(45 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 ampicillin-sulbactam at concentrations of 2/1 - 32/16 ug/mL to Gram Positive ID/AST or AST only Phoenix panels. Ampicillin-sulbactam has been shown to be active 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:
Staphylococcus aureus (beta-lactamase producing)
Active In Vitro Against:
Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing)
Staphylococcus epidermidis (beta-lactamase and non-beta-lactamase producing)
Staphylococcus saprophyticus (beta-lactamase and non-beta-lactamase producing)
Enterococccus faecalis (formally Streptococcus faecalis)
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 . or 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 polystyrent tray with 136 micro-wells containing dried reagents. Organisms for succeptive solate. For each isolate, an inoculation premimatily nonthrou as a Sean dard is prepared in Phoenix ID broth.
The Phoenix AST method is a broth based microdilution test. The Phoenix System uilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Measurements of the material to the material 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 55 ℃. THe instrument takes roading of unimum inhibitory concentration (MIC) values and category interpretations, S, I, R or N (susceptible, intermediate, resistant or not susceptible).
Here's a breakdown of the acceptance criteria and study information for the BD Phoenix™ Automated Microbiology System for ampicillin-sulbactam, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the benchmarks set by the NCCLS reference broth microdilution method and the FDA draft guidance. While specific numeric acceptance criteria are not explicitly stated as "must be greater than X%", the study aims to demonstrate "substantially equivalent performance" to the reference method and achieve high reproducibility.
The relevant performance metrics and the reported results for the BD Phoenix™ System with ampicillin-sulbactam in Gram-positive organisms are:
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Ampicillin-sulbactam, Gram-Positive) |
|---|---|---|
| Reproducibility | Intra-site reproducibility greater than 90% (for this antimicrobial agent) | Overall intra-site reproducibility > 90% |
| Inter-site reproducibility greater than 95% (for this antimicrobial agent) | Overall inter-site reproducibility > 95% | |
| 95% reproducibility or greater within ± 1 dilution (for this antimicrobial agent) | Demonstrated 95% reproducibility or greater within ± 1 dilution | |
| Accuracy (Essential Agreement - EA) | Substantially equivalent performance to NCCLS reference method. Typically, high agreement is expected (e.g., >90%). | 97.4% |
| Accuracy (Category Agreement - CA) | Substantially equivalent performance to NCCLS reference method. Typically, high agreement is expected (e.g., >90%). | 88.7% |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The "Clinical Studies" section notes that 1616 isolates (clinical, stock, and challenge) were used to calculate Essential Agreement (EA) and Category Agreement (CA) for ampicillin-sulbactam.
- Data Provenance:
- Clinical isolates: Tested across "multiple geographically diverse sites" within the United States. This implies prospective collection from various clinical settings.
- Stock and challenge isolates: Also tested, but their specific origin (e.g., specific culture collections or laboratory strains) is not detailed.
- Overall: Mixture of prospective (clinical) and possibly retrospective or banked (stock/challenge) isolates.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document states that the Phoenix System results were compared to the NCCLS reference broth microdilution method. This laboratory method itself serves as the "ground truth" or reference standard. It's a standardized laboratory technique, not based on expert interpretation like radiology images. Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth doesn't directly apply in the same way it would for imaging diagnostics. The ground truth is derived from the established and validated laboratory procedure.
4. Adjudication Method for the Test Set
Not applicable. The ground truth is established by a standardized laboratory method (NCCLS reference broth microdilution) which yields a definitive result (MIC and category interpretation) rather than requiring adjudication among human experts.
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
Not applicable. This device is an automated microbiology system that performs in vitro antimicrobial susceptibility testing. It does not involve human "readers" interpreting results that would then be enhanced or compared with AI assistance. The system provides a direct measurement and interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, this study is inherently a standalone performance evaluation. The BD Phoenix™ Automated Microbiology System is designed to provide automated identification and AST results. The comparison is between the automated system's output and the NCCLS reference method's output. While human technicians operate the system and prepare inoculations, the "performance" being evaluated is the algorithm's ability to accurately determine MICs and category interpretations without human interpretive intervention beyond standard laboratory procedures.
7. The Type of Ground Truth Used
The ground truth used is the NCCLS reference broth microdilution method. This is a well-established and standardized laboratory method for determining antimicrobial minimum inhibitory concentrations (MICs) and susceptibility categories.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" for the BD Phoenix™ System or the specific ampicillin-sulbactam agent. This type of device, an automated laboratory instrument, is typically developed and validated using a structured approach that may involve internal R&D data for algorithm development, but this "training set" information is not part of the regulatory submission summary provided. The submission focuses on the validation or test set performance against a reference standard.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is described in the provided summary, information on how its ground truth was established is not available. However, based on typical device development, any internal development or optimization would likely have also used comparison to standardized laboratory methods like the NCCLS broth microdilution method as the ground truth.
