(287 days)
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Not Found
Unknown
While the device uses image processing for automated interpretation, the summary does not explicitly mention AI, ML, or related terms like neural networks or deep learning. The description of the software analysis module and performance studies does not provide enough detail to definitively confirm or deny the use of these technologies.
No
The device is an in vitro diagnostic system used for automated imaging and analysis of urine culture plates to aid in the diagnosis of urinary tract infections, not for direct therapeutic intervention.
Yes
The device is described as an "in vitro diagnostic system" and its urine analysis module provides a "semiquantitative assessment of colony counts that are used as an aid in the diagnosis of urinary tract infection."
No
The device description explicitly states it is an "instrumented system" comprising an "imaging station" and software, indicating it includes hardware components in addition to the software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states that the APAS Compact is an "in vitro diagnostic system" and describes its use in automating urine culture plate imaging and interpretation to detect microbial growth. It also states that the results are used as an "aid in the diagnosis of urinary tract infection." These are all hallmarks of an IVD.
- Device Description: The description reinforces its function in screening urine culture plates for microbial growth, which is an in vitro process.
- Input Imaging Modality: The input is digital images of microbial colonies cultured on agar plates, which is an in vitro sample.
- Intended User/Care Setting: The intended user is a trained microbiologist in a laboratory setting, which is where in vitro diagnostic testing is typically performed.
- Summary of Performance Studies: The studies described involve testing remnant urine samples and comparing the device's performance to a manual reference method for reading culture plates. This is consistent with the evaluation of an IVD.
The core function of the device is to analyze biological samples (urine, after being cultured on agar) outside of the body to provide information that aids in diagnosis. This directly aligns with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
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, automates urine culture plate imaging and interpretation to detect the presence of microbial growth on sheep blood and MacConkey agar culture plates that are inoculated with a 1uL sample volume. The APAS Compact, 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 Compact, when using its urine analysis module, must be reviewed by a trained microbiologist.
Product codes
PPU
Device Description
The APAS Compact with Urine Analysis Module is an instrumented system that is designed for screening of urine culture plates for the presence of microbial growth. The device comprises an imaging station for capture of digital images of the culture plates, together with software for analysis of the images, the determination and enumeration of microbial growth and reporting of results. 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
Component: Imaging Station
Function: Light Emitting Diode (LED) illumination of culture plates and image capture using a Charge Coupled Device (CCD) camera
Component: APAS Controller Personal Computer (PC) Urine Analysis Module Software
Function: Image capture, storage and analysis Installed on the APAS Controller PC to provide the configuration and instructions for image capture and analysis
Component: Instrument Controller Software LIMS Interface Software
Function: User interface for operation of the APAS Compact Installed on the Instrument Controller PC and used 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
Component: Color Calibration Tool
Function: Multicolored disk for calibration of the system optics
The imaging station comprises a fixed CCD camera, top and bottom LED illumination for the culture plates and a plate handling mechanism, all of which are housed in a light-sealed chassis. The Instrument Controller PC provides the user interface and sends instructions to the APAS Controller PC which in turn controls the imaging station.
The plate handling mechanism of the imaging station comprises a manual lever that allows the operator to load a single culture plate into the system and position it for imaging. The operator then initiates image capture using the Instrument Controller PC. Once an image is taken by the camera it is sent to the APAS Controller PC for assessment and storage. APAS Compact reports are viewed on a separate computer through a dedicated user interface.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Digital images
Anatomical Site
Not Found
Indicated Patient Age Range
The summary indicates that samples were enrolled from subjects ranging from 80 years of age, with the majority from subjects between 20 and 79 years of age. However, the performance has not been evaluated with urine samples from pregnant women.
Intended User / Care Setting
Trained microbiologist / Clinical laboratory
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Sample Size: 9224 compliant urine samples (5634 from Site 1 (US), 1769 from Site 2 (ex-US), 1821 from Site 3 (ex-US)). Excluded 876 samples due to reasons like complicated UTI, read time, incomplete record, or LIMS Flag.
Data Source: Remnant urine samples leftover from standard of care culture for suspected UTI.
Annotation Protocol: Each urine sample was inoculated onto one sheep blood agar and one MacConkey agar culture plate (both Remel) and incubated for 18 hours at 35±2℃. Plates were analyzed by the APAS Compact and by an independent panel of three microbiologists. The microbiologists were trained to read the plates in a standard fashion and were blinded to other panel members' results and APAS Compact results. Colony counts by both methods were categorized into "No Growth," "10^3 CFU/mL," "10^4 CFU/mL," and "≥10^5 CFU/mL." For performance analysis, APAS Compact designations of "Review" and "Positive" were regarded as positive.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Clinical Studies (multi-site) and in-house analytical studies (precision/reproducibility, linearity/assay reportable range, analytical specificity, detection limit).
Sample Size:
- Clinical Studies: 9224 compliant urine samples from three sites.
- Precision/Reproducibility: Multiple runs using log10-fold dilutions of 0.5 McFarland standard suspensions of representative uropathogenic species on blood and MacConkey agar. Images were taken at 5 different orientations on each of 3 APAS Compact instruments.
- Linearity/Assay Reportable Range: 10-fold serial dilutions of bacterial cultures plated, read by two microbiologists manually (reference) and by APAS Compact in 5 different orientations.
- Analytical Specificity: Serial dilutions of pure and mixed cultures inoculated onto plates, incubated, and imaged by APAS Compact in 3 different orientations.
- Detection Limit: Representative panel of UTI pathogens diluted and inoculated onto plates, incubated until pinpoint colonies visible. APAS Compact used to capture images and measure colony diameter.
Standalone Performance (APAS Compact designates "Review" and "Positive" as positive):
- Detection of Growth on Blood Agar (Clinical Study):
- Overall Correct Designation for Any Growth: 99.0% (95% CI: 98.7, 99.2)
- False negative rate for detection of microbial growth on blood agar ranged from 0% to 2.9%.
- Detection of Growth on MacConkey Agar (Clinical Study):
- Overall Correct Designation for Any Growth: 99.5% (95% CI: 99.2, 99.7)
- False negative rate for detection of microbial growth on MacConkey agar ranged from 0% to 1.3%.
- Detection of Growth by Sample (Blood and MacConkey agars combined) (Clinical Study):
- Overall Correct Designation for Any Growth: 99.0% (95% CI: 98.7, 99.2)
Key Results:
- Precision/Reproducibility: Acceptable reproducibility of colony counts between instruments and rotations of the same plate was demonstrated.
- Linearity/Assay Reportable Range: All low counts obtained by APAS Compact were within 1-log10 of manual reference. APAS Compact did not incorrectly designate any cultures with growth as "Negative." Several cases where APAS Compact designated positive growth (≥10^3 CFU/mL) but reference reported no growth (mitigated by required microbiologist review).
- Analytical Specificity (Colony Morphology Assignment):
- Pure Cultures on Blood Agar: Agreed more than 98% for most species, except Aerococcus urinae (98.12%), Lactobacillus rhamnosus (22.23%), and Staphylococcus epidermidis (70.45%).
- Pure Cultures on MacConkey Agar: Agreed 100% for most species, Serratia marcescens at 77.8%.
- Mixed Cultures on Blood Agar (1:1 ratio): Mostly 100% agreement for both expected colony types, except for one instance with S. agalactiae in presence of E. faecalis (44.4% for S. agalactiae in 1:10 ratio, but still reported as "Positive").
- Mixed Cultures on MacConkey Agar: Mostly 100% agreement, with one image failing to detect both types but still reported as "Positive".
- The risk from incorrect colony morphology assignment is mitigated because any detected growth requires follow-up by a trained microbiologist.
- Detection Limit (LOD in mm at 95% CI):
- Blood Agar: Ranged from 0.625 mm (Streptococcus agalactiae) to 4.037 mm (Pseudomonas aeruginosa).
- MacConkey Agar: Ranged from 1.170 mm (Pseudomonas aeruginosa) to 1.613 mm (Serratia marcescens).
- Clinical Performance:
- Low false negative rates for growth detection (0-2.9% on blood agar, 0-1.3% on MacConkey agar).
- Colony count categories reported by APAS Compact were generally the same or higher than the reference.
- Instances where APAS Compact reported "Positive" or "Review" for "No Growth" reference results were deemed acceptable due to required microbiologist follow-up.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Overall Sensitivity for Detection of Growth (Any Growth on Blood Agar): 99.0% (95% CI: 98.7, 99.3)
- Overall Sensitivity for Detection of Growth (Any Growth on MacConkey Agar): 99.5% (95% CI: 99.2, 99.8)
- Overall Sensitivity for Detection of Growth (Any Growth on Blood and MacConkey Agars combined): 99.0% (95% CI: 98.7, 99.2)
Additional detailed percentages for correct designation in various growth categories and sites are provided in Tables 19, 20, and 21.
