← Product Code [PPU](/submissions/MI/subpart-c%E2%80%94microbiology-devices/PPU) · K183648

# APAS Independence with Urine Analysis Module (K183648)

_Clever Culture Systems AG · PPU · May 15, 2019 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-c%E2%80%94microbiology-devices/PPU/K183648

## Device Facts

- **Applicant:** Clever Culture Systems AG
- **Product Code:** [PPU](/submissions/MI/subpart-c%E2%80%94microbiology-devices/PPU.md)
- **Decision Date:** May 15, 2019
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.2190
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The APAS Independence is an in vitro diagnostic system comprised of an instrument and software analysis module(s) for specific indications that are used to automate imaging and interpretation of microbial colonies on plates of solid culture media.

## Device Story

Automated in vitro diagnostic system for urine culture plate screening. Instrument uses LED illumination and CCD camera to capture digital images of sheep blood and MacConkey agar plates. Plate handling system moves plates from input to imaging station and output. Software analysis module processes images to differentiate growth from background, identify colony morphology, and estimate CFU/mL. System designates plates as 'Positive', 'Review', 'Negative', or 'Indeterminate'. Positive/Review plates require manual review by a trained microbiologist. Used in clinical laboratories; operated by laboratory personnel. Integrates with LIMS to import patient context for result interpretation. Benefits include automated plate sorting and reduced manual screening of negative cultures.

## Clinical Evidence

Confirmatory method comparison study using 350 leftover clinical urine samples compared APAS Independence to the predicate APAS Compact. Results showed high agreement in plate designation (Positive/Review/Negative) and colony enumeration. Reproducibility and precision were assessed across three instruments using various organisms (E. coli, S. agalactiae, E. faecalis) at different dilutions, showing acceptable %CV values similar to the predicate. No new clinical studies were required as the predicate's clinical performance was leveraged.

## Technological Characteristics

Constructed of general engineering plastics and metals. Imaging station powered by 24VDC; automated plate handling system. Connectivity includes laboratory network integration (LIS, LDAP, NTP, DNS/DHCP). Software is moderate level of concern. Complies with IEC 61010-1, IEC 61010-2-101, UL 61010-1, IEC 61326-1, IEC 61326-2-6, and FCC Part 15B. Non-sterile device.

## Regulatory Identification

An automated image assessment system for microbial colonies on solid culture media is a system that is intended to assess the presence or absence of microbial colonies on solid microbiological culture medium, and to interpret their number, and phenotypic and morphologic characteristics through analysis of two dimensional digital images as an aid in diagnosis of infectious disease.

## Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include a detailed description of the device, including the technology employed, components and software modules, as well as a detailed explanation of the result algorithms and any expert rules that are used to assess colony characteristics and enumerate colonies from image capture through end result.
(2) Premarket notification submissions must include detailed documentation of the analytical studies performed to characterize device performance to support the intended use, as appropriate.
(3) Premarket notification submissions must include detailed documentation from clinical studies performed on a population that is consistent with the intended use population.
(i) The clinical studies must establish the device performance based on comparison to results obtained by an acceptable reference method, as appropriate.
(ii) The clinical study documentation must include the study protocol with a predefined statistical analysis plan and the final report documenting support for the Indications for Use and the results of the statistical analysis, as appropriate.
(4) Premarket notification submissions must include detailed documentation for device software, including but not limited to software applications and hardware based components that incorporate software, and any decision-making thresholds used to generate results for the device. If a part of a Total Laboratory Automation System, the premarket notification submission must include detailed documentation addressing the instrument and software system integration.
(5) Premarket notification submissions must include detailed documentation of appropriate instructions for use regarding the intended user's device quality control procedures for the instrument system and components, as appropriate.
(6) The 21 CFR 809.10 compliant device labeling must include:
(i) Detailed user instructions to mitigate the risk of failure to operate the instrument correctly.
(ii) A detailed explanation of the interpretation of results and limitations regarding the need for review of culture plates by a qualified microbiologist, as appropriate.
(iii) A summary of performance data obtained from the analytical studies used to support device performance, as appropriate.
(iv) A summary of performance data obtained from clinical studies performed on a population that is consistent with the intended use population, as appropriate.
(7) Under 21 CFR 820.10(c) design and development, device manufacturers must, as appropriate:
(i) Conduct human factors/usability validation testing with the final version of the labeling and related materials to adequately mitigate the risk of failure to operate the instrument correctly.
(ii) Document a device training program that will be offered to the end user to adequately mitigate the risk of failure to operate the instrument correctly.

## Predicate Devices

- APAS Compact with Urine Analysis Module ([DEN150059](/device/DEN150059.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number
K183648

B Applicant
Clever Culture Systems AG

C Proprietary and Established Names
APAS Independence

D Regulatory Information
|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  PPU | Class II | 21 CFR 866.2190 - Automated Image Assessment System For Microbial Colonies On Solid Culture Media | IM - Immunology & MI - Microbiology  |

## II Submission/Device Overview:

A Purpose for Submission:
To obtain a substantial equivalence determination for the APAS Independence.

B Measurand:
Digital images of microbial colonies cultured on blood and MacConkey agar plates.

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C Type of Test:

The APAS Independence when using its Urine Analysis Module is an in vitro diagnostic test system for automated assessment and enumeration of microbial colonies on solid culture media. The system is for use on urine cultures from suspected cases of urinary tract infection (UTI).

III Intended Use/Indications for Use:

A Intended Use(s):

The APAS Independence is an in vitro diagnostic system comprised of an instrument and software analysis module(s) for specific indications that are used to automate imaging and interpretation of microbial colonies on plates of solid culture media.

