(140 days)
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 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.
APAS Independence with Urine Analysis Module is a device designed to be used in a microbiology laboratory to automate the initial screening for the presence of growth on urine culture plates. It is an in vitro diagnostic device and has no direct contact with patients.
APAS Independence consists of an automated plate handling mechanism to move the plates through the instrument, an imaging station to capture an image of the culture plate, combined with software for analysis of the image, determination of growth and presentation of reports.
The APAS Independence with Urine Analysis Module is intended to determine whether growth is present or not, and to provide a semi-quantitative assessment of the colony count (if present). This information will then be combined with other available clinical information to screen out biological samples without growth. All other plates will be presented to a microbiologist for examination, determination of status and further testing according to conventional laboratory practice. This enables the microbiologist to focus on plates with potentially significant growth, thereby reducing the time until results can be reported.
The APAS Independence is intended to have different software modules, each of which will provide an assessment of growth for specific clinical indications. This submission covers only the APAS Independence with Urine Analysis Module. The APAS Independence with Urine Analysis Module is indicated for screening of culture plates for assessment of urinary tract infections where the urine specimens are collected and 1μl is plated onto Blood and MacConkey Agars and incubated at 35±2°C for 18 to 22 hours.
The provided text describes the acceptance criteria and the study proving the device meets these criteria for the APAS Independence with Urine Analysis Module (K183648).
1. Table of Acceptance Criteria (Implicit) and Reported Device Performance:
The document establishes substantial equivalence to a predicate device, APAS Compact with Urine Analysis Module. Therefore, the acceptance criteria are implicitly tied to the performance of the predicate device. The performance data presented focuses on agreement with the predicate.
| Acceptance Criterion (Implicit) | Reported Device Performance |
|---|---|
| Device Designation Agreement with Predicate (Blood Agar) | Positive: 98.7% (96.3-99.6%) agreement. APAS Independence did not return any Negative results when APAS Compact reported Positive. Review: 86.5% (72.0-94.1%) agreement. Negative: 79.5% (69.2-87.0%) agreement. For samples classified as Negative by APAS Compact, APAS Independence either agreed or assigned Review/Positive (requiring microbiologist investigation). Combined Positive and Review: 100% (98.6-100%) agreement. |
| Device Designation Agreement with Predicate (MacConkey Agar) | Positive: 99.3% (95.9-99.9%) agreement. One instance where APAS Compact reported Positive, APAS Independence was Negative. Review: 80.0% (37.6-96.4%) agreement. Negative: 89.1% (84.2-92.6%) agreement. For samples classified as Negative by APAS Compact, APAS Independence either agreed or assigned Review/Positive. Combined Positive and Review: 98.6% (94.9-99.6%) agreement. |
| Colony Count Agreement with Predicate (Blood Agar) | High level of agreement between the two systems. APAS Independence was more likely to overestimate than underestimate enumeration. (Specific percentages vary by CFU/mL range in Table 5.5). Example: 79.5% agreement for 0 CFU/mL, 90.4% for 10^3 CFU/mL, 90.5% for 10^4 CFU/mL, 99.2% for 10^5 CFU/mL. |
| Colony Count Agreement with Predicate (MacConkey Agar) | High level of agreement between the two systems. APAS Independence was more likely to overestimate than underestimate enumeration. (Specific percentages vary by CFU/mL range in Table 5.6). Example: 89.1% agreement for 0 CFU/mL, 89.7% for 10^3 CFU/mL, 87.5% for 10^4 CFU/mL, 100% for 10^5 CFU/mL. |
| Colony Morphology Detection Rate (Blood Agar) | Probability of >95% detection across all colony types. (Specific percentages in Table 5.7, e.g., Alpha hemolysis: 0.971, Beta hemolysis: 0.963, Coliform: 0.989, Cream white: 0.951, Granular: 0.997, Small: 0.983, Swarming: 1.000). APAS Independence likely to overestimate some colony morphologies (AC-/Al+ > AC+/Al-). |
| Colony Morphology Detection Rate (MacConkey Agar) | Probability of >95% detection across all colony types. (Specific percentages in Table 5.8, e.g., Lactose fermenter: 0.991, Non-fermenter: 0.994, Non-pigmented: 1.000, Red Pink: 1.000). |
| Reproducibility and Precision (Colony Counts) | Similar to APAS Compact with Urine Analysis Module. Inversely proportional to colony count. Exemplar %CV values (from Table 5.9): MacConkey (E. coli): Lowest Dilution 7.2%, Middle Dilution 5.6%, Highest Dilution 21.7%. TS-SBA (E. coli): Lowest Dilution 5.0%, Middle Dilution 6.7%, Highest Dilution 20.4%. |
| Software Verification and Validation | Documentation provided as recommended by FDA guidance. Considered "moderate" level of concern. |
| Safety and EMC | Complies with IEC 61010-1: 2010, IEC 61010-2-101: 2017, UL 61010-1: 2012 for safety, and IEC 61326-1: 2013, IEC 61326-2-6: 2013, FCC Part 15B for EMC. |
2. Sample Size and Data Provenance for Test Set:
- Sample Size: 350 leftover clinical urine samples.
