(234 days)
The BD Phoenix™ Automated Microbiology System is intended for the in vitro rapid identification (ID) and quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of Gram Negative aerobic and facultative anaerobic bacteria belonging to the family Enterobacteriaceae and non-Enterobacteriaceae
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, Enterococcus and Streptococcus.
Imipenem has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active In Vitro and in Clinical Infections Against: Acinetobacter spp. Citrobacter spp. Enterobacter cloacae Escherichia coli Klebsiella spp.
Pseudomonas aeruginosa Serratia marcescens
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 trav 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. Phoenix panels are inoculated with a specified organism density and placed into the instrument. Inoculum for use with the Phoenix system may be prepared either manually or may be automated using the BD Phoenix™ AP System.
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° ± 1°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, R or N (susceptible, intermediate, resistant or not susceptible).
This document describes the validation study for the BD Phoenix™ Automated Microbiology System's ability to determine antimicrobial susceptibility for Imipenem (0.0625-32 µg/mL) against Gram-negative organisms.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied by FDA Guidance) | Reported Device Performance |
|---|---|---|
| Clinical Isolates | ||
| Essential Agreement (EA) | Not explicitly stated but typically > 90% | 94.6% (n=1348) |
| Category Agreement (CA) | Not explicitly stated but typically > 90% | 95.3% (n=1348) |
| Site Reproducibility | > 95% (+/- 1 dilution) | > 95% (+/- 1 dilution) |
Note: The FDA guidance "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems" (August 28, 2009) implicitly sets the acceptance criteria through its recommendations for demonstrating substantial equivalence. The reported values meet or exceed these typical expectations.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The document reports n=1348 for clinical isolates used in the Essential Agreement (EA) and Category Agreement (CA) calculations for Imipenem. The number of challenge isolates is not separately reported but is included in the overall performance summary.
- Data Provenance:
- Country of Origin: United States. The clinical studies were conducted "across multiple geographically diverse sites across the United States."
- Retrospective or Prospective: Not explicitly stated, but the description of "clinical, stock and challenge isolates were tested" suggests a mix, likely involving prospective testing of newly acquired clinical isolates and retrospective testing of archived stock and challenge isolates.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
There is no mention of "experts" in the context of establishing ground truth for AST systems. The ground truth (reference method) for antimicrobial susceptibility testing is a standardized laboratory procedure, not an expert opinion.
4. Adjudication Method for the Test Set
Not applicable. The ground truth is established by a standardized reference method (CLSI broth microdilution), not through expert adjudication. Discrepancies between the device and the reference method are analyzed as part of the performance evaluation (e.g., major errors, very major errors), but not "adjudicated" in the sense of a consensus review.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically used for image-based diagnostic systems where human interpretation is involved. For an automated microbiology system that measures MIC values, the comparison is against a reference laboratory method rather than human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the study presents standalone performance. The BD Phoenix™ Automated Microbiology System is an automated system where the "algorithm only" (the instrument and its software) determines the MIC values and categorical interpretations. Human intervention is limited to sample preparation and instrument loading; the interpretation itself is automated.
7. The Type of Ground Truth Used
The ground truth used was the CLSI reference broth microdilution method (AST panels prepared according to CLSI M7). This is a standardized laboratory method for determining antimicrobial susceptibility. For challenge set isolates, "expected results" were used, which are typically pre-determined and validated MIC values for specific strains.
8. The Sample Size for the Training Set
The document does not provide information on the sample size for the training set. The described studies focus on the validation performance of the device against the reference standard. The BD Phoenix™ system would have been developed and trained (or "calibrated") using a large, undisclosed dataset of bacterial isolates with known susceptibilities, but this information is not part of this 510(k) summary.
9. How the Ground Truth for the Training Set Was Established
The document does not provide information on how the ground truth for the training set was established. Similar to the test set, it would have been established using a standardized reference method, most likely the CLSI broth microdilution method, during the development phase of the BD Phoenix™ system.
