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 antimicrobial agent nitrofurantoin at concentrations of 16-512 µg/mL to Gram Positive ID/AST or AST only Phoenix panels. Nitrofurantoin has been shown to be active in viro 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
Enterococcus faecalis

Active In Vitro Against:
Staphylococcus species

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.

The Phoenix panel is a sealed and self-inoculating molded polystyrene tray with 136 micro-wells containing dried reagents. Organisms for susceptibility testing must be a pure culture and preliminarily identified as a Gram-negative or Gram-positive isolate. For each isolate, an inoculation equivalent to a 0.5 McFarland standard is prepared in Phoenix ID broth.

The Phoenix AST method is a broth based microdilution test. The Phoenix system utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Measurements of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. Each AST panel configuration contains several antimicrobial agents with a wide range of two-fold doubling dilution concentrations.

The instrument houses the panels where they are continuously incubated at a nominal temperature of 35°C. The instrument takes readings of the panels every 20 minutes. The readings are interpreted to give an identification of the isolate, minimum inhibitory concentration (MIC) values and category interpretations, S. I, or R (sensitive, intermediate, or resistant).

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided text for the BD Phoenix™ Automated Microbiology System – Nitrofurantoin 16-512 µg/mL:

Acceptance Criteria and Device Performance Study

The study aimed to demonstrate substantial equivalence of the BD Phoenix™ Automated Microbiology System's performance with Nitrofurantoin to the NCCLS reference broth microdilution method.

1. Table of Acceptance Criteria and Reported Device Performance

Measure	Acceptance Criteria (Implicit)	Reported Device Performance (Table 1: Performance of BD Phoenix System for Gram-Positive Organisms by Drug)
Essential Agreement (EA)	Not explicitly stated but implied to be high, generally ≥ 90% in similar premarket notifications for AST devices.	Not explicitly detailed in the provided "Table 1" for Nitrofurantoin. The table lacks clear performance metrics despite its heading.
Category Agreement (CA)	Not explicitly stated but implied to be high, generally ≥ 90% for clinical isolates in similar premarket notifications for AST devices, comparing to reference.	Not explicitly detailed in the provided "Table 1" for Nitrofurantoin. The table lacks clear performance metrics despite its heading.
Intra-site Reproducibility	Greater than 90% (explicitly stated)	Greater than 90%
Inter-site Reproducibility	Greater than 95% (explicitly stated)	Greater than 95%

Note: The provided "Table 1: Performance of BD Phoenix System for Gram-Positive Organisms by Drug" for Nitrofurantoin is incomplete and unreadable in the given text (e.g., "CA ( m (0/p 0 4 4 3 1 1 (0)01" and "Fre 00 € 1 5 C F 00 2"). Therefore, the specific EA and CA values for Nitrofurantoin cannot be extracted from this table. However, the text states "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." and "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." This strongly implies that the system met the FDA's expected performance criteria for EA and CA, even if the numbers are redacted/unreadable.

2. Sample Size Used for the Test Set and Data Provenance

Test Set Description: Clinical, stock, and challenge isolates.
Sample Size: Not explicitly stated for each category of isolates. The study mentions "all isolates tested" when discussing EA and CA, but the total number is not provided.
Data Provenance: Multiple geographically diverse sites across the United States. The text indicates that these were both clinical (patient-derived) and stock/challenge (laboratory culture) isolates.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Number of Experts: Not applicable in the typical sense for this device.
Qualifications of Experts: The ground truth for antimicrobial susceptibility testing (AST) is established by the NCCLS reference broth microdilution method. This is a standardized laboratory procedure, not an interpretation by individual human experts. The accuracy of this reference method is maintained through strict protocols and quality control.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The comparison is made directly between the BD Phoenix System's results and the results obtained from the objective NCCLS reference broth microdilution method. There is no human adjudication process described for reconciling differences in interpretations, as the reference method is considered the gold standard.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

MRMC Study Done: No, an MRMC comparative effectiveness study was not performed.
The study design is focused on the performance of the automated system compared to a reference standard, not on how human readers' performance might change with or without AI assistance. The device is a standalone AST system.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Standalone Study Done: Yes, this entire study is a standalone performance evaluation. The BD Phoenix Automated Microbiology System is an automated device designed to rapidly identify and perform antimicrobial susceptibility testing. Its performance is assessed directly against the NCCLS reference method without human interpretation as part of the primary outcome measure (EA and CA). The system "takes readings of the panels every 20 minutes" and "The readings are interpreted to give... MIC values and category interpretations, S. I, or R."