Correlation of colony count categories:
-
% APAS = Reference:
- Blood Agar:
- No Growth: 84.5%
- 10^3 CFU/mL: 82.5%
- 10^4 CFU/mL: 70.8%
- ≥10^5 CFU/mL: 97.0%
- MacConkey Agar:
- No Growth: 98.8%
- 10^3 CFU/mL: 90.5%
- 10^4 CFU/mL: 84.6%
- ≥10^5 CFU/mL: 97.2%
- Combined Agars:
- No Growth: 83.5%
- 10^3 CFU/mL: 82.9%
- 10^4 CFU/mL: 70.9%
- ≥10^5 CFU/mL: 97.5%
- Blood Agar:
-
% APAS Reference (False positive rate on colony counts):
- Blood Agar:
- No Growth: 15.5%
- 10^3 CFU/mL: 14.8%
- 10^4 CFU/mL: 21.7%
- MacConkey Agar:
- No Growth: 1.2%
- 10^3 CFU/mL: 8.1%
- 10^4 CFU/mL: 12.7%
- Combined Agars:
- No Growth: 16.5%
- 10^3 CFU/mL: 14.3%
- 10^4 CFU/mL: 21.7%
- Blood Agar:
(Note: NA means Not Applicable, typically where comparison is not meaningful, e.g., % APAS Manual for a '≥10^5' reference because counts cannot go lower than no growth or higher than the highest category.)
Predicate Device(s)
Not Found (De novo submission)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.2190 Automated image assessment system for microbial colonies on solid culture media.
(a)
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.(b)
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 820.30 compliant design control, 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.
0
EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR THE AGAR PLATE ASSESSMENT SYSTEM (APAS) COMPACT
DECISION MEMORANDUM
A. 510(k) Number:
B. Purpose for Submission:
De novo request for evaluation of automatic class III designation for the Agar Plate Assessment System (APAS) Compact
C. Measurand:
Digital images of microbial colonies cultured on blood and MacConkey agar plates
D. Type of Test:
The APAS Compact when using its Urine Analysis Module (the "APAS Compact" or the "APAS Compact with 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 (UT).
E. Applicant:
Clever Culture Systems AG
F. Proprietary and Established Names:
APAS Compact
G. Regulatory Information:
-
- Regulation section:
21 CFR 866.2190 Automated image assessment system for microbial colonies on solid culture media
- Regulation section:
-
- Classification:
Class II
- Classification:
-
- Product code:
PPU
- Product code:
1
4. Panel:
- 83 Microbiology
H. Indications for Use:
1. Indication(s) for Use:
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, automates urine culture plate imaging and interpretation to detect the presence of microbial growth on sheep blood and MacConkey agar culture plates that are inoculated with a 1uL sample volume. The APAS Compact, 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 Compact, when using its urine analysis module, must be reviewed by a trained microbiologist.
2. Special conditions for use statement(s):
For prescription use only.
The performance of APAS Compact with Urine Analysis Module has not been evaluated with urine samples from pregnant women. The APAS Compact with Urine Analysis Module will detect colonies of GBS if they are present but should not be used for the 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 Compact 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 of the culture result. APAS Compact with Urine Analysis Module should not be used to interpret cultures incubated for greater than 22 hours.
The APAS Compact with Urine Analysis Module is qualified for use with the following culture plates manufactured by Remel: Tryptic Soy Sheep Blood Agar and MacConkey Agar with Crystal Violet.
1 CDC Guidelines, 2010: Prevention of perinatal Group B Streptococcal disease.
2
3. Special instrument requirements:
APAS Compact
I. Device Description:
The APAS Compact with Urine Analysis Module is an instrumented system that is designed for screening of urine culture plates for the presence of microbial growth. The device comprises an imaging station for capture of digital images of the culture plates, together with software for analysis of the images, the determination and enumeration of microbial growth and reporting of results. 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
| Component | Function |
|---|---|
| Imaging Station | Light Emitting Diode (LED) illumination of culture |
| plates and image capture using a Charge Coupled | |
| Device (CCD) camera | |
| APAS Controller Personal Computer (PC) | |
| Urine Analysis Module Software | Image capture, storage and analysis |
| Installed on the APAS Controller PC to provide the | |
| configuration and instructions for image capture and | |
| analysis | |
| Instrument Controller Software | |
| LIMS Interface Software | User interface for operation of the APAS Compact |
| Installed on the Instrument Controller PC and used 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 of the system optics |
Table 1. Sub-components of the APAS Compact
The imaging station comprises a fixed CCD camera, top and bottom LED illumination for the culture plates and a plate handling mechanism, all of which are housed in a light-sealed chassis. The Instrument Controller PC provides the user interface and sends instructions to the APAS Controller PC which in turn controls the imaging station.
The plate handling mechanism of the imaging station comprises a manual lever that allows
3
the operator to load a single culture plate into the system and position it for imaging. The operator then initiates image capture using the Instrument Controller PC. Once an image is taken by the camera it is sent to the APAS Controller PC for assessment and storage. APAS Compact reports are viewed on a separate computer through a dedicated user interface.
J. Standard/Guidance Document Referenced (if applicable):
IEC 61010-1: Safety requirements for electrical equipment for measurement, control and laboratory use - Part 1: General requirements, 3rd Edition.
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, 2nd Edition.
IEC 62304 Medical device software - software lifecycle processes, 1st Edition.
ISO 14971 Medical devices - Application of Risk Management to Medical Devices, 2007.
CISPR 11 Industrial, scientific and medical equipment - radio frequency disturbance characteristics - Limits and methods of measurement, Version 5.1.
K. Test Principle:
The APAS Compact with Urine Analysis Module is designed for the assessment of microbial colonies on urine culture plates. The device comprises an imaging station for capture of images of the culture plates, together with software for analysis of the images, the assessment and enumeration of microbial colonies 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 samples that exhibit growth therefore require follow up according to standard laboratory practice by a trained microbiologist. Plates that are designated by the APAS Compact to have no growth may be discarded without further review.
The APAS Compact with Urine Analysis Module is indicated for screening paired sheep blood and MacConkey agar plates that are each inoculated with 1ul of urine and which are incubated at 35°C ± 2°C for 18 to 22 hours. For each urine sample, both culture plates must be processed on the APAS Compact. The system takes digital images of each plate which are analyzed automatically to determine the number of colonies present and their associated morphologies. For each plate, the APAS Compact 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., α- and β-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 it in terms of colony forming units per milliliter (CFU/mL).
4
The interpretation of the growth on a pair of plates follows a decision tree whereby the two plate reports are combined and a designation is made for the sample.
The colony morphologies reported by the APAS Compact with Urine Analysis Module are shown in Table 2 for sheep blood agar and Table 3 for MacConkey agar. A summary of the result logic used for automated interpretation of the colony counts and morphology is shown in Table 4. A "significant organism" at 103 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" undergo further evaluation by a clinical microbiologist.
Table 2. Colony morphologies on sheep blood agar identified by APAS Compact with Urine Analysis Module
| Morphology Name | Description |
|---|---|
| Coliform | 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 ß-hemolytic | Small colonies with ß-hemolysis |
| Swarming organism | Proteus spp. and related, high-motility species |
Table 3. Colony morphologies on MacConkey agar identified by APAS Compact with Urine Analysis Module
| Morphology Name | Description |
|---|---|
| Lactose fermenter | Pink/red colonies |
| Non-fermenter | Colonies without red/pink pigment |
| Non-fermenter with green pigment | Pseudomonas spp. |
| Red pigmented colonies | Pigmented Serratia marcescens |
Table 4. Result interpretation for APAS Compact with Urine Analysis Module
| Colony Count (CFU/mL) | Morphology | APAS Compact Designation |
|---|---|---|
| Not Applicable | Swarming organism | |
| $>=10^4$ | Any | Positive |
| $10^3$ | Significant organism1 | |
| $10^3$ | No significant organism | Review |
| 0 | Not Applicable | Negative |
1 Defined as growth of coliform or small colonies with B-hemolysis on blood agar or lactose fermenting colonies on MacConkey agar
5
L. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
The reproducibility of colony counts performed by the APAS Compact with Urine Analysis Module was evaluated on different instruments over multiple runs. Testing was performed using logio-fold dilutions of 0.5 McFarland standard suspensions of representative uropathogenic species that produced from 0 to >100 colonies per plate. Each dilution was plated in triplicate and incubated for 18 hours at 35°C. Images of each plate were taken at 5 different orientations (0, 60, 120, 180 and 270°) on each of 3 APAS Compact instruments. The mean and standard deviation of the resulting colony counts was determined for each dilution on each instrument and overall (Tables 5 and 6). The results demonstrated acceptable reproducibility of colony counts between instruments and rotations of the same plate.
