(31 days)
The BD Phoenix™ Automated Microbiology System is intended for the rapid identification and in vitro antimicrobial susceptibility testing of isolates from pure culture of most aerobic and facultative anaerobic Gram-negative and Gram-positive bacteria of human origin.
The BD Phoenix™ Automated Microbiology System is intended for in vitro quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most Gram-negative aerobic and facultative anaerobic bacteria isolates from pure culture for Enterobacteriaceae and Non-Enterobacteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.
This premarket notification is for the addition of the antimicrobial agent meropenem at concentrations of 0.25-16 ug/mL to Gram-negative ID/AST or AST only Phoenix panels. meropenem has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active In Vitro and in Clinical Infections Against:
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Active In Vitro Against:
Acinetobacter species
Aeromonas hydrophila
Citrobacter koseri
Citrobacter freundii
Enterobacter cloacae
Hafnia alvei
Klebsiella oxytoca
Morganella morganii
Proteus mirabilis
Proteus vulgaris
Salmonella species
Serratia marcescens
Shigella species
Yersinia enterocolitica
The BD Phoenix Automated Microbiology System (Phoenix System) is an automated system for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically relevant bacterial isolates. The system includes the following components:
- BD Phoenix instrument and software. .
- . BD Phoenix panels containing biochemicals for organism ID testing and antimicrobial agents for AST determinations.
- BD Phoenix ID Broth used for performing ID tests and preparing AST Broth inoculum.
- . BD Phoenix AST Broth used for performing AST tests only.
- . BD Phoenix AST Indicator solution added to the AST Broth to aid in bacterial growth determination.
The Phoenix panel is a sealed and self-inoculating molded polystyrene tray with 136 micro-wells containing dried reagents. Organisms for susceptibility testing must be a pure culture and preliminarily identified as a Gram-negative or Gram-positive isolate. For each isolate, an inoculation equivalent to a 0.5 McFarland standard is prepared in Phoenix ID Broth.
The Phoenix AST method is a broth based microdilution test. The Phoenix System utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Measurements of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. Each AST panel configuration contains several antimicrobial agents with a wide range of two-fold doubling dilution concentrations.
The instrument houses the panels where they are continuously incubated at a nominal temperature of 35°C. The instrument takes readings of the panels every 20 minutes. The readings are interpreted to give an identification of the isolate, minimum inhibitory concentration (MIC) values and category interpretations, S, I, or R (sensitive, intermediate, or resistant).
Acceptance Criteria and Study for BD Phoenix™ Automated Microbiology System (Meropenem GN)
Here is a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Implicit) | Reported Device Performance (Meropenem, Gram-negative) |
|---|---|
| Overall intra-site reproducibility of > 90% (for this antimicrobial agent) | > 90% |
| Overall inter-site reproducibility of > 95% (for this antimicrobial agent) | > 95% |
| Essential Agreement (EA) with reference method (defined as within +/- one two-fold dilution) | 97.6% (n=2905) |
| Category Agreement (CA) with reference method (S, I, R categories) | 98.3% (n=2905) |
| Substantial equivalence to NCCLS reference broth microdilution method and predicate devices (VITEK® System, BD Phoenix™ with Gatifloxacin, Ofloxacin, Levofloxacin) | Concluded as substantially equivalent |
Note: The document explicitly states the reproducibility criteria. The Essential Agreement (EA) and Category Agreement (CA) percentages are reported as performance metrics, and the conclusion of "substantially equivalent performance" implies these values met the internal acceptance thresholds for the study to deem it equivalent to the reference method.
2. Sample Size Used for the Test Set and Data Provenance
-
Sample Size for Test Set:
- Reproducibility Studies: Not explicitly stated, but involved a "panel of Gram-negative isolates" tested in triplicate on three different days at three sites.
- Clinical Studies: 2905 instances for Essential Agreement (EA) and Category Agreement (CA) with Meropenem against Gram-negative organisms. This number represents the total successful comparisons made.
-
Data Provenance: The isolates were tested across "multiple geographically diverse sites across the United States." The study included "Clinical, stock and challenge isolates."
- Retrospective/Prospective: Not explicitly stated, but the mention of "clinical isolates" usually implies prospective collection during the study period, while "stock and challenge isolates" could be historical or specifically prepared for the study.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not specify the number or qualifications of experts used to establish the ground truth.
However, the ground truth was established by:
- NCCLS reference broth microdilution method: This is a standardized laboratory protocol, not dependent on individual expert interpretation in the same way an image adjudication would be.
- Expected results for challenge isolates: This implies pre-defined and verified results for a set of known strains.
4. Adjudication Method for the Test Set
No explicit human adjudication method (like 2+1 or 3+1) was used for establishing the ground truth for the MIC values or categories. The ground truth was determined by:
- NCCLS reference broth microdilution method: This is a direct laboratory assay result.
