(79 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, Non-Enterobacteriaceae and most glucose nonfermenting gram-positive bacteria isolates from pure culture belonging for Staphylococcus and Enterococcus.
This premarket notification is for the antimicrobial Ofloxacin at concentrations of 0.25-8 µg to Gram negative and Gram positive ID/AST or AST only Phoenix panels. Ofloxacin 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. more 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 tentifyerature of 50 €. The nive an identification of the isolate, minimum inhibitory concentration (MIC) values and category interpretations, S, I, or R (sensitive, intermediate, and resistant).
Here's a summary of the acceptance criteria and study details for the BD Phoenix™ Automated Microbiology System, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criterion (Primary Endpoint for Equivalence) | Target Performance | Reported Device Performance (Ofloxacin) |
|---|---|---|
| Essential Agreement (EA) with reference method | > 90% | > 90% (for all three drugs, including Ofloxacin) |
| Category Agreement (CA) with reference method | Not explicitly stated as a minimum percentage in the provided text, but implied as a key metric for substantiating equivalence. | Reported alongside EA. No specific minimum percentage for CA was given but the statement "Phoenix panels demonstrated essential agreement of > 90% to the expected/reference results for all three drugs" and subsequent tables imply acceptable CA for equivalence. |
| Intra-site Reproducibility (MIC results) | Not explicitly stated, but clinical study results deemed acceptable for equivalence. | > 90% (for both gram-negative and gram-positive isolates tested with Ofloxacin) |
| Inter-site Reproducibility (MIC results) | Not explicitly stated, but clinical study results deemed acceptable for equivalence. | > 95% (for both gram-negative and gram-positive isolates tested with Ofloxacin) |
Notes on the Table:
- The document states that the evaluation was "as defined in the FDA Draft guidance document, 'Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices', March 8, 2000." This guidance document would contain the specific acceptance criteria for EA and CA, which are summarized as "substantially equivalent performance" if the criteria are met. The text here only specifically quantifies >90% EA.
- "All three drugs" refers to the drug(s) tested apart from Ofloxacin. The document specifically provides data for Ofloxacin.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Clinical Studies (Challenge & Clinical Isolates): The exact number of isolates for each organism/antimicrobic combination is not explicitly stated. The study involved "Challenge set isolates" and "clinical isolates."
- Reproducibility Studies: For Ofloxacin, the study involved panels of gram-negative and gram-positive isolates. Each site tested the isolates in triplicate on three different days. The total number of unique isolates is not given, but it implies a significant number to assess reproducibility across 6 sites.
- Data Provenance:
- Clinical Studies: Conducted at "ten geographically diverse sites across the United States." The data is prospective for clinical isolates and retrospective for challenge isolates (as they have "expected results").
- Reproducibility Studies: Conducted at "six external sites" (three for gram-negative, three for gram-positive). The data provenance is broadly "external sites."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Ground Truth for Clinical Isolates: The ground truth was established by the "NCCLS broth microdilution method," which is a standardized laboratory method. This does not involve "experts" in the sense of clinicians making subjective interpretations. Rather, it relies on the established accuracy and reproducibility of the NCCLS method performed by qualified laboratory personnel.
- Ground Truth for Challenge Isolates: The ground truth was "expected results for each organism/antimicrobic combination." This implies a pre-defined standard, likely based on established reference methods or expert consensus in microbiology, but the specific number or qualifications of experts are not mentioned.
4. Adjudication Method for the Test Set
- No explicit adjudication method (e.g., 2+1, 3+1) is mentioned. The comparison is directly between the BD Phoenix System results and the NCCLS reference broth microdilution method (for clinical isolates) or "expected results" (for challenge isolates). Discrepancies would typically be reviewed by laboratory personnel according to standard operating procedures, but a formal adjudication process involving multiple external experts for disagreements is not described.
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. This study is for an automated microbiology system that determines antimicrobial susceptibility (MIC values and categories) and organism identification, not a diagnostic imaging device involving human readers' interpretation. Therefore, an MRMC study and analysis of human reader improvement with AI assistance are not applicable. The device replaces manual interpretation of susceptibility testing rather than assisting it.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
- Yes, this was a standalone performance study. The BD Phoenix™ Automated Microbiology System is an automated system where the instrument takes readings and provides results (identification, MICs, and interpretations) without direct human intervention in the interpretation process of each individual test result. Humans load the panels and interpret the final output from the system, but the core measurement and interpretation for susceptibility are automated. The comparison is between this automated system's output and a reference method.
7. The Type of Ground Truth Used
- For Clinical Isolates: The ground truth was established by the NCCLS broth microdilution method, which is a widely accepted, standardized reference method for antimicrobial susceptibility testing.
- For Challenge Isolates: The ground truth was "expected results," which implies a pre-defined standard based on established microbiological principles or expert consensus in such panels.
8. The Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning model development. This is an older 510(k) (2002) for an automated microbiology system that likely relies on rule-based algorithms or statistical models built from extensive prior research and data, rather than a deep learning model requiring a distinct, large training set as understood today. The data described (analytical and clinical studies) appears to be primarily for verification and validation.
