(438 days)
The BD CTGCTV2 assay incorporates automated DNA extraction and real-time polymerase chain reaction (PCR) for the direct, qualitative detection of DNA from:
- Chlamydia trachomatis (CT)
- . Neisseria gonorrhoeae (GC)
- . Trichomonas vaginalis (TV)
The assay may be used for detection of CT, GC and/or TV DNA in patient- or clinician-collected vaginal swab specimens (in a clinical setting), and male and female urine specimens. The assay may also be used for the detection of CT and GC DNA in endocervical swab and Liquid-Based Cytology (LBC) specimens in ThinPrep PreservCyt Solution using an aliquot that is removed prior to processing for the ThinPrep Pap test.
The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of chlamydial urogenital disease, gonococcal urogenital disease and/or trichomoniasis.
The BD CTGCTV2 assay is available for use on the BD MAX System or the BD COR System.
As with the existing BD CTGCTV2 for BD MAX System, K182692, the BD COR PX/MX (BD COR) high throughput system conducts sample extraction steps to isolate and concentrate DNA which is then amplified to detect specific sequences for diagnostic purposes.
The BD COR System is designed to allow the user to place clinical specimens directly into designated transport racks to be loaded into the System. Once the specimens are loaded, the System will perform the necessary pre-analytical steps such as vortexing, aliquoting into a molecular tube with the correct diluent, sorting/grouping of the secondary samples for testing by assay, pre-warming and cooling of the sample (where required), and transport of the sample into a molecular analyzer, where extraction, amplification and detection will take place.
Additionally, the steps of ordering tests on the instrument for specific samples will be managed directly by the user interaction with the Laboratory Information System (LIS), which communicates with the instrument.
Once the clinical specimens are received in the laboratory and loaded into the transport racks, the user will not be required to directly handle the specimen again prior to result reporting and removal from the system.
Here's a breakdown of the acceptance criteria and study details for the BD CTGCTV2 assay, based on the provided document:
Acceptance Criteria and Device Performance
The core of this submission focuses on demonstrating the substantial equivalence of the BD CTGCTV2 assay when run on the BD COR System to its previously cleared performance on the BD MAX System. Therefore, the acceptance criteria are implicitly tied to demonstrating comparable analytical and clinical performance between the two platforms.
Key Performance Metrics (Implicit Acceptance Criteria) and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Implicit: Equivalence to BD MAX) | Reported Device Performance on BD COR System (Test Set) |
|---|---|---|
| Within-Laboratory Precision | High percentage agreement with expected results across different target concentrations (Moderate Positive, Low Positive, High Negative, True Negative) and low CV for Ct scores. | PreservCyt Samples: |
| - CT (MP): 100% Correct. LP: 98.6% Correct. HN: 38.9% Positive. TN: 100% Negative. | ||
| - GC (MP): 95.8% Correct. LP: 93.1% Correct. HN: 43.1% Positive. TN: 100% Negative. | ||
| Urine Samples: | ||
| - CT (MP): 100% Correct. LP: 100% Correct. HN: 54.2% Positive. TN: 100% Negative. | ||
| - GC (MP): 98.6% Correct. LP: 100% Correct. HN: 44.4% Positive. TN: 100% Negative. | ||
| - TV (MP): 100% Correct. LP: 100% Correct. HN: 37.5% Positive. TN: 100% Negative. | ||
| Variance Component Analysis (PreservCyt Ct.Scores): Total CV ranged from 1.23% (GC2 MP) to 4.50% (GC1 LP). | ||
| Variance Component Analysis (Urine Ct.Scores): Total CV ranged from 1.69% (CT MP) to 3.56% (TV LP). | ||
| Multi-Site Reproducibility | High percentage agreement with expected results across different sites and low overall CV for Ct scores. | PreservCyt Samples (Overall across 3 sites): |
| - TN: 100%. HN: 38.9% to 48.1% positive. LP: 91.7% to 98.1% correct. MP: 98.1% to 100% correct. Overall CV (%) for Ct.Score results ranged from 1.75% to 4.15%. | ||
| Urine Samples (Overall across 3 sites): | ||
| - TN, LP, MP: 100%. HN: 37.0% to 58.3% positive. Overall CV (%) for Ct.Score results ranged from 1.74% to 4.18%. | ||
| Analytical Sensitivity (LoD) Equivalence | Difference in Mean Ct.Score between BD COR and BD MAX should ideally be close to zero, with 95% CI covering zero, indicating equivalent analytical sensitivity. | Vaginal Swabs: Difference in Mean Ct.Score (BD COR - BD MAX) for various targets and concentrations generally close to zero, with 95% CIs mostly crossing zero, indicating equivalence. Largest difference: -0.67 for GC2, 95% CI (-0.857, -0.494). |
| Urine: Differences mostly close to zero. Largest difference: -1.10 for GC2, 95% CI (-1.375, -0.842). | ||
| Manually Converted LBC: Differences mostly close to zero. Largest difference: 0.64 for GC1, 95% CI (0.348, 0.927). | ||
| COR PX Converted LBC: Differences mostly close to zero. Largest difference: 0.71 for GC1, 95% CI (0.316, 1.100). | ||
| Cross-Contamination Rate | A very low cross-contamination rate, typically aiming for near 0% of negative samples yielding false positives when run near high positive samples. | Two false positive results (0.37%, 95% CI: 0.10-1.34%) out of 540 negative samples tested when interspersed with high positive Chlamydia trachomatis samples. |
| Clinical Agreement (PPA & NPA) | High Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) between the BD COR System and the reference BD MAX System (ideally >95% with tight CIs). | CT: Average PPA: 100%, NPA: 100%. |
| GC: Average PPA: 97.6% (95% CI: 95.6%, 99.1%), NPA: 100%. (Individual sites ranged from 95.5% to 99.1% PPA). | ||
| TV: Average PPA: 99.7% (95% CI: 99%, 100%), NPA: 98.5% (95% CI: 96.3%, 100%). (Individual sites ranged from 99.0% to 100% PPA and 97.3% to 99.1% NPA). | ||
| Deming Regression for Ct.Score | Slope close to 1 and intercept close to 0 between BD COR and BD MAX Ct.Scores, indicating a linear and equivalent relationship. Bias estimates also close to zero. | CT: Slope 1.06 (0.99, 1.13), Intercept -1.85 (-3.88, 0.18). Bias estimates mostly low, ranging from -0.22 to 0.93. |
| GC1: Slope 1.02 (0.99, 1.06), Intercept -0.06 (-0.99, 0.87). Bias estimates mostly positive, ranging from 0.47 to 0.92. | ||
| GC2: Slope 1.03 (0.99, 1.07), Intercept -0.72 (-1.76, 0.33). Bias estimates mostly positive, ranging from 0.01 to 0.70. | ||
| TV: Slope 1.09 (0.98, 1.19), Intercept -2.25 (-5.30, 0.80). Bias estimates mostly positive, ranging from 0.03 to 1.68. | ||
| Non-Reportable Rate | Low non-reportable rate (including Unresolved, Indeterminate, Incomplete), indicating reliable assay operation. | Combined Target (Total Initial Rate): 2.4% (31/1298) with 95% CI (1.7%, 3.4%). After retesting (Final Rate), this dropped to 0.0% (0/1297) with 95% CI (0.0%, 0.3%). This includes one non-reportable due to a non-readable label and 26 indeterminate results due to a consumable positioning issue (which were retested successfully). |
Study Information: BD CTGCTV2 Assay on BD COR System
This submission pertains to the BD CTGCTV2 assay being used on the BD COR System. The key study is a clinical agreement study and analytical performance studies designed to demonstrate that the performance of the assay on the BD COR System is equivalent to its already cleared performance on the BD MAX System (K182692).
1. A table of acceptance criteria and the reported device performance:
* See table above.
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
* Analytical Performance (Precision & Reproducibility Test Set):
* Precision (within-laboratory): 72 replicates for each target (CT, GC, TV) at each of 4 concentration levels (MP, LP, HN, TN) for PreservCyt samples and 4 concentration levels for Urine samples. Total N is not explicitly stated as a single number but is derived. For example, for CT in PreservCyt, it's 72 * 4 = 288 data points.
* Reproducibility (multi-site): For each target and concentration level, 36 replicates per site across 3 sites (36 * 3 = 108 total replicates per target/level).