6
| Species | Dilution1 | Replicate | Instrument 1 | Instrument 2 | Instrument 3 | Overall | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | %CV | Mean | %CV | Mean | %CV | Mean | %CV | Mean | %CV | |||
| E. coli | 3 | 1 | 76.2 | 1.9 | 83.2 | 4.4 | 74.0 | 2.1 | 77.8 | 6.0 | 78.3 | 7.0 |
| 3 | 2 | 85.8 | 3.6 | 82.8 | 4.2 | 82.6 | 1.8 | 83.7 | 3.6 | |||
| 3 | 3 | 72.8 | 2.5 | 73.6 | 2.6 | 73.4 | 3.7 | 73.3 | 2.8 | |||
| 4 | 1 | 8.6 | 10.3 | 8.2 | 5.5 | 8.2 | 5.5 | 8.3 | 7.5 | 18.6 | 39.2 | |
| E. coli | 4 | 2 | 23.2 | 1.9 | 23.8 | 1.9 | 23.0 | 0.0 | 23.3 | 2.1 | ||
| 4 | 3 | 23.8 | 1.9 | 23.8 | 6.2 | 24.4 | 2.3 | 24.0 | 3.9 | |||
| 5 | 1 | 5.6 | 9.8 | 5.6 | 9.8 | 5.6 | 9.8 | 5.6 | 9.1 | 3.2 | 75.0 | |
| 5 | 2 | 4.0 | 0.0 | 4.0 | 0.0 | 4.0 | 0.0 | 4.0 | 0.0 | |||
| 5 | 3 | 0.0 | NA | 0.0 | NA | 0.0 | NA | 0.0 | NA | |||
| 3 | 1 | 207.8 | 5.54 | 242.4 | 6.16 | 165.0 | 5.7 | 205.1 | 16.9 | 202.2 | 38.0 | |
| 3 | 2 | 141.8 | 6.09 | 135.6 | 10.18 | 108.6 | 4.3 | 128.7 | 13.6 | |||
| 3 | 3 | 345.6 | 10.60 | 297.6 | 4.23 | 175.6 | 4.0 | 272.9 | 28.2 | |||
| 4 | 1 | 14.4 | 6.18 | 16.4 | 13.35 | 15.2 | 7.2 | 15.3 | 10.7 | 19.6 | 29.6 | |
| E. coli/S. agalactiae | 4 | 2 | 18.8 | 7.87 | 19.2 | 12.97 | 14.2 | 17.5 | 17.4 | 17.9 | ||
| 4 | 3 | 28.8 | 5.14 | 29.4 | 7.45 | 20.2 | 13.7 | 26.1 | 18.4 | |||
| 5 | 1 | 2.8 | 46.4 | 3.4 | 53.5 | 6.0 | 26.3 | 4.1 | 50.0 | 7.8 | 79.5 | |
| 5 | 2 | 15.6 | 17.3 | 17.6 | 9.5 | 14.8 | 13.9 | 16.0 | 14.8 | |||
| 5 | 3 | 3.4 | 33.5 | 3.0 | 23.7 | 3.6 | 50.6 | 3.3 | 37.3 | |||
| 3 | 1 | 326.0 | 9.0 | 317.6 | 3.6 | 292.8 | 1.8 | 312.1 | 7.2 | 271.1 | 18.6 | |
| 3 | 2 | 208.0 | 3.0 | 201.6 | 3.3 | 203.2 | 1.8 | 204.3 | 2.9 | |||
| 3 | 3 | 310.2 | 1.8 | 285.0 | 2.6 | 295.4 | 1.7 | 296.9 | 4.1 | |||
| 4 | 1 | 33.6 | 11.0 | 33.2 | 6.5 | 24.2 | 15.3 | 30.3 | 17.9 | 36.7 | 19.3 | |
| E. faecalis | 4 | 2 | 45.0 | 10.1 | 41.8 | 13.0 | 41.2 | 4.7 | 42.7 | 10.0 | ||
| 4 | 3 | 41.6 | 11.9 | 35.6 | 14.9 | 33.8 | 5.7 | 37.0 | 14.3 | |||
| 5 | 1 | 8.4 | 18.1 | 7.0 | 20.1 | 4.4 | 34.5 | 6.6 | 33.3 | 9.6 | 38.5 | |
| 5 | 2 | 8.4 | 27.4 | 9.4 | 17.8 | 8.8 | 14.8 | 8.9 | 19.4 | |||
| 5 | 3 | 14.4 | 18.8 | 14.6 | 20.9 | 11.4 | 17.1 | 13.5 | 21.1 | |||
| Saline | NA | 1 | 0.0 | NA | 0.2 | 225 | 0.0 | NA | 0.1 | 260.0 | 0.0 | NA |
| Saline | NA | 2 | 0.0 | NA | 0.0 | NA | 0.0 | NA | 0.0 | NA | ||
| Saline | NA | 3 | 0.0 | NA | 0.0 | NA | 0.2 | 225.0 | 0.1 | 260.0 |
Table 5. Reproducibility of colony counts on blood agar obtained by the APAS Compact with Urine Analysis Module
NA: Not Applicable; %CV: Percent Coefficient of Variation
¹ log10-fold dilution of 0.5 McFarland standard suspension
¹log₁₀-fold dilution of 0.5 McFarland standard suspension
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| Species | Dilution1 | Replicate | Instrument 1 | Instrument 2 | Instrument 3 | Overall | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | %CV | Mean | %CV | Mean | %CV | Mean | %CV | |||
| E. coli | 3 | 1 | 152.2 | 3.0 | 140.2 | 3.2 | 140.2 | 2.3 | 144.2 | 4.8 |
| 2 | 174.6 | 4.5 | 162.4 | 1.3 | 160.0 | 1.8 | 165.7 | 4.9 | ||
| 3 | 247.2 | 2.1 | 233.0 | 3.4 | 231.8 | 2.8 | 237.3 | 4.0 | ||
| E. coli | 4 | 1 | 48.2 | 5.4 | 41.0 | 1.7 | 42.4 | 5.9 | 43.9 | 8.6 |
| 2 | 48.8 | 3.9 | 49.2 | 2.2 | 47.6 | 3.2 | 48.5 | 3.3 | ||
| 3 | 44.2 | 2.5 | 44.6 | 7.9 | 43.6 | 3.5 | 44.1 | 4.9 | ||
| E. coli | 5 | 1 | 4.2 | 20.0 | 4.6 | 19.3 | 3.8 | 28.9 | 4.2 | 22.4 |
| 2 | 2.0 | 0.0 | 1.0 | 0.0 | 1.0 | 0.0 | 1.3 | 37.7 | ||
| 3 | 8.8 | 21.8 | 7.6 | 20.0 | 8.2 | 15.9 | 8.2 | 19.1 | ||
| Saline | 1 | 1 | 0.0 | NA | 0.0 | NA | 0.0 | NA | 0.0 | NA |
| 2 | 0.0 | NA | 0.0 | NA | 0.0 | NA | 0.0 | NA | ||
| 3 | 1.0 | 71.0 | 0.2 | 225.0 | 0.0 | NA | 0.4 | 157.5 | ||
| 182.4 | 22.5 | |||||||||
| 45.5 | 7.5 | |||||||||
| 4.6 | 65.2 | |||||||||
| 0.1 | 400.0 |
Table 6. Reproducibility of colony counts on MacConkey agar obtained by the APAS Compact with Urine Analysis Module
NA: Not Applicable; %CV: Percent Coefficient of Variation
1 log10-fold dilution of 0.5 McFarland standard suspension
8
b. Linearity/assay reportable range:
To determine the accuracy of colony counts obtained using the APAS Compact with Urine Analysis Module, a study was conducted using 10-fold serial dilutions of bacterial cultures that were plated on blood and/or MacConkey agar, as appropriate to the organism/organism combination. The plates were incubated and read independently by two microbiologists who each estimated colony counts. The mean of the two manual counts was used as the reference result for each plate. Each plate was also analyzed in 5 different orientations using APAS Compact with Urine Analysis Module (0, 60, 120, 180 and 270°). Note: plates that exhibited no growth on initial reading were imaged once and were not rotated to different orientations. The individual APAS Compact colony counts obtained with each plate in each orientation were compared to those obtained by the manual reference method. For analysis of the data, counts obtained by both APAS Compact and the reference method were each grouped into four categories as shown below:
| Colonies/plate | Category (CFU/mL)1 |
|---|---|
| 0 | No Growth |
| 1-9 | $10^3$ |
| 10-99 | $10^4$ |
| ≥100 | ≥ $10^5$ |
1 Based on a 1uL inoculum volume
The results presented in Tables 7 and 8 show that all low counts obtained by APAS Compact with Urine Analysis Module were within 1-log10 of those obtained by the manual reference method. APAS Compact did not incorrectly designate any of the cultures with growth as "Negative" and there were several cases in which APAS Compact designated plates as positive for growth (i.e., ≥10° CFU/mL) but for which no growth was reported by the reference method. Together with the results of the Clinical Study in Section L(3), these data indicate that there is low probability that the APAS Compact with Urine Analysis Module will produce false negative results due to the failure to detect visible microbial colonies. In addition, because any growth detected by the APAS Compact is subject to follow-up by a trained microbiologist. the risk to patients from incorrect assignment of colony counts by the instrument is mitigated. The results of this study are therefore acceptable and provide evidence of the accuracy of colony counts obtained using the APAS Compact with Urine Analysis Module.