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510(k) SUMMARY
Becton, Dickinson and Company
JUN 2 7 2013
| SUBMITTED BY: | 7 Loveton CircleSparks, MD 21152Phone: 410-316-4827Fax: 410-316-4499 |
|---|---|
| CONTACT NAME: | Monica Giguere, RACRegulatory Affairs Project Manager |
| DATE PREPARED: | June 19, 2013 |
| DEVICE TRADE NAME: | BD Phoenix™ Automated Microbiology System –Imipenem (0.0625-32 µg/mL) |
| DEVICE COMMON NAME: | Antimicrobial susceptibility test system-short incubation |
| DEVICE CLASSIFICATION: | 21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility System.(Product Code LON) |
| PREDICATE DEVICES: | VITEK® System (PMA No. N50510) |
| INTENDED USE: | The BD Phoenix Automated Microbiology System is intendedfor the in vitro rapid identification (ID) and quantitativedetermination of antimicrobial susceptibility by minimalinhibitory concentration (MIC) of Gram Negative aerobic andfacultative anaerobic bacteria belonging to the familyEnterobacteriaceae and non-Enterobacteriaceae |
DEVICE DESCRIPTION:
SUBMITTED BY:
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 trav 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. Phoenix panels are inoculated with a specified organism density and placed into the instrument. Inoculum for use with the Phoenix system may be prepared either manually or may be automated using the BD Phoenix™ AP System.
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° ± 1°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, R or N (susceptible, intermediate, resistant or not susceptible).
DEVICE COMPARISON:
The BD Phoenix™ Automated Microbiology System demonstrated substantially equivalent performance for inoculum prepared manually and inoculum prepared with the BD Phoenix™ AP instrument when compared with the CLSI reference broth microdilution method. This premarket notification provides data supporting the use of the BD Phoenix™ Automated Microbiology System Gram negative ID/AST or AST only Phoenix panels with this antimicrobial agent.
SUMMARY OF SUBSTANTIAL EQUIVALENCE TESTING:
The BD Phoenix™ Automated Microbiology System has demonstrated substantially equivalent performance when compared to the CLSI reference broth microdilution method (AST panels prepared according to CLSI M7). The system has been evaluated as defined in the FDA guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", August 28, 2009.
Site Reproducibility
Intra- and inter-site reproducibility of this antimicrobial agent in the BD Phoenix System was evaluated at three sites using a panel of Gram-negative isolates. Each site tested the isolates in triplicate on three different days using one lot of Gram Negative Phoenix panels containing this antimicrobial agent and associated reagents.
The results of the study demonstrate that for this antimicrobial agent and the Gram-negative organisms tested there was an overall reproducibility across test sites of greater than 95% (+/- 1 dilution) agreement when compared to the test mode.
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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 a Gram Negative Phoenix Panel 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 CLSI 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, resistant or not susceptible).
The following table summarizes the performance for Clinical and Challenge isolates tested in this study.
| Antimicrobial | Concentration | EA (n) | EA (%) | CA (n) | CA (%) |
|---|---|---|---|---|---|
| Imipenem | 0.0625-32 µg/mL | 1348 | 94.6 | 1348 | 95.3 |
Performance of BD Phoenix System for Gram-Negative Organisms by Imipenem
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, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems: Guidance for Industry and FDA". August 28, 2009. 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
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Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Becton, Dickinson and Company c/o Monica Giguere Regulatory Affairs Project Manager BD Diagnostic System 7 Loveton Circle- MC614 Sparks. MD. 21152
June 27, 2013
Re: K123404
Trade/Device Name: BD Phoenix™ Automated Microbiology System- Imipenem (0.0625-32ug/mL) - Gram Negative ID/AST or AST only Phoenix Panels Regulation Number: 21 CFR §866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: II Product Code: LON Dated: May 28, 2013 Received: June 4, 2013
Dear Ms. Giguere:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the
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Page 2-Ms. Giguere
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers. International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/McdicalDevices/Safety/ReportaProblem/default.htm-for the CDRH's Office of Surveillance and Biometries/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Uwe Scherf -S for
Sally A. Hojvat, M.Sc., Ph.D Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Page 1 of 1
510(k) Number: K123404
Device Name: BD Phoenix™ Automated Microbiology System for use with the antimicrobial agent Imipenem (0.0625-32 ug/mL) - Gram-negative 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 and Non-Enterobacteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus, Enterococcus and Streptococcus.
Imipenem has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active In Vitro and in Clinical Infections Against: Acinetobacter spp. Citrobacter spp. Enterobacter cloacae Escherichia coli Klebsiella spp.
Pseudomonas aeruginosa Serratia marcescens
Prescription Use V (21 CFR 801 Subpart D) And/Or
Over the Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
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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.”