(57 days)
FaStep Early Pregnancy Rapid Test Strip is used for qualitative detection of Human Chorionic Gonadotropin (HCG) in human urine. This test is intended for use as an aid in early detection of pregnancy, in some cases as early as six (6) days before the day of the missed period, (i.e. as early as five (5) days before the day of the expected period). For over thecounter use.
FaStep Early Pregnancy Rapid Test Cassette is used for qualitative detection of Human Chorionic Gonadotropin (HCG) in human urine. This test is intended for use as an aid in early detection of pregnancy, in some cases as early as six (6) days before the day of the missed period, (i.e. as early as five (5) days before the day of the expected period). For over thecounter use.
FaStep Early Pregnancy Rapid Test Midstream is used for qualitative detection of Human Chorionic Gonadotropin (HCG) in human urine. This test is intended for use as an aid in early detection of pregnancy, in some cases as early as six (6) days before the day of the missed period, (i.e. as early as five (5) days before the day of the expected period). For overthe-counter use.
FaStep Early Pregnancy Rapid Test will be sold in Strip, Cassette and Midstream format. The Strip format is a single test strip. The Cassette format consists of a single test strip assembled in a plastic housing. The Midstream format consists of a single test strip assembled in a plastic housing with an absorbent tip, and is designed to be tested in dip or midstream mode.
FaStep Early Pregnancy Rapid Test Strip, FaStep Early Pregnancy Rapid Test Cassette and FaStep Early Pregnancy Rapid Test Midstream each contains a pouch with the device and instructions, and in addition, cassette format is packaged with pipette dropper.
The devices utilize a combination of antibodies to detect hCG in urine as well as to serve as a run control. Each device contains mouse monoclonal anti-ß-hCG antibody colloidal gold conjugate pre-dried on the sample pad. Mouse monoclonal anti-a-hCG antibody (on the Test Line) and goat anti mouse IgG polyclonal antibody (on the Control Line) are coated and immobilized on a nitrocellulose membrane. The result is displayed to the user in the test window as two lines for a 'Pregnant' positive result and one line for a 'Not Pregnant' negative result.
The provided document describes the performance and acceptance criteria for the FaStep Early Pregnancy Rapid Test Strip, Cassette, and Midstream devices.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly derived from the performance claims made for the device and the comparison to the predicate device. The primary performance metrics revolve around sensitivity (detection limit for hCG) and accuracy (agreement with professional testing and predicate devices, and lack of interference/cross-reactivity).
| Acceptance Criteria Category | Specific Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity | Detect 10 mIU/mL hCG with 100% positivity. No false positives at 0 or 5 mIU/mL hCG. | All three formats (Strip, Cassette, Midstream - both dip & in-stream methods) showed 0% positive at 0 and 5 mIU/mL hCG concentrations and 100% positive at 10 mIU/mL hCG and above. |
| Hook Effect | No hook effect up to 200,000 mIU/mL hCG. | No hook effect observed up to 200,000 mIU/mL hCG. |
| Interfering Substances | No interference from a specified list of common substances at given concentrations. | No interference observed at tested concentrations for all listed substances. |
| Cross-reactivity | No cross-reactivity with hLH, hFSH, and hTSH at specified concentrations. | No cross-reactivity observed with 500 mIU/mL hLH, 1000 mIU/mL hFSH, 1000 µIU/mL hTSH. |
| hCG ß-core fragment effect | Performance not affected by hCGBcf up to 500,000 pmol/L. | Performance not affected by hCGBcf concentrations up to 500,000 pmol/L. |
| Urine pH effect | Performance not affected by urine pH between 4 and 9. | Performance not affected by urine pH ranges between 4 and 9. |
| Urine Density effect | Performance not affected by urine density between 1.000 and 1.035. | Performance not affected by urine with a relative density range of 1.000 to 1.035. |
| Method Comparison (Professional Use) | 100% conformity with the predicate device for positive and negative samples. | The conformity between FaStep Early Pregnancy Rapid Test (strip/cassette/midstream) and the predicate device was 100%. |