* Analytical Sensitivity Confirmation: 4 panel members (A, B, C, D) created with 1.5x LoD and 3x LoD for various target organisms and strains in pooled female urine, pooled vaginal swab, and pooled PreservCyt LBC matrix. The study compared performance between BD COR and BD MAX. The exact number of replicates for each panel member for this confirmation study is not explicitly stated as a total N, but implied to be sufficient for statistical comparison (mean Ct.Scores and 95% CIs are reported).
* Cross-Contamination: 540 positive samples and 540 negative samples for a total of 1080 samples.
* Clinical Agreement Study (Test Set):
* Sample Size: 433 independent panel members.
* Provenance: "Remnant urine specimens from the previous clinical trial for BD CTGCTV2 on BD MAX as well as urine specimens obtained from both internal and external collections were used for the comparison study." This suggests a retrospective collection of remnant urine specimens combined with potentially prospective collections from internal and external sources to create the clinical panels. The country of origin is not explicitly stated, but given the FDA submission, it can be inferred to be primarily US-based or at least compliant with US regulations.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
* For the Precision, Reproducibility, Analytical Sensitivity, and Cross-Contamination studies: The ground truth was established by the known concentrations or presence/absence of organisms in contrived samples or spiked matrices. These are analytical studies, not clinical studies requiring expert interpretation.
* For the Clinical Agreement Study: The BD MAX System results served as the reference/ground truth. The positive or negative status of a panel member was defined by "≥2 out of 3 evaluable results obtained on the BD MAX." This is a comparator method, not direct expert consensus on patient samples. Therefore, no human experts were used to establish the ground truth for the clinical agreement study beyond the definition of the BD MAX as the reference standard.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
* For the Clinical Agreement Study: The "ground truth" (reference comparator result from BD MAX) was established by "≥2 out of 3 evaluable results obtained on the BD MAX". This functions as a form of "consensus" or adjudication among multiple runs (3 aliquots) on the reference system.
* For the analytical studies (precision, reproducibility), ground truth was based on known concentrations, so no adjudication by a panel of experts was necessary.
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 MRMC comparative effectiveness study was done. This device is an in vitro diagnostic (IVD) assay that detects nucleic acids. It's an automated molecular system, not an AI-assisted diagnostic tool that human readers would interpret. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
* Yes, this is a standalone performance study in the context of an IVD assay. The BD CTGCTV2 assay on the BD COR System is an automated system for qualitative detection of DNA. The studies described (analytical and clinical agreement) evaluate the performance of this automated system directly, without human interpretation of its diagnostic output. The output itself (positive/negative) is the final result.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
* Analytical Studies (Precision, Reproducibility, Cross-Contamination, Analytical Sensitivity): The ground truth was based on known concentrations of purified organisms or specific strains spiked into negative matrices. This is an analytical ground truth.
* Clinical Agreement Study: The ground truth was the result from the legally marketed predicate device, the BD MAX System, determined by a "consensus" of ≥2 out of 3 evaluable results from the BD MAX. This is a (predicate) comparator ground truth.
8. The sample size for the training set:
* The document describes studies for validation and equivalency demonstration of the BD CTGCTV2 assay on the BD COR System compared to the BD MAX System. It does not mention "training sets" in the context of machine learning or AI models.
* For IVD assays, "training" typically refers to the initial development and optimization of the assay performed by the manufacturer. The data used for this developmental phase is not typically detailed in 510(k) summaries, which focus on formal validation studies.
* The assay itself incorporates "automated DNA extraction and real-time PCR," which are well-established molecular biology techniques, not typically "trained" in the AI sense.
9. How the ground truth for the training set was established:
* As noted above, the document does not describe a "training set" in the context of an AI/machine learning model. Therefore, this question is not applicable. The development of the PCR assay and its parameters would have involved extensive laboratory work by the manufacturer, but the "ground truth" for those developmental phases would be based on well-characterized materials and samples, similar to the analytical studies described for validation.
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May 10, 2022
Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym and name on the right. The Department of Health & Human Services logo is a stylized depiction of a human figure, while the FDA acronym and name are written in blue, with the acronym in a square and the name in a sans-serif font.
Becton Dickinson and Company Jessica Dewyer Senior Manager, Regulatory Affairs 7 Loveton Circle Sparks, Maryland 21152
Re: K210585
Trade/Device Name: BD CTGCTV2 Regulation Number: 21 CFR 866.3393 Regulation Name: Device To Detect Nucleic Acids From Non-Viral Microorganism(S) Causing Sexually Transmitted Infections And Associated Resistance Marker(S) Regulatory Class: Class II Product Code: QEP, OUY, LSL, MKZ Dated: February 25, 2021 Received: February 26, 2021
Dear Jessica Dewyer:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Himani Bisht, Ph.D. Assistant Director Viral Respiratory and HPV Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use Statement
| DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug AdministrationIndications for Use | Form Approved: OMB No. 0910-0120Expiration Date: 06/30/2023See PRA Statement below. |
|---|---|
| ------------------------------------------------------------------------------------------------ | --------------------------------------------------------------------------------------------- |
| 510(k) Number (if known) | K210585 |
|---|---|
| Device Name | BD CTGCTV2 |
Indications for Use (Describe)
The BD CTGCTV2 assay incorporates automated DNA extraction and real-time polymerase chain reaction (PCR) for the direct, qualitative detection of DNA from:
- Chlamydia trachomatis (CT)
- . Neisseria gonorrhoeae (GC)
- . Trichomonas vaginalis (TV)
The assay may be used for detection of CT, GC and/or TV DNA in patient- or clinician-collected vaginal swab specimens (in a clinical setting), and male and female urine specimens. The assay may also be used for the detection of CT and GC DNA in endocervical swab and Liquid-Based Cytology (LBC) specimens in ThinPrep PreservCyt Solution using an aliquot that is removed prior to processing for the ThinPrep Pap test.
The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of chlamydial urogenital disease, gonococcal urogenital disease and/or trichomoniasis.
The BD CTGCTV2 assay is available for use on the BD MAX System or the BD COR System.
Type of Use (Select one or both, as applicable) 区 Prescription Use (Part 21 CFR 801 Subpart D) □ Over-The Counter Use (21 CFR 801 Subpart C)
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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
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FORM FDA 3881 (6/20)
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510(k) Summary
BD CTGCTV2 on BD COR System K210585
Summary Preparation Date:
4/27/2022
Submitted by:
BD Integrated Diagnostic Solutions Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152
Contact:
Jessica Dewyer, Senior Manager, Regulatory Affairs Becton Dickinson and Company 7 Loveton Circle, Sparks, MD 21152 USA (520) 486-8516 Jessica.dewyer@bd.com
Proprietary Names:
For the instrument: BD COR PX/MX System For the assay: BD CTGCTV2
Common Names:
For the instrument: High-throughput molecular system
For the assay: CT, GC and TV assay
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Regulatory Information
Regulation section:
21 CFR &866.3393, Nucleic Acid Detection System For Non-Viral Microorganism(S) Causing Sexually Transmitted Infections
Classification: Class II
Panel: Microbiology (83)
Product Code(s): QEP MKZ LSL OUY
Predicate Device
BD CTGCTV2 on BD MAX System (K182692)
Intended Use
The BD CTGCTV2 assay incorporates automated DNA extraction and real-time polymerase chain reaction (PCR) for the direct, qualitative detection of DNA from:
- Chlamydia trachomatis (CT)
- . Neisseria gonorrhoeae (GC)
- Trichomonas vaginalis (TV) .
The assay may be used for detection of CT, GC and/or TV DNA in patient- or clinician-collected vaginal swab specimens (in a clinical setting), and male and female urine specimens. The assay may also be used for the detection of CT and GC DNA in endocervical swab and Liquid-Based Cytology (LBC) specimens in ThinPrep PreservCyt Solution using an aliquot that is removed prior to processing for the ThinPrep Pap test.
The assay is indicated for use with asymptomatic individuals to aid in the diagnosis of chlamydial urogenital disease, gonococcal urogenital disease and/or trichomoniasis.
The BD CTGCTV2 assay is available for use with the BD MAX System or the BD COR System.
Special Conditions for Use Statement: For Prescription Use Only
Special Instrument Requirements: BD COR PX/MX System
Device Description
As with the existing BD CTGCTV2 for BD MAX System, K182692, the BD COR PX/MX (BD COR) high throughput system conducts sample extraction steps to isolate and concentrate DNA which is then amplified to detect specific sequences for diagnostic purposes.