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510(k) SUMMARY
| SUBMITTED BY: | Becton, Dickinson and Company7 Loveton CircleSparks, MD 21152Phone: 410-316-4287Fax: 410-316-4499 | FEB 2 2005 |
|---|---|---|
| CONTACT NAME: | Monica Evelyn Giguere,RA Specialist | |
| DATE PREPARED: | January 12, 2005 | |
| DEVICE TRADE NAME: | BD Phoenix™ Automated Microbiology System -Ampicillin-sulbactam 2/1-32/16 $\mu$ g/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 (K020323May 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 . or 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 polystyrent tray with 136 micro-wells The Phoenix panel is a seated and self-movations allows ship must be a pure culture and containing dried reagents. Organisms for succeptive solate. For each isolate, an inoculation premimatily nonthrou as a Sean dard is prepared in Phoenix ID broth.
The Phoenix AST method is a broth based microdilution test. The Phoenix System uilizes a redox I he Phoenix AST method is a broth bases intention of an antimicrobial agent.
indicator for the detection of organism growth in the presence of an antimicrobial agent. indicator for the uelection of organism growsin growsing turbidity are used in the determination Measurements of the material to the material 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 I Its instrument takes readings of the panels every 20 minutes. The readings are interpreted to 55 ℃. THe instrument takes roading of unimum inhibitory concentration (MIC) values and category interpretations, S, I, R or N (susceptible, intermediate, resistant or not susceptible).
DEVICE COMPARISON:
The BD Phoenix™ Automated Microbiology System demonstrated substantially equivalent performance when compared with the NCCLS reference broth microdilution method. This premarket periormance which comporting the use of the BD Phoenix™ Automated Microbiology System Gram positive 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 performance with volung to NCCLS M7). The system has been evaluated as defined in the FDA Draft propared according "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-positive isolates. Each site tested the isolates in ttriplicate on three different days using one lot of Gram Positive 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-positive isolates tested.
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Clinical Studies
Clinical, stock and challenge isolates were tested across multiple geographically diverse itsearch Climical, stock and chances were coroes were corben antimicrobial susceptibility test with the United States to demonstrate the performation of this antimicrobial agent. Phoenix System results for clinical the Gram Positive Photon's I and formal contained to the expected results for clinical for Chailenge set isolates were compared to the new the NCCLS reference broth microdilution method.
The performance of the Phoenix System was assessed by calculating Essential Agreement (EA) and I he periormance of the Phoenix System was assessed on the solates tested. Essential Agreement Calegory Agreement (CT) to exports Automated Microbiology System agrees exactly or within ± (CA) occurs when are DD Do reference result. Category Agreement (CA) occurs when the BD one two-rold diration to the reference with the reference method with respect to the I hound - Tatomated Microsoftop (susceptible, intermediate, resistant or not susceptible).
Table 1 summarizes the performance for the isolates tested in this study.
Performance of BD Phoenix System for Gram-Positive Organisms by Drug Table 1:
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Antimicrobial | Concentration | EA (n) | EA (%) | CA (n) | CA (%) |
|---|---|---|---|---|---|
| Ampicillin- | 2/1-32/16 µg/mL | 1616 | 97.4 | 1616 | 88.7 |
| sulbactam |
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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SUMMARY INFORMATION FOR AMPICILLIN-SULBACTAM Available Range 2/1-32/16 µg/mL
Performance
Accuracy
| and the contraction of the contraction of the comments of the comments of the comments of the comments of the comments of the comments ofAntimicrobial | Concentration | EA (n) | EA (%) | CA (n) | " CA (%)Concession of Concession of School |
|---|---|---|---|---|---|
| AAmpicillin- | 2/1-32/16 µg/mL | 1616 | 97.4 | 1616 | 88.7 |
| sulbactam |
Reproducibility
Testing performed at multiple clinical sites demonstrated 95% reproducibility or greater within ± 1 dilution.
Breakpoints - NCCLS, FDA
| Organism | S | I | R |
|---|---|---|---|
| Staphylococcus aureus | $\leq$ 8/4 | 16/8 | $\geq$ 32/16 |
| Staphylococcus spp, coagulase-negative | $\leq$ 8/4 | 16/8 | $\geq$ 32/16 |
NCCLS Quality Control Organisms
| Quality Control Strain | MIC Range | Source |
|---|---|---|
| Escherichia coli ATCC 25922* | 2/1 - 8/4 $\u03bc$ g/mL | NCCLS |
| Escherichia coli ATCC 35218* | 8/4 - 32/16 $\u03bc$ g/mL | NCCLS |
*Testing of Gram-negative QC strains in the Phoenix Gram-positive panel is not appropriate.