- Expected results: For challenge isolates, the "expected results" serve as the ground truth.
Deviations from these reference methods were measured as Essential Agreement and Category Agreement.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned or performed. This device is an automated system for antimicrobial susceptibility testing, designed to perform the test without human interpretation of results in the traditional sense of a diagnostic image. Its performance is compared to a reference standard method, not human readers.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone study was performed. The entire study describes the performance of the "BD Phoenix™ Automated Microbiology System" (the algorithm/device) against a reference standard without human intervention in the result interpretation process. The device directly outputs the MIC values and categorical interpretations (S, I, R).
7. Type of Ground Truth Used
The primary ground truth used was:
- NCCLS reference broth microdilution method: For clinical isolates, the results from this gold-standard laboratory method were considered the truth.
- Expected results: For challenge isolates, pre-defined "expected results" served as the ground truth.
8. Sample Size for the Training Set
The document does not provide information on the sample size used for the training set. This is typical for a 510(k) submission for an automated microbiology system, as the "training" (calibration and development) processes are often proprietary and not detailed in the same way as, for example, a machine learning model for image analysis. The focus here is on the system's performance after its development.
9. How the Ground Truth for the Training Set Was Established
The document does not explicitly describe how the ground truth for any potential "training set" (development/calibration data for the instrument) was established. However, given the nature of the device, it would have been established through well-defined laboratory protocols, likely also using reference methods such as the NCCLS broth microdilution method, and potentially including expert microbiological analysis during the initial development and validation phases of the system.
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BD PHOENIX™ Automated Microbiology System Meropenem GN
510(K) SUMMARY
| SUBMITTED BY: | Becton, Dickinson and Company7 Loveton CircleSparks, MD 21152Phone: (410)-316-4260Fax: 410-316-4499 |
|---|---|
| CONTACT NAME: | Kathryn Babka PowersRegulatory Affairs Specialist |
| DATE PREPARED: | May 2, 2003 |
| DEVICE TRADE NAME: | BD Phoenix™ Automated Microbiology System –Meropenem 0.25-16 µg/mL |
| DEVICE COMMON NAME: | Antimicrobial susceptibility test system-short incubation |
| DEVICE CLASSIFICATION: | Fully Automated Short-Term Incubation Cycle AntimicrobialSusceptibility Device, 21 CFR 866.1645 |
| PREDICATE DEVICES: | VITEK® System (PMA No. N50510) and BD Phoenix™Automated Microbiology System with Gatifloxacin (K020321May 23, 2002), Ofloxacin (K020323, April 14, 2002), andLevofloxacin (K020322, March 27, 2002). |
| INTENDED USE: | The BD Phoenix™ Automated Microbiology System isintended for the rapid identification and in vitro antimicrobialsusceptibility testing of isolates from pure culture of mostaerobic and facultative anaerobic Gram-negative and Gram-positive bacteria of human origin. |
DEVICE DESCRIPTION:
The BD Phoenix Automated Microbiology System (Phoenix System) is an automated system for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically relevant bacterial isolates. The system includes the following components:
- BD Phoenix instrument and software. .
- . BD Phoenix panels containing biochemicals for organism ID testing and antimicrobial agents for AST determinations.
- BD Phoenix ID Broth used for performing ID tests and preparing AST Broth inoculum.
- . BD Phoenix AST Broth used for performing AST tests only.
- . BD Phoenix AST Indicator solution added to the AST Broth to aid in bacterial growth determination.
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The Phoenix panel is a sealed and self-inoculating molded polystyrene tray with 136 micro-wells containing dried reagents. Organisms for susceptibility testing must be a pure culture and preliminarily identified as a Gram-negative or Gram-positive isolate. For each isolate, an inoculation equivalent to a 0.5 McFarland standard is prepared in Phoenix ID Broth.
The Phoenix AST method is a broth based microdilution test. The Phoenix System utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Measurements of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. Each AST panel configuration contains several antimicrobial agents with a wide range of two-fold doubling dilution concentrations.
The instrument houses the panels where they are continuously incubated at a nominal temperature of 35°C. The instrument takes readings of the panels every 20 minutes. The readings are interpreted to give an identification of the isolate, minimum inhibitory concentration (MIC) values and category interpretations, S, I, or R (sensitive, intermediate, or resistant).
DEVICE COMPARISON:
The BD Phoenix™ Automated Microbiology System demonstrated substantially equivalent performance when compared with the NCCLS reference broth microdilution method. This premarket notification provides data supporting the use of the BD Phoenix™ Automated Microbiology System Gram-negative ID/AST or AST only Phoenix panels with this antimicrobial agent.