The BD COR System is designed to allow the user to place clinical specimens directly into designated transport racks to be loaded into the System. Once the specimens are loaded, the System will perform the necessary pre-analytical steps such as vortexing, aliquoting into a molecular tube with the correct diluent, sorting/grouping of the secondary samples for testing by assay, pre-warming and
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cooling of the sample (where required), and transport of the sample into a molecular analyzer, where extraction, amplification and detection will take place.
Additionally, the steps of ordering tests on the instrument for specific samples will be managed directly by the user interaction with the Laboratory Information System (LIS), which communicates with the instrument.
Once the clinical specimens are received in the laboratory and loaded into the transport racks, the user will not be required to directly handle the specimen again prior to result reporting and removal from the system.
Test Principle
The BD CTGCTV2 assay, performed on the BD COR system (hereafter referred to as BD CTGCTV2) is designed for use with the applicable BD Molecular specimen collection and transport devices for male and female urine, vaginal swabs, endocervical swabs, and LBC specimens (PreservCyt). Specimens are collected and transported to the testing laboratory using their respective transport devices under conditions of time and temperature that have been determined to maintain the integrity of the target nucleic acids.
The BD COR MX Instrument, when combined with the BD COR PX Instrument, is to be used for automated sample preparation, 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 real-time PCR for simultaneous and differential detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.
The BD CTGCTV2 assay extraction reagents are dried in 96-well microtiter plates that contain binding magnetic affinity beads and Sample Processing Control (SPC). Each tube is capable of binding and eluting sample nucleic acids. The SPC monitors the integrity of the reagents and the process steps involved in DNA extraction, amplification and detection, as well as for the presence of potential assay inhibitors.
The BD CTGCTV2 assay liquid reagent plate includes Wash, Elution and Neutralization buffers. The beads (described above), together with the bound nucleic acids, are washed and the nucleic acids are eluted by a combination of heat and pH. When performed on BD COR MX, there is an additional buffer to rehydrate the dried extraction mix. Eluted DNA is neutralized and transferred to the Amplification reagent (described below) to rehydrate the PCR reagents. After reconstitution, the BD COR PX/MX System dispenses a fixed volume of PCR-ready solution contaming extracted nucleic acids into the BD PCR Cartridge.
Microvalves in the BD PCR Cartridge are sealed by the system prior to initiating PCR in order to contain the amplification mixture and thus prevent evaporation and contamination.
The BD CTGCTV2 assay is comprised of two targets for Chlamydia trachomatis (detected on the same optical channel), two targets for Neisseria gonorrhoeae (detected on two different optical channels) and one target for Trichomonas vaginalis (detected on one optical channel). Only one Chlamydia trachomatis target is required to be positive in order to report a positive result. Both Neisseria gonorrhoeae targets are required to be positive in order to report a positive result.
The amplified DNA targets are detected using hydrolysis (TaqMan) probes, labeled at one end with a fluorescent reporter dye (fluorophore), and at the other end, with a quencher moiety. Probes labeled with different fluorophores are used to detect the target analytes in different optical channels of the BD COR PX/MX System. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5'-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a
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result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The BD COR PX/MX System monitors these signals at each cycle of the PCR and interprets the data at the end of the reaction to provide qualitative test results for each analyte (i.e., positive or negative).
Substantial Equivalence1
Table 1 provides the similarities and differences between the BD CTGCTV2 assay and the predicate device.
The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under which a device can be marketed without pre-market approval or reclassification. A determination of substantial equivalency under this not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission aganst interest under the US Patent Laws or the courts.
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| Items | BD CTGCTV2 | BD CTGCTV2 for BD MAX System |
|---|---|---|
| 510(k)# | K210585 | K182692 |
| Regulation | 866.3393, 866.3120, 866.3390, 866.3860 | 866.3120, 866.3390, 866.3860 |
| Product Code | QEP, MKZ, LSL, OUY | MKZ, LSL, OUY |
| Device Class | II | II |
| Intended Use | The BD CTGCTV2 assay incorporatesautomated DNA extraction and real-timepolymerase chain reaction (PCR) for the direct,qualitative detection of DNA from:Chlamydia trachomatis (CT)Neisseria gonorrhoeae (GC)Trichomonas vaginalis (TV)The assay may be used for detection of CT, GCand/or TV DNA in patient- or clinician-collectedvaginal swab specimens (in a clinical setting),and male and female urine specimens. The assaymay also be used for the detection of CT and GC DNA in endocervical swab and Liquid-BasedCytology (LBC) specimens in ThinPrepPreservCyt Solution using an aliquot that isremoved prior to processing for the ThinPrep Paptest.The assay is indicated for use with asymptomaticand symptomatic individuals to aid in thediagnosis of chlamydial urogenital disease,gonococcal urogenital disease and/ortrichomoniasis.The BD CTGCTV2 assay is available for usewith the BD MAX System or the BD CORSystem. | The BD CTGCTV2 for BD MAXTM System,performed on the BD MAXTM System, incorporatesautomated DNA extraction and real-time polymerasechain reaction (PCR) for the direct, qualitativedetection of DNA from:Chlamydia trachomatis (CT)Neisseria gonorrhoeae (GC)Trichomonas vaginalis (TV)The assay may be used for detection of CT, GCand/or TV DNA in patient- or clinician-collectedvaginal swab specimens (in a clinical setting), andmale and female urine specimens. The assay mayalso be used for the detection of CT and GC DNA inendocervical swab and Liquid-Based Cytology(LBC) specimens in ThinPrep PreservCyt Solutionusing an aliquot that is removed prior to processingfor the ThinPrep Pap test.The assay is indicated for use withasymptomatic and symptomatic individuals to aid inthe diagnosis of chlamydial urogenital disease,gonococcal urogenital disease and/or trichomoniasis. |
| Indicationsfor Use | Same | Asymptomatic and Symptomatic Patients |
| Specimen Type | Same | Clinician-collected vaginal swab, patient collectedvaginal swab, endocervical swab,PreservCyt LBC, female and male urine |
| Technology | Same | PCR |
| Organisms Detected | Same | CT, GC, and TV |
| DNA extraction,amplification anddetection | Automated by BD COR System | Automated by BD MAX System |
| Assay Controls | Same | Sample Processing Control |
Table 1: Comparison to the Predicate Device
Analytical Performance
Analytical performance of the BD CTGCTV2 assay was evaluated on the BD MAX System and the results may be found under K182692. As the formulation of the BD CTGCTV2 assay reagents for use on the BD COR System has not changed from those used with the BD MAX System, certain analytical studies performed and documented in the package insert on BD MAX can be leveraged for and are applicable to the BD COR System (specimen stability, analytical sensitivity, inclusivity, cross-reactivity,
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and interfering substances). The following sections describe the analytical studies that were performed to demonstrate that the assay performance, when used on BD COR, is unchanged from the performance demonstrated on the BD MAX System. The new analytical studies included: within-laboratory precision and multi-site reproducibility, confirmation of the analytical sensitivity and a cross-contamination study, all performed on the BD COR System.
Precision for BD COR System
Within-laboratory precision was evaluated for the BD CTGCTV2 assay on the BD COR System at one site with one reagent lot. Testing was performed over 12 days, with 3 runs per day (2 technologists, 6 days per technologist), for a total of 36 runs. Test samples were contrived in female urine, and in PreservCytLBC specimen matrix and included Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis (urine only) panel member was tested in two replicates. The following target concentrations were used for spiking levels of the target organisms contained in each panel member:
- . Moderate Positive (MP): 3x LoD
- Low Positive (LP): 1.5x LoD ●
- High Negative (HN): < 1x LoD (expected negative 5% to 95% of the time)
- True negative (TN): no target .
Precision study results for the BD CTGCTV2 assay on the BD COR System are described in Table 2 and Table 3, while the variance component analyses are described in Table 5.
