The binx health io CT/NG Assay, when tested using the binx health io Instrument, is a fully automated, rapid, qualitative test intended for use in point-of-care or clinical laboratory settings for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in female vaginal swab specimens collected either by a clinician or self-collected by a patient in a clinical setting, to aid in the diagnosis of symptomatic or asymptomatic infection in female patients with Chlamydia trachomatis and/or Neisseria gonorrhoeae.

Device Description

The binx health io CT/NG Assay System (the "binx io System", "binx io CT/NG Assay" or the "System") is a rapid qualitative in vitro diagnostic system consisting of the following:

The binx io Instrument for running the Cartridge (the "Instrument")
The binx io CT/NG Cartridge (the "CT/NG Cartridge", "Cartridge" or "Cartridges"), which contains all the necessary reagents to perform the binx io CT/NG Assay (the "Assay") on the binx io Instrument
A single-use, fixed-volume transfer pipet (packaged with the Cartridge) for transferring the sample to the Cartridge
A female Vaginal Swab Specimen Collection Kit consisting of a swab and a sample Collection tube containing preservation medium (the "Vaginal Swab Specimen Collection Kit")

The binx io CT/NG Cartridge is a single-use assay-specific cartridge for use on a single patient. All reagents are contained in the Cartridge as a combination of liquid reagents in blister packs and dried reagents. The Instrument is a small, bench top, fully integrated Instrument that uses air pressure to open and close valves on the CT/NG Cartridge which, in turn, controls the movement of solutions within the Cartridge; the Instrument takes full control of the Cartridges once they are inserted. The operation of the Instrument requires a minimal number of steps that a user follows via a graphical user interface (GUI) screen to load the Cartridge onto the Instrument. Once the Cartridge is loaded, no further interaction by the user is required as no sample preparation is needed. Turnaround time from adding a raw patient sample to a result on the Instrument takes about 30 minutes.

The Vaginal Swab Collection Kit consists of a sterile flocked swab and a tube of preservative medium. The Cartridge has a visual sample loading indicator window which turns from light to dark to confirm to the user that a sample has been added to the Cartridge.

The Cartridge has three fully automated assay steps, (i) sample preparation to isolate and purify target DNA, (ii) ultra-rapid polymerase chain reaction (PCR), which amplifies specific regions of DNA from the target organisms, and (iii) a proprietary electrochemical detection to identify the presence of amplified DNA.

When the specimen is added to the Cartridge, it is automatically mixed with a lysis solution to disrupt the cells present and release DNA which also rehydrates the Internal Process Control (IPC) sample. DNA extraction takes place and the eluted DNA is transferred to a homogenization chamber.

Ultra-rapid PCR is carried out using sequence-specific primers for CT, NG (two separate genomic targets) and the IPC.

Amplified target DNA is detected by hybridization to electrochemically labeled probes and cleavage of the label using a double-strand specific exonuclease. The free label diffuses to the electrode surface and generates an electrical current measured at a distinct voltage in nano Amps (nA) for each electrochemical label used.

The presence of a measurable peak to a fixed cut-off parameter for each target returns a qualitative result with no requirement for interpretation or calculations.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets before the results are presented. However, the study aims to demonstrate substantial equivalence to predicate devices and acceptable clinical performance. We can infer the performance targets from the reported results and the fact that the device received clearance. The performance is reported as sensitivity, specificity, and predictive values against a Composite Infected Status (CIS).

Criterion	Target Performance (Implied for Clearance)	Reported Device Performance (binx health io CT/NG Assay)
Chlamydia trachomatis (CT)
Overall Sensitivity	High (e.g., >90%)	96.1% (95% CI: 91.2% - 98.3%)
Overall Specificity	High (e.g., >98%)	99.1% (95% CI: 98.4% - 99.5%)
PPV (Asymptomatic - 9.5% prev)	High (context-dependent)	92.9% (84.1% - 97.6%)
NPV (Asymptomatic - 9.5% prev)	Very High (context-dependent)	99.7% (98.9% - 100.0%)
PPV (Symptomatic - 7.6% prev)	High (context-dependent)	88.1% (77.8% - 94.7%)
NPV (Symptomatic - 7.6% prev)	Very High (context-dependent)	99.6% (98.8% - 99.9%)
Neisseria gonorrhoeae (NG)
Overall Sensitivity	High (e.g., >95%)	100.0% (95% CI: 92.1% - 100.0%)
Overall Specificity	High (e.g., >99%)	99.9% (95% CI: 99.5% - 100.0%)
PPV (Asymptomatic - 2.3% prev)	High (context-dependent)	94.1% (71.3% - 99.9%)
NPV (Asymptomatic - 2.3% prev)	Very High (context-dependent)	100.0% (99.5% - 100.0%)
PPV (Symptomatic - 3.5% prev)	High (context-dependent)	96.7% (82.8% - 99.9%)
NPV (Symptomatic - 3.5% prev)	Very High (context-dependent)	100.0% (99.5% - 100.0%)
Invalid Result Rate	Low (e.g., <5%)	1.10%

2. Sample Size Used for the Test Set and Data Provenance

Sample Size (Clinical Performance Study):
- Total participants enrolled: 1,634
- Participants after exclusions: 1,524 (for whom CIS could be determined)
- Fully evaluable vaginal swab specimens: 1,523
- Self-collected vaginal swabs (SCVS): 736
- Clinician-collected vaginal swabs (CCVS): 787
Data Provenance: Prospective, multi-center study conducted at nine investigational sites throughout the U.S.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The ground truth (Composite Infected Status - CIS) was established using three reference NAAT (Nucleic Acid Amplification Test) comparator systems:

Hologic Aptima Combo 2 (AC2) Chlamydia/Gonorrhea Assay run on Panther
BD ProbeTec Chlamydia trachomatis (CT) Qx and BD ProbeTec Neisseria gonorrhoeae (GC) Qx assays run on the Viper XTR™
Roche cobas CT/NG v2.0 test run on the cobas 4800 System.

