(39 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 cetriaxone at concentrations of 0.5-64 ug/mL to Gram-negative ID/AST or AST only Phoenix panels. cetriaxone 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:
Acinetobacter calcoaceticus Enterobacter aerogenes Enterobacter cloacae Escherichia coli
Klebsiella oxytoca Klebsiella pneumoniae Morganella morganii Proteus mirabilis
Serratia marcescens Pseudomonas aeruginosa
Active In Vitro Against:
Citrobacter koseri (formerly C. diversus) Citrobacter freundii Providencia species (including Providencia rettgeri) Salmonella species Shigella species
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 isolation 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).
Here's a breakdown of the acceptance criteria and study details based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct numerical targets but are implied through the comparison with the NCCLS reference method and the FDA's guidance document for "Essential Agreement" (EA) and "Category Agreement" (CA). The study demonstrates the device meets the implied criteria by achieving high agreement percentages.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Ceftriaxone) |
|---|---|---|
| Intra-site Reproducibility | >90% | >90% |
| Inter-site Reproducibility | >95% | >95% |
| Essential Agreement (EA) | Substantially equivalent to NCCLS reference broth microdilution method (as defined in FDA guidance) | 95.8% (n=1791) |
| Category Agreement (CA) | Substantially equivalent to NCCLS reference broth microdilution method (as defined in FDA guidance) | 91.0% (n=1791) |
2. Sample Size Used for the Test Set and the Data Provenance
- Sample Size for Test Set:
- Clinical Studies (Clinical, Stock, and Challenge Isolates): 1791 isolates for which EA and CA are reported for Ceftriaxone.
- Site Reproducibility (Gram-negative isolates): Not explicitly stated, but "a panel of Gram-negative isolates" was tested, with each site testing isolates in triplicate on three different days.
- Data Provenance: Clinical, stock, and challenge isolates were tested across multiple geographically diverse sites across the United States. This indicates prospective data collection from multiple sites within the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This information is not explicitly provided in the document. The document states that the ground truth for clinical isolates was established by comparing Phoenix System results to the NCCLS reference broth microdilution method. For challenge isolates, results were compared to "expected results." The document does not detail how these "expected results" were derived or whether expert adjudication was involved in establishing the NCCLS reference method results or the expected results for challenge isolates in this specific study.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method involving expert review for the test set. The primary comparison for clinical isolates was against the NCCLS reference broth microdilution method. For challenge isolates, it was against "expected results." This suggests a direct comparison to a reference standard rather than an adjudication process between human readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an automated system for determining antimicrobial susceptibility (MIC values and category interpretations) directly, not an AI-assisted tool for human readers. Therefore, the concept of improving human readers with vs. without AI assistance does not apply here.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, a standalone performance study was done. The BD Phoenix Automated Microbiology System is itself an automated system ("algorithm only") that determines antimicrobial susceptibility without human interpretation in the results generation phase. The study directly assesses the performance of this automated system against a reference method.
7. The Type of Ground Truth Used
- Clinical Isolates: The ground truth was established by the NCCLS reference broth microdilution method. This is a laboratory-based, standardized, and validated method for determining antimicrobial susceptibility.
- Challenge Isolates: The ground truth was based on "expected results." The document does not detail how these "expected results" were defined, but they typically refer to results from well-characterized strains where susceptibility is known.
8. The Sample Size for the Training Set
The document does not specify a sample size for a training set. As an automated microbiology system that assesses growth and inhibition, it's more likely that the system's underlying algorithms (e.g., for interpreting redox indicator changes and bacterial turbidity) were developed and validated using extensive physiological and microbiological data, rather than a specific "training set" in the machine learning sense described here. The study focuses on the validation of the device's performance with a new antimicrobial agent.
9. How the Ground Truth for the Training Set Was Established
Since a specific "training set" in the context of machine learning is not mentioned, the method for establishing its ground truth is also not described. The device's operation is based on established microbiological principles (broth microdilution, redox indicators, turbidity measurement), rather than being a purely AI-driven predictive model that requires a labeled training set in the typical sense.
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Image /page/0/Picture/1 description: The image shows a sequence of handwritten characters, specifically 'K032655'. The characters are written in a dark ink, and the handwriting appears somewhat stylized. The numbers are clearly distinguishable, and the overall impression is that of a serial number or identification code.
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: | August 25, 2003 |
| DEVICE TRADE NAME: | BD Phoenix™ Automated Microbiology System -Ceftriaxone 0.5-64 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 (K020321,May 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 isolation 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 guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", February 5, 2003.
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 (%) |
|---|---|---|---|---|---|
| Ceftriaxone | 0.5-64 μg/mL | 1791 | 95.8 | 1791 | 91.0 |
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 guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems: Guidance for Industry and FDA", February 5, 2003. 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
Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized eagle with three lines forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular fashion around the eagle.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
OCT - 6 2003
Ms. Kathryn Babka Powers Regulatory Affairs Specialist BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152
K032655 Re:
Trade/Device Name: BD Phoenix™ Automated Microbiology System Ceftriaxone (0.5-64 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: August 26, 2003 Received: August 28, 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, listing 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 (OS) regulation (21 CFR Part 820).
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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: KO 326 T
Device Name: BD Phoenix™ Automated Microbiology System for use with the antimicrobial agent ceriaxone (0.5-64 µg/mL) - Gram-negative ID/AST or AST only Phoenix panels. 1
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 cetriaxone at concentrations of 0.5-64 ug/mL to Gram-negative ID/AST or AST only Phoenix panels. cetriaxone 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:
Acinetobacter calcoaceticus Enterobacter aerogenes Enterobacter cloacae Escherichia coli
Klebsiella oxytoca Klebsiella pneumoniae Morganella morganii Proteus mirabilis
Serratia marcescens Pseudomonas aeruginosa
Active In Vitro Against:
Citrobacter koseri (formerly C. diversus) Citrobacter freundii Providencia species (including Providencia rettgeri) Salmonella species Shigella species
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Division Sign-Off
| 11/3/03 | |
|---|---|
| -- | --------- |
Office of In Vitro Diagnostic Device
Evaluation and Safety
| Prescription Use | |
|---|---|
| (Per 21 CFR 801.109) |
| 510(k) | K032655 |
|---|---|
| -------- | --------- |
| Over-the-Counter Use | |
|---|---|
| -- | ---------------------- |
BD Diagnostic Systems
Becton, Dickinson and Company
Page 9
§ 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.”