(71 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 antinicrobial susceptibility by minimal inhibitory concentration (MIC) of gram-negative aerobic and facultative anamerolia bacteria isolates from pure culture belonging to the family Enterobacteriaceae and most glucose nonfermenting gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.
This premarket notification is for the addition of the antimicrobial Levofloxacin at concentrations of 0.25-8 μg to Gram negative and Gram positive ID/AST or AST only Phoenix panels. Levofloxacin 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 antimicrobic.
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 inoculum suspension equivalent to a 0.5 McFarland standard is prepared in the Phoenix ID broth. Prior to inoculating the Phoenix AST broth, one drop of Phoenix AST indicator solution is added to the uninoculated AST broth. The AST broth is then inoculated using the organism suspension from the ID broth. The Phoenix antimicrobial susceptibility test is inoculated with the AST broth. Inoculated panels are loaded into the Phoenix instrument.
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, and resistant).
Here's a breakdown of the acceptance criteria and study information for the BD Phoenix™ Automated Microbiology System for use with Levofloxacin, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Essential Agreement, EA) | Reported Device Performance (EA) | Acceptance Criteria (Category Agreement, CA) | Reported Device Performance (CA) |
|---|---|---|---|
| > 90% essential agreement to reference results | > 90% (for all three drugs, unspecified exact value for Levofloxacin but implied as meeting criteria) | Not explicitly stated as a numerical criterion in the same way as EA, but assessed for agreement with reference method. | Not explicitly stated as a numerical criterion, but implied as meeting criteria. |
Note: The document states "Phoenix panels demonstrated essential agreement of > 90% to the expected/reference results for all three drugs." It does not provide specific numerical values for Levofloxacin alone, but rather a blanket statement for "all three drugs" tested in the clinical studies. The "three drugs" likely refer to the combination of antimicrobials tested, with Levofloxacin being one of them. For Category Agreement (CA), the document mentions it was "assessed" but doesn't provide a specific numerical performance target or attained percentage.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Challenge set isolates: Number not specified, but these were used for comparison against "expected results."
- Clinical isolates: Number not specified, but these were compared to the reference broth microdilution method.
- Data Provenance: Prospective, from "ten geographically diverse sites across the United States."
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their qualifications. The ground truth for the clinical studies was established by:
- Challenge set isolates: "Expected results for each organism/antimicrobic combination." (Implies a known, perhaps previously validated, standard).
- Clinical isolates: Comparison to the "NCCLS broth microdilution method" (AST panels manufactured according to NCCLS M7). This method itself is a standardized reference.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method involving multiple human readers for disagreements. Instead, the performance was assessed by comparing Phoenix System results directly to either "expected results" (for challenge set) or the "reference broth microdilution method" (for clinical isolates).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study involving human readers and AI assistance was not done. This study is focused on the performance of the automated system itself, not its impact on human reader performance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance study was done. The entire study describes the performance of the "BD Phoenix™ Automated Microbiology System" (algorithm/device only) in determining MIC values and category interpretations, comparing its output directly to reference methods.
7. The Type of Ground Truth Used
- For Challenge Set Isolates: "Expected results for each organism/antimicrobic combination."
- For Clinical Isolates: The results obtained from the "NCCLS broth microdilution method" (AST panels manufactured according to NCCLS M7). This is a widely accepted laboratory reference standard for antimicrobial susceptibility testing.
8. The Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its sample size. The study describes "clinical studies" and "analytical studies" to evaluate the system's performance, but it doesn't characterize distinct training and test sets in the typical machine learning sense. The organism identification and AST determinations are based on the system's design and internal algorithms, likely developed and validated using various data over time, but not specified in this document.
9. How the Ground Truth for the Training Set Was Established
As no specific training set is outlined, the method for establishing its ground truth is not described in this document. The system's underlying principles for growth determination and MIC interpretation are inherent to its design, which would have been established through a combination of scientific knowledge, laboratory testing, and potentially proprietary data from the manufacturer during its development.