The document does not specify the number or qualifications of human experts who interpreted these comparator test results to establish the CIS. The CIS itself is defined by a concordance rule of at least two out of the three reference tests being positive or negative. The personnel who carried out testing using the binx io CT/NG Assay were "point-of-care personnel trained in the use of the binx io CT/NG System, but not trained or experienced in general laboratory testing procedures" (96% overall). This indicates the binx io test was operated by non-experts in laboratory medicine, which is relevant to its point-of-care intended use, but the establishment of the ground truth relies on the established performance of the comparator NAATs.

4. Adjudication Method for the Test Set

The adjudication method used to establish the Composite Infected Status (CIS) was a 2 out of 3 concordance rule. A patient was considered:

Infected: If at least two out of the three reference NAAT tests were positive.
Not Infected: If at least two out of the three reference NAAT tests were negative.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done in the context of human readers improving with or without AI assistance, as this is a diagnostic device for direct detection of pathogens and not an AI-assisted diagnostic imaging or interpretation system. The device itself performs the detection.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the study presents standalone performance of the binx health io CT/NG Assay. This device is a fully automated, qualitative test designed to be run without complex human interpretation. The reported sensitivity, specificity, PPV, and NPV are measures of its standalone diagnostic accuracy against the established ground truth.

7. The Type of Ground Truth Used

The type of ground truth used was a Composite Infected Status (CIS), defined by a 2 out of 3 concordance rule of three legally marketed and established reference NAATs (Nucleic Acid Amplification Tests). This is a robust method for establishing ground truth in diagnostic studies for infectious diseases when a single "gold standard" may not always be definitive or available for all samples.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of a machine learning algorithm. This is a molecular diagnostic assay, not an AI/ML-based diagnostic. Therefore, there isn't a "training set" in the typical sense for algorithm development.

Instead, the device's design and analytical performance were established through various analytical studies (e.g., Limit of Detection, Analytical Reactivity, Analytical Specificity, Interference, Reproducibility). These analytical studies would involve testing known concentrations of target organisms and interfering substances, following established laboratory practices for assay development and validation.

9. How the Ground Truth for the Training Set Was Established

As noted above, there is no typical "training set" for an AI/ML algorithm. For the analytical studies, the ground truth was inherently known based on the controlled spiking of specific organisms at known concentrations (e.g., GE/mL, CFU/mL, PFU/mL) and known interfering substances into negative matrices.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the seal of the Department of Health & Human Services. To the right of that is the FDA logo in blue, with the words "U.S. FOOD & DRUG" stacked on top of the word "ADMINISTRATION".

August 8, 2019

binx health, Inc. Sarah Kalil Regulatory Advisor 77 N. Washington Street, 5th Floor Boston, Massachusetts 02114

Re: K191352

Trade/Device Name: binx health io CT/NG Assay 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: OEP, LSL, MKZ, NSU Dated: May 20, 2019 Received: May 20, 2019

Dear Sarah Kalil:

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

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statutes and regulations administered by other Federal agencies. You must comply with all the Act's 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 (QS) 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 medical devices and radiation-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,

Steven Gitterman, M.D., Ph.D. Deputy Director 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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510(k) SUMMARY

SUBMITTER NAME:	binx health, Inc.
SUBMITTER ADDRESS:	77 N. Washington Street5th FloorBoston, MA 02114USA
CONTACT PERSON:	Sarah KalilRegulatory Advisorbinx health, Inc.Phone: (646) 847 8573Email: sarah.kalil@mybinxhealth.com
DATE PREPARED:	20th May 2019
DEVICE TRADE NAME:	Binx health io CT/NG Assay
CLASSIFICATION:	21 C.F.R. § 866.3393 (Nucleic acid detection system fornon-viral microorganism(s) causing sexually transmittedinfections)Class II
PRODUCT CODE:	QEP
SUBSEQUENT PRODUCT CODES:	LSL, MKZ, NSU
REVIEW PANEL	Microbiology
PREDICATE DEVICES:	BD ProbeTec Neisseria gonorrhoeae (GC) Qx AmplifiedDNA Assay (K091730) and BD ProbeTec Chlamydiatrachomatis (CT) Qx Amplified DNA Assay (K091724) onthe BD Viper™ System (Becton Dickinson, Sparks, MD).
INTENDED USE:	The binx health io CT/NG Assay, when tested using thebinx health io Instrument, is a fully automated, rapid,qualitative test intended for use in point-of-care or clinicallaboratory settings for the detection of Chlamydiatrachomatis and Neisseria gonorrhoeae DNA in femalevaginal swab specimens collected either by a clinician orself-collected by a patient in a clinical setting, to aid in thediagnosis of symptomatic or asymptomatic infection infemale patients with Chlamydia trachomatis and/orNeisseria gonorrhoeae.