- Data Provenance: The document states "leftover clinical urine samples." The country of origin is not explicitly stated but is implicitly Australia, given the submitter's country for the predicate device's de novo application (DEN150059) was Australia. The data is retrospective as it uses "leftover clinical urine samples."
3. Number of Experts and Qualifications for Ground Truth for Test Set:
Not applicable for this section as the study's ground truth for the comparison was the predicate device's performance, not human expert consensus, for the new device's equivalence study.
4. Adjudication Method for the Test Set:
Not applicable. The study compares the new device (APAS Independence) to the predicate device (APAS Compact) itself, not to human expert reads requiring adjudication. Discrepancies between the two devices are analyzed, and the clinical implications (e.g., misclassification leading to microbiologist review) are discussed.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- Was it done? No, an MRMC study comparing human readers with and without AI assistance was not conducted directly for the APAS Independence with Urine Analysis Module in this submission.
- The document states that the predicate device (APAS Compact with Urine Analysis Module) had three clinical studies (LBT001, LBT002, LBT003) submitted for its de novo applicationDEN150059, which "showed that APAS performed similarly to a microbiologist in reading and interpreting agar plates." This indicates that the predicate device's performance was evaluated against human microbiologists. The current submission established equivalence to this predicate.
- Effect Size: Not applicable since an MRMC study was not performed as part of this specific submission.
6. Standalone (Algorithm Only) Performance:
- Was it done? Yes, the entire study presented for the APAS Independence with Urine Analysis Module is a standalone (algorithm only) performance comparison between the new device and the predicate device. Both the APAS Independence and the APAS Compact are automated systems that read and interpret images without direct human intervention in the initial classification process.
7. Type of Ground Truth Used:
The ground truth for the APAS Independence performance evaluation was the performance of the predicate device (APAS Compact with Urine Analysis Module). The study aimed to demonstrate that the new device performs equivalently to the already-cleared predicate.
8. Sample Size for the Training Set:
The document does not explicitly state the sample size for the training set of the APAS Independence with Urine Analysis Module. It only details the test set used for the comparison with the predicate device (350 samples). However, it mentions that both devices "utilize the same core APAS technology and the same urine analysis module," implying shared underlying algorithmic development and training.
9. How the Ground Truth for the Training Set was Established:
The document does not provide details on how the ground truth for the training set (if any specific to APAS Independence's development rather than its use of the predicate's technology) was established. However, given that the "same core APAS technology and the same urine analysis module" are utilized as the predicate, it is highly likely that the training methodologies and ground truth establishment for the predicate device would apply. For the predicate device (APAS Compact), the clinical studies (LBT001, LBT002, LBT003) referenced for the de novo application would have established ground truth, likely through expert consensus of microbiologists, as it stated "APAS performed similarly to a microbiologist."
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the symbol of the Department of Health & Human Services on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out next to it.
May 15, 2019
Clever Culture Systems AG Julie Winson Regulatory Affairs Manager Seestrasse 204a Bach, CH-8806 CH
Re: K183648
Trade/Device Name: APAS Independence with Urine Analysis Module Regulation Number: 21 CFR 866.2190 Regulation Name: Automated Image Assessment System For Microbial Colonies On Solid Culture Media Regulatory Class: Class II Product Code: PPU Dated: December 20, 2018 Received: December 26, 2018
Dear Julie Winson:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Image /page/2/Picture/0 description: The image shows the logo for Clever Culture Systems. The logo consists of a red atom-like symbol on the left, followed by the text "CLEVER CULTURE SYSTEMS" in black. To the right of the logo, the text "Traditional 510(k) APAS Independence with Urine Analysis Module" is displayed in a smaller font size.