Table 2: Percent Agreement with Expected Results for Within-lab Precision on BD COR with PreservCyt Samples
| Target | Level | N | N Correct | % Correct | 95% CI | |
|---|---|---|---|---|---|---|
| Lower Bound | Upper Bound | |||||
| CT | MP | 72 | 72 | 100% | 94.9% | 100% |
| LP | 72 | 71 | 98.6% | 92.5% | 99.8% | |
| HNb | 72 | 28 | 38.9% | 28.5% | 50.4% | |
| TNa | 72 | 72 | 100% | 94.9% | 100% | |
| GC | MP | 72 | 69 | 95.8% | 88.5% | 98.6% |
| LP | 72 | 67 | 93.1% | 84.8% | 97.0% | |
| HNb | 72 | 31 | 43.1% | 32.3% | 54.6% | |
| TNa | 72 | 72 | 100% | 94.9% | 100% |
a For the True Negative (TN) category, the reported agreement indicates the percent of negative results.
b For the High Negative (HN) category, the reported agreement indicates the percent of positive results.
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| Target | Level | N | N Correct | % Correct | 95% CI | |
|---|---|---|---|---|---|---|
| Lower Bound | Upper Bound | |||||
| CT | MP | 72 | 72 | 100% | 94.9% | 100% |
| LP | 72 | 72 | 100% | 94.9% | 100% | |
| HNb | 72 | 39 | 54.2% | 42.7% | 65.2% | |
| TNa | 72 | 72 | 100% | 94.9% | 100% | |
| GC | MP | 72 | 71 | 98.6% | 92.5% | 99.8% |
| LP | 72 | 72 | 100% | 94.9% | 100% | |
| HNb | 72 | 32 | 44.4% | 33.5% | 55.9% | |
| TNa | 72 | 72 | 100% | 94.9% | 100% | |
| TV | MP | 72 | 72 | 100% | 94.9% | 100% |
| LP | 72 | 72 | 100% | 94.9% | 100% | |
| HNb | 72 | 27 | 37.5% | 27.2% | 49.0% | |
| TNa | 72 | 72 | 100% | 94.9% | 100% |
Table 3: Percent Agreement with Expected Results for Within-lab Precision on BD COR with Urine Samples
a For the True Negative (TN) category, the reported agreement indicates the percent of negative results.
b For the High Negative (HN) category, the reported agreement indicates the percent of positive results.
Table 4: Variance component analysis results, BD COR PreservCyt
| Within Run | Between Run | Between Day | Total | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Target | Level | N | Mean | SD | CV | SD | %CV | SD | %CV | SD | CV |
| CT | MP | 72 | 32.86 | 0.55 | 1.67 | 0.26 | 0.78 | 0.00 | 0.00 | 0.61 | 1.85 |
| LP | 71 | 34.06 | 1.25 | 3.68 | 0.31 | 0.90 | 0.00 | 0.00 | 1.29 | 3.79 | |
| GC1 | MP | 69 | 31.89 | 0.68 | 2.14 | 0.00 | 0.00 | 0.00 | 0.00 | 0.68 | 2.14 |
| LP | 67 | 33.78 | 1.52 | 4.50 | 0.00 | 0.00 | 0.00 | 0.00 | 1.52 | 4.50 | |
| GC2 | MP | 72 | 30.24 | 0.36 | 1.18 | 0.07 | 0.23 | 0.07 | 0.23 | 0.37 | 1.23 |
| LP | 70 | 31.63 | 0.66 | 2.10 | 0.00 | 0.00 | 0.00 | 0.00 | 0.66 | 2.10 |
Table 5: Variance component analysis results, BD COR Urine
| Within Run | Between Run | Between Day | Total | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Target | Level | N | Mean | SD | CV | SD | CV | SD | CV | SD | CV |
| CT | MP | 72 | 1.71 | 0.50 | 1.57 | 0.00 | 0.00 | 0.2 | 0.62 | 0.54 | 1.69 |
| LP | 72 | 32.93 | 0.95 | 2.87 | 0.65 | 1.99 | 0.00 | 0.00 | 1.15 | 3.49 | |
| CG1 | MP | 71 | 31.52 | 1.03 | 3.28 | 0.33 | 1.04 | 0.00 | 0.00 | 1.08 | 3.44 |
| LP | 72 | 32.47 | 0.80 | 2.45 | 0.38 | 1.18 | 0.00 | 0.00 | 0.88 | 2.72 | |
| GC2 | MP | 71 | 29.57 | 0.66 | 2.25 | 0.16 | 0.55 | 0.14 | 0.49 | 0.70 | 2.36 |
| LP | 72 | 30.54 | 0.51 | 1.66 | 0.00 | 0.00 | 0.14 | 0.44 | 0.53 | 1.72 | |
| TV | MP | 72 | 32.00 | 0.86 | 2.70 | 0.08 | 0.26 | 0.00 | 0.00 | 0.87 | 2.71 |
| LP | 72 | 33.2 | 1.18 | 3.56 | 0.00 | 0.00 | 0.00 | 0.00 | 1.18 | 3.56 |
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Reproducibility for BD COR System
For the Site-to-Site reproducibility study, three (3) sites (2 external and one internal) were provided the same panels as described for the Precision study, above. Each site performed testing on 6 distinct days (consecutive or not), wherein three (3) panels were tested by each of two (2) technologists (3 days per technologist) with one lot of reagents.
The overall PreservCyt site-to-site reproducibility percent agreement was 100% for TN and ranged from 38.9% to 48.1% for HN, 91.7% to 98.1% for LP and 98.1% to 100% MP categories (see Table 6).
The overall (across sites) Urine site-to-site reproducibility percent agreement was 100% for TN, LP and MP and ranged from 37.0% to 58.3% for HN categories (see Table 7).
Analysis of variance of the Ct.Score results from valid tests performed on PreservCyt positive panel members (see Table 8) yielded overall CV (%) ranged from 1.75% to 4.15%.
Analysis of variance of the Ct.Score results from valid tests performed on Urine positive panel members (see Table 9) yielded overall CV (%) ranged from 1.74% to 4.18%.
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| Target | Level | Site | N Total | N Correct | % Correct | BD COR System (PreservCyt)95% CI | |
|---|---|---|---|---|---|---|---|
| LowerBound | Upper Bound | ||||||
| MP | 1 | 36 | 36 | 100% | 90.4% | 100% | |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| 1 | 36 | 35 | 97.2% | 85.8% | 99.5% | ||
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| LP | 3 | 36 | 35 | 97.2% | 85.8% | 99.5% | |
| CT | Overall | 108 | 106 | 98.1% | 93.5% | 99.5% | |
| 1 | 36 | 16 | 44.4% | 29.5% | 60.4% | ||
| 2 | 36 | 21 | 58.3% | 42.2% | 72.9% | ||
| HNb | 3 | 36 | 15 | 41.7% | 27.1% | 57.8% | |
| Overall | 108 | 52 | 48.1% | 39.0% | 57.5% | ||
| 1 | 36 | 36 | 100% | 90.4% | 100% | ||
| TNa | 2 | 36 | 36 | 100% | 90.4% | 100% | |
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| 1 | 36 | 34 | 94.4% | 81.9% | 98.5% | ||
| MP | 2 | 36 | 36 | 100% | 90.4% | 100% | |
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 106 | 98.1% | 93.5% | 99.5% | ||
| 1 | 36 | 32 | 88.9% | 74.7% | 95.6% | ||
| 2 | 36 | 33 | 91.7% | 78.2% | 97.1% | ||
| LP | 3 | 36 | 34 | 94.4% | 81.9% | 98.5% | |
| GC | Overall | 108 | 99 | 91.7% | 84.9% | 95.6% | |
| 1 | 36 | 12 | 33.3% | 20.2% | 49.7% | ||
| 2 | 36 | 12 | 33.3% | 20.2% | 49.7% | ||
| HNb | 3 | 36 | 18 | 50.0% | 34.5% | 65.5% | |
| Overall | 108 | 42 | 38.9% | 30.2% | 48.3% | ||
| 1 | 36 | 36 | 100% | 90.4% | 100% | ||
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| TNa | 3 | 36 | 36 | 100% | 90.4% | 100% | |
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| Target | Level | Site | N Total | NCorrect | %Correct | LowerBound | Upper Bound |
| CT | MP | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| CT | LP | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| CT | HNb | 1 | 36 | 23 | 63.9% | 47.6% | 77.5% |
| 2 | 36 | 21 | 58.3% | 42.2% | 72.9% | ||
| 3 | 36 | 19 | 52.8% | 37.0% | 68.0% | ||
| Overall | 108 | 63 | 58.3% | 48.9% | 67.2% | ||
| CT | TNa | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| GC | MP | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| GC | LP | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| GC | HNb | 1 | 36 | 17 | 47.2% | 32.0% | 63.0% |
| 2 | 36 | 18 | 50.0% | 34.5% | 65.5% | ||
| 3 | 36 | 10 | 27.8% | 15.8% | 44.0% | ||
| Overall | 108 | 45 | 41.7% | 32.8% | 51.1% | ||
| GC | TNa | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| TV | MP | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| TV | LP | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| TV | HNb | 1 | 36 | 11 | 30.6% | 18.0% | 46.9% |
| 2 | 36 | 17 | 47.2% | 32.0% | 63.0% | ||
| 3 | 36 | 12 | 33.3% | 20.2% | 49.7% | ||
| Overall | 108 | 40 | 37.0% | 28.5% | 46.4% | ||
| TV | TNa | 1 | 36 | 36 | 100% | 90.4% | 100% |
| 2 | 36 | 36 | 100% | 90.4% | 100% | ||
| 3 | 36 | 36 | 100% | 90.4% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| Overall | 108 | 108 | 100% | 96.6% | 100% | ||
| a For the True Negative (TN) category, the reported agreement indicates the percent of negative results. |
Table 6: Percent Agreement with Expected Results for Site to Site with PreservCyt for BD COR System
