Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description details a fully automated, rapid, qualitative test using PCR and electrochemical detection with fixed cut-off parameters for result determination. There is no mention of AI, ML, or any learning algorithms used in the analysis or interpretation of results.

Therapeutic

No
This device is an in vitro diagnostic (IVD) system used to detect the DNA of specific bacteria, Chlamydia trachomatis and Neisseria gonorrhoeae, to aid in the diagnosis of infection. It does not provide therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section states that the device is "intended... to aid in the diagnosis of symptomatic or asymptomatic infection". Additionally, the "Device Description" explicitly refers to it as a "rapid qualitative in vitro diagnostic system".

SaMD (Software as a Medical Device)

No

The device description clearly states that the system consists of an instrument, cartridges, transfer pipet, and collection kit, in addition to any software components.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the binx health io CT/NG Assay is a "qualitative test intended for use in point-of-care or clinical laboratory settings for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA... to aid in the diagnosis of symptomatic or asymptomatic infection". This clearly describes a test performed on a biological sample (vaginal swab) outside of the body to provide information for diagnosis.
Device Description: The "Device Description" section refers to the system as a "rapid qualitative in vitro diagnostic system".
Mechanism: The description of the assay process (sample preparation, PCR, electrochemical detection) involves analyzing components of a biological sample to detect specific DNA sequences, which is a hallmark of in vitro diagnostics.

The entire document describes a system designed to perform diagnostic testing on patient samples in a laboratory or point-of-care setting, fitting the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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.

Product codes (comma separated list FDA assigned to the subject device)

OEP, LSL, MKZ, NSU

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")

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

female vaginal swab specimens

Indicated Patient Age Range

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

Intended User / Care Setting

point-of-care or clinical laboratory settings

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

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.

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.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Analytical Performance 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.
- CT serovar E (ATCC-VR-348B): 407.4 GE/mL, 5.6 IFU/mL
- CT serovar F (ATCC-VR-346): 755.5 GE/mL, 0.3 IFU/mL
- NG strain ATCC 49226: 245.6 GE/mL, 2.1 CFU/mL
- NG strain ATCC 700825: 206.1 GE/mL, 2.5 CFU/mL
Analytical reactivity (Inclusivity): Evaluated additional CT serovars and NG strains.
- 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.
- 30 additional NG strains tested; 16 strains detected at 245.6 GE/mL in all 3 replicates, remaining 14 strains detected at 1,228.0 GE/mL in ge 19/20 replicates.
Analytical reactivity: Exclusivity: A panel of sixty-two species was investigated for cross-reactivity. All isolates 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.
Analytical specificity: Interference: Evaluated the performance in the presence of 12 potentially interfering substances and 10 microorganisms. No interference was observed.
Precision: Reproducibility: Evaluated reproducibility at point-of-care settings at three U.S. locations using two non-laboratorians as operators at each site.
- Sample panel of 11 specimens tested twice/day for 7 consecutive days by 2 operators at 3 sites (total 84 replicates per panel member).
- Overall agreement for CT ranged from 92.9% to 100.0%.
- Overall agreement for NG ranged from 98.8% to 100.0%.
Sample storage and stability: Evaluated stability of samples stored at 25°C for 25 hours and 2-8°C for 8 days.
- Samples stable for up to 24 hours at 25°C and 7 days at 2-8°C.
- One false positive CT result after 8 days at 2-8°C storage for a negative sample. Positive agreement for CT and NG was 100% at both time points.
Operational environment: Insruments operated at extended temperature (9°C, 37°C) and humidity (15%, 83%) ranges. 100% correct results for both positive and negative samples.
Open pack stability: Cartridges and samples generated correct results after up to 6 hours of storage at +30°C in high and low humidity.
Cartridge performance when run immediately from 2-8°C storage: All replicates generated correct results.
Shipping stability: All samples tested generated correct results after simulated shipping conditions.
Cross contamination: 200 cartridges (100 negative, 100 very high positive) run on 4 instruments in alternating sequence. All negative samples were correctly detected as CT, NG Not Detected and all positive samples were correctly identified as CT, NG Detected.
Internal Control Function: Cartridges manufactured without IPC delivered the expected Assay Invalid result.