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DEVICE DESCRIPTION:

The binx health io CT/NG Assay System (the "binx io System", "binx io CT/NG Assay" or the "System") is a rapid qualitative in vitro diagnostic system consisting of the following:

1. The binx io Instrument for running the Cartridge (the "Instrument")
1. The binx io CT/NG Cartridge (the "CT/NG Cartridge", "Cartridge" or "Cartridges"), which contains all the necessary reagents to perform the binx io CT/NG Assay (the "Assay") on the binx io Instrument
1. A single-use, fixed-volume transfer pipet (packaged with the Cartridge) for transferring the sample to the Cartridge
1. A female Vaginal Swab Specimen Collection Kit consisting of a swab and a sample Collection tube containing preservation medium (the "Vaginal Swab Specimen Collection Kit")

Ultra-rapid PCR is carried out using sequence-specific primers for CT, NG (two separate genomic targets) and the IPC.

The presence of a measurable peak to a fixed cut-off parameter for each target returns a qualitative result with no requirement for interpretation or calculations.

INTERNAL PROCESS CONTROL

The Assay also incorporates a positive IPC which is processed along with a patient sample and therefore is exposed to the same testing steps as the sample from DNA extraction and purification through to detection.

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The IPC verifies all aspects of the Assay process have functioned as expected. In an Assay where CT and/or NG is not detected, the IPC is measured by the Instrument to ensure it is within an acceptable range to validate a negative result. If it is outside the acceptable range the Instrument will return an "Assay Invalid" message and no result will be displayed or recorded against that specimen. If it is within the acceptable range the result(s) "CT Not Detected" and/or "NG Not Detected" will be displayed and recorded by the Instrument.

ASSAY OUTCOMES

Qualitative results are provided to the user in text format only. Assay results are displayed with the Specimen ID and Assay type. To maintain patient confidentiality, the Patient ID (if one has been entered) will not be displayed on the same screen as the Assay result.

The results shown below are the only results the Instrument will return following completion of a test.

Assay Result	Interpretation of Assay Result
CT Not Detected	Chlamydia trachomatis target DNA was not detected in the patient specimen.The IPC passed specification. This is a valid result.
CT Detected	Chlamydia trachomatis target DNA was detected in the patient specimen.This is a valid result.
NG Not Detected	At least one of the DNA targets for Neisseria gonorrhoeae was not detected in the patient specimen.The IPC passed specification. This is a valid result.
NG Detected	Both DNA targets for Neisseria gonorrhoeae were detected in the patient specimen.This is a valid result.
Assay Invalid	The presence or absence of the DNA targets for Chlamydia trachomatis and/or Neisseria gonorrhoeae could not be ascertained in the patient specimen.If a CT or NG Not Detected result is obtained, and the IPC was outside the acceptable range indicating a failure in the Assay process.The Assay should be repeated using the same patient specimen.
User Aborted	A user cancelled the Assay. No result is given.
Error	An internal fault occurred that terminated the Assay before it finished.

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PERFORMANCE EVALUATION:

ANALYTICAL PERFORMANCE

Analytical testing was performed to evaluate the performance of the binx io CT/NG Assay using the following studies:

Analytical sensitivity: Limit of Detection

Studies were carried out to determine the analytical limit of detection (LoD) of the binx io CT/NG Assay using cellular CT and NG material. for which the genome equivalents (GE)/mL were quantified. Two cartridge lots were used for each estimate of LoD to enable a lot to lot reproducibility comparison.

At least five separate input concentrations were used to cover a wide range (0.01-99%) of detection rates and each input concentration was tested with at least 20 replicates. A probit regression analysis was used to model the 'CT Detected' rate and identify the concentration level that demonstrated a detection rate of 95%. The LoD was then verified for each CT serovar and each NG strain. using a further total of 40 Cartridges per serovar/strain per Cartridge lot using two further preparations of the claimed LoD generated by two different operators. The LoD for each CT serovar and NG strain was set as the highest value generated from the two reagent lots and of the two tested serovars/strains.

Organism	GE/mL	IFU/mL	CFU/mL
CT serovar E (ATCC-VR-348B)	407.4	5.6	N/A
CT serovar F (ATCC-VR-346)	755.5	0.3	N/A
NG strain ATCC 49226	245.6	N/A	2.1
NG strain ATCC 700825	206.1	N/A	2.5

LoD of CT serovars and NG strains

Analytical reactivity (Inclusivity)

Analytical reactivity of additional CT serovars and NG strains was evaluated in the LoD studies described above.

CT serovars B, Ba, C, D, G, H, J, K, L2, nvCT were detected at 377.8 GE/mL. Serovars A, I, L1, L3 were detected at 755.5 GE/mL in at least 19/20 replicates.

Thirty additional NG strains (including two fluoroquinolone resistant isolates) and the reported detectable level was confirmed by testing replicates of three at or near the LoD of the 30 NG strains tested, 16 strains were detected at 245.6 GE/mL in all three replicates. The remaining 14 strains were further tested, and all were detected at 1,228.0 GE/mL in ≥19/20 replicates.

Analytical reactivity: Exclusivity

A panel of sixty-two species was investigated for cross-reactivity using cultured organisms at a concentration of 1 x 10°CFU/mL for bacteria, 1 x 105 PFU/mL for viruses or, GE, equivalent to a concentration of 2 ng/mL of genomic DNA generated by reverse transcription as available. Two further species were evaluated in silico by bioinformatic analysis of the genetic targets used in the Assay against the published genome sequences for these organisms. All isolates were reported as CT Not Detected/NG Not Detected with the exception of one strain of Neisseria sicca which gave a single CT Detected result from 20 replicates and may therefore be cross-reactive with the CT analyte.