5. 510(k) Summary
510(k) Number: K183648
5.1 Submitter
Clever Culture Systems AG Seestrasse 204a, CH-8806 Bach, Switzerland
Contact person: Julie.Winson@cleverculturesystems.com
Telephone: p +61 (0) 88227 1555
Date prepared: 8th May 2019
5.2 Device
Name of Device: APAS Independence with Urine Analysis Module.
Common or usual name: APAS Independence.
Classification name: Automated image assessment system for microbial colonies on solid culture media (21 CFR 866.2190).
Regulatory Class: II (special controls).
Product Code: PPU.
5.3 Predicate Device
APAS Compact with Urine Analysis Module, DEN150059.
This predicate has not been subject to a design related recall.
No reference devices were used in this submission.
5.4 Device Description
APAS Independence with Urine Analysis Module is a device designed to be used in a microbiology laboratory to automate the initial screening for the presence of growth on urine culture plates. It is an in vitro diagnostic device and has no direct contact with patients.
APAS Independence consists of an automated plate handling mechanism to move the plates through the instrument, an imaging station to capture an image of the culture plate, combined with software for analysis of the image, determination of growth and presentation of reports.
The APAS Independence with Urine Analysis Module is intended to determine whether growth is present or not, and to provide a semi-quantitative assessment of the colony count (if present). This information will then be combined with other available clinical information to screen out biological samples without growth. All other plates will be presented to a microbiologist for examination, determination of status and further testing according to conventional laboratory practice. This enables the microbiologist to focus on plates with potentially significant growth, thereby reducing the time until results can be reported.
The information contained herein this document is the property of Clever Culture Systems AG. Unauthorised disclosure to public is prohibited.
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Image /page/3/Picture/0 description: The image shows the logo for Clever Culture Systems. Next to the logo is the text "Traditional 510(k) APAS Independence with Urine Analysis Module". The logo is a red circle with a white design inside.
The APAS Independence is intended to have different software modules, each of which will provide an assessment of growth for specific clinical indications. This submission covers only the APAS Independence with Urine Analysis Module. The APAS Independence with Urine Analysis Module is indicated for screening of culture plates for assessment of urinary tract infections where the urine specimens are collected and 1μl is plated onto Blood and MacConkey Agars and incubated at 35±2°C for 18 to 22 hours.
Figure 5.1 shows a photograph of the instrument from the input area on the left, the imaging area in the middle and the output area on the right. The user controls the instrument via the screen at the top middle of the instrument.
Image /page/3/Picture/3 description: The image shows a Clever Culture Systems APAS Independence machine. The machine is white and gray, and it has a screen on the front. There are several containers on the right side of the machine, and they have red handles. The machine is on a white background.
Figure 5.1 - APAS Independence
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Figure 5.2 provides a logical connection diagram of the components that make up the complete system (the hatched components are not part of the predicate device).
Image /page/4/Figure/2 description: The image shows a diagram of the APAS Independence system. The system includes automated plate handling, an imaging station, a plate controller, an instrument controller, and an APAS controller PC. The system is connected to a laboratory network that includes a LIS server, a web review PC, an LDAP server, an NTP server, and a DNS/DHCP server.
Figure 5.2 – The APAS Independence with Urine Analysis Module
The major sub-systems within the APAS Independence are:
- Imaging Station;
- APAS Controller; .
- Instrument Controller;
- Plate Controller; ●
- . Automated plate handling.
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Image /page/5/Picture/0 description: The image contains the logo for Clever Culture Systems. On the left is a red circle with a white design inside that looks like three circles connected to a central point. To the right of the circle are the words "CLEVER CULTURE" in bold, black letters on the top line and "SYSTEMS" in bold, black letters on the bottom line.
| Sub-system | Includes | Description |
|---|---|---|
| APAS Independence | Four-stack Carriers | Used to transport approximately sixty plates to and from the instrument |
| Single-stackCarriers | Used to transport approximately twenty plates to and from the instrument | |
| Color CalibrationTool | Used to calibrate and check the color response of the imaging system | |
| System Check Tool | Used to perform a quick end-to-end check of the instrument hardware andsoftware | |
| User Manual | Provides instructions for use of the instrument | |
| User TrainingMaterial | Provides training details on the use of the instrument | |
| Service Manual | Provides instructions for the servicing of the instrument | |
| Urine AnalysisModule | Installer | The software to be installed on an APAS Independence instrument |
| User Manual | Provides instructions for use of the Analysis Manual | |
| User TrainingMaterial | Provides training details on the use of the Analysis Module |
The additional components supplied with the system are shown in Table 5.1.