9. How the Ground Truth for the Training Set Was Established
- As mentioned above, a "training set" for a machine learning model is not explicitly discussed. The system's underlying capabilities (e.g., how it interprets redox changes and turbidity to determine growth/MIC) would have been developed based on extensive microbiology research and correlation with reference methods over time. The "ground truth" for developing the system's internal algorithms would have relied on data from reference methods (like microbroth dilution) and known biological responses of microorganisms to antimicrobials.
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APR = 4 2002
510(k) SUMMARY
SUBMITTED BY:
Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152 Phone: 410-316-4206 Fax: 410-316-4499
CONTACT NAME:
Bradford Spring, Manager Regulatory Affairs
DATE PREPARED:
April 3, 2002
BD Phoenix™ Automated Microbiology System DEVICE TRADE NAME:
Antimicrobial susceptibility test system-short incubation DEVICE COMMON NAME:
DEVICE CLASSIFICATION:
In accordance with FDA's reclassification order issued December 28, 2001. Docket # 97P-0313. the BD PhoenixTM Automated Microbiology System has been classified as a Class II device, Automated Antimicrobial Susceptibility System Test, short incubation (Product Code LON)
VITEK® System (PMA No. N50510)
INTENDED USE:
PREDICATE DEVICES:
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.
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.
1
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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. more 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 tentifyerature of 50 €. The nive 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 Offoxacin.
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 Ofloxacin 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 Ofloxacin 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 acmontated 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 |
|---|
| Comments of the consisted on the comments of the control of the contribution of the contribution of the contribution of the contribution of the contribution of the contributi |
| Antimicrobial | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------oncentration | 0/0 | |||
|---|---|---|---|---|---|
| ู้)tloxacın | mco/m | 0070 | 00 | 2070 |
Table 2: Performance of Phoenix System for Gram-Positive Organisms by Drug
| a more a mossa codely a la ? 400 . 1. " 400 . 1. " 400 . 1. " 400 . 1. " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " . " .------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Antimicrobial | The First First First of the Research andAnd Character Coll College College Come ofoncentration | ( m | 0A carder, and the capital and | 101こ |
|---|---|---|---|---|
| To and Conceller The ResearchOfloxacin | IN MILLEPP PI I T IT THE FIN FREE FREE FREE FREE FREE FREE WARREN FOR THE FORMICIAL CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTERS CONTRACTION CONSULTERS Cn nemcg/mL | 10 /104 | S | 00 0U.L. |
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 Ofloxacin 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 logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines representing hair or clothing.
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
Re: K020323
Trade/Device Name: BD PhoenixTM Automated Microbiology Systems, Ofloxacin (0.25-8 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: 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 forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Page 2 -
This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact 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 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 Butman
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: K020323
Device Name: BD Phoenix™ Automated Microbiology System for use with the antimicrobial Ofloxacin (0.25-8 ug) on Gram negative and Gram positive 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, Non-Enterobacteriaceae and most glucose nonfermenting gram-positive bacteria isolates from pure culture belonging for Staphylococcus and Enterococcus.
This premarket notification is for the antimicrobial Ofloxacin at concentrations of 0.25-8 µg to Gram negative and Gram positive ID/AST or AST only Phoenix panels. Ofloxacin 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 and in Clinical Infections Against: | Active In Vitro Against: |
|---|---|
| Aerobic Gram-positive microorganisms | Aerobic Gram-positive microorganisms |
| Staphylococcus aureus | Staphylococcus epidermidis (excluding methicillin-resistant strains) |
| Aerobic Gram-negative microorganisms | Staphylococcus haemolyticus |
| Citrobacter koseri (formerly Citrobacter diversus) | Staphylococcus saprophyticus |
| Enterobacter aerogenes | Aerobic Gram-negative microorganisms |
| Escherichia coli | Acinetobacter calcoaceticus |
| Klebsiella pneumoniae | Aeromonas caviae |
| Proteus mirabilis | Aeromonas hydrophila |
| Pseudomonas aeruginosa | Citrobacter freundii |
| Enterobacter cloacae | |
| Klebsiella oxytoca | |
| Morganella morganii | |
| Proteus vulgaris | |
| Providencia rettgeri | |
| Providencia stuartii | |
| Serratia marcescens |
Results for Enterobacteriaceae, Pseudomonas aeruginosa and other Non-Enterobacteriaceae tested with Ofloxacin should only be reported for isolates recovered from the urinary tract.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
| (Division Sign-Off) | |
| Division of Clinical Laboratory Devices | |
| 510(k) Number | K020323 |
Image /page/5/Picture/10 description: The image shows the words "Prescription Use" followed by the text "(Per 21 CFR 801.109)". There is a check mark above the line after the words "Prescription Use". The text is in black and the background is white.
Over-The-Counter Use Optional Format 1-2-96
§ 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.”