B Indication(s) for Use:

The APAS Independence is an in vitro diagnostic system comprised of an instrument for automated imaging of agar culture plates and a software analysis module for the following use:

The APAS Independence, when using its urine analysis module, automates urine culture plate imaging and interpretation to detect the presence or absence of microbial growth on sheep blood and MacConkey agar culture plates that are inoculated with a 1μL sample volume. The APAS Independence, when using its urine analysis module, provides a semi-quantitative assessment of colony counts that are used as an aid in the diagnosis of urinary tract infection. All urine culture plates that are identified as positive for growth by the APAS Independence, when using its urine analysis module, must be reviewed by a trained microbiologist.

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

The performance of the APAS Independence with Urine Analysis Module has not been evaluated with urine samples from pregnant women. The APAS Independence with Urine Analysis Module will detect colonies of GBS if they are present but should not be used for primary screening for Group B Streptococcus (GBS) carriers. Follow recommended guidelines for identification of pregnant women who are colonized with GBS.

The performance of the APAS Independence with Urine Analysis Module has not been evaluated with urine samples from suspected cases of complicated urinary tract infection e.g., those with underlying urinary tract pathology, suspected cases of persistent urinary tract infection, urine collected by invasive procedures or urine samples from immunocompromised subjects.

Slow growing organisms such as Corynebacterium spp. and Gardnerella vaginalis may not exhibit detectable growth within 18-22 hours. If infection with a slow growing species is suspected, extension of the incubation time may be required, followed by manual interpretation

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of the culture result. The APAS Independence with Urine Analysis Module should not be used to interpret cultures incubated for greater than 22 hours.

The APAS Independence with Urine Analysis Module is for use with the following culture plates manufactured by Remel: Tryptic Soy Sheep Blood Agar (R01202A) and MacConkey Agar with Crystal Violet (R01552A).

APAS Independence has been designed and validated for use only with whole plates. Bi-plates have not been evaluated and should not be used.

## D Special Instrument Requirements:

APAS Independence

## IV Device/System Characteristics:

## A Device Description:

The APAS Independence with Urine Analysis Module is an automated system that for screening of urine culture plates for the presence of microbial growth. The device comprises a plate handling system that moves culture plates loaded by the operator into and out of an imaging station where digital images of the plates are captured, as well as software for image analysis, determination of the presence/absence of microbial growth and enumeration of colonies (if present). A list of the major sub-components of the APAS Compact is depicted in Table 1. The Urine Analysis Module software is compatible with the following types of culture media:

- Tryptic Soy Sheep Blood Agar
- MacConkey Agar with Crystal Violet

Both the optical hardware for image acquisition and the Urine Analysis Module software used by the APAS Independence to analyze and interpret the digital images are the same as those used by the predicate APAS Compact with Urine Analysis Module (DEN150059).

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Table 1. Sub-components of the APAS Independence

|  Component | Function  |
| --- | --- |
|  Imaging Station | LED illumination of culture plates and image capture using a CCD camera  |
|  Plate Handling System | Movement, positioning and sorting of culture plates within the instrument  |
|  APAS Controller PC | Image capture, storage and analysis  |
|  Plate Controller PC | Controls movement of culture plates between the input carriers, imaging station and output carriers or stacks  |
|  Instrument Controller PC | Provides the user interface for operation of the APAS Independence and coordinates the functions of the APAS and Plate Controller PCs  |
|  Urine Analysis Module Software | Installed on the APAS Controller PC to provide the configuration and instructions for image capture and analysis  |
|  LIMS Interface Software | Installed on the Instrument Controller PC to import other diagnostic information, such as microscopy or chemistry results, and provide context for interpretation of urine culture results Imported information may be applied to the system: “LIMS Force Flag”: automatically forces an APAS result to “Review” irrespective of the growth characteristics observed “LIMS Complementary Test Flag”: automatically changes a “Negative” designation to “Review” based on user defined rules applied to additional diagnostic information  |
|  Color Calibration Tool | Multicolored disk for calibration/checking of system optics  |
|  System Check | Simulated culture plates used to confirm instrument function  |

CCD: Charge Coupled Device LED: Light Emitting Diode; LIMS: Laboratory Information Management System; PC: Personal Computer

# B Principle of Operation:

The APAS Independence with Urine Analysis Module is designed for the assessment of microbial colonies on urine culture plates. The instrument comprises an imaging station for

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capture of images of urine culture plates, a plate handling system that moves plates between the input carriers, imaging station and output carriers or stacks, together with software for analysis of the images, assessment and enumeration of microbial colonies (if present) and result designation. Plates with growth are designated as either "Positive" or "Review" depending on the number of colonies present and their morphologic characteristics. All plates that exhibit growth therefore require follow up according to standard laboratory practice by a trained microbiologist. Those plates that are designated by the APAS Independence to have no growth may be discarded without further review.

The APAS Independence with Urine Analysis Module is indicated for screening paired sheep blood and MacConkey agar plates that are each inoculated with $1\mu \mathrm{L}$ of urine and which are incubated at $35\pm 2^{\circ}\mathrm{C}$ for 18 to 22 hours. The system takes digital images of each plate that are analyzed automatically to determine the number of colonies present and their associated morphologies. For each plate, the APAS Independence performs the following tasks:

a) Differentiates between areas of growth (colonies) and no growth (e.g., agar, labels, handwriting);
b) Differentiates areas that are required for interpretation of colony morphology (e.g., $\alpha$- and $\beta$-hemolysis);
c) Assigns to each area of growth a code that corresponds to a morphology type;
d) Estimates the number of colonies present, converts this number to an organism concentration in the original urine sample and reports this value in terms of colony forming units per milliliter (CFU/mL).
e) Generates a growth report including the sample and patient identifiers, type of growth present (if any), the colony count and any additional information pertaining to the patient that is obtained from the Laboratory Information Management System (LIMS).