Table 5.1 - System Components
5.5 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.
5.6 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 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.
5.7 Comparison of Technological Characteristics with the Predicate Device
The nominated predicate device is APAS Compact with Urine Analysis Module, which was cleared via de novo DEN150059.
APAS Independence adds automated plate handling to the existing functionality of automated plate interpretation within APAS Compact.
The two devices have the same Intended Use and same Indications for Use and use the same technology to provide an interpretation of growth from urine cultures as an aid in the diagnosis of urinary tract infection.
Both devices have been developed by Clever Culture Systems (CCS).
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Image /page/6/Picture/0 description: The image contains the logo for Clever Culture Systems. On the left is a red circle with a white design inside that looks like a molecule. To the right of the circle are the words "CLEVER CULTURE" stacked on top of the word "SYSTEMS" in black font.
culture
Urine samples
Microbiology laboratory
IEC 61326-1: 2012
CISPR-11: 2010
ISO 14971: 2007
IEC 62304: 2006
FCC 15B
IEC 61326-2-6: 2012
IEC 61010-1: 2010 (3ª ed)
EN 55011: 2009/A1:2010
IEC 61010-1: 2010 (3rd ed)
Anatomical site
Standards met
Where used
Electrical
safety
| Characteristic | Commonalities | Differences | Comments |
|---|---|---|---|
| Intended Use | Same | Change of device name fromCompact to Independence | |
| Indications forUse | Same | Change of device name fromCompact to Independence | |
| Targetpopulation | All patients suspected ofurinary tract infection whosubmit urine specimens for | None |
The subject device also meets:
IEC 61010-2-101: 2015
IEC 62366-1: 2015
UL 61010-1 (3rd ed), rev 2015-07
The subject device also meets:
IEC 61010-2-101: 2015
UL 61010-1 (3ª ed), rev 2015-07
None
None
Traditional 510(k) APAS Independence with Urine Analysis Module
| Mechanicalsafety | IEC 61010-1: 2010 (3rd ed) | The subject device also meets:UL 61010-1 (3rd ed), rev 2015-07IEC 61010-2-101: 2015 | |
|---|---|---|---|
| Chemicalsafety | No exposure to chemicalsubstances | None | |
| Thermal safety | IEC 61010-1: 2010 (3rd ed) | The subject device also meets:UL 61010-1 (3rd ed), rev 2015-07IEC 61010-2-101: 2015 | |
| Radiationsafety | LED lightsBarcode scanner | In the subject device, the imagingstation is closed to operators duringprocessing and barcode reading isenclosed within the instrument | |
| Energy usedand/ordelivered | Imaging station poweredfrom 24VDC.APAS Controller andInstrument Controller PCspower from standard ATXsupplies | The subject device has anautomated plate handling systempowered from 24VDC. | The subject device is the same asthe predicate device in that it uses24VDC rather than AC mains forall possible areas of theinstrument including all operatoraccessible areas. |
The predicate was tested against
standards that were relevant for
that device. The subject device
of the 61010 standard and the
family.
guidelines.
has been tested against the same
standards but also the UL version
IVD specific sub-standard in that
Usability engineering has followed IEC 62366-1 for the subject device in addition to the FDA
the safety and EMC/EMI
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Image /page/7/Picture/0 description: The image shows the logo for Clever Culture Systems. The logo consists of a red circle with a white abstract design inside, resembling interconnected nodes. To the right of the circle are the words "CLEVER CULTURE" stacked on top of "SYSTEMS" in a bold, sans-serif font.
| Characteristic | Commonalities | Differences | Comments |
|---|---|---|---|
| Materials | General engineeringplastics and metals | None | |
| Biocompatibility | No body contact | None | |
| Compatibilitywith theenvironmentand otherdevices | IEC 61326-1: 2012IEC 61326-2-6: 2012EN 55011: 2009/A1:2010CISPR-11: 2010FCC 15B | None | |
| Sterility | Not a sterile device | None |
Table 5.2- Comparison of Characteristics Between Predicate and New Device
5.8 Performance Data
The following performance data were provided in support of the substantial equivalence determination.