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Microorganisms tested in the binx io CT/NG Assay

Bacteriodes fragilis*	Neisseria meningitidis Serogroup D*
Bacteriodes ureolyticus*	Neisseria meningitidis Serogroup W135*
Clostridium perfringens*	Neisseria meningitidis Serogroup Y*
Corynebacterium genitalium	Neisseria cinerea
Corynebacterium xerosis	Neisseria denitrificans
Escherichia coli	Neisseria elongata (4)
Gardnerella vaginalis*	Neisseria gonorrhoeae*
Haemophilus ducreyi*	Neisseria flava
Herpes simplex virus 1*	Neisseria flavescens (3)
Homo sapiens*	Neisseria lactamica (3)
Human papilloma virus 16*	Neisseria mucosa (4)
Kingella dentrificans	Neisseria perflava (2)
Kingella kingae	Neisseria polysaccharea
Lactobacillus acidophilus	Neisseria sicca (4) *
Lactobacillus brevis	Neisseria subflava (2)
Lactobacillus jensenii	Trichomonas vaginalis
Lactobacillus lactis	Ureaplasma urealyticum*
Moraxella lacunata	Ureaplasma parvum*
Staphylococcus epidermidis	Atopobium vaginae*
Streptococcus agalactiae	Bifidobacterium longum*
Candida albicans	BVAB-2†
Candida glabrata	Enterococcus faecalis
Candida parapsilosis	Herpes Simplex Virus 2*
Chlamydia pneumoniae*	Klebsiella pneumoniae
Chlamydia psittaci*	Megasphaera type 1†
Mycoplasma genitalium*	Mobiluncus curtisii*
Mycoplasma hominis*	Mobiluncus mulieris*
Neisseria meningitidis Serogroup A*	Peptostreptococcus anaerobius*
Neisseria meningitidis Serogroup B*	Proteus mirabilis
Neisseria meningitidis Serogroup C*	Pseudomonas aeruginosa
-	Staphylococcus aureus
-	Chlamydia trachomatis*

(n) number of strains tested

*Organisms tested with genomic DNA (2 ng/mL)

† In silico analysis

Analytical specificity: Interference

The analytical performance of the CT/NG Assay was evaluated in the presence of a panel of potentially interfering substances that may be found in vaginal swab specimens. The substances were diluted to the concentrations shown in the table below and spiked into negative vaginal matrix. The substances were tested in the absence of CT and NG (negative) and at 2 x LoD of both CT serovar F (ATCC VR-346) and NG strain ATCC 49226. No interference was observed.

Interfering substances tested in the binx io CT/NG Assay

Substance	Concentration
Human blood	10% (v/v)
Contraceptive Jelly	0.25% (v/v)
Mucus	0.8% (v/v)
Seminal fluid	5.0% (v/v)
Vaginal Moisturiser	0.25% (w/v)
Anti-fungal cream (Canesten)	0.25% (v/v)

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Anti-fungal cream (Daktarin)	0.25% (v/v)
Vaginal lubricant	0.25% (v/v)
Feminine anti-itch cream (2%lidocaine)	0.25% (v/v)
Leukocytes	1x106 cells/mL
Progesterone	7 mg/mL
β-Estradiol (Estrace cream)	0.25% (v/v)
Anti-viral cream (Acyclovir)	0.25% (v/v)
Haemorrhoidal cream	0.25% (v/v)

Microbial Interference

The performance of the CT/NG Assay was evaluated when 2x LoD of both CT serovar F (ATCC VR-346) and NG strain ATCC 49226 were spiked into negative vaginal matrix, aliquots of which were subsequently spiked with a panel of ten microorganisms (see Table 10) at a concentration of 1 x 105 CFU/mL. No interference was observed and an expected result of CT, NG Detected was obtained in all cases.

Panel of organisms used for microbial interference testing with vaginal swab matrix

Organism
Corynebacterium xerosis
Escherichia coli
Lactobacillus acidophilus
Lactobacillus brevis
Lactobacillus jensenii
Lactobacillus lactis
Staphylococcus epidermidis
Streptococcus agalactiae
Candida albicans
Candida glabrata

Precision: Reproducibility

The reproducibility of the CT/NG Assay was evaluated at point-of-care settings at three U.S. locations using two non-laboratorians as operators at each site. CT and NG organisms were seeded into pooled vaginal swab matrix at concentrations representing low positive (1x LoD), moderate positive (3x LoD) and high positive (2.26 x 108 GE/mL CT or 1.18 x 108 GE/mL NG) samples. Negative (non-seeded) pooled vaginal swab matrix samples were also included. The resulting panel of 11 specimens was tested twice per day for seven consecutive days by two operators at three sites (11 specimens x 2 replicates x 7 days x 3 sites x 2 operators). CT/NG Assays were performed according to the Assay procedure. The rate of agreement with expected CT and NG results for each panel member is shown.