9
| E. coli | Reference Method (CFU/mL) | |||||
|---|---|---|---|---|---|---|
| No Growth | 103 | 104 | ≥105 | Total | ||
| No Growth | 0 | 0 | 0 | 0 | 0 | |
| 103 | 3 | 37 | 2 | 0 | 42 | |
| APAS | ||||||
| (CFU/mL) | 104 | 0 | 8 | 50 | 5 | 63 |
| ≥105 | 0 | 0 | 13 | 110 | 123 | |
| Total | 3 | 45 | 65 | 115 | 228 | |
| % APAS Manual | 100 | 17.8 | 20.0 | NA | ||
| E. faecalis | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| No Growth | 0 | 0 | 0 | 0 | 0 | |
| 103 | 14 | 43 | 0 | 0 | 57 | |
| APAS | ||||||
| (CFU/mL) | 104 | 0 | 37 | 10 | 0 | 47 |
| ≥105 | 0 | 0 | 45 | 105 | 150 | |
| Total | 14 | 80 | 55 | 105 | 254 | |
| % APAS Manual | 100 | 46.3 | 81.8 | NA | ||
| P. vulgaris | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| No Growth | 0 | 0 | 0 | 0 | 0 | |
| 103 | 8 | 54 | 2 | 0 | 64 | |
| APAS | ||||||
| (CFU/mL) | 104 | 3 | 1 | 73 | 30 | 107 |
| ≥105 | 0 | 0 | 0 | 80 | 80 | |
| Total | 11 | 55 | 75 | 110 | 251 | |
| % APAS Manual | 100 | 1.8 | 0.0 | NA | ||
| P. aeruginosa | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| No Growth | 0 | 0 | 0 | 0 | 0 | |
| 103 | 0 | 38 | 0 | 0 | 38 | |
| APAS | ||||||
| (CFU/mL) | 104 | 0 | 21 | 32 | 0 | 53 |
| ≥105 | 0 | 0 | 23 | 125 | 148 | |
| Total | 0 | 59 | 55 | 125 | 239 | |
| % APAS S. saprophyticus | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 0 | 0 | 0 | 0 | 0 |
| 103 | 10 | 79 | 0 | 0 | 89 | |
| 104 | 5 | 1 | 50 | 5 | 61 | |
| ≥105 | 0 | 0 | 0 | 95 | 95 | |
| Total | 15 | 80 | 50 | 100 | 245 | |
| % APAS Manual | 100 | 1.3 | 0 | NA | ||
| E. coli/E. faecalis 1 | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 0 | 0 | 0 | 0 | 0 |
| 103 | 9 | 47 | 5 | 0 | 61 | |
| 104 | 0 | 21 | 65 | 8 | 94 | |
| ≥105 | 0 | 0 | 0 | 92 | 92 | |
| Total | 9 | 68 | 70 | 100 | 245 | |
| % APAS Manual | 100 | 30.9 | 0 | NA | ||
| E. coli/P. vulgaris/ | ||||||
| G. vaginalis 2 | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 0 | 0 | 0 | 0 | 0 |
| 103 | 5 | 61 | 0 | 0 | 66 | |
| 104 | 0 | 14 | 55 | 15 | 84 | |
| ≥105 | 0 | 0 | 0 | 85 | 85 | |
| Total | 5 | 75 | 55 | 100 | 235 | |
| % APAS Manual | 100 | 18.7 | 0 | NA |
Table 7. Correlation of colony count categories obtained on blood agar using the APAS Compact with Urine Analysis Module and the manual reference method
10
- I we spection of culture plates determined the presence of colonies of both 2. coli and be ratio of
equal numbers (1:1 ratio). However, no colonies with morphology consistent with G. vaginalis were observed.
11
| E. coli | Reference Method (CFU/mL) | |||||
|---|---|---|---|---|---|---|
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 0 | 0 | 0 | 0 | 0 |
| 103 | 0 | 56 | 0 | 0 | 56 | |
| 104 | 0 | 19 | 65 | 0 | 84 | |
| ≥105 | 0 | 0 | 5 | 105 | 110 | |
| Total | 0 | 75 | 70 | 105 | 250 | |
| % APAS Manual | NA | 25.3 | 7.1 | NA | ||
| P. aeruginosa | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 0 | 0 | 0 | 0 | 0 |
| 103 | 0 | 29 | 0 | 0 | 29 | |
| 104 | 0 | 26 | 40 | 5 | 71 | |
| ≥105 | 0 | 0 | 35 | 69 | 104 | |
| Total | 0 | 55 | 75 | 74 | 204 | |
| % APAS Manual | NA | 47.3 | 46.7 | NA | ||
| P. vulgaris | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 0 | 0 | 0 | 0 | 0 |
| 103 | 0 | 64 | 9 | 0 | 73 | |
| 104 | 0 | 1 | 61 | 7 | 69 | |
| ≥105 | 0 | 0 | 0 | 103 | 103 | |
| Total | 0 | 65 | 70 | 110 | 245 | |
| % APAS Manual | NA | 1.5 | 0 | NA |
Table 8. Correlation of colony count categories obtained on MacConkey agar using the APAS Compact with Urine Analysis Module and the manual reference method
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The instructions for use indicate that the APAS Compact requires daily calibration using a dedicated optical tool that is provided with the instrument. Daily calibration of the instruments was performed throughout the analytical and clinical studies that were conducted to evaluate the performance of the device. None of the instruments failed calibration during the course of these studies.
In addition to daily optical calibration, the instructions for use indicate that operators should also perform a daily functional quality control check with cultures of Enterococcus faecalis and Escherichia coli grown on blood and MacConkey agar, respectively. In order to pass, the results from both culture media must meet the prescribed acceptance criteria for colony count and morphological designation. In
12
addition, uninoculated plates of both types should exhibit no growth. Table 9 shows the results obtained from Quality Controls runs performed during the APAS Compact clinical studies. The expected results were obtained with all (100%) positive controls on both blood and MacConkey agar. For the negative controls, the expected results were obtained with 98.4% on blood agar and 100% on MacConkey agar.
| Site | Instrument | Positive Control | Negative Control | ||
|---|---|---|---|---|---|
| Tested | Expected Result (%) | ||||
| Blood MacConkey | Tested | Expected Result (%) | |||
| Blood MacConkey | |||||
| 1 | 11 | 50 | 50 (100) 50 (100) | 50 | 49 (98.0)3 50 (100) |
| 1 | 22 | 49 | 49 (100) 49 (100) | 49 | 49 (100) 49 (100) |
| 2 | 3 | 13 | 13 (100) 13 (100) | Note Done4 | Not Done Not Done |
| 3 | 4 | 29 | 29 (100) 29 (100) | 30 | 29 (96.7)3 30 (100) |
| Total | 141 | 141 (100) 141 (100) | 129 | 127 (98.4) 129 (100) |
Table 9. Results of Quality Control testing performed during the APAS Compact clinical studies
1 Negative Control for blood agar and 1 for MacConkey agar gave positive results due to artifacts on the plate. Positive and Negative QC runs for both days were repeated successfully.