4 For the True Negative (TN) category, the reported agreement indicates the percent of negative results.
b For the High Negative (HN) category, the reported agreement indicates the percent of positive results.
{12}------------------------------------------------
Table 7: Percent Agreement with Expected Results for Site to Site with Urine for BD COR System
{13}------------------------------------------------
b For the High Negative (HN) category, the reported agreement indicates the percent of positive results.
{14}------------------------------------------------
| Table 8: | |
|---|---|
| -- | ---------- |
| Within Run(Residual) | Between Run | Between Day | Between Site | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Target | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| CT | MP | 108 | 33.05 | 0.65 | 1.96 | 0.19 | 0.58 | 0.00 | 0.00 | 0.26 | 0.78 | 0.72 | 2.18 |
| CT | LP | 106 | 33.98 | 0.78 | 2.28 | 0.00 | 0.00 | 0.29 | 0.87 | 0.00 | 0.00 | 0.83 | 2.44 |
| GC1 | MP | 106 | 32.07 | 0.94 | 2.93 | 0.00 | 0.00 | 0.27 | 0.86 | 0.33 | 1.02 | 1.03 | 3.22 |
| GC1 | LP | 99 | 33.73 | 1.40 | 4.15 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 1.40 | 4.15 |
| GC2 | MP | 108 | 30.43 | 0.50 | 1.66 | 0.00 | 0.00 | 0.00 | 0.00 | 0.18 | 0.58 | 0.53 | 1.75 |
| GC2 | LP | 105 | 31.79 | 0.74 | 2.33 | 0.00 | 0.00 | 0.00 | 0.00 | 0.26 | 0.83 | 0.79 | 2.47 |
Table 9: Variance Component Analysis Results for Site to Site with Urine on BD COR
| Within Run(Residual) | Between Run | Between Day | Between Site | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Target | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| CT | MP | 108 | 31.76 | 0.52 | 1.65 | 0.00 | 0.00 | 0.18 | 0.56 | 0.00 | 0.00 | 0.55 | 1.74 |
| CT | LP | 108 | 33.03 | 0.99 | 2.98 | 0.28 | 0.84 | 0.00 | 0.00 | 0.00 | 0.00 | 1.02 | 3.10 |
| GC1 | MP | 108 | 31.39 | 0.89 | 2.84 | 0.37 | 1.18 | 0.10 | 0.30 | 0.00 | 0.00 | 0.97 | 3.09 |
| GC1 | LP | 108 | 32.36 | 0.89 | 2.74 | 0.18 | 0.54 | 0.00 | 0.00 | 0.33 | 1.03 | 0.96 | 2.98 |
| GC2 | MP | 108 | 29.75 | 0.50 | 1.68 | 0.03 | 0.09 | 0.14 | 0.49 | 0.15 | 0.50 | 0.54 | 1.82 |
| GC2 | LP | 108 | 30.69 | 0.53 | 1.71 | 0.18 | 0.58 | 0.00 | 0.00 | 0.19 | 0.63 | 0.59 | 1.92 |
| TV | MP | 108 | 32.29 | 0.72 | 2.23 | 0.12 | 0.37 | 0.12 | 0.36 | 0.23 | 0.71 | 0.77 | 2.40 |
| TV | LP | 108 | 33.49 | 1.37 | 4.09 | 0.17 | 0.52 | 0.00 | 0.00 | 0.22 | 0.65 | 1.40 | 4.18 |
Quality Controls
External Control materials are not provided by BD; however, Quality Control procedures are included in the package insert. Various types of External Controls are recommended to allow the user to select the most appropriate for their laboratory quality control program:
- Commercially available positive control materials
- Chlamydia trachomatis serovar H (ATCC VR-879) ●
- Neisseria gonorrhoeae (ATCC 19424)
- Trichomonas vaginalis (ATCC 30001) ●
- . External negative control
- . Use a non-inoculated BD Molecular Swab Sample Buffer Tube
The assay includes a Specimen Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances.
Analytical Sensitivity Confirmation Study for BD COR System
The analytical sensitivity/Limit of Detection (LoD) of the BD CTGCTV2 assay in urine, vaginal swab and PreservCyt LBC specimen matrix on the BD COR System was confirmed to be equivalent to that of the BD MAX System. Four panel members (Table 10) were created using the LoD previously determined on the BD MAX System at the following target levels in pooled female urine, pooled vaginal swab and pooled PreservCyt LBC matrix: Low Positive (1.5x LoD) and Moderate Positive (3x LoD). The
{15}------------------------------------------------
panel members were prepared with microbial suspensions from each of two (2) representative strains of the target organisms detected by the BD CTGCTV2 assay. Each target organism was quantified prior to spiking into negative clinical matrix. Urine and Swab panel members were tested on the BD COR and BD MAX Systems. Each panel member in PreservCyt had pre-analytical sample dilution performed by BD COR System. Additionally, pre-analytical samples were manually pipetted for testing on the BD COR System and the BD MAX System.
Results from this study demonstrate that the analytical sensitivity (LoD, Table 11) of the BD CTGCTV2 assay in vaginal, urine and PreservCyt LBC samples on BD COR is equivalent to the analytical sensitivity (LoD) demonstrated on the BD MAX as shown in Tables 12-15.
| PanelMember | CT | GC | TV | Target Level |
|---|---|---|---|---|
| A | Serovar D | 49226 | 30001 | 1.5x LoD |
| B | Serovar H | 19424 | 50143 | 1.5x LoD |
| C | Serovar D | 49226 | 30001 | 3x LoD |
| D | Serovar H | 19424 | 50143 | 3x LoD |
Table 10: Analytical Sensitivity Confirmation Panel Members
| Table 11: Limit of Detection of the BD CTGCTV2 Assay (performed on BD MAX) | |
|---|---|
| Organism | Strain | Specimen | LoD Concentration(units/mL)a |
|---|---|---|---|
| Chlamydia trachomatis | Serovar H | Urine | 2.5 |
| Serovar H | Swab | 2.5 | |
| Serovar H | PreservCyt | 5 | |
| Chlamydia trachomatis | Serovar D | Urine | 1.25 |
| Serovar D | Swab | 5 | |
| Serovar D | PreservCyt | 5 | |
| Neisseria gonorrhoeaeb | ATCC 19424 | Urine | 30 |
| ATCC 19424 | Swab | 40 | |
| ATCC 19424 | PreservCyt | 30 | |
| Neisseria gonorrhoeaeb | ATCC 49226 | Urine | 20 |
| ATCC 49226 | Swab | 30 | |
| ATCC 49226 | PreservCyt | 40 | |
| Trichomonas vaginalis | ATCC 30001 | Urine | 5 |
| ATCC 30001 | Swab | 7.5 | |
| Trichomonas vaginalis | ATCC 50143 | Urine | 2.5 |
| ATCC 50143 | Swab | 1.88 |
4 Units/mL LoD concentration represented in Elements, CFU/mL for Chlanydia trachomatis, CFU/mL for Neisseria gonorrhoeae and TV/mL for Trichomonas vaginalis.
b The presented LoDs for Neisseria gonorrhoeae in the three speciment types were re-established in CFU/mL on the BD MAX and were shown to the assay LoDs previously established on the BD MAX instrument in cells/mL.