Summary of reproducibility results in vaginal swab matrix: percent agreement by study site

Panel No.	Sample	Analyte	Site 1% agreement	Site 2% agreement	Site 3% agreement	% TotalAgreement
1	CT: neg	CT	92.9%(26/28)	100.0%(28/28)	92.9%(26/28)	95.2%(80/84)
	NG: 1.18 x 106 GE/mL	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)

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2	CT: neg	CT	89.3%(25/28)	96.4%(27/28)	92.9%(26/28)	92.9%(78/84)
	NG: 3x LoD	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
3	CT: neg	CT	100.0%(28/28)	100.0%(28/28)	92.9%(26/28)	97.6%(82/84)
	NG: 1x LoD	NG	100.0%(28/28)	100.0%(28/28)	96.4%(27/28)	98.8%(83/84)
	CT: 2.26 x 105 GE/mL	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	4	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	5	CT: 3x LoD	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	6	CT: 1x LoD	CT	96.4%(27/28)	92.9%(26/28)	100.0%(28/28)	96.4%(81/84)	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	CT: 2.26 x 105 GE/mL	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	7	NG: 1.18 x 106 GE/mL	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	8	CT: 2.26 x 105 GE/mL	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	NG: 1x LoD	NG	100.0%(28/28)	96.4%(27/28)	100.0%(28/28)	98.8%(83/84)	9	CT: 1x LoD	CT	100.0%(28/28)	96.4%(27/28)	96.4%(27/28)	97.6%(82/84)	NG: 1.18 x 106 GE/mL	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	10	CT: 1x LoD	CT	100.0%(28/28)	92.9%(26/28)	100.0%(28/28)	97.6%(82/84)	NG: 1x LoD	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)	11	CT: neg	CT	92.9%(26/28)	100.0%(28/28)	92.9%(26/28)	95.2%(80/84)	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
	CT: 2.26 x 105 GE/mL	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
4	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
5	CT: 3x LoD	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
6	CT: 1x LoD	CT	96.4%(27/28)	92.9%(26/28)	100.0%(28/28)	96.4%(81/84)
	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
	CT: 2.26 x 105 GE/mL	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
7	NG: 1.18 x 106 GE/mL	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
8	CT: 2.26 x 105 GE/mL	CT	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
	NG: 1x LoD	NG	100.0%(28/28)	96.4%(27/28)	100.0%(28/28)	98.8%(83/84)
9	CT: 1x LoD	CT	100.0%(28/28)	96.4%(27/28)	96.4%(27/28)	97.6%(82/84)
	NG: 1.18 x 106 GE/mL	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
10	CT: 1x LoD	CT	100.0%(28/28)	92.9%(26/28)	100.0%(28/28)	97.6%(82/84)
	NG: 1x LoD	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)
11	CT: neg	CT	92.9%(26/28)	100.0%(28/28)	92.9%(26/28)	95.2%(80/84)
	NG: neg	NG	100.0%(28/28)	100.0%(28/28)	100.0%(28/28)	100.0%(84/84)

Sample storage and stability

Specimen stability studies were carried out to determine the length of time samples can be stored prior to testing on the binx CT/NG Assay. Pooled vaginal swab matrix was spiked with 3x LoD for CT Serovar F (ATCC-VR-346), and NG (strain ATCC 49226). Twenty replicates were run immediately and a further 20 of each were run after samples had been stored for 25 hours at 25°C or eight days at 2-8°C.

All positive samples correctly returned CT Detected/NG Detected results, all negative samples correctly returned CT Not Detected/NG Not Detected except one sample after storage of eight days at 2-8ºC that generated a false positive result. The positive agreement for CT and NG was 100% at both t=25 hours at 25°C and t=8 days at 2-8°C. The study indicates that vaginal

{9}------------------------------------------------

swab samples are stable for up to 24 hours at 25°C and 7 days at 2-8°C prior to testing with the Assay.

Operational environment

A study was carried out to verify the performance of Instruments and Cartridges when run beyond the extremes of typical ambient temperatures and at high and low levels of relative humidity. Performance of the binx io Instruments was evaluated by placing the Instruments in validated and monitored environmental chambers held at a range of temperatures and humidity levels that were outside the typical normal Instrument operating range.

EnvironmentalTemperature(°C)	EnvironmentHumidity(RH%)	Expected results:Positive samples	% correctresults	Expected results:Negative samples	% correctresults
9°C	40%	CT DetectedNG Detected	100%	CT Not DetectedNG Not Detected	100%
37°C	40%	CT DetectedNG Detected	100%	CT Not DetectedNG Not Detected	100%
22°C	83%	CT DetectedNG Detected	100%	CT Not DetectedNG Not Detected	100%
30°C	83%	CT DetectedNG Detected	100%	CT Not DetectedNG Not Detected	100%
20°C	15%	CT DetectedNG Detected	100%	CT Not DetectedNG Not Detected	100%

Summary of operational environment testing

Open pack stabilitv

A study was carried out to verify the performance of the Instrument and Cartridge when subjected to a range of temperature and humidity levels.

The study was carried out using CT/NG Cartridges tested with 4x LoD for CT serovar F (ATCC-VR-346) and NG strain ATCC 49226 spiked into eNAT buffer. Cartridges were removed from their packaging and samples (positives) or eNAT buffer (negatives) were added. Cartridges were placed in a controlled and monitored incubator for 1, 2, 3, 4, 5 and 6 hours at +30°C. In addition, a set of Cartridges were loaded with a sample and incubated for six hours at +30°C at low (≤20% Relative Humidity (RH)) and high humidity (≥60% RH) using a monitored environmental chamber.