5.8.1 Safety and EMC
Electrical safety and EMC testing were conducted on the subject device, consisting of the instrument, carriers and qualification tools. The system complies with IEC 61010-1: 2010, IEC 61010-2-101: 2017 and UL 61010-1: 2012 for safety and IEC 61326-1: 2013, IEC 61326-2-6: 2013 and FCC Part 15B for EMC.
5.8.2 Software Verification and Validation
Software verification and validation testing were conducted, and documentation was provided as recommended by FDA's Guidance for Industry and Staff, Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices. The software for this device was considered as a "moderate" level of concern as a malfunction of, or latent design flaw in the software could lead to an erroneous diagnosis or a delay in delivery of appropriate medical care that would likely lead to a Minor injury to the patient.
5.8.3 Clinical Studies
The predicate device, APAS Compact with Urine Analysis Module and the new device, APAS Independence with Urine Analysis Module both utilize the same core APAS technology and the same urine analysis module to image culture plates and read and interpret growth.
Therefore, the clinical performance of the predicate device represents the clinical performance of the new device, APAS Independence with Urine Analysis Module.
The results of three clinical studies (LBT001, LBT002 and LBT003) were submitted to support the de novo application DEN150059 and showed that APAS performed similarly to a microbiologist in reading and interpreting agar plates cultured for screening for uncomplicated urinary tract infection (UTI).
A confirmatory Method Comparison Study between the APAS Independence and APAS Compact was performed using 350 leftover clinical urine samples that were accepted for screening for UTL. 1ul of each urine sample was inoculated onto each of a pair of blood and MacConkey agar plates and incubated at 35±2ºC for 18 hr. The plates were read by both APAS Compact and APAS Independence with the same urine analysis module and the results compared.
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The APAS Compact and APAS Independence provided a screening result of the sample on each agar of either Positive, Review or Negative. A 3x3 confusion matrix is provided for blood and MacConkey agar in Table 5.3. and Table 5.4, respectively.
Table 5.3 shows that when APAS Compact reported a Positive result on blood agar, APAS Independence either agreed or returned a Review result. There were no cases where APAS Independence returned a Negative result and which therefore would not be looked at by a microbiologist. For those samples originally classified as Negative by APAS Compact, APAS Independence either agreed or assigned a Review and Positive designation which requires investigation by a microbiologist. The results indicate that on blood agar, there is a high level of agreement between APAS Independence and APAS Compact and that APAS Independence is slightly more likely than APAS Compact to assign a Positive or Review result (288 cases for APAS Independence compared with 272 cases for APAS Compact).
Table 5.3: Plate designation for blood agar: APAS Compact (predicate) vs APAS Independence with Urine Analysis Module
| Blood AgarPlate 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) | 232/23598.7%(96.3-99.6%) | 32/3786.5%(72.0-94.1%) | 62/7879.5%(69.2-87.0%) | ||
| 272/272100% 1(98.6-100%) |
1 "Positive" and "Review" designations combined
The results for MacConkey agar in Table 5.4 follow a similar pattern. When APAS Compact reported a Positive result, APAS Independence agreed, with the exception of a single sample that was reported as Negative by APAS Independence. For those samples originally classified as Negative by APAS Compact, APAS Independence either agreed or assigned a Review and Positive designation which requires investigation by a microbiologist. The results indicate that on MacConkey agar, there is a high level of agreement between APAS Independence and APAS Compact and that APAS Independence is more likely than APAS Compact to assign a Positive or Review result (161 cases for APAS Independence compared with 139 cases for APAS Compact).
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Table 5.4: Plate designation for MacConkey agar: APAS Compact (predicate) vs APAS Independence with Urine Analysis Module
| MacConkey AgarPlate Designation | APAS Compact (predicate) | ||||
|---|---|---|---|---|---|
| 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 | 4/5 | 188/211 | ||
| 99.3% | 80.0% | 89.1% | |||
| (95.9-99.9%) | (37.6-96.4%) | (84.2-92.6%) | |||
| 137/139 | |||||
| 98.6% 1 | |||||
| (94.9-99.6%) |
1 "Positive" and "Review" designations combined
The findings for plate designation are supported by comparative data for agreement of colony counts presented in Table 5.6 for blood agar and Table 5.7 for MacConkey agar, which demonstrate that for both agars, while overall there was a high level of agreement between the two systems, APAS Independence was more likely to overestimate than underestimate enumeration. This is acceptable because all plates with growth are subject to additional follow-up by a trained microbiologist and there is no increased risk to patients.