{16}------------------------------------------------
| BD MAX vs BD COR Vaginal Swab | ||||
|---|---|---|---|---|
| Panel | Assay Target | BD MAXMean Ct.Score | BD CORMean Ct.Score | Difference inMean Ct.Score (BD COR- BD MAX) with 95% CI |
| A | CT | 31.66 | 31.14 | -0.52(-0.857, -0.178) |
| GC1 | 31.16 | 31.08 | -0.08(-0.347, 0.183) | |
| GC2 | 29.98 | 29.34 | -0.64(-0.876, -0.407) | |
| TV | 33.17 | 33.29 | 0.12(-0.283, 0.527) | |
| B | CT | 33.56 | 33.1 | -0.46(-0.793, -0.122) |
| GC1 | 30.53 | 30.49 | -0.04(-0.276, 0.204) | |
| GC2 | 29.41 | 28.74 | -0.67(-0.857, -0.494) | |
| TV | 33.17 | 33.6 | 0.43(-0.155, 1.010) | |
| C | CT | 30.41 | 30.2 | -0.21(-0.377, -0.033) |
| GC1 | 29.89 | 30.08 | 0.19(0.006, 0.383) | |
| GC2 | 28.74 | 28.36 | -0.38(-0.575, -0.193) | |
| TV | 32.03 | 32.47 | 0.44(0.163, 0.722) | |
| D | CT | 32.51 | 31.95 | -0.56(-0.842, -0.271) |
| GC1 | 29.34 | 29.47 | 0.13(-0.027, -0.290) | |
| GC2 | 28.44 | 27.79 | -0.65(-0.841, -0.458) | |
| TV | 31.94 | 32.07 | 0.13(-0.139, 0.404) |
Table 12: Analytical Sensitivity Confirmation in Vaginal Swabs on BD COR System
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| BD MAX vs BD COR Urine | ||||
|---|---|---|---|---|
| Panel | Assay Target | BD MAXMean Ct.Score | BD CORMean Ct.Score | Difference inMean Ct.Score (BDCOR - BD MAX)with 95% CI |
| A | CT | 32.95 | 32.54 | -0.41(-0.802, -0.013) |
| GC1 | 31.21 | 31.54 | 0.33(0.054, 0.603) | |
| GC2 | 30.59 | 29.49 | -1.10(-1.375, -0.842) | |
| TV | 32.95 | 32.99 | 0.04(-0.244, 0.339) | |
| B | CT | 32.46 | 32.12 | -0.34(-0.629, -0.061) |
| GC1 | 29.96 | 30.3 | 0.34(0.197, 0.486) | |
| GC2 | 29.34 | 28.52 | -0.82(-0.989, -0.662) | |
| TV | 31.29 | 31.66 | 0.37(0.208, 0.518) | |
| C | CT | 31.78 | 31.64 | -0.14(-0.378, 0.111) |
| GC1 | 30.08 | 30.7 | 0.62(0.442, 0.792) | |
| GC2 | 29.37 | 28.68 | -0.69(-0.888, -0.494) | |
| TV | 31.86 | 32.15 | 0.29(0.077, 0.500) | |
| D | CT | 31.3 | 31.24 | -0.06(-0.267, 0.134) |
| GC1 | 28.83 | 29.26 | 0.43(0.283, 0.564) | |
| GC2 | 28.28 | 27.52 | -0.76(-0.893, -0.621) | |
| TV | 30.32 | 30.57 | 0.25(0.103, 0.414) |
Table 13: Analytical Sensitivity Confirmation in Urine on BD COR System
{18}------------------------------------------------
| BD MAX vs BD COR Manually Converted LBC | ||||
|---|---|---|---|---|
| Panel | Assay Target | BD MAX MeanCt.Score | BD COR MeanCt.Score | Difference in MeanCt.Score (BD COR - BDMAX) with 95% CI |
| A | CT | 32.54 | 32.45 | -0.09(-0.281, 0.105) |
| GC1 | 32.4 | 32.63 | 0.23(-0.261, 0.723) | |
| GC2 | 30.56 | 30.69 | 0.13(-0.027. 0.300) | |
| B | CT | 33.65 | 33.77 | 0.12(-0.225, 0.450) |
| GC1 | 32.61 | 33.04 | 0.43(0.066, 0.794) | |
| GC2 | 30.99 | 31.06 | 0.07(-0.118, 0.262) | |
| C | CT | 31.72 | 31.49 | -0.23(-0.419, -0.022) |
| GC1 | 31 | 31.58 | 0.58(0.341, 0.804) | |
| GC2 | 29.57 | 29.74 | 0.17(0.040, 0.296) | |
| D | CT | 32.74 | 32.57 | -0.17(-0.396, 0.056) |
| GC1 | 31.42 | 32.06 | 0.64(0.348, 0.927) | |
| GC2 | 29.86 | 30.05 | 0.19(0.043, 0.332) |
Table 14: Analytical Sensitivity Confirmation in Manually Converted® LBC on BD COR System
4 Sample transfer from Preserv yt vial to BD Molecular LBC SBT manually performed prior to loading onto the COR System. This
represents one of the possible workflows for LBC
{19}------------------------------------------------
| MAX vs COR PX Converted LBC | ||||
|---|---|---|---|---|
| Panel | AssayTarget | MAXMean Ct.Score | BD CORMean Ct.Score | Difference inMean Ct.Score (COR -MAX) with 95% CI |
| A | CT | 32.54 | 32.83 | 0.29(0.076, 0.516) |
| GC1 | 32.4 | 32.64 | 0.24(-0.243, 0.734) | |
| GC2 | 30.56 | 31.02 | 0.46(0.279, 0.650) | |
| B | CT | 33.65 | 33.85 | 0.20(-0.130, 0.523) |
| GC1 | 32.61 | 33.32 | 0.71(0.316, 1.100) | |
| GC2 | 30.99 | 31.34 | 0.35(0.160, 0.551) | |
| C | CT | 31.72 | 31.72 | 0(-0.179, 0.185) |
| GC1 | 31 | 31.64 | 0.64(0.419, 0.861) | |
| GC2 | 29.57 | 30.03 | 0.46(0.332, 0.587) | |
| D | CT | 32.74 | 32.81 | 0.07(-0.157, 0.297) |
| GC1 | 31.42 | 32.26 | 0.54(0.544, 1.144) | |
| GC2 | 29.86 | 30.26 | 0.40(0.250, 0.537) |
Table 15: Analytical Sensitivity Confirmation in LBC Convertedª on BD COR System
4 Sample transfer from PreservCyt vial to BD Molecular LBC SBT performed automatically by BD COR System
Cross-Contamination for BD COR System
A study was conducted to investigate cross-contamination while processing samples with high microbial load of Chlamydia trachomatis in the BD CTGCTV2 assay. High positive samples contained Chlamydia trachomatis (VR-885, Serovar D) spiked into pooled PreservCyt LBC matrix at a concentration of ≥1 x 106 EB/mL. The negative samples consisted of PreservCyt media vials without any target analyte. Twelve (12) replicates of the high positive panel member and 12 replicates of the negative panel member were alternated in the BD COR™ T-Rack and tested across 45 runs, using three BD COR Systems for a total of 540 positive and 540 negative samples tested. Of the 540 negative samples tested, two false positive results were obtained (0.37%, 95% CI: 0.10-1.34%).
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Clinical Agreement Study between BD MAX and BD COR Systems
The clinical performance of the BD CTGCTV2 assay was established based on the data from BD MAX. For the purpose of demonstrating that use of the assay with the BD COR doesn't compromise the safety and effectiveness of the assay, clinical comparison studies were performed on both the BD MAX and BD COR Systems. The performance of the BD CTGCTV2 assay on the BD COR was evaluated in a clinical agreement study by comparing the assay results obtained on the BD COR System to the results obtained on the BD MAX System. BD MAX results served as reference in the clinical agreement study.
Remnant urine specimens from the previous clinical trial for BD CTGCTV2 on BD MAX as well as urine specimens obtained from both internal and external collections were used for the comparison study. Clinical panels were created either with individual specimens, or negative clinical specimens spiked with a positive clinical specimen. No more than two negative specimens were combined as background negative matrix, and no more than one clinical positive was used per panel. The clinical agreement study included 433 independent panel members. The panels were prepared so that a majority of the positive specimens for CT, GC or TV were at analyte levels of Low Positive and Moderate Positive. Six aliquots were prepared from each panel member. Among them, three aliquots were tested on the BD COR System with two aliquots each being tested at an external site and the third aliquot being tested at an internal site. The other three aliquots were all tested internally with each aliquot being tested on a separate BD MAXTM System.