The colony morphologies reported by the APAS Independence with Urine Analysis Module are shown in Table 2 for sheep blood agar and Table 3 for MacConkey agar. A "significant organism" at $10^{3}$ CFU/mL on the plate will trigger designation of that plate as "Positive," as opposed to "Review." Plates that are designated as "Positive" or "Review" are required to undergo further evaluation by a clinical microbiologist.

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Table 2. Colony morphologies on sheep blood agar identified by APAS Independence with Urine Analysis Module

|  Morphology Name | Description  |
| --- | --- |
|  Coliform^{1} | Gram-negative and coliform-like colonies  |
|  Cream-white | Staphylococcus and related species  |
|  Granular | Granular morphologies (e.g., Pseudomonas spp.)  |
|  Small | Enterococcus spp. and related species  |
|  Small α-hemolytic | Small colonies with α-hemolysis or very small colonies  |
|  Small β-hemolytic^{1} | Small colonies with β-hemolysis  |
|  Swarming organism | Proteus spp. and related, high-motility species  |

1 “Significant organism;” refer to Table 4

Table 3. Colony morphologies on MacConkey agar identified by APAS Independence with Urine Analysis Module

|  Morphology Name | Description  |
| --- | --- |
|  Lactose fermenter^{1} | Pink/red colonies  |
|  Non-fermenter | Colonies without red/pink pigment  |
|  Non-fermenter with green pigment | Pseudomonas spp.  |
|  Red pigmented colonies | Pigmented Serratia marcescens  |

1 “Significant organism;” refer to Table 4

The interpretation of the growth follows a decision tree that combines information regarding the number of colonies present with their morphological characteristics to designate each plate as either “Positive”, “Review”, “Negative” or “Indeterminate,” as shown in Table 4.

Table 4. Result interpretation for APAS Independence with Urine Analysis Module

|  Colony Count (CFU/mL) | Morphology | APAS Compact Designation  |
| --- | --- | --- |
|  Indeterminate | Swarming organism | Positive  |
|  ≥10^{4} | Any  |   |
|  10^{3} | Significant organism^{1}  |   |
|  10^{3} | No significant organism | Review  |
|  0 | Not Applicable | Negative  |

1 Defined as growth of coliform-like colonies or small colonies with β-hemolysis on blood agar, or colonies of lactose fermenting bacteria on MacConkey agar

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C Instrument Description Information:

|  Modes of Operation | Yes | No  |
| --- | --- | --- |
|  Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? | ☑ | ☐  |
|  Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? | ☐ | ☑  |
|  Software  |   |   |
|  FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types. | ☑ | ☐  |

1. Instrument Name:
APAS Independence

2. Specimen Identification:
Plates are identified using an integrated barcode scanner within the Imaging Module of the APAS Independence. The identity of each plate is displayed on the results screen and transmitted automatically to the LIS.

3. Specimen Sampling and Handling:
The operator loads carriers containing culture plates into the Input Module of the APAS Independence from which they are moved automatically, one plate at a time, to the Imaging Module where the barcode is read, the lid is removed and images of the agar surface are captured. Upon completion of image capture and analysis, the plate lid is replaced and the system automatically sorts each plate based on its designation into the appropriate carrier in the Output Module.

4. Calibration:
The APAS Independence requires daily color calibration prior to use. Calibration is performed using the Color Calibration Tool provided with the instrument. Instructions for calibration are included in the APAS Independence User Manual.

5. Quality Control:
In addition to daily calibration, a System Check must be performed using the manufacturer-supplied Part 1 and Part 2 plate tools prior to analysis of urine culture plates. If the System Check fails, the instrument should be locked to prevent processing of additional culture plates until has been service has been performed.

Instructions for daily Quality Control testing using reference culture plates inoculated with Enterococcus faecalis and Escherichia coli are provided in the User Manual for the APAS Independence with Urine Analysis Module. Both the appropriate colony morphology and colony count must be obtained for the results of the Quality Control testing to be considered acceptable.

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In the event of a failure, Quality Control testing should be repeated. If the repeated failure occurs, the instrument should not be used until it has been serviced.

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V Substantial Equivalence Information:

A Predicate Device Name(s):
APAS Compact with Urine Analysis Module

B Predicate 510(k) Number(s):
DEN150059

C Comparison with Predicate(s):

|  Device & Predicate Device(s): | K183648 | DEN150059  |
| --- | --- | --- |
|  Device Trade Name | APAS Independence with Urine Analysis Module | APAS Compact with Urine Analysis Module  |
|  General Device Characteristic Similarities |  |   |
|  Intended Use | The APAS Independence is an in vitro diagnostic system comprised of an instrument and software analysis module(s) for specific indications that are used to automate imaging and interpretation of microbial colonies on plates of solid culture media. | The APAS Compact is an in vitro diagnostic system comprised of an instrument and software analysis module(s) for specific indications that are used to automate imaging and interpretation of microbial colonies on plates of solid culture media.  |
|  Indications For Use | The APAS Independence is an in vitro diagnostic system comprised of an instrument for automated imaging of agar culture plates and a software analysis module for the following use: The APAS Independence, when | The APAS Compact is an in vitro diagnostic system comprised of an instrument for automated imaging of agar culture plates and a software analysis module for the following use: The APAS Compact, when using its urine analysis module,  |