| Lay Person Use (Accuracy) | 100% positive and 100% negative conformity with professional results in direct comparison. High percentage agreement with professional results for spiked samples (e.g., 100% at 5 and 10 mIU/mL, ≥97% at challenge concentrations like 7.5 and 8 mIU/mL). | First study: 100% positive and 100% negative conformity with professional results. |
| Second study (spiked samples): 100% agreement at 5 mIU/mL and 10 mIU/mL. For 7.5 mIU/mL, agreement ranged from 97% to 98%. For 8.0 mIU/mL, agreement ranged from 98% to 99%. | ||
| Early Pregnancy Detection Rate | Detect early pregnancy consistent with the claimed "six (6) days before the day of the missed period" (EMP-5). Specifically, the clinical claim mentions "as early as five (5) days before the day of the expected period)" (EMP-5). | Detection rate in EMP-5 was 69.1% across all formats. Detection rate in EMP-4 was 89.7%. Detection rate in EMP-1 was 100%. |
| False-Positive Rate (Specificity) | No false positive results in non-pregnant females across various age groups. | No false positive results observed in 900 non-pregnant females (pre-menopausal, peri-menopausal, post-menopausal) across all three device formats and three lots. (0+/100- per age group per format/lot). |
2. Sample Size and Data Provenance
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Test Set Sample Sizes:
- Analytical Sensitivity (Precision/Reproducibility): For each format (Strip, Cassette, Midstream), 9 hCG concentrations tested. Each concentration had 10 replicates per day for 5 days, across 3 device lots, with 3 different operators. This sums to (9 concentrations * 10 replicates * 5 days * 3 lots * 3 operators = 1350 tests per format and per method for Midstream). More simply, the tables show 150 total results for each concentration level (50 per operator/lot). So, 9 concentrations * 150 results = 1350 tests per format.
- Hook Effect: Multiple hCG concentrations (6,250 to 200,000 mIU/mL). Specific number of replicates not stated, but results demonstrated.
- Interfering Substances: 3 hCG concentrations (0, 5, 10 mIU/mL) spiked with 25 substances. Number of replicates per substance not stated.
- Cross-reactivity: 3 hCG concentrations (0, 5, 10 mIU/mL) spiked with 3 cross-reactants. Number of replicates per cross-reactant not stated.
- hCG ß-core fragment effect: 4 hCG concentrations (0, 5, 10, 20,000 mIU/mL) spiked with 4 hCGBcf concentrations.
- Urine pH effects: 3 hCG concentrations (0, 5, 10 mIU/mL) tested at 6 pH values.
- Urine Density effects: 3 hCG concentrations (0, 5, 10 mIU/mL) tested at 8 density values.
- Method Comparison: 321 urine samples collected from women.
- Strip format: 110 samples.
- Cassette format: 105 samples.
- Midstream format (dip): 106 samples.
- Midstream format (in-stream): 106 samples.
- Lay Person Study (First Study - direct comparison): Total of 321 females.
- Strip format: 110 subjects.
- Cassette format: 105 subjects.
- Midstream format (dip): 53 subjects.
- Midstream format (in-stream): 53 subjects.
- Lay Person Study (Second Study - spiked samples): Total of 300 laypersons (100 per device format). Each tested 4 blind-labeled samples. So, 400 tests per format.
- Early Pregnancy Detection Study: 68 pregnant women provided 680 early pregnancy urine samples (from day -9 to 0 relative to expected period, presumably 10 samples per woman across these days). Each sample was tested with each format.
- Specificity Study (False-Positive Rate): 900 urine samples collected from non-pregnant females. 300 participants per age group (pre-menopausal, peri-menopausal, post-menopausal). For each age group, 100 tested strip, 100 tested cassette, 100 tested midstream (method not specified, but likely implies dip or in-stream was representative, or it was split). Three batches of each format were used.
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Data Provenance:
- Country of Origin: Not explicitly stated, but clinical studies were conducted at "three clinical sites," which typically implies the country where the manufacturer is located or seeking approval (likely USA given FDA submission).
- Retrospective or Prospective:
- Analytical studies (sensitivity, interference, etc.) are inherently prospective as they involve specific preparation and testing of samples.
- Method comparison, lay person studies, early pregnancy detection study, and specificity study likely involved prospective collection of samples and testing as described (e.g., "Urine samples were collected from 321 women... at three clinical sites," "A lay user study was performed at three sites," "680 early pregnancy urine samples... were collected from 68 pregnant women," "900 urine samples were collected from non-pregnant females").