7. Type of Ground Truth Used

Type of Ground Truth: The ground truth used for performance comparison was the NCCLS reference broth microdilution method. For challenge isolates, "expected results" (presumably pre-determined by the reference method or established concentrations) were used.

8. Sample Size for the Training Set

Sample Size for Training Set: The document does not explicitly mention a separate "training set" or its size. This type of device's "training" for new antimicrobial agents typically involves extensive characterization and validation of the reagent formulations, the optical detection system's algorithms, and the interpretive criteria (breakpoints) based on established microbiological principles and a large body of data. The "challenge" and "stock" isolates, along with clinical isolates, might contribute to the refinement or validation of the system's interpretive algorithms for a new drug, but a distinct "training set" in the machine learning sense is not detailed.

9. How the Ground Truth for the Training Set Was Established

How Ground Truth for Training Set Was Established: As above, if "training" refers to the development and internal validation of the system's algorithms and interpretive logic for a new antimicrobial agent, the ground truth would be established through:
- NCCLS reference broth microdilution method: Providing the gold standard for MIC values and category interpretations.
- Extensive microbiological data: Including known strains with characterized susceptibility profiles, and possibly retrospective or prospective data used during the internal development phase.
- FDA guidance and clinical breakpoints: The system's interpretations (S, I, R) are based on FDA categorical interpretive criteria and established clinical breakpoints, which are derived from comprehensive clinical and pharmacological data for the antimicrobial agent against various organisms.

Summary

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K031589

JUL 1 1 2003

CONFIDENTIAL AND PROPRIETARY

510(k) SUMMARY

SUBMITTED BY:	Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152 Phone: (410) 316-4778 Fax: 410-316-4499
CONTACT NAME:	Michelle B. Bandy, Regulatory Affairs Specialist
DATE PREPARED:	May 20, 2003
DEVICE TRADE NAME:	BD Phoenix™ Automated Microbiology System – Nitrofurantoin 16-512 µg/mL
DEVICE COMMON NAME:	Antimicrobial susceptibility test system-short incubation
DEVICE CLASSIFICATION:	Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility 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), and Levofloxacin (K020322, March 27, 2002).
INTENDED USE:	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:

. 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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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 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 prepared according to NCCLS M7). The system has been evaluated as defined in the FDA Draft guidance document, "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", March 8, 2000.

Site Reproducibility

Intra- and inter-site reproducibility of this antimicrobial agent in the BD Phoenix System was evaluated at three sites using a panel of Gram-positive isolates. Each site tested the isolates in triplicate 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 sites across the United States to demonstrate the performance of the Phoenix antimicrobial susceptibility test with the Gram Positive 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-Positive Organisms by Drug

Antimicrobial------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	Concentration	CA( m	(0/p0 4 4 31	1	(0)01
Nitrofurantoin	16-512	Fre	00 €	1 5 C F	00 2
	' ug/mL

Conclusions Drawn from Substantial Equivalence Studies

The data collected from the substantial equivalence studies demonstrate that testing on the BD Phoenix™ Automated Microbiology System with this antimicrobial agent is substantially equivalent as outlined in the FDA draft guidance document, "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", March 8, 2000. Technological characteristics of this system are substantially equivalent to those used in the VITEK® system, which received approval by the FDA under PMA number N50510 and BD Phoenix™ Automated Microbiology System with Gatifloxacin (K020321, May 23, 2002), Ofloxacin (K020323, April 14, 2002), and Levofloxacin (K020322, March 27, 2002).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three lines representing its body and wings. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A." surrounding it.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 1 1 2003

Ms. Michelle B. Bandy Regulatory Affairs Specialist BD Diagnostics Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

Re: K031589

Trade/Device Name: BD Phoenix™ Automated Microbiology System Nitrofurantoin (16-512 ug/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility Devices Regulatory Class: Class II Product Code: LON Dated: May 20, 2003 Received: May 22, 2003

Dear Ms. Bandy:

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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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number: K031589

Device Name: BD Phoenix™ Automated Microbiology System for use with the antimicrobial agent nitrofurantoin (16-512 µg/mL) - Gram positive ID/AST or AST only Phoenix panels.

Indications for Use:

Active In Vitro and in Clinical Infections Against:

Staphylococcus aureus Enterococcus faecalis

Active In Vitro Against: Staphylococcus 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

Office of In Vitro Diagnostic Device Evaluation and Safety

Prescription Use
(Per 21 CFR 801.109)

510(k)	K031589
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	Over-the-Counter Use
--	----------------------

BD Diagnostic Systems Becton, Dickinson and Company

Page 8

Regulation Number and Section

§ 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.”