Table 5.5: Colony counts on blood agar obtained with the Urine Analysis Module using the APAS Compact (predicate) and APAS Independence
| Colony Counts onBlood Agar | APAS Compact CFU/mL (predicate) | ||||||
|---|---|---|---|---|---|---|---|
| 0 | 103 | 104 | 105 | IND | Total | ||
| 0 | 62 | 0 | 0 | 0 | 0 | 62 | |
| APASIndependenceCFU/mL | 103 | 15 | 47 | 0 | 0 | 0 | 62 |
| 104 | 1 | 5 | 67 | 1 | 0 | 74 | |
| 105 | 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)
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| Colony Counts onMacConkey Agar | APAS Compact CFU/mL (predicate) | |||||
|---|---|---|---|---|---|---|
| 0 | 103 | 104 | 105 | Total | ||
| 0 | 188 | 11 | 0 | 0 | 189 | |
| APASIndependenceCFU/mL | 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 |
Table 5.6: Colony counts on MacConkey agar obtained with the Urine Analysis Module using the APAS Compact (predicate) and APAS Independence
1 APAS Compact detected a single lactose fermenting colony that was not identified by APAS Independence
The test also compared colony morphology detection between paired sample plate images assessed by APAS Compact and APAS Independence. The results are presented in Table 5.7 for blood agar and Table 5.8 for MacConkey agar.
The results demonstrate a probability of >95% detection across all colony types. In general, the APAS Independence is likely to overestimate some colony morphologies (AC-/Al+ > AC+/Al-).
The columns in the tables are:
| ColonyMorphology | denotes the target colony morphologies |
|---|---|
| AC+/Al+ | means that the colony morphology was detected by both APAS Compact (AC) and APASIndependence (AI). |
| AC+/AI- | means that the colony morphology was detected by APAS Compact but not by APASIndependence [ie false negative] |
| AC-/Al+ | means that the colony morphology was not detected by APAS Compact but was detected byAPAS Independence [ie false positive] |
| AC- / Al- | means that the colony morphology was not detected by either instrument |
| Equiv(Equivalent) | is the number of plates where the colony morphology was;detected by both instruments, ornot detected by both instruments, ordetected by APAS Independence only.1 |
| Percent | is the proportion calculated as Equivalent divided by the Cases, with 95% confidence intervalscalculated using the Wilson score method. |
1 Detection by APAS Independence only was considered acceptable and included in the equivalence calculation because all plates with growth are subject to additional follow-up by a trained microbiologist and there is no additional risk to the patient
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| Colonymorphology | PresentAPAS Compact | Not PresentAPAS Compact | Cases | Equiv | Percent (95%confidence interval) | ||
|---|---|---|---|---|---|---|---|
| AC+/AI+ | AC+/AI- | AC-/AI+ | AC-/AI- | ||||
| Alpha hemolysis | 61 | 10 | 43 | 236 | 350 | 340 | 0.971 (0.948, 0.984) |
| Beta hemolysis | 106 | 13 | 38 | 193 | 350 | 337 | 0.963 (0.937, 0.978) |
| Coliform | 165 | 4 | 13 | 168 | 350 | 346 | 0.989 (0.971, 0.996) |
| Cream white | 176 | 17 | 12 | 145 | 350 | 333 | 0.951 (0.924, 0.969) |
| Granular | 18 | 1 | 1 | 330 | 350 | 349 | 0.997 (0.984, 0.999) |
| Small | 195 | 6 | 44 | 105 | 350 | 344 | 0.983 (0.963, 0.992) |
| Swarming | 13 | 0 | 0 | 337 | 350 | 350 | 1.000 (0.989, 1.000) |
Table 5.7: APAS Independence detection of colony morphologies compared to APAS Compact detection of colony morphologies on TS-SBA agar
Table 5.8: APAS Independence detection of colony morphologies compared to APAS Compact detection of colony morphologies on MacConkey agar
| Colonymorphology (PIC) | PresentAPAS Compact | Not PresentAPAS Compact | Cases | Equiv | Percent (95%confidence interval) | ||
|---|---|---|---|---|---|---|---|
| AC+/AI+ | AC+/AI- | AC-/AI+ | AC-/AI- | ||||
| Lactose fermenter | 110 | 3 | 1 | 236 | 350 | 347 | 0.991 (0.975, 0.997) |