3. Number of Experts and Qualifications for Ground Truth
- Ground Truth for Analytical Studies (Sensitivity, Interfering substances, etc.): The ground truth for hCG concentration was established by spiking negative female urine with hCG standard traceable to the 5th WHO (World Health Organization) standard. This indicates a highly standardized and globally recognized reference. The "operators" who performed the tests are not explicitly described as "experts" in establishing ground truth, but rather trained personnel conducting the tests.
- Ground Truth for Method Comparison & Lay Person Studies (First Study): Ground truth was established by professional testing (laboratory professionals) and comparison to a predicate device. The document refers to "at least one professional at each site using the candidate device and by one professional at each site using the predicate device." Their specific qualifications are not detailed beyond "professional."
- Ground Truth for Lay Person Study (Second Study - Spiked Samples): The samples were blind labeled by the person who prepared the samples (and did not take part in testing). The ground truth for the spiked samples was their known hCG concentration. These spiked urine samples were also tested by professionals to generate professional results for comparison with layperson results.
- Ground Truth for Early Pregnancy Detection Study: The "positive results of B-ultrasound" (beta-ultrasound) served as the definitive ground truth for confirmed pregnancy at specific days relative to the expected menstrual period (EMP). This is a widely accepted clinical method for confirming pregnancy and gestational age.
- Ground Truth for Specificity Study: "Non-pregnant females" were tested. The ground truth for "non-pregnant" would inherently be established by clinical assessment, possibly including absence of a positive ultrasound and absence of HCG in other clinical tests at the time of study enrollment.
4. Adjudication Method for the Test Set
- No explicit "adjudication method" like 2+1 or 3+1 is mentioned for reconciling discordant results in the human studies.
- For the analytical studies (e.g., sensitivity), reproducibility involves comparing results across multiple operators and lots.
- For the method comparison and lay person studies, results are simply compared to the professional result or predicate device result. For the second lay person study, samples were "blind-labeled" with known concentrations, minimizing the need for adjudication of ground truth, but discrepancies between layperson and professional results are simply reported (e.g., "Percent Agreement").
- For the early pregnancy detection study, results were correlated with B-ultrasound findings, which serves as a definitive clinical ground truth, reducing the need for consensus-based adjudication of the test results themselves.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done. This device is a rapid diagnostic test (HCG test strip/cassette/midstream) for direct visual reading by a single user (professional or layperson), not an imaging device that would typically involve multiple readers interpreting complex images. Therefore, a study comparing human readers with and without AI assistance is not applicable.
6. Standalone (Algorithm Only) Performance
- This is not an AI/algorithm-based device. It is a visually read immunoassay. Therefore, a standalone performance study of an algorithm is not applicable. The device's performance is inherently tied to the user's visual interpretation, even for "professional" use. However, the "Analytical performance" section could be considered the "standalone" performance in the sense of the device's inherent capability under controlled conditions, demonstrating sensitivity and specificity based on the chemical reaction.
7. Type of Ground Truth Used
The types of ground truth used varied by study:
- Known hCG concentrations: For analytical sensitivity, hook effect, interfering substances, cross-reactivity, and effects of pH/density. These were generated in a lab setting by spiking negative urine samples with certified hCG standards.
- Results from a legally marketed predicate device: For the method comparison study.
- Professional testing/interpretation: For comparison in the lay person studies.
- B-ultrasound (beta-ultrasound): For the early pregnancy detection study, serving as the definitive clinical confirmation of pregnancy.
- Clinical status of "non-pregnant": For the specificity study, based on a cohort of non-pregnant females.
8. Sample Size for the Training Set
- This document describes a 510(k) premarket notification for an in vitro diagnostic (IVD) test kit, not an AI/ML software device. As such, there is no "training set" in the context of machine learning model development. The data presented here are for validation/testing of the device's performance against its claims to establish substantial equivalence.
9. How the Ground Truth for the Training Set was Established
- As explained in point 8, there is no "training set" for an AI/ML model for this type of IVD device. The various ground truths used for the validation studies are described in point 7.
§ 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.