(25 days)
The illumigene Group B Streptococcus (GBS) assay, performed on the illumipro-10, is a qualitative in vitro diagnostic for the detection of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens from antepartum women. Enriched cultures are obtained by 18-24 hour incubation of vaginal/rectal swab specimens in selective broth medium, Lim Broth, TransVag Broth or Carrot Broth.
The illumigene GBS assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus agalactiae by targeting a segment of the Streptococcus agalactiae genome. Results from the illumigene GBS assay can be used as an aid in establishing the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The illumigene GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
illumigene Group B Streptococcus is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Group B Streptococcus (GBS) DNA Amplification Test Kit, the illumigene Group B Streptococus (GBS) External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene Group B Streptococcus (GBS) DNA amplification assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens taken from antepartum women. Each illumigene GBS assay is completed using illumigene Control Reagent, illumigene Reaction Buffer, an illumigene GBS Test Device and an illumigene Heat Treatment Tube. Samples are diluted with the illumigene Control Reagent, target DNA is made available for isothermal amplification via heat-treatment in the illumigene Heat Treatment Tube and DNA amplification occurs in the illumigene GBS Test Device.
The illumipro-10 heats each illumigene GBS Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When S. agalactiae is present in the enriched culture sample, a conserved sequence of the S. ggdractiae is amplified and magnesium pyrophosphate is formed. Magnesium pyrophosphate forms a precipitate in the reaction mixture. The illumipro-10 detects the change in light transmission through the reaction mixture created by the precipitating magnesium pyrophosphate. Sample results are reported as Positive or Negative based on the detected change in light transmission.
The illumigene Group B Streptococcus (GBS) External Control Kit consists of a Positive Control Reagent and a Negative Control Reagent. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors. The illumigene Group B Streptococcus External Control Kit is required for routine Quality Control.
Here's a breakdown of the acceptance criteria and the study details for the illumigene® Group B Streptococcus (GBS) DNA Amplification Assay, based on the provided text:
illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the reported performance figures from the clinical studies. For the purpose of this summary, the reported performance is presented.
| Performance Metric | Acceptance Criteria (Implied/Reported) | Reported Device Performance (Combined for all enrichment broths) |
|---|---|---|
| Overall Sensitivity | High sensitivity for GBS detection | 98.6% [95% CI: 96.5% - 99.5%] |
| Overall Specificity | High specificity for GBS detection | 93.2% [95% CI: 91.6% - 94.5%] |
| Limit of Detection (LoD) | Low CFU/Test for various serotypes | Ranged from 60 CFU/Test to 1280 CFU/Test (specific for serotype) |
| Reproducibility | 100% agreement expected across sites for controls and high/low samples | 100% agreement across all sites for Negative, High Negative, Low Positive, and Positive samples |
| Interference | No significant interference from common vaginal/rectal substances | Most tested substances (e.g., amniotic fluid, urine, meconium) did not interfere. Lubricating gel and Body Powder showed false negatives in a small fraction of replicates. Whole Blood >2.5% v/v interferes. |
| Cross-Reactivity | No significant cross-reactivity with common microorganisms | One instance of cross-reactivity with Enterococcus dispar (one of seven replicates). Most tested microorganisms showed no interference. |
| Invalid Rate | Low invalid rate | 1.3% (Lim and TransVag Broth), 0.8% (Carrot Broth) |
2. Sample Size Used for the Test Set and Data Provenance
The clinical studies were conducted in two phases:
- Lim and TransVag Broth Enrichment Study:
- Sample Size: 826 qualified patient samples.
- Data Provenance: Retrospective, collected from four independent clinical test sites located in the Midwestern and Southern regions of the United States.
- Carrot Broth Enrichment Study:
- Sample Size: 600 qualified patient samples.
- Data Provenance: Retrospective, collected from three independent clinical test sites located in the Midwestern and Southern regions of the United States.
Both studies involved vaginal/rectal swab specimens from antepartum women.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number or qualifications of experts used to establish the ground truth. However, the ground truth was "GBS bacterial culture." This implies that the standard laboratory methods for identifying GBS via bacterial culture, typically performed by trained microbiologists or laboratory technicians, served as the reference standard.
4. Adjudication Method for the Test Set
- Discrepant Analysis: For samples where the illumigene GBS assay results differed from the GBS bacterial culture (ground truth), a "discrepant result" analysis was performed.
- Method: Discrepant samples were further evaluated by independent testing laboratories using FDA-cleared or laboratory-validated molecular assays. This suggests a form of 2+1 or 3+1 (original culture + illumigene + alternate molecular method) adjudication, where the alternate molecular method acted as an adjudicator for discordant results.
- Results of Adjudication:
- Lim Broth: 16 of 19 false positive results (illumigene positive, culture negative) were positive by an alternate molecular method.
- TransVag Broth: All 32 false positive results were positive by an alternate molecular method.
- Carrot Broth: 16 of 24 discrepant samples (illumigene positive, culture negative) were positive by an alternate molecular amplification assay.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study involving human readers improving with AI vs. without AI assistance was not mentioned. The illumigene GBS assay is an automated molecular diagnostic test designed for standalone performance, not as an AI-assisted tool for human readers.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) was Done
Yes, the studies conducted were standalone performance studies of the illumigene GBS assay. The device (illumipro-10™ Automated Isothermal Amplification and Detection System utilizing LAMP technology) processes samples and reports results (Positive or Negative) without human interpretation of the amplification signal beyond what the instrument automates. The performance characteristics (sensitivity, specificity) compare the device's output directly against the bacterial culture ground truth.
7. The Type of Ground Truth Used
The primary ground truth used for establishing clinical performance was GBS bacterial culture of enriched vaginal/rectal swab specimens. For discrepant samples, alternate FDA-cleared or laboratory-validated molecular assays were used for adjudication.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" sample size. As a molecular diagnostic assay, the "training" for such devices typically refers to the development and optimization of the assay's biochemical parameters, primer design, and cut-off values using laboratory-controlled samples and potentially internal sample sets. The clinical studies described are performance validation studies (test sets) rather than separate training data sets for a machine learning model.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" with established ground truth is not explicitly mentioned as a clinical data set for model development (as would be typical for AI/ML devices), this question is not fully applicable. However, the fixed cut-off values for the assay were "based on well characterized clinical specimens." This implies that during the development phase (which could be considered analogous to "training" for a traditional IVD), a set of clinical specimens, with their GBS status determined by established laboratory methods (likely bacterial culture), was used to define and validate the assay's final threshold for reporting a positive or negative result.
§ 866.3740
Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.