Clinical Performance Study:

Study Type: Prospective, multi-center study
Sample Size: 1523 evaluable vaginal swab specimens (736 self-collected, 787 clinician-collected) from 1524 participants.
Reference Method: Composite Infected Status (CIS) using Hologic Aptima Combo 2 (AC2), BD ProbeTec CT Q*/GC Q*, and Roche cobas CT/NG v2.0.
Key Results:
- Chlamydia trachomatis (CT):
  - Asymptomatic: Sensitivity 97.0% (95% CI: 89.8%-99.2%), Specificity 99.2% (95% CI: 98.2%-99.7%), PPV 92.9% (95% CI: 84.1%-97.6%), NPV 99.7% (95% CI: 98.9%-100.0%)
  - Symptomatic: Sensitivity 95.2% (95% CI: 86.7%-98.3%), Specificity 98.9% (95% CI: 97.9%-99.5%), PPV 88.1% (95% CI: 77.8%-94.7%), NPV 99.6% (95% CI: 98.8%-99.9%)
  - Total: Sensitivity 96.1% (95% CI: 91.2%-98.3%), Specificity 99.1% (95% CI: 98.4%-99.5%), PPV 90.5% (95% CI: 84.3%-94.9%), NPV 99.6% (95% CI: 99.2%-99.9%)
- Neisseria gonorrhoeae (NG):
  - Asymptomatic: Sensitivity 100.0% (95% CI: 80.6%-100.0%), Specificity 99.9% (95% CI: 99.2%-100.0%), PPV 94.1% (95% CI: 71.3%-99.9%), NPV 100.0% (95% CI: 99.5%-100.0%)
  - Symptomatic: Sensitivity 100.0% (95% CI: 88.3%-100.0%), Specificity 99.9% (95% CI: 99.3%-100.0%), PPV 96.7% (95% CI: 82.8%-99.9%), NPV 100.0% (95% CI: 99.5%-100.0%)
  - Total: Sensitivity 100.0% (95% CI: 92.1%-100.0%), Specificity 99.9% (95% CI: 99.5%-100.0%), PPV 95.7% (95% CI: 85.5%-99.5%), NPV 100.0% (95% CI: 99.8%-100.0%)
Rate of Invalid Results: 17 of 1,541 cartridges (1.10%) returned a Test Invalid result. One specimen that returned an Invalid result after three successive tests was excluded from analysis.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Chlamydia trachomatis (CT):

Sensitivity: 96.1% (91.2% - 98.3%)
Specificity: 99.1% (98.4% - 99.5%)
PPV: 90.5% (84.3% - 94.9%) (Total)
NPV: 99.6% (99.2% - 99.9%) (Total)

Neisseria gonorrhoeae (NG):

Sensitivity: 100.0% (92.1% - 100.0%)
Specificity: 99.9% (99.5% - 100.0%)
PPV: 95.7% (85.5% - 99.5%) (Total)
NPV: 100.0% (99.8% - 100.0%) (Total)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

BD ProbeTec Neisseria gonorrhoeae (GC) Qx Amplified DNA Assay (K091730), BD ProbeTec Chlamydia trachomatis (CT) Qx Amplified DNA Assay (K091724)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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.

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

1

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 Street
5th Floor
Boston, MA 02114
USA
CONTACT PERSON:	Sarah Kalil
Regulatory Advisor
binx health, Inc.
Phone: (646) 847 8573
Email: 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 for
non-viral microorganism(s) causing sexually transmitted
infections)
Class II
PRODUCT CODE:	QEP
SUBSEQUENT PRODUCT CODES:	LSL, MKZ, NSU
REVIEW PANEL	Microbiology
PREDICATE DEVICES:	BD ProbeTec Neisseria gonorrhoeae (GC) Qx Amplified
DNA Assay (K091730) and BD ProbeTec Chlamydia
trachomatis (CT) Qx Amplified DNA Assay (K091724) on
the BD Viper™ System (Becton Dickinson, Sparks, MD).
INTENDED USE:	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.

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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")

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.

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.