To demonstrate that the performance of the BD CTGCTV2 assay on the BD COR System is equivalent to the performance of BD MAX, both positive/negative percent agreement analysis and Deming regression analysis of the Ct.Score values were performed. Positive Percent Agreement (PPA) and Negative percent Agreement (NPA) between the BD MAX and BD COR Systems were calculated separately for each target. For each target, the PPA and NPA were calculated for each of the three sites where BD COR testing occurred, against comparator results where the positive or negative status of a panel member is defined by ≥2 out of 3 evaluable results obtained on the BD MAX. Out of 214 panel members assessed for CT, 106 were positive by BD MAX and 108 were negative by BD MAX. Out of 218 panel members assessed for GC, 111 were positive by BD MAX and 107 were negative by BD MAX. Out of the 215 panel members assessed for TV, 105 were positive by BD MAX and 110 were negative by BD MAX. Two panel members, each with a valid BD MAX result and a non-evaluable BD COR result (one non-evaluable BD COR result due to a non-readable label and the other non-evaluable BD COR result due to a non-compliant event), were not included in the calculation of the PPA or NPA.
PPA and NPA estimates were also averaged across the three BD COR testing sites. The PPA and NPA results as well as the corresponding 95% confidence interval at each BD COR testing site and the average across all BD COR testing sites are summarized in Table 18, for each target. The denominator for PPA and NPA calculations includes panel members with equivocal comparator results from BD MAX, as indicated at the bottom of the tables. Equivocal BD MAX comparator result is defined as one positive, one negative and one non-evaluable result from the BD MAX.
The systematic differences in numeric value between Ct.Score results from BD COR and BD MAX were evaluated by the Weighted Deming regression analysis based on the average Ct.Score of BD COR results and the average Ct.Score of BD MAX results of a given panel member across all corresponding testing sites. The results from the Deming regression analysis are provided in Figures 1 through 4 for CT, GC1, GC2 and TV, respectively. The point estimate of intercept and slope, as well as the corresponding 95% confidence interval of each Deming regression line are provided in Table 19. Additionally, the Weighted Deming regression bias estimate along with 95% confidence interval at different analyte levels are presented in Table 20. The "Ct.Score for BD MAX" in the table were calculated as the average Ct.Score from all samples at the corresponding analyte level.
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| BD CORTest Site | BD MAX Result | ||
|---|---|---|---|
| BD MAX Positive Result | BD MAX Negative Result | ||
| 1 | Positive | 105 | 0 |
| Negative | 0 | 108 | |
| Total | 105 | 108 | |
| PPA: 100.0% (105/105), 95%CI: (96.5%, 100.0%)bNPA: 100.0% (108/108), 95%CI: (96.6%, 100.0%) | |||
| 2 | Positive | 106 | 0 |
| Negative | 0 | 108 | |
| Total | 106 | 108 | |
| PPA: 100.0% (106/106), 95%CI: (96.5%, 100.0%)NPA: 100.0% (108/108), 95%CI: (96.6%, 100.0%) | |||
| 3 | Positive | 106 | 0 |
| Negative | 0 | 108 | |
| Total | 106 | 108 | |
| PPA: 100.0% (106/106), 95%CI: (96.5%, 100.0%)NPA: 100.0% (108/108), 95%CI: (96.6%, 100.0%) | |||
| Average PPA: 100%, 95% CI: N/Aa | |||
| Average NPA: 100%, 95% CI: N/Aa | |||
| Number of BD MAX equivocal results: 0 |
Table 16: Percent Agreement of BD COR versus BD MAX Result by Test Site for CT
4 Confidence intervals calculated by the bootstrap method for point estimates close to 100% have not been included, as suggested by FDA guidance for assay migration studies.
® Confidence intervals for point estimates at each and by a score method and confidence intervals for point estimates averaged over 3 sites were calculated by a bootstrap method.
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| BDCORTestSite | BD MAX Result | |||
|---|---|---|---|---|
| BD MAX Positive | BD MAX Negative | |||
| 1 | BDCORResult | Positive | 110 | 0 |
| Negative | 1 | 107 | ||
| Total | 111 | 107 | ||
| PPA: 99.1% (110/111), 95%CI: (95.1%, 99.8%)bNPA: 100.0% (107/107), 95%CI: (96.5%, 100.0%) | ||||
| 2 | BD MAX Result | |||
| BDCORResult | Positive | 108 | 0 | |
| Negative | 2 | 107 | ||
| Total | 110 | 107 | ||
| PPA: 98.2% (108/110), 95%CI: (93.6%, 99.5%)NPA: 100.0% (107/107), 95%CI: (96.5%, 100.0%) | ||||
| 3 | BD MAX Result | |||
| BDCORResult | Positive | 106 | 0 | |
| Negative | 5 | 107 | ||
| Total | 111 | 107 | ||
| PPA: 95.5% (106/111), 95%CI: (89.9%, 98.1%)NPA: 100.0% (107/107), 95%CI: (96.5%, 100.0%) | ||||
| Average PPA: 97.6%, 95% CI: (95.6%, 99.1%) | ||||
| Average NPA: 100%, 95% CI: N/Aa | ||||
| Number of BD MAX equivocal results: 0 |
Table 17: Percent Agreement of BD COR versus BD MAX Result by Test Site for GC
ª Confidence intervals calculated by the bootstrap method for point estimates close to 100% have not been included, as suggested by FDA guidance for assay migration studies.
b Confidence intervals for point estimates at each ated by a score method and confidence intervals for point estimates averaged over 3 sites were calculated by a bootstrap method.
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| BD CORTest Site | BD MAX Result | ||||
|---|---|---|---|---|---|
| BD MAX Positive Result | BD MAX Negative Result | ||||
| 1 | BDCORResult | Positive | 105 | 1 | |
| Negative | 0 | 109 | |||
| Total | 105 | 110 | |||
| PPA: 100.0% (105/105), 95%CI: (96.5%, 100.0%)aNPA: 99.1% (109/110), 95%CI: (95.0%, 99.8%) | |||||
| BD MAX Result | |||||
| BD MAX Positive Result | BD MAX Negative Result | ||||
| 2 | BDCORResults | Positive | 105 | 3 | |
| Negative | 0 | 107 | |||
| Total | 105 | 110 | |||
| PPA: 100.0% (105/105), 95%CI: (96.5%, 100.0%)NPA: 97.3% (107/110), 95%CI: (92.3%, 99.1%) | |||||
| BD MAX Result | |||||
| BD MAX Positive Result | BD MAX Negative Result | ||||
| 3 | BDCORResults | Positive | 104 | 1 | |
| Negative | 1 | 109 | |||
| Total | 105 | 110 | |||
| PPA: 99.0% (104/105), 95%CI: (94.8%, 99.8%)NPA: 99.1% (109/110), 95%CI: (95.0%, 99.8%) | |||||
| Average PPA: 99.7%, 95% CI: (99%, 100%) | |||||
| Average NPA: 98.5%, 95% CI (96.3%, 100%) | |||||
| Number of BD MAX equivocal results: 0 |
Table 18: Percent Agreement of BD COR™ versus BD MAX™ Result by Test Site for TV
ª Confidence intervals for point estimates at each ated by a score method and confidence intervals for pont estimates averaged over 3 sites were calculated by a bootstrap method.