SUMMARY OF SUBSTANTIAL EQUIVALENCE TESTING:
The BD Phoenix™ Automated Microbiology System has demonstrated substantially equivalent performance when compared to the NCCLS reference broth microdilution method (AST panels prepared according to NCCLS M7). The system has been evaluated as defined in the FDA Draft guidance document, "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", March 8, 2000.
Site Reproducibility
Intra- and inter-site reproducibility of this antimicrobial agent in the BD Phoenix System was evaluated at three sites using a panel of Gram-negative isolates. Each site tested the isolates in triplicate on three different days using one lot of Gram-negative Phoenix panels containing this antimicrobial agent and associated reagents.
The results of the study demonstrate for the this antimicrobial agent there was an overall intra-site reproducibility of greater than 90% and an overall inter-site reproducibility greater than 95% for the Gram-negative isolates tested.
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Clinical Studies
Clinical, stock and challenge isolates were tested across multiple geographically diverse sites across the United States to demonstrate the performance of the Phoenix antimicrobial susceptibility test with the Gram-negative Phoenix panel format containing this antimicrobial agent. Phoenix System results for Challenge set isolates were compared to the expected results. Phoenix System results for clinical isolates were compared to the results obtained from the NCCLS reference broth microdilution method.
The performance of the Phoenix System was assessed by calculating Essential Agreement (EA) and Category Agreement (CA) to expected/reference results for all isolates tested. Essential Agreement (EA) occurs when the BD Phoenix™ Automated Microbiology System agrees exactly or within + one two-fold dilution to the reference result. Category Agreement (CA) occurs when the BD Phoenix™ Automated Microbiology System agrees with the reference method with respect to the FDA categorical interpretive criteria (susceptible, intermediate, and resistant).
Table 1 summarizes the performance for the isolates tested in this study.
Table 1: . Performance of BD Phoenix System for Gram-negative Organisms by Drug
| Antimicrobial | Concentration | EA (n) | EA (%) | CA (n) | CA (%) |
|---|---|---|---|---|---|
| Meropenem | 0.25-16 μg/mL | 2905 | 97.6 | 2905 | 98.3 |
Conclusions Drawn from Substantial Equivalence Studies
The data collected from the substantial equivalence studies demonstrate that testing on the BD Phoenix™ Automated Microbiology System with this antimicrobial agent is substantially equivalent as outlined in the FDA draft guidance document, "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", March 8, 2000. Technological characteristics of this system are substantially equivalent to those used in the VITEK® system, which received approval by the FDA under PMA number N50510 and BD Phoenix™ Automated Microbiology System with Gatifloxacin (K020321, May 23, 2002), Ofloxacin (K020323, April 14, 2002), and Levofloxacin (K020322, March 27, 2002).
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/3/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like symbol with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the bird symbol.
JUN - 6 2003
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Kathryn Babka Powers Regulatory Affairs Specialist BD Diagnostics Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152
K031429 Re:
Trade/Device Name: BD Phoenix™ Automated Microbiology System Meropenem (0.25-16 ug/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility Devices Regulatory Class: Class II Product Code: LON Dated: May 2, 2003 Received: May 6, 2003
Dear Ms. Powers:
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. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 requirements. including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Page 1 of 1
510(k) Number: K831425
Device Name: BD Phoenix™ Automated Microbiology System for use with the antimicrobial agent meropenem (0.25-16 µg/mL) - Gram-negative ID/AST or AST only Phoenix panels.
Indications for Use:
The BD Phoenix™ Automated Microbiology System is intended for in vitro quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most Gram-negative aerobic and facultative anaerobic bacteria isolates from pure culture for Enterobacteriaceae and Non-Enterobacteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.
This premarket notification is for the addition of the antimicrobial agent meropenem at concentrations of 0.25-16 ug/mL to Gram-negative ID/AST or AST only Phoenix panels. meropenem has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active In Vitro and in Clinical Infections Against:
Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa
Active In Vitro Against:
Acinetobacter species Aeromonas hydrophila Citrobacter koseri Citrobacter freundii Enterobacter cloacae
Hafnia alvei Klebsiella oxvtoca Morganella morganii Proteus mirabilis Proteus vulgaris
Salmonella species Serratia marcescens Shigella species Yersinia enterocolitica
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
| Concurrence of CDRH, Office of Device Evaluation (ODE) | |
|---|---|
| -------------------------------------------------------- | -- |
Leeddie tu. Paxlo
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
Image /page/5/Picture/19 description: The image shows the words "Prescription Use" followed by a check mark. Below that, the text "(Per 21 CFR 801.109)" is visible. The check mark indicates that the prescription use is being acknowledged or selected. The text in parentheses refers to a specific section of the Code of Federal Regulations.
510(k) KD31427
Over-the-Counter Use
BD Diagnostic Systems Becton, Dickinson and Company
§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.
(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”