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|  Device & Predicate Device(s): | K183648 | DEN150059  |
| --- | --- | --- |
|   | using its urine analysis module, automates urine culture plate imaging and interpretation to detect the presence or absence of microbial growth on sheep blood and MacConkey agar culture plates that are inoculated with a 1μL sample volume. The APAS Independence, when using its urine analysis module, provides a semiquantitative assessment of colony counts that are used as an aid in the diagnosis of urinary tract infection. All urine culture plates that are identified as positive for growth by the APAS Independence, when using its urine analysis module, must be reviewed by a trained microbiologist. | automates urine culture plate imaging and interpretation to detect the presence or absence of microbial growth on sheep blood and MacConkey agar culture plates that are inoculated with a 1μL sample volume. The APAS Compact, when using its urine analysis module, provides a semi-quantitative assessment of colony counts that are used as an aid in the diagnosis of urinary tract infection. All urine culture plates that are identified as positive for growth by the APAS Compact, when using its urine analysis module, must be reviewed by a trained microbiologist.  |
|  Imaging Station | Light Emitting Diode (LED) illumination of culture plates and image capture using a Charged Coupled Device (CCD) camera | Same  |
|  APAS Controller PC | Controls image capture, analysis, report generation and result storage | Same  |
|  Urine Analysis Module | Installed on the APAS Controller PC to provide the configuration and instructions for image | Same  |

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|  Device & Predicate Device(s): | K183648 | DEN150059  |
| --- | --- | --- |
|   | capture and analysis |   |
|  Calibration | Performed daily using a manufacturer-provided Color Calibration Tool | Same  |
|  Biological Quality Control | Performed daily using standardized suspensions of Escherichia coli and Enterococcus faecalis | Same  |
|  General Device Characteristic Differences |  |   |
|  Plate Handling | Automated | Manual  |
|  Instrument Controller PC | Provides the user interface for the APAS Independence and controls plate movement | Provides the user interface for the APAS Compact  |
|  Laboratory Information System (LIS) data import | Instrument Controller PC interfaces with an external LIS server | LIS simulator installed on the Instrument Controller PC  |
|  System Check | Performed daily using the manufacturer-provided System Check Tools to verify instrument and software functionality | None  |
|  Result Report | Separate report for each culture plate | Results for blood and MacConkey agar plates combined to provide a summary report for the sample  |

VI Standards/Guidance Documents Referenced:

ISO 14971 Medical devices - Application of Risk Management to Medical Devices; 2007.

IEC 61010-1: Safety requirements for electrical equipment for measurement, control and laboratory use - Part 1: General requirements; 2010, 3rd edition.

IEC 62304: Medical device software - Software life cycle processes; 2006.

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IEC 62366-1: Medical devices – Part 1: Application of usability engineering to medical devices; 2015.

IEC 61326-1: Electrical equipment for measurement, control and laboratory use - EMC Requirements – Part 1: General requirements; 2012.

IEC 61326-2-6: Electrical equipment for measurement, control and laboratory use - EMC Requirements - Part 2-6: Particular Requirements - In vitro diagnostic (IVD) medical Equipment; 2012.

CISPR 11 Ed. 5.1: Industrial, scientific and medical equipment - Radio frequency disturbance characteristics - Limits and methods of measurement; 2010.

## VII Performance Characteristics (if/when applicable):

### A Analytical Performance:

1. Precision/Reproducibility:

The precision and reproducibility of colony counts obtained with the APAS Independence with Urine Analysis Module was evaluated with three different instruments using dilutions of representative uropathogenic bacterial species (Escherichia coli, Streptococcus agalactiae and Enterococcus faecalis) grown on blood and MacConkey agar. Each dilution of organisms was plated in triplicate and incubated at $35 \pm 2^{\circ}\mathrm{C}$ for 18 hours. Plates from three dilutions that exhibited 0 to $>100$ colonies plate were included in the study. Five images of each plate were captured on each APAS Independence instrument in each of three different orientations (0, 120 and $270^{\circ}$). The mean, standard deviation and percent coefficient of variation of colony counts obtained for each organism dilution on each instrument and overall is presented in Tables 5 and 6, for blood and MacConkey agar respectively. The results of the study demonstrated that the precision and reproducibility of colony counts within and between instruments was acceptable.

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Table 5. Precision and reproducibility of colony counts on blood agar obtained with the APAS Independence with Urine Analysis Module