All samples qenerated the expected results and verified that the CT/NG Assay generates the correct results when a sample is loaded into a Cartridge and stored at 30°C in both high and low humidity conditions following up to six hours storage.

Cartridge performance when run immediately from 2-8°C storage

A study was carried out using Cartridges that had been stored at 2-8℃ for a minimum of 12 hours using samples that had either been stored at room temperature or stored refrigerated at 2-8°C for a minimum of 12 hours. All replicates generated correct results.

Shipping stability

The performance of the Assay was assessed following simulated shipping conditions in order to demonstrate performance after undergoing two temporary storage and shipping cycles. This study was carried out using eNAT samples spiked with 4x LoD for positives, or eNAT buffer for negatives. All samples tested generated correct results.

ISTA3A testing

An ISTA (International Safe Transit Association) 3A study was carried out by an accredited test site followed by subsequent inspection and test performance. The study used a total of 50 Cartridges within a shipper of five cartons containing ten CT/NG Cartridges each. No damage was observed to the packaging or Cartridges and all Cartridges tested with 4x LoD

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CT/NG spiked into eNAT buffer for positives and eNAT buffer for negatives generated correct results.

Cross contamination

A study was conducted to demonstrate that the CT/NG Cartridge prevents run-to-run cross contamination when negative samples containing pooled vaginal matrix were run following very high CT/NG double positive samples (containing 2.26 x 10° GE/mL CT and 1.18 x 107 GE/mL NG). The study consisted of four separate Instruments, with 50 Cartridges run per Instrument, alternating between negative samples and very high CT/NG double positive samples (200 Cartridges run across all instruments, comprising 100 negative and 100 very high positive). All neqative samples were correctly detected as CT, NG Not Detected and all positive samples were correctly identified as CT, NG Detected.

Internal Control Function

A study was carried out to demonstrate the IPC function. The objective was to demonstrate that a Cartridge lacking internal control DNA would report an Assay Invalid result. A panel of conditions was tested including Cartridge manufactured specifically with no IPC present. All samples tested generated the expected results including the Cartridges with no IPC which delivered the expected Assay Invalid result.

All experiments carried out to evaluate analytical performance met established acceptance criteria.

CLINICAL PERFORMANCE

A prospective, multi-center study was carried out to evaluate the performance of the binx io CT/NG Assay with specimens collected at nine investigational sites throughout the U.S. The Assay was compared to the (i) Hologic Aptima Combo 2 (AC2) Chlamydia/Gonorrhea Assay run on Panther, (ii) BD ProbeTec Chlamydia trachomatis (CT) Q*, and BD ProbeTec Neisseria gonorrhoeae (GC) Q* assays run on the Viper XTR™, and (iii) Roche cobas CT/NG v2.0 test run on the cobas 4800 System. The three reference tests were used to form a Composite Infected Status (CIS) where a patient was considered if at least two out of the three reference tests were positive and not infected if at least two out of the three reference tests was negative. Vaginal swabs were obtained from women with and without symptoms of infection from a variety of clinical venues and both self-collected and clinician-collected vaginal swabs were tested.

Site personnel that carried out testing using the CT/NG Assay were, in the vast majority (96% overall), point-of-care personnel trained in the use of the binx io CT/NG System, but not trained or experienced in general laboratory testing procedures.

A total of 1,634 participants were enrolled into the Study. Twenty-one participants were ineligible or withdrew consent. Eighty-nine participants were excluded due to deviations to the study protocol. Of the 1.524 specimens for which a CIS could be determined, one specimen generated an Invalid result after three successive tests and was considered Indeterminate (IND) with respect to the Assay. This sample was excluded from the final data analysis.

A total of 1.523 vaginal swab specimens were fully evaluable. Of these, 736 were selfcollected vaginal swabs (SCVS) and 787 were clinician-collected vaginal swabs (CCVS). Of the total number of vaginal specimens collected, 706 were from asymptomatic participants and 817 from symptomatic participants.

A total of 129 eligible subjects were classified as infected for CT, of which 62 were symptomatic and 67 were asymptomatic. A total of 1,394 participants were classified as not infected for CT, of which 755 were symptomatic and 639 were asymptomatic.

A total of 45 participants were classified as infected for NG, of which 29 were symptomatic and 16 were asymptomatic. A total of 1,478 participants were classified as not infected for NG, of which 788 were symptomatic and 690 were asymptomatic.

The median age of participants was 27, ranging from 16 to 74 years.

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Cill	Comparator System		binx	Symptom		Total
	NAAT1	NAAT2	NAAT3	io	ടു	Asx
NI	-	-	-	-	731	620	1351
NI	-	-	+	-	2	3	5
NI	-	+	-	-	5	7	12
NI	+	-	-	-	0	0	0
NI	-	-	IND	-	2	1	3
NI	-	IND	-	-	1	2	3
NI	IIND	-	-	-	6	1	7
NI	-	-	-	+	8	5	13
NI	-	-	+	+	0	0	0
NI	-	+	-	+	0	0	0
NI	+	-	-	+	0	0	0
NI	-	-	IND	+	0	0	0
NI	-	IND	-	+	0	0	0
NI	IIND	-	-	+	0	0	0
		Total not Infected			755	639	1394
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	+	+	56	દર્ડ	119
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	-	+	0	1	1
-	+	-	+	+	0	1	1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	-	+	+	+	1	0	1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	IND	+	0	0	0
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	IND	+	+	1	0	1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	IND	+	+	+	1	0	1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	+	-	1	2	3
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	-	-	2	0	2
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	-	+	-	0	0	0
-	-	+	+	-	0	0	0
l	+	+	IND	-	0	0	0
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	IND	+	-	0	0	0
-	IND	+	+	-	0	0	0
		Total Infected			62	67	129
d Status	NI = Not Infected	I = Infected		IND = Indeterminate