2 Negative Controls for blood agar gave positive results due to artifacts on the plate. Positive and Negative QC runs for that day were repeated successfully.
3 Both Negative Control failures on blood agar were due to the presence of a single contaminating colony.
4 The study at Site 2 was completed prior to the implementation of daily Negative Control testing.
d. Detection Limit:
Detection of colonies by the APAS Compact is, in part, dependent upon colony size. A study was therefore conducted using a representative panel of UTI pathogens to determine the effect of colony size of the ability to detect growth. The organisms in the study were selected to include species that exhibit each of the characteristic morphologies used by the Urine Analysis Module software for designation of results.
Each organism in the study was diluted to different concentrations and inoculated onto blood and/or MacConkey agar plates which were incubated at 35±2°C until pin point colonies were visible to the naked eye. Images of the plates were then captured by the APAS Compact and the operator digitally labeled multiple isolated colonies to measure their diameter. The image of each plate was then analyzed using the Urine Analysis Module software to generate the corresponding APAS Compact result. The measurements of the colonies that were successfully detected by the APAS Compact were used to calculate the minimum colony size for each organism that could be detected with 95% probability. Results of the study are presented in Tables 10 and 11 and demonstrate the limits of colony size that can be detected reliably by the APAS Compact with Urine Analysis Module.
13
Table 10. Limits of detection (LOD) of the APAS Compact with Urine Analysis Module for organisms cultured on blood agar
| Detected | | | Not Detected | | | LOD in mm
(95% CI) | |
|---------------------------------|-----|----------------------|--------------|-----|----------------------|-----------------------|-------------------------|
| | N | Colony Diameter (mm) | | N | Colony Diameter (mm) | | |
| | | Min | Max | | Min | Max | |
| Aerococcus viridans | 141 | 0.272 | 1.268 | 81 | 0.272 | 1.178 | 1.258
(1.049, 1.692) |
| Enterococcus faecalis | 225 | 0.181 | 1.178 | 165 | 0.181 | 1.087 | 0.856
(0.776, 0.980) |
| Escherichia coli | 240 | 0.181 | 1.721 | 123 | 0.181 | 0.906 | 0.899
(0.821, 1.024) |
| Proteus mirabilis | 140 | 0.634 | 2.808 | 281 | 0.181 | 2.717 | 2.501
(2.168, 3.091) |
| Pseudomonas aeruginosa | 238 | 0.453 | 3.442 | 153 | 0.181 | 2.355 | 4.037
(2.881, 7.121) |
| Staphylococcus
saprophyticus | 121 | 0.362 | 0.996 | 98 | 0.181 | 0.906 | 0.877
(0.784, 1.049) |
| Streptococcus agalactiae | 120 | 0.362 | 0.725 | 138 | 0.181 | 0.725 | 0.625
(0.584, 0.697) |
N: number of colonies; Min: minimum; Max: maximum
Table 11. Limits of detection (LOD) of the APAS Compact with Urine Analysis Module for organisms cultured on MacConkey agar
| Detected | Not Detected | |||||||
|---|---|---|---|---|---|---|---|---|
| N | Colony Diameter (mm) | Colony Diameter (mm) | LOD in mm | |||||
| (95% CI) | ||||||||
| Min | Max | N | Min | Max | ||||
| Escherichia coli | 112 | 0.996 | 2.264 | 136 | 0.362 | 1.178 | 1.253 | |
| (1.214, 1.324) | ||||||||
| Morganella morganii | 170 | 0.634 | 1.721 | 170 | 0.272 | 1.268 | 1.262 | |
| (1.164, 1.421) | ||||||||
| Pseudomonas aeruginosa | 48 | 0.634 | 2.989 | 78 | 0.181 | 1.087 | 1.170 | |
| (1.020, 1.596) | ||||||||
| Serratia marcescens | 76 | 0.725 | 1.087 | 296 | 0.181 | 1.087 | 1.613 | |
| (1.398, 2.093) |
N: number of colonies; Min: minimum; Max: maximum
e. Analytical Specificity:
The ability of the APAS Compact with Urine Analysis Module to assign the appropriate colony morphology to different clinically relevant organisms associated with UTIs was evaluated by testing serial dilutions of both pure and mixed cultures. Dilutions of each organism or organism combination were inoculated in triplicate onto the appropriate culture plates which were incubated at 35±2℃ for 18 hours. The APAS Compact was used to capture images of plates that exhibited 1-100 individual colonies or areas of confluent growth and >100 isolated colonies. Each plate was read on the APAS Compact instrument in 3 different orientations (0, 120 and 270°). The plates were then re-incubated and imaged again after 20 and 22 hours. Results for assignment of colony morphology are shown for pure and mixed cultures below in Tables 12-15. The percentage of plate images with at least one colony of the expected morphology is reported as agreement.
14
Pure Cultures
With pure cultures on blood agar, the APAS Compact with Urine Analysis Module reported detection of the expected colony morphology on each image for all the species tested at each time point except with Aerococcus urinae, Lactobacillus rhamnosus, Pseudomonas aeruginosa and Staphylococcus epidermidis (Table 12). For all species except A. urinae and L. rhamnosus, the APAS Compact designation of each plate at each time point was either "Positive" or "Review."
For S. marcescens on MacConkey agar, the expected morphology was observed on all plates after 20 and 22 hours of incubation but not after 18 hours (Table 13). All images of cultures on MacConkey agar were designated as "Positive" by the APAS Compact.
Table 12. Detection of expected colony morphology by the APAS Compact with Urine Analysis Module: pure cultures on blood agar
| Species | Expected Colony
Morphology | Agreement1 | |
|------------------------------|-------------------------------|--------------|---------|
| | | Number/Total | Percent |
| Aerococcus urinae | Small, alpha hemolytic | 53/54 | 98.12 |
| Aerococcus viridans | Small, alpha hemolytic | 54/54 | 100 |
| Candida albicans | Small | 54/54 | 100 |
| Enterobacter cloacae | Coliform | 54/54 | 100 |
| Escherichia coli (strain 1) | Coliform | 54/54 | 100 |
| Escherichia coli (strain 2) | Coliform | 54/54 | 100 |
| Enterococcus faecalis | Small | 54/54 | 100 |
| Klebsiella pneumoniae | Coliform | 52/52 | 100 |
| Lactobacillus rhamnosus | Small | 6/27 | 22.23 |
| Morganella morganii | Coliform | 54/54 | 100 |
| Proteus mirabilis | Swarming | 54/54 | 100 |
| Pseudomonas aeruginosa | Granular | 50/51 | 98.04 |
| Staphylococcus aureus | Cream white | 54/54 | 100 |
| Staphylococcus epidermidis | Cream white | 38/54 | 70.45 |
| Staphylococcus saprophyticus | Cream white | 51/51 | 100 |
| Streptococcus agalactiae | Beta-hemolytic | 54/54 | 100 |
| Streptococcus dysgalactiae | Beta-hemolytic | 51/51 | 100 |
Note: The APAS Compact designation of each plate at each time point was either "Positive" for all species except A. urinae and L. rhamnosus
Number of plate images with at least one colony of the expected morphology (all time points and plate rotations combined)/total
ର Expected morphology detected: 18 hours: 18/18 (88.9%): 20 hours: 18/18 (100%): 22 hours: 17/18 (94.4%)
3 Expected morphology detected: 18 hours: 0/9 (0%); 20 hours: 0/9 (0%); 22 hours: 6/9 (66.7%)
4 Expected morphology detected: 18 hours: 18/18 (100%); 20 hours: 17/18 (94.4%); 22 hours: 15/15 (100%)
్ Expected morphology detected: 18 hours: 9/18 (50.0%); 20 hours: 11/18 (61.1%); 22 hours: 18/18 (100%)
15
Table 13. Detection of expected colony morphology by the APAS Compact with Urine Analysis Module: pure cultures on MacConkey agar
| Species | Expected Colony
Morphology | Agreement1 | |
|------------------------------|-------------------------------|--------------|---------|
| | | Number/Total | Percent |
| Citrobacter koseri | Non-fermenter | 53/53 | 100 |
| Escherichia coli | Lactose fermenter | 54/54 | 100 |
| Klebsiella pneumoniae | Lactose fermenter | 54/54 | 100 |
| Morganella morganii | Non-fermenter | 54/54 | 100 |
| Serratia marcescens 2 | Red pigment | 21/27 | 77.8 |
Note: All plate images of pure cultures on MacConkey agar were designated by APAS Compact as "Positive"
Number of plate images with at least one colony of the expected morphology (all time points and plate rotations combined)/total
2 Expected morphology detected: 3/9 (33.3%); 20 hours: 9/9 (100%); 22 hours: 9/9 (100%)
Mixed Cultures
For blood agar plates inoculated with two organisms at a 1:1 ratio, the APAS Compact reported detection of both the expected colony types at each time point in all but two images (Table 14). In both cases, the APAS Compact failed to detect the expected morphology for S. agalactiae in the presence of E. faecalis, although both images were reported as "Positive" indicating of the need for microbiological followup. With plates inoculated using a 1:10 ratio of S. agalactiae:E. faecalis there was a higher proportion of images in which colonies with the characteristic morphology of S. agalactiae were not detected. Nevertheless, all the images were still reported as "Positive."