|  Escherichia coli  |   |   |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Dilution (Nominal CFU/plate) |   |   | 2 (>100) |   |   | 3 (10-99) |   |   | 5 (1-9)  |   |   |
|  Plate |   |   | 1 | 2 | 3 | 1 | 2 | 3 | 1 | 2 | 3  |
|  CFU | APAS 1 (by plate) | Mean | 72.6 | 113.0 | 123.1 | 70.7 | 47.5 | 50.1 | 1.7 | 9.9 | 3.3  |
|   |   |  SD | 1.6 | 2.4 | 1.1 | 2.7 | 0.6 | 0.9 | 0.5 | 0.4 | 0.5  |
|   |   |  %CV | 2.3 | 2.1 | 0.9 | 3.8 | 1.3 | 1.8 | 26.4 | 3.6 | 14.0  |
|   |  APAS 2 (by plate) | Mean | 74.1 | 116.7 | 123.0 | 66.3 | 45.8 | 46.4 | 1.1 | 8.0 | 3.3  |
|   |   |  SD | 8.0 | 9.3 | 6.2 | 2.0 | 1.8 | 1.0 | 0.5 | 0.7 | 0.5  |
|   |   |  %CV | 10.8 | 8.0 | 5.0 | 3.1 | 3.9 | 2.1 | 45.6 | 8.2 | 14.0  |
|   |  APAS 3 (by plate) | Mean | 77.0 | 116.3 | 125.6 | 83.9 | 48.9 | 52.5 | 1.9 | 10.5 | 3.8  |
|   |   |  SD | 2.5 | 2.3 | 0.8 | 4.6 | 0.7 | 1.1 | 0.3 | 0.6 | 0.4  |
|   |   |  %CV | 3.3 | 2.0 | 0.7 | 5.4 | 1.4 | 2.0 | 13.4 | 6.1 | 10.9  |
|   |  All APAS (by plate) | Mean | 74.6 | 115.3 | 123.9 | 73.6 | 47.4 | 49.6 | 1.6 | 9.5 | 3.4  |
|   |   |  SD | 5.2 | 5.8 | 3.8 | 8.2 | 1.7 | 2.7 | 0.5 | 1.2 | 0.5  |
|   |   |  %CV | 6.9 | 5.0 | 3.0 | 11.1 | 3.6 | 5.4 | 33.7 | 12.9 | 14.6  |
|   |  All APAS (by dilution) | Mean | 104.6 |   |   | 56.9 |   |   | 4.8  |   |   |
|   |   |  SD | 22.2 |   |   | 12.9 |   |   | 3.5  |   |   |
|   |   |  %CV | 21.2 |   |   | 22.7 |   |   | 71.7  |   |   |
|  Escherichia coli/Streptococcus agalactiae (mixed growth)  |   |   |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Dilution (Nominal CFU/plate) |   |   | 2 (>100) |   |   | 3 (10-99) |   |   | 5 (1-9)  |   |   |
|  Replicate (Plate) |   |   | 1 | 2 | 3 | 1 | 2 | 3 | 1 | 2 | 3  |
|  CFU | APAS 1 (by plate) | Mean | 218.5 | 184.7 | 159.2 | 78.9 | 59.8 | 80.6 | 9.9 | 8.7 | 18.1  |
|   |   |  SD | 7.8 | 9.6 | 8.5 | 4.1 | 4.4 | 4.4 | 2.7 | 1.8 | 3.7  |
|   |   |  %CV | 3.6 | 5.2 | 5.4 | 5.1 | 7.4 | 5.4 | 27.6 | 20.1 | 20.2  |
|   |  APAS 2 (by plate) | Mean | 179.1 | 174.9 | 147.9 | 83.7 | 54.5 | 73.2 | 13.1 | 6.1 | 18.3  |
|   |   |  SD | 5.5 | 5.4 | 7.2 | 4.1 | 4.1 | 4.6 | 2.7 | 2.4 | 3.4  |
|   |   |  %CV | 3.1 | 3.1 | 4.9 | 4.9 | 7.5 | 6.2 | 21.0 | 39.6 | 18.3  |
|   |  APAS 3 (by plate) | Mean | 193.7 | 155.4 | 174.8 | 96.0 | 56.1 | 77.6 | 15.2 | 6.1 | 14.9  |
|   |   |  SD | 20.9 | 6.5 | 22.2 | 15.3 | 13.6 | 6.8 | 2.0 | 3.0 | 2.0  |
|   |   |  %CV | 10.8 | 4.2 | 12.7 | 15.9 | 24.3 | 8.8 | 13.4 | 48.5 | 13.3  |
|   |  All APAS (by plate) | Mean | 197.1 | 171.7 | 160.6 | 86.2 | 56.8 | 77.1 | 12.7 | 7.0 | 17.1  |
|   |   |  SD | 20.9 | 14.3 | 17.9 | 11.7 | 8.7 | 6.1 | 3.3 | 2.7 | 3.4  |
|   |   |  %CV | 10.6 | 8.3 | 11.1 | 13.6 | 15.3 | 7.9 | 26.1 | 38.5 | 19.9  |
|   |  All APAS (by dilution) | Mean | 176.5 |   |   | 73.4 |   |   | 12.3  |   |   |
|   |   |  SD | 23.5 |   |   | 15.3 |   |   | 5.2  |   |   |
|   |   |  %CV | 13.3 |   |   | 20.9 |   |   | 42.5  |   |   |

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|  Enterococcus faecalis  |   |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Dilution (Nominal CFU/plate) |   |   | 2 (>100) |   |   | 3 (10-99) |   |   | 5 (1-9)  |   |
|  Replicate (Plate) |   |   | 1 | 2 | 3 | 1 | 2 | 3 | 1 | 2  |
|  CFU | APAS 1(by plate) | Mean | 458.8 | 705.1 | 526.9 | 150.7 | 119.1 | 138.7 | 11.3 | 8.4  |
|   |   |  SD | 44.7 | 27.7 | 18.0 | 13.3 | 5.9 | 11.9 | 1.8 | 1.6  |
|   |   |  %CV | 9.7 | 3.9 | 3.4 | 8.8 | 4.9 | 8.6 | 15.9 | 19.0  |
|   |  APAS 2(by plate) | Mean | 504.1 | 721.0 | 531.1 | 137.3 | 134.7 | 152.3 | 12.3 | 5.7  |
|   |   |  SD | 8.6 | 54.8 | 14.7 | 7.5 | 9.6 | 7.7 | 1.5 | 1.2  |
|   |   |  %CV | 1.7 | 7.6 | 2.8 | 5.4 | 7.1 | 5.0 | 12.5 | 20.7  |
|   |  APAS 3(by plate) | Mean | 591.3 | 793.6 | 543.5 | 183.7 | 143.9 | 172.1 | 9.4 | 9.8  |
|   |   |  SD | 17.0 | 7.1 | 15.1 | 13.3 | 6.8 | 7.4 | 2.7 | 2.1  |
|   |   |  %CV | 2.9 | 0.9 | 2.8 | 7.2 | 4.7 | 4.3 | 29.2 | 21.5  |
|   |  All APAS(by plate) | Mean | 518.0 | 739.9 | 533.9 | 157.2 | 132.6 | 154.4 | 11.0 | 8.0  |
|   |   |  SD | 62.0 | 52.3 | 17.2 | 22.8 | 12.8 | 16.5 | 2.4 | 2.4  |
|   |   |  %CV | 12.0 | 7.1 | 3.2 | 14.5 | 9.6 | 10.7 | 21.7 | 30.0  |
|   |  All APA | Mean | 597.3 |   |   | 148.1 |   |   | 8.1  |   |
|   |   |  SD | 112.0 |   |   | 20.9 |   |   | 3.2  |   |
|   |   |  %CV | 18.8 |   |   | 14.1 |   |   | 38.8  |   |