Composite Infected Status for Chlamydia trachomatis by symptom status

CIS = Comparator Infected
Sx = Symptomatic Asx = Asymptomatic

Composite Infected Status for Neisseria gonorrhoeae by symptom status

ટાડ	Comparator System			binx		Symptom	Total
	NAAT1	NAAT2	NAAT3	io	Sx	Asx
NI	-	-	-	-	776	681	1457
NI	-	-	+	-	3	4	7
NI	-	+	-	-	0	0	O
NI	+	-	-	-	O	0	0
NI	-	-	IND	-	2	1	3
NI	-	IND	-	-	O	2	2
NI	IND	-	-	-	ട്	1	7
NI	-	-	-	+	O	0	0
NI	-	-	+	+	0	0	O
NI	-	+	-	+	0	0	0
NI	+	-	-	+	1	0	1
NI	-	-	IND	+	O	0	0
NI	-	IND	-	+	0	1	1
NI	IND		-	+	O	0	0
	Total not Infected				788	690	1478
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	+	+	24	15	39
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	-	+	1	0	1
-	+	-	+	+	2	1	3
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	-	+	+	+	1	0	1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	+	IIND	+	0	0	0
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	+	IND	+	+	0	0	0
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	IND	+	+	+	1	0	1
-	+	+	+	-	O	O	O

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	+	+			0
	+		+	O	0	0
		+	+	O	0
	+	+	IND	O	0
	+	IND	+	O	0
	IND	+		O	0
		Total Infected		29	16	45
= Comparator Infected StatusSymptomatic	NI = Not Infectedl = InfectedAsx = Asymptomatic				IND = Indeterminate

Results from the CT/NG Assay were compared to the CIS for CT for the determination of sensitivity, specificity and predictive values. Sensitivity and specificity for CT and NG by specimen type, symptom status and prevalence rates.

Clinical Performance of the binx health io CT/NG Assay against CIS for Chlamydia trachomatis with vaginal swab specimens

	N	TP	FN	TN	FP	Prevalence	Sensitivity(95% CI)	Specificity(95% CI)	PPV(95% CI)	NPV(95% CI)
Asymptomatic	706	65	2	634	5	9.5%	97.0%(89.8% - 99.2%)	99.2%(98.2% - 99.7%)	92.9%(84.1% - 97.6%)	99.7%(98.9% - 100.0%)
Symptomatic	817	59	3	747	8	7.6%	95.2%(86.7% - 98.3%)	98.9%(97.9% - 99.5%)	88.1%(77.8% - 94.7%)	99.6%(98.8% - 99.9%)
Total	1523	124	5	1381	13	8.5%	96.1%(91.2% - 98.3%)	99.1%(98.4% - 99.5%)	90.5%(84.3% - 94.9%)	99.6%(99.2% - 99.9%)

N= Number of specimens TP = True Positive FN = False Negative TN = True Negative FP = False Positive

DDV = Positive Predictive Value NPV = Negative Predictive Value

Confidence Intervals (CI) for Sensitivity and specificity: Wilson Score Method

Confidence Intervals (CI) for NPV, PPV :Exact Method

ટાક Sx =

Clinical Performance of the binx health io CT/NG Assay against CIS for Neisseria gonorrhoeae with vaginal swab specimens

	N	TP	TN	FP	Prevalence	Sensitivity(95% CI)	Specificity(95% CI)	PPV(95% CI)	NPV(95% CI)
Asymptomatic	706	16	689	1	2.3%	100.0%(80.6% - 100.0%)	99.9%(99.2% - 100.0%)	94.1%(71.3% - 99.9%)	100.0%(99.5% - 100.0%)
Symptomatic	817	29	787	1	3.5%	100.0%(88.3% - 100.0%)	99.9%(99.3% - 100.0%)	96.7%(82.8% - 99.9%)	100.0%(99.5% - 100.0%)
Total	1523	45	1476	2	3.0%	100.0%(92.1% - 100.0%)	99.9%(99.5% - 100.0%)	95.7%(85.5% - 99.5%)	100.0%(99.8% - 100.0%)

N= Number of specimens TP = True Positive FN = False Negative TN = True Negative
PPV = Positive Predictive Value NPV = Neqative Predictive Value

PPV = Positive Predictive Value NPV = Negative Predictive Value

Confidence Intervals (CI) for Sensitivity and specificity: Wilson Score Method
Confidence Intervals (CI) for NPV, PPV :Exact Method

Confidence Intervals (CI) for NPV, PPV :Exact Method

Overall clinical performance

Organism	No. of binxPos/TP	OverallSensitivity(95% CI)	No. of binxNeg/TN	OverallSpecificity(95% CI)
CT	124/129	96.1%(91.2% - 98.3%)	1381/1394	99.1%(98.4% - 99.5%)
NG	45/45	100.0%(92.1% - 100.0%)	1476/1478	99.9%(99.5% - 100.0%)

Rate of Invalid Results

In cases where the Assay returned a Test Invalid result, the patient specimen was retested. The result of the retest was used in the analysis. A Test Invalid result was reported in 17 of the 1,541 cartridges tested (1.10%) in this study. If three successive assays returned a Test Invalid result on a single specimen this was recorded as Indeterminate. Of the 1,524 specimens for which a CIS could be determined, one specimen generated a final invalid (Indeterminate (IND)) result and was excluded from analysis.