| Non-fermenter | 51 | 2 | 33 | 264 | 350 | 348 | 0.994 (0.979, 0.998) |
| Non-pigmented | 1 | 0 | 0 | 349 | 350 | 350 | 1.000 (0.989, 1.000) |
| Red Pink | 7 | 0 | 13 | 330 | 350 | 350 | 1.000 (0.989, 1.000) |
5.8.4 Reproducibility & Precision
A study was performed using three APAS Independence instruments equipped with a Urine Analysis Module to show that the extent of variability in colony counts within and between these instruments is equivalent to that found with APAS Compact with Urine Analysis Module. The test was conducted using three dilutions of cultured organisms which were selected as being representative of those found in urine samples. The organisms used on blood agar were E. coli, Streptococcus agalactiae and Enterococcus faecalis. The organism used on MacConkey agar was E. coli. The test included blank plates inoculated with sterile saline. 1µL from a dilution of an organism representing 10° CFU/mL, 10° CFU/mL or 105 CFU/mL was inoculated onto one of 3 replicates per dilution and incubated for 35°C ± 2°C for 18 hrs. Each culture plate was imaged five times at three different orientations within each of the three instruments and the resulting colony counts per plate were compared to determine the repeatability of colony count as a percent coefficient of variation (%CV) within an instrument, and reproducibility of colony count as a %CV across instruments. The results are shown in Table 5.9.
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Image /page/12/Picture/0 description: The image shows the logo for Clever Culture Systems on the left. To the right of the logo is the text "Traditional 510(k) APAS Independence with Urine Analysis Module". The logo consists of a red circle with a white design inside. The design appears to be three circles connected by lines.
| Agar | Species | APAS 1 | APAS2 | APAS3 | ALL APAS | APAS 1 | APAS2 | APAS3 | ALL APAS | APAS 1 | APAS2 | APAS3 | ALL APAS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lowest Dilution (>100 CFU/mL) | Middle Dilution (10-99 CFU/mL) | Highest Dilution (1-9 CFU/mL) | |||||||||||
| MacConkey | E coli | 4.4 | 1.9 | 3.0 | 7.2 | 5.4 | 3.0 | 4.5 | 5.6 | 14.0 | 24.6 | 13.6 | 21.7 |
| MacConkey | Saline | 0.0 | 0.0 | 0.0 | 0.0 | ||||||||
| TS-SBA | E coli | 1.7 | 7.9 | 2.0 | 5.0 | 2.3 | 3.0 | 3.0 | 6.7 | 14.7 | 22.6 | 10.1 | 20.4 |
| TS-SBA | E coli /Strep | 4.7 | 3.7 | 9.2 | 10.0 | 6.0 | 6.2 | 16.3 | 12.3 | 22.6 | 26.3 | 25.1 | 28.1 |
| TS-SBA | Efaecalis | 5.7 | 4.0 | 2.2 | 7.4 | 7.5 | 5.9 | 5.4 | 11.6 | 22.4 | 19.3 | 27.6 | 27.7 |
| TS-SBA | Saline | 0.0 | 0.0 | 0.0 | 0.0 |
Table 5.9: Collation of %CV values obtained by the APAS Independence with Urine Analysis Module
As noted with APAS Compact with Urine Analysis Module, the value for %CV is inversely proportional to colony count. Overall, the reproducibility and precision of colony counts with the APAS Independence with Urine Analysis Module was similar to that of observed with the APAS Compact with Urine Analysis Module and was therefore acceptable.
5.9 Conclusions
The predicate device, APAS Compact with Urine Analysis Module and the new device, APAS Independence with Urine Analysis Module both utilize the same core APAS technology and the same urine analysis module to image culture plates and read and interpret growth.
The non-clinical data support the safety of the device and the hardware and software verification and validation demonstrate that the subject device should perform as intended in the specified use conditions. The equivalence study confirms that the two devices return the same clinical result. The results obtained with the new device also demonstrated acceptable reproducibility and precision.
Therefore, the data demonstrate that the subject device is substantially equivalent to the predicate device.
§ 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.