146✓
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.