CFU: Colony Forming Units; %CV: Percent Coefficient of variation; SD: Standard Deviation
Note: No colonies were detected by any of the APAS Independence Instruments on blood agar plates inoculated with saline (i.e., Mean CFU and SD = 0, in all cases).

Table 6. Precision and reproducibility of colony counts on MacConkey agar obtained with the APAS Independence with Urine Analysis Module

|  Escherichia coli  |   |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Dilution (Nominal CFU/plate) |   |   | 2 (>100) |   |   | 3 (10-99) |   |   | 5 (1-9)  |   |
|  Plate |   |   | 1 | 2 | 3 | 1 | 2 | 3 | 1 | 2  |
|  CFU | APAS 1(by plate) | Mean | 174.5 | 127.1 | 152.9 | 55.9 | 65.4 | 50.7 | 4.7 | 2.0  |
|   |   |  SD | 5.7 | 7.0 | 6.6 | 4.3 | 2.1 | 2.8 | 0.5 | 0.0  |
|   |   |  %CV | 3.3 | 5.5 | 4.3 | 7.7 | 3.2 | 5.5 | 10.5 | 0.0  |
|   |  APAS 2(by plate) | Mean | 163.7 | 121.2 | 142.0 | 54.8 | 70.3 | 46.5 | 4.0 | 2.2  |
|   |   |  SD | 3.7 | 1.9 | 2.4 | 1.1 | 1.6 | 2.2 | 0.7 | 0.4  |
|   |   |  %CV | 2.3 | 1.6 | 1.7 | 2.0 | 2.3 | 4.7 | 16.4 | 18.8  |
|   |  APAS 3(by plate) | Mean | 186.8 | 139.0 | 171.9 | 56.7 | 70.7 | 50.9 | 4.5 | 2.0  |
|   |   |  SD | 3.9 | 4.1 | 6.8 | 1.3 | 2.1 | 4.2 | 0.5 | 0.0  |
|   |   |  %CV | 2.1 | 3.0 | 4.0 | 2.3 | 2.9 | 8.3 | 11.4 | 0.0  |
|   |  All APAS(by plate) | Mean | 175.0 | 129.1 | 155.6 | 55.8 | 68.8 | 49.4 | 4.4 | 2.1  |
|   |   |  SD | 10.5 | 8.8 | 13.7 | 2.7 | 3.1 | 3.7 | 0.6 | 0.3  |
|   |   |  %CV | 6.0 | 6.8 | 8.8 | 4.8 | 4.5 | 7.6 | 14.0 | 12.2  |
|   |  All APAS(by dilution) | Mean | 153.2 |   |   | 58.0 |   |   | 2.8  |   |
|   |   |  SD | 21.9 |   |   | 8.7 |   |   | 1.3  |   |
|   |   |  %CV | 14.3 |   |   | 15.1 |   |   | 46.3  |   |

CFU: Colony Forming Units; %CV: Percent Coefficient of variation; SD: Standard Deviation
Note: No colonies were detected by any of the APAS Independence Instruments on MacConkey agar plates inoculated with saline (i.e., Mean CFU and SD = 0, in all cases).

K183648 - Page 13 of 20

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2. Linearity:

Agreement between manual colony counts and those obtained with the predicate APAS Compact with Urine Analysis Module was demonstrated under DEN150059. Because the APAS Independence with Urine Analysis Module uses the same hardware and software for image acquisition and analysis as the APAS Compact, additional testing to characterize the accuracy and linearity of colony counts was not needed. Please refer to the Decision Summary for DEN150059 for additional information.

3. Analytical Specificity/Interference:

The analytical specificity of the predicate APAS Compact with Urine Analysis Module was demonstrated under DEN150059. Because the APAS Independence with Urine Analysis Module uses the same hardware and software for image acquisition and analysis as the APAS Compact, additional testing to characterize the analytical specificity of the system was not needed. Please refer to the Decision Summary for DEN150059 for additional information.

4. Assay Reportable Range:

Refer to Table 4 and to Section VII A(2).

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

The device labeling indicates that the APAS Independence with Urine Analysis Module should not be used unless the system has passed the appropriate daily Quality Control (QC) checks. These include Color Calibration and a System Check using the optical tools that are provided with each instrument, as well as biological QC with standardized cultures of Enterococcus faecalis and Escherichia coli. Please refer to the Decision Summary for DEN150059 for information regarding the performance of the biological Quality Controls.

6. Detection Limit:

The limit of detection of the predicate APAS Compact with Urine Analysis Module was demonstrated under DEN150059. Because the APAS Independence with Urine Analysis Module uses the same hardware and software for image acquisition and analysis as the APAS Compact, additional testing to characterize the analytical sensitivity of the system was not needed. Please refer to the Decision Summary for DEN150059 for additional information.