For mixed cultures plated on MacConkey agar, both the expected colony types were detected in all but 1 image, although this image was still reported "Positive" by the instrument (Table 15).
Note: Because any growth detected by the APAS Compact with Urine Analysis Module is subject to follow-up by a trained microbiologist, the risk to patients from incorrect assignment of colony morphology by the instrument is mitigated.
Instructions for appropriate laboratory follow-up of any growth detected by the APAS Compact with Urine Analysis Module are included in the device labeling.
16
Table 14. Detection of expected colony morphology by the APAS Compact with Urine Analysis Module: mixed cultures on blood agar
| Species Name & Expected Morphology | Agreement (%) 2 | |||||
|---|---|---|---|---|---|---|
| Species 1 | Species 2 | Mixture 1 | Species 1 | Species 2 | ||
| Escherichia coli | Coliform | Enterococcus faecalis | Small | 1:1 | 63/63 | |
| (100) | 63/63 | |||||
| (100) | ||||||
| 1:10 | 81/81 | |||||
| (100) | 81/81 | |||||
| (100) | ||||||
| Streptococcus agalactiae | Beta- | |||||
| hemolytic | Enterococcus faecalis | Small | 1:1 | 81/81 | ||
| (100) | 81/81 | |||||
| (100) | ||||||
| 1:10 | 28/63 | |||||
| (44.4) 3 | 63/63 | |||||
| (100) | ||||||
| Escherichia coli | Coliform | Staphylococcus | ||||
| saprophyticus | Cream | |||||
| white | 1:1 | 54/54 | ||||
| (100) | 54/54 | |||||
| (100) | ||||||
| 1:10 | 81/81 | |||||
| (100) | 81/81 | |||||
| (100) | ||||||
| Escherichia coli | Coliform | Aerococcus viridans | Alpha- | 1:1 | 81/81 | |
| (100) | 81/81 | |||||
| (100) | ||||||
| hemolytic | 1:10 | 81/81 | ||||
| (100) | 81/81 | |||||
| (100) |
Note: All plate images of mixed cultures on blood agar were designated by APAS Compact as "Positive"
Approximate ratio of concentration, Species 1:Species 2
ରା Number of plate images with at least one colony of the expected morphology (all time points and plate rotations combined)/total
3 Expected morphology detected: 18 hours: 12/21 (57.1%); 20 hours: 10/21 (47.6%); 22 hours: 6/21 (28.6%)
Table 15. Detection of expected colony morphology by the APAS Compact with Urine Analysis Module: mixed cultures on MacConkey agar
| Species Name & Expected Morphology | Agreement (%) 2 | |||||
|---|---|---|---|---|---|---|
| Species 1 | Species 2 | Mixture 1 | Species 1 | Species 2 | ||
| Escherichia coli | Lactose | |||||
| Fermenter | Morganella morganii | Non- | ||||
| fermenter | 1:1 | 53/53 | ||||
| (100) | 53/53 | |||||
| (100) | ||||||
| Escherichia coli | Lactose | |||||
| Fermenter | Morganella morganii | Non- | ||||
| fermenter | 1:10 | 79/80 | ||||
| (98.8) 3 | 80/80 | |||||
| (100) | ||||||
| Escherichia coli | Lactose | |||||
| Fermenter | Pseudomonas aeruginosa | Non- | ||||
| fermenter | 1:1 | 81/81 | ||||
| (100) | 81/81 | |||||
| (100) | ||||||
| Escherichia coli | Lactose | |||||
| Fermenter | Pseudomonas aeruginosa | Non- | ||||
| fermenter | 1:10 | 72/72 | ||||
| (100) | 72/72 | |||||
| (100) |
Instances of agreement with the expected morphology 80 years of age, with the majority from subjects between 20 and 79 years of age.
| Site1 | Male | Female | Not Known | Total | % Male | % Female |
|---|---|---|---|---|---|---|
| 1 | 972 | 4659 | 3 | 5634 | 17.3 | 82.7 |
| 2 | 702 | 1066 | 1 | 1769 | 39.7 | 60.3 |
| 3 | 810 | 1007 | 4 | 1821 | 44.6 | 55.4 |
| Total | 2484 | 6732 | 8 | 9224 | 27.0 | 73.0 |
Table 17. Gender distribution of donors of urine samples enrolled in the clinical studies
- Site 1: US; Sites 2 and 3: ex-US
| Site1 | |||||
|---|---|---|---|---|---|
| Age (years) | 1 | 2 | 3 | Total | % |
| ≤20 | 747 | 154 | 97 | 998 | 10.8 |
| 20-39 | 1611 | 415 | 458 | 2384 | 25.9 |
| 40-59 | 1247 | 440 | 450 | 2137 | 23.2 |
| 60-79 | 1460 | 548 | 614 | 2622 | 28.4 |
| ≥80 | 567 | 212 | 300 | 1079 | 11.7 |
| Not Known | 2 | 0 | 2 | 4 | 0.0 |
| 5634 | 1769 | 1821 | 9224 | 100 |
Table 18. Age distribution of urine sample donors in the clinical studies
1 Site 1: US; Sites 2 and 3: ex-US
A summary of the APAS Compact designation for samples from the clinical studies in relation to colony counts as determined by the reference microbiologist panel is shown in Tables 19-21. Colony counts by both methods were categorized as described in Section L(1)(b). Across all sites combined, the APAS Compact correctly designated 99.0% (95% confidence interval: 98.7-99.2%) of cultures on blood agar and 99.5% (95% CI: 99.2-99.7%) of cultures on MacConkey agar as positive for growth. Depending on the colony count observed by the microbiologist panel, the false negative rate for detection of microbial growth on blood agar ranged from 0% to 2.9% and on MacConkey agar from 0% to 1.3%.
False-negative results with the APAS Compact for the detection of growth could lead to discard of culture plates without further review. The results of this study demonstrate that the likelihood of such results is acceptably low.
Tables 22, 23 and 24 show the correlation of colony count categories obtained by the APAS Compact and by the reference method. In general, the colony count categories reported by the APAS Compact were the same or higher than those obtained by the reference method, and there were multiple instances in which APAS Compact designated plates that exhibited "No Growth" according to the reference method as "Positive" or "Review." This is acceptable because all cultures designated by APAS Compact as "Positive" or "Review" are subject to further microbiological follow-up and any such incorrect designations do not increase risks to patients.
