(231 days)
BD MAX™ GBS Assay:
The BD MAX™ GBS Assay as implemented on the BD MAX™ System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA in Lim Broth cultures, after incubation for greater than or equal to (≥) 18 hours, obtained from vaginal-rectal swab specimens from antepartum pregnant women. The test incorporates automated DNA extraction to isolate the target nucleic acid from the specimen and real-time polymerase chain reaction (PCR) to detect a 124 bp region of the cfb gene sequence of the Streptococcus agalactiae chromosome. Results from the BD MAX™ GBS Assay can be used as an aid to determining colonization status in antepartum women.
The BD MAX™ GBS Assay does not provide susceptibility results. Cultured isolates are necessary for performing susceptibility testing as recommended for penicillin-allergic women. Subculture to solid media for additional testing when indicated.
BD MAX™ System:
The BD MAX™ System is intended for in vitro diagnostic (IVD) use in performing FDA cleared or approved nucleic acid testing in clinical laboratories. The BD MAX System is capable of automated extraction and purification of nucleic acids from multiple specimen types, as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR.
The BD MAX™ System is intended for in vitro diagnostic (IVD) use in performing FDA cleared or approved nucleic acid testing in clinical laboratories. The BD MAX System is capable of automated extraction and purification of nucleic acids from multiple specimen types, as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR.
A vaginal-rectal swab is collected and transported to the laboratory using standard bacterial swab transport systems containing a non-nutritive transport medium (e.g. Amies or Stuart). In the lab, the swab is removed from the transport medium and placed into selective Lim Broth (Todd-Hewitt Broth supplemented with colistin (10ug/mL) and nalidixic acid (15ug/mL)). After incubation of inoculated Lim Broth culture for ≥ 18 hours at 37℃ in ambient air or 5% CO2, a 15 µL aliquot of the broth is mixed with BD MAX GBS Sample Preparation Reagent and processed on the BD MAX System using the BD MAX GBS Assay. The BD MAX System automatically extracts the target nucleic acid and amplifies a section of the cfb gene sequence of the GBS chromosome, if present. The BD MAX GBS Assay includes an Internal Process Control to monitor for the presence of potential inhibitory substances as well as system or reagent failures that may be encountered during the entire process.
Here's a breakdown of the acceptance criteria and study details for the BD MAX GBS Assay, based on the provided text:
Acceptance Criteria and Device Performance
The provided text focuses on demonstrating substantial equivalence to a predicate device rather than explicit, numerical acceptance criteria for a novel device. The primary method of demonstrating performance is through a comparison study against the predicate device.
Table 1: Summary of Study Comparing 2nd Generation BD MAX System to 1st Generation BD MAX System using the BD MAX GBS Assay
| Metric | Acceptance Criteria (Implied - Agreement with Predicate) | Reported Device Performance (2nd Gen BD MAX GBS Assay) |
|---|---|---|
| Positive Percent Agreement (PPA) | High agreement with 1st Generation BD MAX System | 100% (330/330) (95% CI: 100% - 100%) combined across sites |
| Negative Percent Agreement (NPA) | High agreement with 1st Generation BD MAX System | 99.0% (309/312) (95% CI: 97.8% - 100%) combined across sites |
Note: The "acceptance criteria" here are implied by the goal of demonstrating substantial equivalence to the predicate device, meaning the new device should perform very similarly to the established one. Specific numerical thresholds for PPA and NPA are not explicitly stated as "acceptance criteria" but are demonstrated through the study results.
Study Details
1. Sample Size and Data Provenance
- Test Set Sample Size: 214 non-contrived, residual clinical Lim Broth specimens.
- Data Provenance: The specimens were obtained from five (5) clinical laboratories. The origin country is not explicitly stated, but the context of the document being a 510(k) submission to the US FDA suggests it's likely U.S.-based or regulated. The data is retrospective, as it used residual clinical specimens.
2. Number of Experts and Qualifications for Ground Truth
- The ground truth for the test set was not established by human experts in a traditional sense. Instead, the 1st Generation BD MAX (2 channel) System served as the "gold standard" or ground truth to which the new 2nd Generation system was compared.
- Therefore, the "experts" were the established performance of the predicate device. No human experts were used to establish the ground truth for the comparison study itself.
3. Adjudication Method for the Test Set
- The ground truth was determined by the 1st Generation BD MAX (2 channel) System.
- In the event of a discordant or invalid (IND) result generated by two (2) of the three (3) 1st Generation instruments, then the majority result from the 1st Generation instruments determined the GBS status. This implies a form of "majority rule" adjudication among the predicate devices when there was disagreement.
4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted in the traditional sense involving human readers and AI.
- This study was a comparison between two automated diagnostic systems (the 1st Generation BD MAX GBS Assay and the 2nd Generation BD MAX GBS Assay) to demonstrate substantial equivalence, not to measure the improvement of human readers with AI assistance.
5. Standalone Performance Study
- Yes, a standalone performance study was conducted. The "Clinical Performance/Comparison Study" section describes the performance of the 2nd Generation BD MAX GBS Assay (algorithm only, without human-in-the-loop performance) when compared against the 1st Generation BD MAX GBS Assay.
- Additionally, several analytical performance studies (Precision, Reproducibility, Carry Over/Cross Contamination, Interfering Substances, Analytical Sensitivity/Limit of Detection, Microbial Variants, Analytical Specificity) were conducted to characterize the standalone technical performance of the device.
6. Type of Ground Truth Used
- The primary ground truth for the clinical performance comparison was the results generated by the predicate device (1st Generation BD MAX GBS Assay).
- For analytical studies (LoD, specificity, etc.), the ground truth was established by spiking known concentrations of GBS culture (ATCC strains) or other organisms/substances into negative samples and observing the device's detection capabilities. This represents engineered or contrived ground truth based on known quantities and identities.
7. Sample Size for the Training Set
- The document does not explicitly state the sample size for a training set.
- Molecular diagnostic assays like the BD MAX GBS Assay are typically developed (or "trained" in a broader sense) using extensive analytical studies involving known strains, concentrations, and interferents. They are not typically "trained" on large clinical datasets in the same way machine learning algorithms are.
- The "Substantial Equivalence" section describes the new device as an update to an existing system, implying refinement rather than de novo development requiring a distinct clinical training dataset.
8. How Ground Truth for the Training Set Was Established
- Given that a specific "training set" with established ground truth is not detailed in the context of a machine learning model, this question isn't directly applicable for this device.
- However, the underlying scientific and analytical principles for defining what constitutes a "positive" or "negative" GBS result in a molecular assay are based on established microbiology laboratory standards, pure culture analysis, and defined concentrations of genetic material (CFU/mL). This forms the basis for the development and validation of such assays.
§ 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.