6

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)

7

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 | % Total
Agreement |
|-----------|----------------------|---------|-----------------------|-----------------------|-----------------------|----------------------|
| 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) |

8

| 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.

| Environmental
Temperature
(°C) | Environment
Humidity
(RH%) | Expected results:
Positive samples | % correct
results | Expected results:
Negative samples | % correct
results |
|--------------------------------------|----------------------------------|---------------------------------------|----------------------|---------------------------------------|----------------------|
| 9°C | 40% | CT Detected
NG Detected | 100% | CT Not Detected
NG Not Detected | 100% |
| 37°C | 40% | CT Detected
NG Detected | 100% | CT Not Detected
NG Not Detected | 100% |
| 22°C | 83% | CT Detected
NG Detected | 100% | CT Not Detected
NG Not Detected | 100% |
| 30°C | 83% | CT Detected
NG Detected | 100% | CT Not Detected
NG Not Detected | 100% |
| 20°C | 15% | CT Detected
NG Detected | 100% | CT Not Detected
NG 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

10

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.

11

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

12

	+	+				0
	+		+		O	0	0
		+	+		O	0
	+	+	IND		O	0
	+	IND	+		O	0
	IND	+			O	0
		Total Infected			29	16	45
= Comparator Infected Status
Symptomatic	NI = Not Infected
l = Infected
Asx = 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 | FN | TN | FP | Prevalence | Sensitivity
(95% CI) | Specificity
(95% CI) | PPV
(95% CI) | NPV
(95% CI) |
|--------------|------|----|----|------|----|------------|----------------------------|---------------------------|--------------------------|----------------------------|
| Asymptomatic | 706 | 16 | 0 | 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 | 0 | 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 | 0 | 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 binx
Pos/TP | Overall
Sensitivity
(95% CI) | No. of binx
Neg/TN | Overall
Specificity
(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.

13

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 Assay
binx io CT/NG System | Predicate Devices
BD ProbeTec Q* CT (K091724); and
BD ProbeTec Q* GC (K091730) |
|----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulation | 866.3393 | K091724: 866.3120
K091730: 866.3390 |
| Regulation
Specialty | Microbiology | Microbiology |
| Device Class | Class II | K091724: Class I
K091730: Class II |
| Technology | Automated multiplex
polymerase chain reaction with
electrochemical detection | Automated multiplex strand
displacement amplification with
fluorescence detection |
| Intended Use | 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 . | The BD ProbeTec Chlamydia
trachomatis (CT) Q* Amplified DNA
Assay, when tested with the BD Viper
System in Extracted Mode, uses Strand
Displacement Amplification technology
for the direct, qualitative detection of
Chlamydia trachomatis DNA in
clinician-collected female endocervical
and male urethral swab specimens,
patient-collected vaginal swab
specimens (in a clinical setting), and
male and female urine specimens (both
UPT and Neat). The Assay is also
intended for use with gynecological
specimens collected in BD SurePath™
Preservative Fluid using an aliquot that
is removed prior to processing for the
BD SurePath Pap test. The Assay is
indicated for use with asymptomatic
and symptomatic individuals to aid in
the diagnosis of chlamydial urogenital
disease.
The BD ProbeTec Neisseria
gonorrhoeae (GC) Q* Amplified DNA
Assay, when tested with the BD Viper
System in Extracted Mode, uses Strand
Displacement Amplification technology |
| | | |
| | | for the direct, qualitative detection of
Neisseria gonorrhoeae DNA in |
| | | clinician-collected female endocervical |
| | | and male urethral swab specimens, |
| | | patient-collected vaginal swab
specimens (in a clinical setting), and |
| | | male 2 and female urine specimens
(both UPT and Neat). The Assay is also |
| | | intended for use with gynecological
specimens collected in BD SurePath™ |
| | | Preservative Fluid using an aliquot that
is removed prior to processing for the |
| | | BD SurePath™ Pap test. The Assay is
indicated for use with asymptomatic |
| | | and symptomatic individuals to aid in
the diagnosis of gonococcal urogenital
disease. |
| Indications | Symptomatic and asymptomatic
female patients | Same |
| Assay Target | DNA from Chlamydia
trachomatis and/or Neisseria
gonorrhoeae | Same |
| Specimen
Types | Clinician-collected female
vaginal swabs

14

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.