(260 days)
The APTIMA Combo 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) in clinician-collected endocervical, vaginal, and male urethral swab specimens, patientcollected vaginal swab specimens*, and female and male urine specimens. The assay is also intended for use with testing of gynecological specimens collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease.
*Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.
The GEN-PROBE® APTIMA® Specimen Transfer Kit is only for use with GEN-PROBE APTIMA assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae. The GEN-PROBE APTIMA Specimen Transfer Kit allows for APTIMA Assay testing of gynecological specimens collected and processed by the Cytyc ThinPrep 2000 Processor according to the instructions provided.
Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Combo 2 Assay to include PreservCyt liquid Pap specimens (collected and processed by the Cytyc ThinPrep 2000 Processor) as acceptable testing specimens. The ancillary kit formulated for this specific application is the GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for use regarding decontamination and specimen processing procedures. The APTIMA Specimen Transfer Kit may only be used in conjunction with GEN-PROBE APTIMA Assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae..
The GEN-PROBE® APTIMA COMBO2® Assay performance has been evaluated through a multi-center clinical study.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria | Reported Device Performance (Overall) - Chlamydia trachomatis | Reported Device Performance (Overall) - Neisseria gonorrhoeae |
|---|---|---|---|
| Clinical Sensitivity | Not explicitly stated in the provided document, but typically expected to be high for a diagnostic assay. Implied by the study's aim to demonstrate equivalent performance to reference NAATs. | 96.7% (87/90) with 95% CI (90.6-99.3) | 92.3% (12/13) with 95% CI (64.0-99.8) |
| Clinical Specificity | Not explicitly stated in the provided document, but typically expected to be high for a diagnostic assay. Implied by the study's aim to demonstrate equivalent performance to reference NAATs. | 99.2% (1545/1557) with 95% CI (98.7-99.6) | 99.8% (1630/1633) with 95% CI (99.5-100) |
| Prevalence | Prevalence of C. trachomatis and N. gonorrhoeae in the study population. Not an acceptance criterion in itself, but a characteristic of the test population. The prevalence rates in the study (CT: 3.2% to 14.0%, GC: 0% to 5.0%) were considered appropriate. | C. trachomatis only: 5.6% (93/1647) | N. gonorrhoeae only: 0.6% (10/1647) |
| Analytical Sensitivity (Limit of Detection) | 1 Inclusion-Forming Unit (IFU) per assay (9.75 IFU/mL PreservCyt liquid Pap) for C. trachomatis; 50 cells/assay (488 cells/mL PreservCyt liquid Pap) for N. gonorrhoeae. | All 15 C. trachomatis serovars tested positive at less than 1 IFU/assay. | All N. gonorrhoeae strains tested positive at less than 50 cells/assay. |
| Analytical Specificity | Not explicitly stated as a numerical criterion, but the expectation is no cross-reactivity with a panel of common related and unrelated organisms. | All 50 culture isolates (47 Neisseria strains, Chlamydia psittaci, Chlamydia pneumoniae) produced negative results. | All 50 culture isolates (47 Neisseria strains, Chlamydia psittaci, Chlamydia pneumoniae) produced negative results. |
| Interference | No interference observed from common cervical specimen substances. | No interference was observed with any of the tested substances (10% blood, contraceptive jelly, spermicide, moisturizer, hemorrhoidal anesthetic, body oil, powder, anti-fungal cream, vaginal lubricants, feminine spray, and leukocytes). | No interference was observed with any of the tested substances (10% blood, contraceptive jelly, spermicide, moisturizer, hemorrhoidal anesthetic, body oil, powder, anti-fungal cream, vaginal lubricants, feminine spray, and leukocytes). |
| Recovery | Not explicitly stated, but the expectation is that co-existing common bacteria do not interfere with detection. | The addition of Escherichia coli, Gardnerella vaginalis, Lactobacillus acidophilus, Bacteroides ureolyticus, and Staphylococcus epidermidis did not interfere with detection. | The addition of Escherichia coli, Gardnerella vaginalis, Lactobacillus acidophilus, Bacteroides ureolyticus, and Staphylococcus epidermidis did not interfere with detection. |
| Stability | PreservCyt liquid Pap samples should demonstrate stable detection of C. trachomatis and N. gonorrhoeae under recommended shipping and storage conditions. | All tested conditions were positive for both C. trachomatis and N. gonorrhoeae at all specified times and temperatures (30℃ for 7 days, 4℃, 10℃, 30℃, and -20℃ for up to 106 days). | All tested conditions were positive for both C. trachomatis and N. gonorrhoeae at all specified times and temperatures (30℃ for 7 days, 4℃, 10℃, 30℃, and -20℃ for up to 106 days). |
| Precision (Reproducibility) | Not explicitly stated as a numerical criterion, but consistent results across sites, operators, and runs are expected. | Summarized in a table (refer to document Section {7}), showing varying Coefficients of Variation (CV%) for inter-site, inter-operator, inter-run, and intra-run for spiked samples. Specificity ranged from 97.7% to 100%. | Summarized in a table (refer to document Section {7}), showing varying Coefficients of Variation (CV%) for inter-site, inter-operator, inter-run, and intra-run for spiked samples. Specificity ranged from 99.0% to 100%. |
2. Sample size used for the test set and the data provenance:
- Test Set Sample Size: 1,647 female subjects (1,288 asymptomatic, 359 symptomatic).