7. Assay Cut-Off:

Not applicable.

8. Accuracy (Instrument):

Not applicable.

9. Carry-Over:

Not applicable.

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# B Comparison Studies:

# 1. Method Comparison with Predicate Device:

A Method Comparison Study was performed to demonstrate that the predicate APAS Compact (DEN150059) and APAS Independence exhibit similar performance with clinical specimens. In brief, residual clinical urine specimens that had originally been submitted for urinalysis, were inoculated onto bar code-labeled blood and MacConkey agar plates according to the instructions for use for the APAS Urine Analysis Module (1μL inoculum volume). The plates were incubated for 18 hours at  $35 \pm 2^{\circ}\mathrm{C}$  and images of each plate were then captured using one APAS Independence and one APAS Compact instrument system, each equipped with the Urine Analysis Module software. The images on each instrument were taken within 4 hours of completion of the specified incubation period.

A total of 550 urine specimens were initially enrolled in the study. Of these, the first 200 were excluded from the analysis of performance because the plate incubator exceeded the specified temperature. The results from the remaining 350 specimens were included in the analysis. A summary of the plate designations assigned by each instrument is shown on Table 7 and 8. In general, there was a high level of agreement ( $\sim99\%$ ) for plates designated as "Positive" by the two systems and there was a tendency for APAS Independence to designate more plates as "Positive" or "Review" than APAS Compact. This is also reflected in the tendency for higher colony counts to be reported by APAS Independence than by APAS Compact (Tables 9 and 10) and is considered acceptable without additional risk mitigation because both these designations require follow-up by a trained microbiologist.

Table 7. Summary of agreement in blood agar plate designation using the Urine Analysis Module software on the APAS Compact (predicate) and APAS Independence

|  Blood Agar Plate Designation | APAS Compact (predicate)  |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  Positive | Review | Negative | Total  |
|  APAS Independence | Positive | 232 | 5 | 1 | 238  |
|   |  Review | 3 | 32 | 15 | 50  |
|   |  Negative | 0 | 0 | 62 | 62  |
|   |  Total | 235 | 37 | 78 | 350  |
|  Designation Agreement (95% Confidence Interval) | 232/235 98.7% (96.3-99.6%) | 32/37 86.5% (72.0-94.1%) | 62/78 79.5% (69.2-87.0%) |   |   |
|   |   |  272/272 100%1 (98.6-100%) |   |   |   |

"Positive" and "Review" designations combined

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Table 8. Summary of agreement in MacConkey agar plate designation using the Urine Analysis Module software on the APAS Compact (predicate) and APAS Independence

|  MacConkey Agar Plate Designation | APAS Compact (predicate)  |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  Positive | Review | Negative | Total  |
|  APAS Independence | Positive | 133 | 1 | 8 | 142  |
|   |  Review | 0 | 4 | 15 | 19  |
|   |  Negative | 1 | 0 | 188 | 189  |
|   |  Total | 134 | 5 | 211 | 350  |
|  Designation Agreement (95% Confidence Interval) | 133/134 99.3% (95.9-99.9%) | 4/5 80.0% (37.6-96.4%) | 188/211 89.1% (84.2-92.6%) |   |   |
|   |   |  137/139 98.6%1 (94.9-99.6%) |   |   |   |

1 "Positive" and "Review" designations combined

Table 9. Summary of colony counts on blood agar obtained with the Urine Analysis Module software using the APAS Compact (predicate) and APAS Independence

|  Colony Counts on Blood Agar | APAS Compact CFU/mL (predicate)  |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  0 | \(10^3\) | \(10^4\) | \(10^5\) | IND | Total  |
|  APAS Independence CFU/mL | 0 | 62 | 0 | 0 | 0 | 0 | 62  |
|   |  \(10^3\) | 15 | 47 | 0 | 0 | 0 | 62  |
|   |  \(10^4\) | 1 | 5 | 67 | 1 | 0 | 74  |
|   |  \(10^5\) | 0 | 0 | 7 | 132 | 0 | 139  |
|   |  IND | 0 | 0 | 0 | 0 | 13 | 13  |
|   |  Total | 78 | 52 | 74 | 133 | 13 | 350  |
|  % Independence < Compact |   | NA | 0 | 0 | 0.8 | NA |   |
|  % Independence = Compact |   | 79.5 | 90.4 | 90.5 | 99.2 | 100  |   |
|  % Independence > Compact |   | 20.5 | 9.6 | 9.5 | NA | NA  |   |

IND: Indeterminate (swarming organism); NA: Not applicable

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Table 10. Summary of colony counts on MacConkey agar obtained with the Urine Analysis Module software using the APAS Compact (predicate) and APAS Independence

|  Colony Counts on MacConkey Agar | APAS Compact CFU/mL (predicate)  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |   |  0 | 103 | 104 | 105 | Total  |
|  APAS Independence CFU/mL | 0 | 188 | 11 | 0 | 0 | 189  |
|   |  103 | 15 | 26 | 0 | 0 | 41  |
|   |  104 | 8 | 2 | 21 | 0 | 31  |
|   |  105 | 0 | 0 | 3 | 86 | 89  |
|   |  Total | 211 | 29 | 24 | 86 | 350  |
|  % Independence < Compact |   | NA | 3.4 | 0 | 0 |   |
|  % Independence = Compact |   | 89.1 | 89.7 | 87.5 | 100  |   |
|  % Independence > Compact |   | 10.9 | 6.9 | 12.5 | NA  |   |

NA: Not applicable
1 APAS Compact detected a single lactose fermenting colony that was not identified by APAS Independence

Tables 11 and 12 show a comparison of the colony morphology designations assigned to each plate by the APAS Compact and APAS Independence using the Urine Analysis Module. Although the positive and negative agreement differed for each colony morphology, these designations are provided to the operator for informational purposes and are not used in disposition of the plates as "Positive", "Review" or "Negative" and the performance was therefore determined to be acceptable without the need for additional risk mitigation.