| Target | Site | Parameter | Estimate | 95% CI |
|---|---|---|---|---|
| CT | Overall | Intercept | -1.85 | (-3.88, 0.18) |
| CT | Overall | Slope | 1.06 | (0.99, 1.13) |
| GC1 | Overall | Intercept | -0.06 | (-0.99, 0.87) |
| GC1 | Overall | Slope | 1.02 | (0.99, 1.06) |
| GC2 | Overall | Intercept | -0.72 | (-1.76, 0.33) |
| GC2 | Overall | Slope | 1.03 | (0.99, 1.07) |
| TV | Overall | Intercept | -2.25 | (-5.30, 0.80) |
| TV | Overall | Slope | 1.09 | (0.98, 1.19) |
Table 19: Weighted Deming Regression Coefficients for Ct.Score for BD COR versus BD MAX
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| Target | Site | Actual Level | Ct. Score ofBD MAX | Bias Estimate atCt. Score | 95% CI |
|---|---|---|---|---|---|
| CT | Overall | High Positive | 26.36 | -0.22 | -0.42, -0.02 |
| CT | Overall | ModeratePositive | 29.49 | -0.03 | -0.20, 0.13 |
| CT | Overall | Low Positive | 32.79 | 0.17 | -0.18, 0.52 |
| CT | Overall | Negative | 45.00 | 0.93 | -0.27, 2.13 |
| GC1 | Overall | High Positive | 24.15 | 0.47 | 0.32, 0.61 |
| GC1 | Overall | ModeratePositive | 29.54 | 0.58 | 0.38, 0.78 |
| GC1 | Overall | Low Positive | 32.67 | 0.65 | 0.36, 0.94 |
| GC1 | Overall | Negative | 45.00 | 0.92 | 0.21, 1.63 |
| GC2 | Overall | High Positive | 22.96 | 0.01 | -0.16, 0.17 |
| GC2 | Overall | ModeratePositive | 28.21 | 0.17 | -0.03, 0.37 |
| GC2 | Overall | Low Positive | 30.74 | 0.25 | -0.03, 0.53 |
| GC2 | Overall | Negative | 45.00 | 0.70 | -0.15, 1.54 |
| TV | Overall | High Positive | 26.08 | 0.03 | -0.33, 0.38 |
| TV | Overall | ModeratePositive | 29.49 | 0.32 | 0.16, 0.48 |
| TV | Overall | Low Positive | 32.82 | 0.61 | 0.20, 1.03 |
| TV | Overall | Negative | 45.00 | 1.68 | 0.01, 3.34 |
Table 20: Weighted Deming Regression Bias Estimate for BD COR versus BD MAX
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Image /page/25/Figure/0 description: Figure 1 shows the Deming Regression for the BD CTGCTV2 assay on the BD COR System versus the BD MAX System - CT. The figure is a Deming Regression, which is a statistical method for estimating the relationship between two variables when both variables are subject to error. The assay is a laboratory test that is used to detect the presence of a specific substance in a sample. The BD COR System and the BD MAX System are both automated laboratory systems that are used to perform assays.
Image /page/25/Figure/1 description: This figure is a scatter plot that shows the relationship between COR_FINAL_CT_CT and MAX_FINAL_CT_CT. The plot includes a weighted Deming regression fit with the equation -1.85 + 1.06 * MAX_FINAL_CT_CT, based on 106 data points. The Pearson's r correlation coefficient is 0.934, indicating a strong positive correlation between the two variables. The 0.95-confidence bounds are calculated with the jackknife method.
Deming Regression for the BD CTGCTV2 on the BD COR System versus the BD MAX Figure 2: System - GC1
Image /page/25/Figure/3 description: The image is a scatter plot that compares COR_FINAL_GC1_CT and MAX_FINAL_GC1_CT. The plot includes a weighted Deming regression fit with the equation -0.06 + 1.02 * MAX_FINAL_GC1_CT, based on a sample size of n=111. An identity line is also plotted for reference. The Pearson's r correlation coefficient is 0.975.
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Figure 3: Deming Regression for the BD CTGCTV2 assay on the BD COR System versus the BD MAX System - GC2
Image /page/26/Figure/1 description: This scatter plot shows the correlation between MAX_FINAL_GC2_CT and COR_FINAL_GC2_CT. The plot includes a weighted Deming regression fit with the equation -0.72 + 1.03 * MAX_FINAL_GC2_CT, based on a sample size of n=111. The Pearson's r correlation coefficient is 0.974, indicating a strong positive correlation. The 0.95-confidence bounds are calculated with the jackknife method.
Figure 4: Deming Regression for the BD CTGCTV2 assay on the BD COR System versus the BD MAX System - TV
Image /page/26/Figure/3 description: The image is a scatter plot that compares 'COR_FINAL_TV_CT' and 'MAX_FINAL_TV_CT'. The plot includes a weighted Deming regression fit with the equation -2.25 + 1.09 * MAX_FINAL_TV_CT, based on 108 data points. The Pearson's r correlation coefficient is 0.936, and the 0.95-confidence bounds are calculated with the jackknife method.
BD CTGCTV2 for BD COR System Non-Reportable Results
Non-reportable results on the BD COR are reported in the same manner as on the BD MAX and the definitions of all possible Non-reportable events are summarized in Table 21. Error results on the BD COR System were marked noncompliant if they were due to an operator error
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and were not included in the Non-reportable rate calculation. Non-reportable rates on BD COR System are shown in Table 22.
| BD COR Non-reportable Result | Non-reportableResult Definition |
|---|---|
| UNR - Unresolved | Invalid SPC due to presence of inhibitory substances or reagent failure |
| IND – Indeterminate | BD COR System failure (with Warning or Error Codes) |
| INC - Incomplete | Aborted run or BD COR System failure that halts robot operations (withWarning or Error Codes) |
Table 21: Definition of Non-reportable events on the BD COR system
Table 22: Summary of BD COR Total Non-Reportable Rate for Combined Target by BD COR Test Site
| Unresolved Rate | Indeterminate Rate | Incomplete Rate | Total Rate | |||||
|---|---|---|---|---|---|---|---|---|
| Site | Initial(95% CI) | Finala,b(95% CI) | Initial(95% CI) | Finala(95% CI) | Initial(95% CI) | Finala(95% CI) | Initial(95% CI) | Finala(95% CI) |
| 1 | 0.0%(0/433)(0.0%,0.9%) | 0.0%(0/432)(0.0%,0.9%) | 0.2%(1/433)(0.0%,1.3%) | 0.0%(0/432)(0.0%,0.9%) | 0.0%(0/433)(0.0%,0.9%) | 0.0%(0/432)(0.0%,0.9%) | 0.2%(1/433)(0.0%, 1.3%) | 0.0%(0/432)(0.0%,0.9%) |
| 2 | 0.0%(0/432)(0.0%,0.9%) | 0.0%(0/432)(0.0%,0.9%) | 6.0%(26/432)(4.1%,8.7%) | 0.0%(0/432)(0.0%,0.9%) | 0.0%(0/432)(0.0%,0.9%) | 0.0%(0/432)(0.0%,0.9%) | 6.0%(26/432)(4.1%, 8.7%) | 0.0%(0/432)(0.0%,0.9%) |
| 3 | 0.2%(1/433)(0.0%,1.3%) | 0.0%(0/433)(0.0%,0.9%) | 0.7%(3/433)(0.2%,2.0%) | 0.0%(0/433)(0.0%,0.9%) | 0.0%(0/433)(0.0%,0.9%) | 0.0%(0/433)(0.0%,0.9%) | 0.9%(4/433)(0.4%,2.4%) | 0.0%(0/433)(0.0%,0.9%) |
| Total | 0.1%(1/1298)(0.0%,0.4%) | 0.0%(0/1297)(0.0%,0.3%) | 2.3%(30/1298)(1.6%,3.3%) | 0.0%(0/1297)(0.0%,0.3%) | 0.0%(0/1298)(0.0%,0.3%) | 0.0%(0/1297)(0.0%,0.3%) | 2.4%(31/1298)(1.7%,3.4%) | 0.0%(0/1297)(0.0%,0.3%) |
a The final rate is calculated with the number of remaining non-reportable events after repeat testing.
b The denominator in the final non-reportable rate for the BD site (and ultimately Total rate) is decreased by one due to a missing BD COR™ result.
C The 26 initial indeterminate results occurred on two runs, 12 and 14 for each run. Each occurrence was due to a consumable positioning issue. Reteaching of the robot was completed, and all samples were retested and generated results.
§ 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s).
(a)
Identification. A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) is an in vitro diagnostic device intended for the detection and identification of nucleic acids from non-viral microorganism(s) and their associated resistance markers in clinical specimens collected from patients suspected of sexually transmitted infections. The device is intended to aid in the diagnosis of non-viral sexually transmitted infections in conjunction with other clinical and laboratory data. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist that are not detected by the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;
(ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate;
(iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) Limiting statements indicating that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) Reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(D) If appropriate (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that:
(A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present;
(B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora;
(C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and
(D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy.
(4) Design verification and validation must include:
(i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result (
e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate.
(iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses.
(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.