- Data Provenance: Prospective multi-center clinical study conducted in the United States (as implied by the FDA submission and the company's US address). The study involved subjects attending OB/GYN, family planning, public health, women's, and STD clinics.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not explicitly state the number or qualifications of experts used to establish the ground truth. Instead, the ground truth was established by a patient infected status algorithm based on the results of two commercially-available reference NAATs performed on endocervical swab specimens. This implies that the ground truth was determined by laboratory testing protocols rather than direct expert consensus on each individual case.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Adjudication Method: "None" in the sense of expert human adjudication. The ground truth for the "patient infected status" was based on concordant positive results from two reference NAATs (APTIMA Combo 2 Assay and APTIMA CT Assay for C. trachomatis; APTIMA Combo 2 Assay and APTIMA GC Assay for N. gonorrhoeae). If the two reference NAATs disagreed or were negative, the patient was designated as non-infected. This is a form of algorithmic adjudication rather than human expert adjudication.
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:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was NOT done. This study evaluates a laboratory diagnostic assay (APTIMA Combo 2 Assay) and does not involve human readers interpreting images or data to be assisted by AI. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, this was effectively a standalone performance study for the device. The APTIMA Combo 2 Assay, as a nucleic acid amplification test, functions as an algorithm-only device (an in vitro diagnostic test kit that produces a qualitative result based on amplification and detection of rRNA). Its performance was evaluated against a defined ground truth without direct human interpretation in a diagnostic loop that would affect its result. The assay generates a direct qualitative result (positive/negative) which is then used by clinicians for diagnosis.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Algorithm-based Patient Infected Status (Reference NAATs):
- For C. trachomatis: A patient was considered infected if both the APTIMA Combo 2 Assay and the APTIMA CT Assay (both performed on endocervical swabs) returned positive results.
- For N. gonorrhoeae: A patient was considered infected if both the APTIMA Combo 2 Assay and the APTIMA GC Assay (both performed on endocervical swabs) returned positive results.
- A non-infected patient was established if the results from the two reference NAATs disagreed or were negative. This is effectively a composite reference standard based on other validated diagnostic tests.
8. The sample size for the training set:
- The document does not explicitly describe a separate training set for the APTIMA Combo 2 Assay in the context of this submission. The product being submitted for clearance is an existing assay (APTIMA Combo 2 Assay (K003395)) and the clearance sought is an extension of its clinical performance claims to include PreservCyt liquid Pap specimens.
- The non-clinical (analytical) studies (Limit of Detection, Specificity, Interference, Recovery, Stability, Precision) likely involved internal development and optimization, which could be considered an implicit "training" or development phase. However, a distinct "training set" in the machine learning sense is not mentioned. The clinical study described is solely for validation/testing of the assay's performance with the new specimen type.
9. How the ground truth for the training set was established:
- As a distinct training set is not explicitly mentioned for this 510(k) submission, the method for establishing its ground truth is also not detailed. The ground truth for the non-clinical (analytical) studies typically involved controlled laboratory experiments using known concentrations of organisms and interference substances, with results verified by standard laboratory methods.
§ 866.3390
Neisseria spp. direct serological test reagents.(a)
Identification. Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identifyNeisseria spp. from cultured isolates. Additionally, some of these reagents consist ofNeisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence ofNeisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusNeisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.(b)
Classification. Class II (performance standards).