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Positive and Negative Predictive Values

The sensitivity and specificity of the binx health io CT/NG Assay when used with vaginal swabs, was used to calculate the hypothetical Positive Values (PPV) and Negative Predictive Values (NPV) at a range of hypothetical prevalence rates.

		Chlamydia trachomatis (CT)	Neisseria gonorrhoeae (NG)
Prevalence%	Sensitivity%	Specificity%	PPV%	NPV%	Sensitivity%	Specificity%	PPV%	NPV%
1	96.1%	99.1%	51.9%	100.0%	100.0%	99.9%	91.0%	100.0%
5	96.1%	99.1%	84.9%	99.8%	100.0%	99.9%	98.1%	100.0%
10	96.1%	99.1%	92.2%	99.6%	100.0%	99.9%	99.1%	100.0%
15	96.1%	99.1%	95.0%	99.3%	100.0%	99.9%	99.4%	100.0%
20	96.1%	99.1%	96.4%	99.0%	100.0%	99.9%	99.6%	100.0%
25	96.1%	99.1%	97.3%	98.7%	100.0%	99.9%	99.7%	100.0%

Hypothetical PPV and NPV: Female Vaginal Swab specimens

SUBSTANTIAL EQUIVALENCE:

Item	510(k) Device:binx io Assaybinx io CT/NG System	Predicate DevicesBD ProbeTec Q* CT (K091724); andBD ProbeTec Q* GC (K091730)
Regulation	866.3393	K091724: 866.3120K091730: 866.3390
RegulationSpecialty	Microbiology	Microbiology
Device Class	Class II	K091724: Class IK091730: Class II
Technology	Automated multiplexpolymerase chain reaction withelectrochemical detection	Automated multiplex stranddisplacement amplification withfluorescence detection
Intended Use	The binx health io CT/NG Assay,when tested using the binxhealth io Instrument, is a fullyautomated, rapid, qualitative testintended for use in point-of-careor clinical laboratory settings forthe detection of Chlamydiatrachomatis and Neisseriagonorrhoeae DNA in femalevaginal swab specimenscollected either by a clinician orself-collected by a patient in aclinical setting, to aid in thediagnosis of symptomatic orasymptomatic infection in femalepatients with Chlamydiatrachomatis and/or Neisseriagonorrhoeae .	The BD ProbeTec Chlamydiatrachomatis (CT) Q* Amplified DNAAssay, when tested with the BD ViperSystem in Extracted Mode, uses StrandDisplacement Amplification technologyfor the direct, qualitative detection ofChlamydia trachomatis DNA inclinician-collected female endocervicaland male urethral swab specimens,patient-collected vaginal swabspecimens (in a clinical setting), andmale and female urine specimens (bothUPT and Neat). The Assay is alsointended for use with gynecologicalspecimens collected in BD SurePath™Preservative Fluid using an aliquot thatis removed prior to processing for theBD SurePath Pap test. The Assay isindicated for use with asymptomaticand symptomatic individuals to aid inthe diagnosis of chlamydial urogenitaldisease.The BD ProbeTec Neisseriagonorrhoeae (GC) Q* Amplified DNAAssay, when tested with the BD ViperSystem in Extracted Mode, uses StrandDisplacement Amplification technology

		for the direct, qualitative detection ofNeisseria gonorrhoeae DNA in
		clinician-collected female endocervical
		and male urethral swab specimens,
		patient-collected vaginal swabspecimens (in a clinical setting), and
		male 2 and female urine specimens(both UPT and Neat). The Assay is also
		intended for use with gynecologicalspecimens collected in BD SurePath™
		Preservative Fluid using an aliquot thatis removed prior to processing for the
		BD SurePath™ Pap test. The Assay isindicated for use with asymptomatic
		and symptomatic individuals to aid inthe diagnosis of gonococcal urogenitaldisease.
Indications	Symptomatic and asymptomaticfemale patients	Same
Assay Target	DNA from Chlamydiatrachomatis and/or Neisseriagonorrhoeae	Same
SpecimenTypes	Clinician-collected femalevaginal swabsPatient-collected female vaginalswabs (in a clinical setting)	Clinician-collected female endocervicalswabsMale urethral swabsPatient-collected vaginal swabspecimens (in a clinical setting)Male & female urine (both UPT andNeat).Specimens collected in BD SurePath™
CT AnalyteTarget	CT Genomic DNA	CT cryptic plasmid DNA
NG AnalyteTarget	NG Genomic DNA	Same
Collection Kit	Vaginal Swab Collection Kit	Same
Nucleic AcidExtraction	Yes	Same
AssayResults	Qualitative	Same
AssayControls	Internal Process ControlExternal controls available butnot supplied	Positive & negative run controlsAutomated control rehydrationExtraction controlSpecimen processing control procedure
Instrument	binx health io ®	BD Viper™

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Based on the data presented in this 510(k) Premarket Notification, the binx io CT/NG Assay has been shown to be substantially equivalent to the predicate device for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in female vaginal swab specimens.

Regulation Number and Section

§ 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.