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MAR 2 7 2002 510(k) SUMMARY
Image /page/0/Picture/1 description: The image shows a handwritten string of characters and numbers. The string is "K020322". The characters are written in black ink on a white background. The handwriting is somewhat messy, but the characters are still legible.
| SUBMITTED BY: | Becton, Dickinson and Company7 Loveton CircleSparks, MD 21152Phone: 410-316-4206Fax: 410-316-4499 |
|---|---|
| CONTACT NAME: | Bradford Spring,Manager Regulatory Affairs |
| DATE PREPARED: | March 25, 2002 |
| DEVICE TRADE NAME: | BD Phoenix ™ Automated Microbiology System |
| DEVICE COMMON NAME: | Antimicrobial susceptibility test system-short incubation |
| DEVICE CLASSIFICATION: | In accordance with FDA's reclassification order issuedDecember 28, 2001, Docket # 97P-0313, the BDPhoenix ™ Automated Microbiology System has beenclassified as a Class II device, Automated AntimicrobialSusceptibility System Test, short incubation (Product CodeLON) |
| PREDICATE DEVICES: | VITEK ® System (PMA No. N50510) |
| INTENDED USE: | The BD Phoenix ™ Automated Microbiology System isintended for the rapid identification and in vitroantimicrobial susceptibility testing of isolates from pureculture of most aerobic and facultative anaerobic Gramnegative 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 inoculum suspension equivalent to a 0.5 McFarland standard is prepared in the Phoenix ID broth. Prior to inoculating the Phoenix AST broth, one drop of Phoenix AST indicator solution is added to the uninoculated AST broth. The AST broth is then inoculated using the organism suspension from the ID broth. The Phoenix antimicrobial susceptibility test is inoculated with the AST broth. Inoculated panels are loaded into the Phoenix instrument.
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, and resistant).
DEVICE COMPARISON:
The BD Phoenix™ Automated Microbiology System demonstrated substantially equivalent performance when compared with the NCCLS broth microdilution method. This premarket notification provides data supporting the use of the BD Phoenix™ Automated Microbiology System Gram negative and Gram positive ID/AST or AST only Phoenix panels with Levofloxacin.
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 manufactured 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.
Analytical Studies
Site Reproducibility
Intra- and inter-site reproducibility of the Phoenix AST system in determining minimum inhibitory concentration (MIC) results was evaluated at six external sites. Three sites tested a panel of gram-negative isolates and three sites tested a panel of gram-positive isolates. Each site tested the isolates in triplicate on three different days. One lot of Gram Negative Phoenix Panels and one lot of Gram Positive Phoenix panels with Levofloxacin and associated reagents was tested at the gram-negative and gram-positive sites, respectively.
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The results of the study demonstrate for the antimicrobial Levofloxacin an overall intra-site reproducibility greater than 90% and an overall inter-site reproducibility greater than 95% for both gram-negative and gram-positive isolates tested.
Clinical Studies
Clinical studies were conducted at ten geographically diverse sites across the United States to demonstrate the performance of the Phoenix antimicrobial susceptibility test. Six study sites evaluated the Phoenix System using the Gram Negative Phoenix Panel format and four study sites evaluated the Phoenix System using the Gram Positive Phoenix Panel format. The study involved testing Challenge set isolates and clinical isolates. Phoenix System results for Challenge set isolates were compared to the expected results for each organism/antimicrobic combination. Phoenix System results for clinical isolates were compared to the results obtained from the reference broth microdilution method. The reference AST panels were manufactured according to NCCLS M7. Antimicrobial agents in the Phoenix and reference panels had similar dilution ranges. The Phoenix organism identification was used as the basis for susceptibility interpretation for both the Phoenix and reference methods.