19
| Site 1 | Reference Result | APAS Designation | | | Total | Correct 2 | % Correct
(95% CI) |
|--------|------------------|------------------|------|------|-------|-----------|-----------------------|
| 1 | No Growth | 1220 | 14 | 256 | 1490 | 1220 | 81.9 (79.8, 83.8) |
| 1 | 103 CFU/mL | 37 | 393 | 845 | 1275 | 1238 | 97.1 (96.0, 97.9) |
| 1 | 104 CFU/mL | 4 | 1089 | 74 | 1167 | 1163 | 99.7 (99.1, 99.9) |
| 1 | ≥105 CFU/mL | 0 | 1700 | 2 | 1702 | 1702 | 100 (99.8, 100) |
| 1 | Any Growth | 41 | 3182 | 921 | 4144 | 4103 | 99.0 (98.7, 99.3) |
| 2 | No Growth | 438 | 18 | 57 | 513 | 438 | 85.4 (82.1, 88.2) |
| 2 | 103 CFU/mL | 13 | 152 | 308 | 473 | 460 | 97.3 (95.4, 98.4) |
| 2 | 104 CFU/mL | 2 | 461 | 25 | 488 | 486 | 99.6 (98.5, 99.9) |
| 2 | ≥105 CFU/mL | 0 | 295 | 0 | 295 | 295 | 100 (98.7, 100) |
| 2 | Any Growth | 15 | 908 | 333 | 1256 | 1241 | 98.8 (98.0, 99.3) |
| 3 | No Growth | 574 | 2 | 61 | 637 | 574 | 90.1 (87.5, 92.2) |
| 3 | 103 CFU/mL | 8 | 101 | 262 | 371 | 363 | 97.8 (95.8, 98.9) |
| 3 | 104 CFU/mL | 2 | 355 | 23 | 380 | 378 | 99.5 (98.1, 99.9) |
| 3 | ≥105 CFU/mL | 3 | 422 | 8 | 433 | 430 | 99.3 (98.0, 99.8) |
| 3 | Any Growth | 13 | 878 | 293 | 1184 | 1171 | 98.9 (98.1, 99.4) |
| Total | No Growth | 2232 | 34 | 374 | 2640 | 2232 | 84.5 (83.1, 85.9) |
| Total | 103 CFU/mL | 46 | 646 | 1415 | 2119 | 2061 | 97.3 (96.5, 97.9) |
| Total | 104 CFU/mL | 8 | 1905 | 122 | 2035 | 2027 | 99.6 (99.2, 99.8) |
| Total | ≥105 CFU/mL | 3 | 2417 | 10 | 2430 | 2427 | 99.9 (99.6, 100) |
| Total | Any Growth | 69 | 4968 | 1547 | 6584 | 6515 | 99.0 (98.7. 99.2) |
Table 19. Performance of the APAS Compact with Urine Analysis Module for detection of growth on blood agar
CI: 95% score Confidence Interval
Site 1: US; Sites 2 and 3: ex-US
4 For the purposes of data analysis, APAS Compact designations of "Positive" were both considered indicative of microbial growth.
For a Reference Result of No Growth, an APAS Compact designation of "Negative" was considered correct.
For Reference Results of 10, 10, ≥10 CFU/nL or Any Growth, an APAS Compact designation of "Positive" or "Review" was considered correct.
20
| Site 1 | Reference Result | APAS Designation | Total | Correct | % Correct 2 (95% CI) | ||
|---|---|---|---|---|---|---|---|
| 1 | No Growth | 3274 | 23 | 37 | 3334 | 3274 | 98.2 (97.7, 98.6) |
| 1 | 103 CFU/mL | 6 | 406 | 67 | 479 | 473 | 98.7 (97.3, 99.4) |
| 1 | 104 CFU/mL | 1 | 469 | 8 | 478 | 477 | 99.8 (98.8, 100) |
| 1 | ≥105 CFU/mL | 2 | 1341 | 0 | 1343 | 1341 | 99.9 (99.5, 100) |
| 1 | Any Growth | 9 | 2216 | 75 | 2300 | 2291 | 99.6 (99.3, 99.8) |
| 2 | No Growth | 1257 | 4 | 4 | 1265 | 1257 | 99.4 (98.8, 99.7) |
| 2 | 103 CFU/mL | 2 | 136 | 48 | 186 | 184 | 98.9 (96.2, 99.7) |
| 2 | 104 CFU/mL | 1 | 152 | 1 | 154 | 153 | 99.4 (96.4, 99.9) |
| 2 | ≥105 CFU/mL | 0 | 164 | 0 | 164 | 164 | 100 (97.7, 100) |
| 2 | Any Growth | 3 | 452 | 49 | 504 | 501 | 99.4 (98.3, 99.8) |
| 3 | No Growth | 1241 | 2 | 0 | 1243 | 1241 | 99.8 (99.4, 100) |
| 3 | 103 CFU/mL | 3 | 105 | 39 | 147 | 144 | 98.0 (94.2, 99.3) |
| 3 | 104 CFU/mL | 1 | 144 | 1 | 146 | 145 | 99.3 (96.2, 99.9) |
| 3 | ≥105 CFU/mL | 0 | 285 | 0 | 285 | 285 | 100 (98.7, 100) |
| 3 | Any Growth | 4 | 534 | 40 | 578 | 574 | 99.3 (98.2, 99.7) |
| Total | No Growth | 5772 | 29 | 41 | 5842 | 5772 | 98.8 (98.5, 99.1) |
| Total | 103 CFU/mL | 11 | 647 | 154 | 812 | 801 | 98.6 (97.6, 99.2) |
| Total | 104 CFU/mL | 3 | 765 | 10 | 778 | 775 | 99.6 (98.9, 99.9) |
| Total | ≥105 CFU/mL | 2 | 1790 | 0 | 1792 | 1790 | 99.9 (99.6, 100) |
| Total | Any Growth | 16 | 3202 | 164 | 3382 | 3366 | 99.5 (99.2, 99.7) |
Table 20. Performance of the APAS Compact with Urine Analysis Module for detection of growth on MacConkey agar
CI: 95% score Confidence Interval ¹ Site 1: US; Sites 2 and 3: ex-US
2 For the purposes of data analysis, APAS Compact designations of "Review" and "Positive" were both considered indicative of microbial growth.
For a Reference Result of No Growth, an APAS Compact designation of "Negative" was considered correct.
For Reference Results of 10, 10, ≥10 CFU/nL or Any Growth, an APAS Compact designation of "Positive" or "Review" was considered correct.
21
Table 21. Performance of the APAS Compact with Urine Analysis Module for detection of growth by sample (blood and MacConkey agars combined)
| Site 1 | Reference Result | APAS Designation | | | Total | Correct | % Correct 2
(95% CI) |
|--------|------------------|------------------|------|------|-------|---------|-------------------------|
| 1 | No Growth | 1166 | 25 | 261 | 1452 | 1166 | 80.3 (78.2, 82.3) |
| | 103 CFU/mL | 37 | 463 | 780 | 1280 | 1243 | 97.1 (96.0, 97.9) |
| 1 | 104 CFU/mL | 4 | 1104 | 64 | 1172 | 1168 | 99.7 (99.1, 99.9) |
| | ≥105 CFU/mL | 0 | 1729 | 1 | 1730 | 1730 | 100 (99.8, 100) |
| | Any Growth | 41 | 3296 | 845 | 4182 | 4141 | 99.0 (98.7, 99.3) |
| 2 | No Growth | 429 | 19 | 57 | 505 | 429 | 85.0 (81.6, 87.8) |
| | 103 CFU/mL | 13 | 166 | 300 | 479 | 466 | 97.3 (95.4, 98.4) |
| 2 | 104 CFU/mL | 1 | 464 | 25 | 490 | 489 | 99.8 (98.9, 100) |
| | ≥105 CFU/mL | 0 | 295 | 0 | 295 | 295 | 100 (98.7, 100) |
| | Any Growth | 14 | 925 | 325 | 1264 | 1250 | 98.9 (98.1, 99.3) |
| 3 | No Growth | 555 | 3 | 60 | 618 | 555 | 89.8 (87.2, 92.0) |
| | 103 CFU/mL | 9 | 115 | 262 | 386 | 377 | 97.7 (95.6, 98.8) |
| 3 | 104 CFU/mL | 2 | 356 | 23 | 381 | 379 | 99.5 (98.1, 99.9) |
| | ≥105 CFU/mL | 3 | 426 | 7 | 436 | 433 | 99.0 (98.0, 99.8) |
| | Any Growth | 14 | 897 | 292 | 1203 | 1189 | 98.8 (98.1, 99.3) |
| Total | No Growth | 2150 | 47 | 378 | 2575 | 2150 | 83.5 (96.7, 99.1) |
| | 103 CFU/mL | 59 | 744 | 1342 | 2145 | 2086 | 97.2 (96.5, 97.9) |
| Total | 104 CFU/mL | 7 | 1924 | 112 | 2043 | 2036 | 99.7 (99.3, 99.8) |
| | ≥105 CFU/mL | 3 | 2450 | 8 | 2461 | 2458 | 99.9 (99.6, 100) |
| | Any Growth | 69 | 5118 | 1462 | 6649 | 6580 | 99.0 (98.7, 99.2) |
CI: 95% score Confidence Interval
¹ Site 1: US; Sites 2 and 3: ex-US
2 For the purposes of data analysis, APAS Compact designations of "Review" and "Positive" were both considered indicative of microbial growth.
For a Reference Result of No Growth, an APAS Compact designation of "Negative" was considered correct.
For Reference Results of 10, 10, ≥10 CFU/nL or Any Growth, an APAS Compact designation of "Positive" or "Review" was considered correct.