BD Recommended Quality Control Organisms
| Quality Control Strain | MIC Range | Source |
|---|---|---|
| Staphylococcus aureus ATCC 29213 | $\le$ 2 $\mu$ g/mL | BD |
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Image /page/4/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal is circular and contains the department's emblem in the center. The emblem consists of a stylized caduceus, a symbol of medicine, with three wavy lines representing the department's mission to promote health, well-being, and human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the emblem within the circle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
FEB 2 8 2005
Ms. Monica Evelyn Giguere Regulatory Affairs Specialist BD Diagnostics Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152
K050089 Re:
R050089
Trade/Device Name: BD Phoenix™ Automated Microbiology System BD Friocillin-sulbactam (2/1-32/16 µg/mL) - Gram-Positive ID/AST Regulation Number: 21 CFR 866.1645 Regulation Name: 21 CFR 000.1016
Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility Devices Regulatory Class: Class II Product Code: LON Dated: January 12, 2005 Received: January 14, 2005
Dear Ms. Giguere:
We have reviewed your Section 510(k) premarket notification of intent to market the device indicati we have reviewed your Section 9 ro(x) premained is substantially equivalent (for the indications referenced and nave decemblied the are are are are are as a marketed in interstate for use stated in the encrosule for legally manated produce Americal Device American be of Drug commerce prior to May 28, 1776, the enations with the provisions of the Federal Food. Drug, devices that have been recure approval of a premarket approval approval application (PMA).
and Cosmetic Act (Act) that do not require approval of a premarket approval of the and Cosmelle ACt (Act) that do not require approvin controls provisions of the Act. The Y ou may, therefore, market the device, basjoct of the more in the manual registration, listing of general controls provisions of the fiel labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), , If your device is Classified (Sec adove) into c. Existing major regulations affecting your device in it may be subject to such additional controllar Enting Might of the one of to 895. In addition, FDA can be found in The 21, Code of I costs and subject in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination and mean Please be advised that FDA s issualled of a butters. In the requirements of the Act that FDA has made a decemination administered by other Federal agencies. You must of any Federal Statutes and regulations adminding, but not limited to: registration and listing (21 comply with an the Act 3 requirements, moraling good manufacturing practice CFR Fall 807), labeling (21 CF 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PFR 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)
The same of the success of the same of the suisely of your device to a legal This letter will allow you to begin marketing your uevice of your device of your device to a legally
premarket notification. The FDA finding of substantial equivales of your premarket notification. The PDA Intonig of substantal organ 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, of In If you desire specific information adounting of your device, please contact the Office of In
or questions on the promotion and advertising of your device, please poterse pote or questions on the promotion and advertising of Jour 2011-0484. Also, please note the Vifro Diagnosic Device Evaluation and Barey at (217). " (210FR Part 807.97).
regulation entitled, "Misbranding by reference to premarket notification Ast from the regulation entitled, "Wisofananing of reference to presponsibilities under the Act from the You may obtain other general information. on your Copsumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html
Sincerely yours,
Sally a Hom
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices 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: Ko50089
Device Name: BD Phoenix™ Automated Microbiology System for use with the antimicrobial agent ampicillin-sulbactam (2/1-32/16 ug/mL) - 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 I III BD I Iioliii - Ausceptibility by minimal inhibitory concentration (MIC) of most Gram-negative aerobic and antinutional suscepating of immer manene 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 ampicillin-sulbactam at This prenance for the abon is for alle assume Positive ID/AST or AST only Phoenix panels. Ampicillinconcentions of 21 - 92 10 pg nize to Chairro 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:
Staphylococcus aureus (beta-lactamase producing)
Active In Vitro Against:
Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing) Staphylococcus epidermidis (beta-lactamase and non-beta-lactamase producing) Staphylococcus saprophyticus (beta-lactamase and non-beta-lactamase producing) Enterococccus faecalis (formally Streptococcus faecalis)
Prescription Use V (Per 21 CFR 801.109) Over-the-Counter Use
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
| Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) | |
|---|---|
| Division Sign-Off | |
| Office of In Vitro Diagnostic DeviceEvaluation and Safety |
BD Diagnostic Systems Becton, Dickinson and Company
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§ 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.”