Phoenix panels demonstrated essential agreement of > 90% to the expected/reference results for all three drugs. 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 + on 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 gram-negative isolates tested by drug. Table 2 summarizes the performance for the gram-positive isolates tested by drug.
| Table 1: Performance of Phoenix System for Gram-Negative Organisms by Drug | ||||||
|---|---|---|---|---|---|---|
| 0 |
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|---|---|---|---|---|---|
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Table 2: Performance of Phoenix System for Gram-Positive Organisms by Drug
| 0 000 1 0 0 1 0 1 0 1 0 1 0 1 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 | COLLECTION COLLEGIAL CALL CALL CLASS OF CLASS OF | CREE INSE WIRER OR WARD AND ANDC | |||
|---|---|---|---|---|---|
| . In the language a fire may continuenced and management1700000000 | ( | C | ------------------------------------------ | 1 | AND ALL PRODUCT CLASS COLLEGE OF COLLECTION OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES OF LEASES |
Conclusions Drawn from Substantial Equivalence Studies
The data collected in the analytical and clinical studies demonstrate that testing on the BD Phoenix™ Automated Microbiology System with Levofloxacin 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.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with three wavy lines emanating from its body, symbolizing health, services, and people. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
MAR 2 7 2002
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Bradford M. Spring Manager, Regulatory Affairs BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152
K020322 Re:
Trade/Device Name: BD Phoenix™ Automated Microbiology Systems, Levofloxacin (0.25-8 µg/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: January 14, 2002 Received: January 15, 2002
Dear Mr. Spring:
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 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set
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Page 2 -
This letter will allow you to begin marketing your device as described in your 510(k) premarket I his letter will and w you wood substantial equivalence of your device to a legally marketed nouthcation. The I Dri intellig of succion for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at additionally 607.10 for millionally, for questions on the promotion and advertising of your device, (2017 59 r 10 the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small nuonnation on your respond and Consumer Assistance at its toll-free number (800) 638-2041 or 1101) 443-6597 or at its internet address "http://www.fda.gov/odrh/dsma/dsmamain.html".
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number: K020322
Indications for Use:
The BD Phoenix™ Automated Microbiology System is intended for in vitro quantitative determination of antinicrobial susceptibility by minimal inhibitory concentration (MIC) of gram-negative aerobic and facultative anamerolia bacteria isolates from pure culture belonging to the family Enterobacteriaceae and most glucose nonfermenting gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.
This premarket notification is for the addition of the antimicrobial Levofloxacin at concentrations of 0.25-8 μg to Gram negative and Gram positive ID/AST or AST only Phoenix panels. Levofloxacin 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 antimicrobic.
Active In Vitro Against: Active In Vitro and in Clinical Infections Against: Aerobic Gram-positive microorganisms Aerobic Gram-positive microorganisms Staphylococcus epidermidis (methicillin susceptible strains) Enterococcus faecalis (many strains are moderately susceptible) Staphylococcus aureus (methicillin-susceptible strains) Aerobic Gram-negative microorganisms Staphylococcus saprophyticus Acinetobacter baumannii Acinetobacter lwoffii Aerobic Gram-negative microorganisms Citrobacter koseri Enterobacter cloacae Citrobacter freundii Escherichia coli Enterobacter aerogenes Klebsiella pneumoniae Enterobacter sakazakii Proteus mirabilis Klebsiella oxytoca Pseudomonas aeruginosa Morganella morganii Pantoea agglomerans Proteus vulgaris Providencia rettgeri Providencia stuartii Pseudomonas fluorescens
Results for Pseudomonas aeruginosa, other Non-Enterobacteriaceae and Enterococcus spp. tested with Levofloxacin should only be reported for isolates recovered from the urinary tract.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Serratia marcescens
Ferdinand Cooke
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
..tuoratory Devices
Prescription Use U (Per 21 CFR 801.109) 510(k) Number_QF
Over-The-Counter Use Optional Format 1-2-96
BD Phoenix™ Automated Microbiology System for use with the antimicrobial Levofloxacin Device Name: (0.25-8 µg) on Gram negative and Gram positive ID/AST or AST only Phoenix panels.
§ 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.”