22
| Site 1 (US) | Reference Method (CFU/mL) | |||||
|---|---|---|---|---|---|---|
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 1220 | 37 | 4 | 0 | 1261 |
| 103 | 262 | 1049 | 87 | 2 | 1400 | |
| 104 | 7 | 182 | 828 | 27 | 1044 | |
| ≥105 | 1 | 7 | 248 | 1673 | 1929 | |
| Total | 1490 | 1275 | 1167 | 1702 | 5634 | |
| % APAS Reference | 18.1 | 14.8 | 21.3 | NA | ||
| Site 2 (ex-US) | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 438 | 13 | 2 | 0 | 453 |
| 103 | 68 | 388 | 31 | 1 | 488 | |
| 104 | 7 | 63 | 368 | 21 | 459 | |
| ≥105 | 0 | 9 | 87 | 273 | 369 | |
| Total | 513 | 473 | 488 | 295 | 1769 | |
| % APAS Reference | 14.6 | 15.2 | 17.8 | NA | ||
| Site 3 (ex-US) | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 574 | 8 | 2 | 3 | 587 |
| 103 | 63 | 312 | 27 | 8 | 410 | |
| 104 | 0 | 45 | 245 | 12 | 302 | |
| ≥105 | 0 | 6 | 106 | 410 | 522 | |
| Total | 637 | 371 | 380 | 433 | 1821 | |
| % APAS Reference | 9.9 | 13.7 | 27.9 | NA | ||
| All Sites Combined | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 2232 | 58 | 8 | 3 | 2301 |
| 103 | 393 | 1749 | 145 | 11 | 2298 | |
| 104 | 14 | 290 | 1441 | 60 | 1805 | |
| ≥105 | 1 | 22 | 441 | 2356 | 2820 | |
| Total | 2640 | 2119 | 2035 | 2430 | 9224 | |
| % APAS Reference | 1.8 | 6.9 | 12.3 | NA | ||
| Site 2 (ex-US) | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 1257 | 2 | 1 | 0 | 1260 |
| 103 | 8 | 168 | 4 | 0 | 180 | |
| 104 | 0 | 16 | 136 | 8 | 160 | |
| ≥105 | 0 | 0 | 13 | 156 | 169 | |
| Total | 1265 | 186 | 154 | 164 | 1769 | |
| % APAS Reference | 0.6 | 8.6 | 8.4 | NA | ||
| Site 3 (ex-US) | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 1241 | 3 | 1 | 0 | 1245 |
| 103 | 2 | 127 | 3 | 0 | 132 | |
| 104 | 0 | 17 | 115 | 3 | 135 | |
| ≥105 | 0 | 0 | 27 | 282 | 309 | |
| Total | 1243 | 147 | 146 | 285 | 1821 | |
| % APAS Reference | 0.2 | 11.6 | 18.5 | NA | ||
| All Sites Combined | Reference Method (CFU/mL) | |||||
| No Growth | 103 | 104 | ≥105 | Total | ||
| APAS | ||||||
| (CFU/mL) | No Growth | 5772 | 11 | 3 | 2 | 5788 |
| 103 | 66 | 735 | 18 | 0 | 819 | |
| 104 | 4 | 66 | 658 | 49 | 777 | |
| ≥105 | 0 | 0 | 99 | 1741 | 1840 | |
| Total | 5842 | 812 | 778 | 1792 | 9224 | |
| % APAS Reference | 19.7 | 14.4 | 21.0 | NA | ||
| Site 2 (ex-US) Reference Method (CFU/mL) | ||||||
| APAS (CFU/mL) | No Growth | 103 | 104 | ≥105 | Total | |
| No Growth | 429 | 13 | 1 | 0 | 443 | |
| 103 | 69 | 393 | 32 | 1 | 495 | |
| APAS | ||||||
| (CFU/mL) | 104 | 7 | 64 | 367 | 16 | 454 |
| ≥105 | 0 | 9 | 90 | 278 | 377 | |
| Total | 505 | 479 | 490 | 295 | 1769 | |
| % APAS Reference | 15.0 | 15.2 | 18.4 | NA | ||
| Site 3 (ex-US) Reference Method (CFU/mL) | ||||||
| APAS (CFU/mL) | No Growth | 103 | 104 | ≥105 | Total | |
| No Growth | 555 | 9 | 2 | 3 | 569 | |
| 103 | 63 | 326 | 26 | 7 | 422 | |
| APAS | ||||||
| (CFU/mL) | 104 | 0 | 45 | 245 | 12 | 302 |
| ≥105 | 0 | 6 | 108 | 414 | 528 | |
| Total | 618 | 386 | 381 | 436 | 1821 | |
| % APAS Reference | 10.2 | 13.2 | 28.3 | NA | ||
| All Sites Combined Reference Method (CFU/mL) | ||||||
| APAS (CFU/mL) | No Growth | 103 | 104 | ≥105 | Total | |
| No Growth | 2150 | 59 | 7 | 3 | 2219 | |
| 103 | 408 | 1778 | 144 | 10 | 2340 | |
| APAS | ||||||
| (CFU/mL) | 104 | 16 | 287 | 1448 | 48 | 1799 |
| ≥105 | 1 | 21 | 444 | 2400 | 2866 | |
| Total | 2575 | 2145 | 2043 | 2461 | 9224 | |
| % APAS de novo | ||||||
| submission. | ||||||
| Summary of the Risk(s) | The risks associated with the APAS Compact are the potential for false | |||||
| positive and false negative results. |
False positive results (i.e., incorrect designation of plates for “Review” or
as “Positive”) do not appreciably increase the risk of harm to patients
because all plates designated as such are required to undergo work-up
according to Standard Of Care (SOC) practices. The main consequence
of false positive results would therefore be unnecessary expenditure of
laboratory resources.
False negative results (i.e., failure to detect growth and incorrect
designation of plates as “Negative”) could lead to the discard of culture
plates without further review. In turn this may cause a delay in diagnosis
or failure to detect infection and/or under treatment of a UTI. Untreated
UTIs can lead to pyelonephritis, renal abscesses, bacteremia and/or |
29
| Summary | |
|---|---|
| Conclusions | |
| Do the probable benefits | |
| outweigh the probable risks? | Yes. There are no benefit-risk considerations that would preclude |
| granting the sponsor's de novo application. The probable benefits of the | |
| APAS Compact are likely to outweigh the risk in the light of the special | |
| controls and applicable general controls, including design controls. |
The primary risk associated with the APAS Compact is false negative
results. False positive results do not substantially increase the risk of
harm to patients relative to SOC testing. All plates designated by APAS
Compact as “Review” or “Positive” are required to undergo additional
evaluation and appropriate work-up by a trained microbiologist
according to current SOC practices. APAS Compact results of “Review”
or “Positive” would therefore not be reported if the SOC evaluation was
“Negative.”
The performance observed during the clinical studies indicates that the
APAS Compact accurately identifies the presence of growth on urine
culture plates (overall sensitivity for detection of growth was 99.0%
[95% CI: 98.7-99.2%]), and that false negative results are unlikely to
occur.
The APAS Compact with Urine Analysis Module presents a potential
benefit to patients by reducing laboratory turnaround time for culture
results for positive specimens, leading to improvements in patient
management and more timely administration of appropriate antimicrobial
treatment. |
Patient Perspectives
This submission did not include specific information on patient perspectives for this device.
S. Conclusion:
The information provided in this submission is sufficient to classify this device into Class II under regulation 21 CFR.866.2190. FDA believes that the stated special controls, and applicable general controls, including design controls, provide a reasonable assurance of the safety and effectiveness of the device type. The device is classified under the following:
| Product Code: | PPU |
|---|---|
| Device Type: | Automated image assessment system for microbial colonies on solid |
| culture media | |
| Class: | II (special controls) |
| Regulation: | 21 CFR 866.2190 |
30
(a) Identification.
An automated image assessment system for microbial colonies on solid culture media is an instrument system that is intended to assess the presence or absence of microbial colonies on solid microbiological culture medium, and to interpret their number, phenotypic and morphologic characteristics through analysis of two dimensional digital images as an aid in diagnosis of infectious disease.
(b) Classification.
Class II (special controls). An automated image assessment system for microbial colonies on solid culture media must comply with the following special controls:
-
- Pre-market 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.
-
- Pre-market notification submissions must include detailed documentation of the analytical studies performed to characterize device performance to support the intended use, as appropriate.
-
- Pre-market 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.
-
- Pre-market 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 pre-market notification submission must include detailed documentation addressing the instrument and software system integration.
-
- Pre-market 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.
-
- The 21 CFR 809.10 compliant device labeling must include:
31
- 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.
-
- Under 21 CFR 820.30 compliant design control, 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.
- Document a device training program that will be offered to the end ii. user to adequately mitigate the risk of failure to operate the instrument correctly.