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Table 11. Comparison of colony morphologies on blood agar designated by the Urine Analysis Module using the APAS Compact (predicate) and APAS Independence

|  Alpha Hemolysis | APAS Compact (predicate)  |   |   |   |
| --- | --- | --- | --- | --- |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 61 | 43 | 104  |
|   |  Negative | 10 | 236 | 246  |
|   |  Total | 71 | 279 | 350  |
|  Agreement (95% Confidence Interval) | 61/71 | 236/279 |   |   |
|   |   |  85.9% (76.0-92.2%) | 84.6% (79.9-88.4%) |   |
|  Beta Hemolysis | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 106 | 38 | 144  |
|   |  Negative | 13 | 193 | 206  |
|   |  Total | 119 | 231 | 350  |
|  Agreement (95% Confidence Interval) | 106/119 | 193/231 |   |   |
|   |   |  89.1% (82.2-93.5%) | 83.5% (78.2-87.8%) |   |
|  Coliform | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 165 | 13 | 178  |
|   |  Negative | 4 | 168 | 172  |
|   |  Total | 169 | 181 | 350  |
|  Agreement (95% Confidence Interval) | 165/169 | 168/181 |   |   |
|   |   |  97.6% (94.1-99.1%) | 92.8% (88.1-95.8%) |   |
|  Swarming | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 13 | 0 | 13  |
|   |  Negative | 0 | 337 | 337  |
|   |  Total | 13 | 337 | 350  |
|  Agreement (95% Confidence Interval) | 13/13 | 337/337 |   |   |
|   |   |  100% (77.2-100%) | 100% (98.9-100%) |   |
|  Granular | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 18 | 1 | 19  |
|   |  Negative | 1 | 330 | 331  |
|   |  Total | 19 | 331 | 350  |
|  Agreement (95% Confidence Interval) | 18/19 | 330/331 |   |   |
|   |   |  94.7% (75.4-99.1%) | 99.7% (98.3-99.9%) |   |
|  Cream White | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 176 | 12 | 188  |
|   |  Negative | 17 | 145 | 162  |
|   |  Total | 193 | 157 | 350  |
|  Agreement (95% Confidence Interval) | 176/193 | 145/157 |   |   |
|   |   |  91.2% (86.3-94.4%) | 92.4% (87.1-95.6%) |   |
|  Small | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 195 | 44 | 239  |
|   |  Negative | 6 | 105 | 111  |
|   |  Total | 201 | 149 | 350  |
|  Agreement (95% Confidence Interval) | 195/201 | 105/149 |   |   |
|   |   |  97.0% (93.6-98.6%) | 70.5% (62.7-77.2%) |   |

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Table 12. Comparison of colony morphologies on MacConkey agar designated by the Urine Analysis Module using the APAS Compact (predicate) and APAS Independence

|  Lactose Fermenter | APAS Compact (predicate)  |   |   |   |
| --- | --- | --- | --- | --- |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 110 | 1 | 111  |
|   |  Negative | 3 | 236 | 239  |
|   |  Total | 113 | 237 | 350  |
|  Agreement (95% Confidence Interval) | 110/113 | 236/237 |   |   |
|   |   |  97.3% (92.5-99.1%) | 99.6% (97.6-99.9%) |   |
|  Non-Fermenter | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 51 | 33 | 84  |
|   |  Negative | 2 | 264 | 266  |
|   |  Total | 53 | 297 | 350  |
|  Agreement (95% Confidence Interval) | 51/53 | 264/297 |   |   |
|   |   |  96.2% (87.2-99.0%) | 88.9% (84.8-92.0%) |   |
|  Non-pigmented | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 1 | 0 | 1  |
|   |  Negative | 0 | 349 | 349  |
|   |  Total | 1 | 349 | 350  |
|  Agreement (95% Confidence Interval) | 1/1 | 349/349 |   |   |
|   |   |  100% (20.7-100%) | 100% (98.9-100%) |   |
|  Red-Pink | APAS Compact (predicate)  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  APAS Independence | Positive | 7 | 13 | 20  |
|   |  Negative | 0 | 330 | 330  |
|   |  Total | 7 | 343 | 350  |
|  Agreement (95% Confidence Interval) | 7/7 | 330/343 |   |   |
|   |   |  100% (64.6-100%) | 96.2% (93.6-97.8%) |   |

2. Matrix Comparison:

Not applicable.

C Clinical Studies:

1. Clinical Sensitivity:

The clinical performance of the predicate APAS Compact with Urine Analysis Module was evaluated under DEN150059. Because the APAS Independence with Urine Analysis Module uses the same hardware and software for image acquisition and analysis as the APAS Compact, additional testing to evaluate the sensitivity and specificity of the system was not needed. Please refer to the Decision Summary for DEN150059 for additional information.

2. Clinical Specificity:

Refer to Section VII C(1), above.

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3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

Not applicable.

D Clinical Cut-Off:

Not applicable.

E Expected Values/Reference Range:

Refer to Section VII C(1), above.

F Other Supportive Instrument Performance Characteristics Data:

Not applicable.

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

K183648 - Page 20 of 20

---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-c%E2%80%94microbiology-devices/PPU/K183648](https://fda.innolitics.com/submissions/MI/subpart-c%E2%80%94microbiology-devices/PPU/K183648)

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