(250 days)
BacT/ALERT® FA Plus Culture Bottles are used with the BacT/ALERT® Microbial Detection System in qualitative procedures for enhanced recovery and detection of aerobic and facultative anaerobic microorganisms (bacteria and yeast) from blood and other normally sterile body fluids.
The new reagent (BacT/ALERT FA Plus Culture Bottle) is an improvement upon the cleared charcoal formulation reagent (BacT/ALERT FA Culture Bottle). The BacT/ALERT FA Culture Bottles are used with the BacT/ALERT Microbial Detection Systems in qualitative procedures for recovery and detection of microorganisms from blood. The predicate BacT/ALERT FA Culture Bottle contains charcoal, for its antimicrobial neutralization properties, in a complex growth medium. Charcoal is eliminated in the proposed BacT/ALERT FA Plus Culture Bottle, and is replaced with two types of adsorbent resins in a complex growth medium. The proposed BacT/ALERT FA Plus Culture Bottle is optimized to increase antimicrobial neutralization properties, and to increase the clarity of Gram stains in comparison to the predicate BacT/ALERT FA Culture Bottle. The BacT/ALERT Microbial Detection System provides both a microbial detection system and a culture medium bottle with suitable nutritional and environmental conditions for microorganisms commonly encountered in blood or other normally sterile body fluid samples (except urine) taken from a patient suspected of having bacteremia/fungemia. An inoculated bottle is placed into the instrument where it is incubated and continuously monitored for the presence of microorganisms that will grow in the BacT/ALERT bottles. The BacT/ALERT Microbial Detection System utilizes a colorimetric sensor and reflected light to monitor the presence and production of carbon dioxide (CO2) that is dissolved in the culture medium. If microorganisms are present in the test sample, carbon dioxide is produced as the microorganisms metabolize the substrates in the culture medium. When growth of the microorganisms produces CO2, the color of the gas-permeable sensor installed in the bottom of each culture bottle changes from blue-green to yellow. The lighter color results in an increase of reflectance units monitored by the system. Bottle reflectance is monitored and recorded by the instrument every 10 minutes.
Here's a breakdown of the acceptance criteria and study information for the BacT/ALERT® FA Plus Culture Bottle, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally demonstrated by the recovery rates and detection times remaining consistent with or improved compared to the predicate device, or meeting specific thresholds for sensitivity (LoD) and reproducibility.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity: | High % Recovery for tested microorganisms (seeded studies) | 100% Recovery for all tested microorganisms (both with and without blood) |
| Time to Detection (TTD) | Consistent TTD across strains and conditions | Reported mean and range of TTD for each organism and condition |
| Antimicrobial Neutralization: | Effective neutralization of a wide range of antimicrobials | Effectively neutralized penicillins, glycylcyclines, polyenes, macrolides, triazoles, echinocandins, cefazolin, cefoxitin, cefotaxime, ceftaroline, aminoglycosides, fluoroquinolones, lincosamides, glycopeptides, and oxazolidinones. |
| Certain antimicrobials may not be fully neutralized | Neutralization not achieved for ceftazidime or cefepime. Less than complete for cefotaxime (50% PSL to 2% PSL) and ceftriaxone (50% PSL to 1% PSL). | |
| Interfering Substances: | No interference with recovery or false positives | No interference with recovery/detection, no false positives (for CSF, pleural, synovial fluid, plasma, blood, blood clots with/without WBCs) |
| Limit of Detection (LoD): | At least 95% detection at LoD (seeded studies) | Achieved at least 95% detection for all listed microorganisms at reported CFU/bottle. |
| Within-Laboratory Precision (Repeatability): | 100% recovery consistently across lots/operators | 100% recovery for all tested organism/antimicrobial combinations across 3 lots. |
| Reproducibility: | High overall % Recovery across multiple sites | Overall 92.0% recovery (698/759) (95% CI: 89.8%, 93.8%). Excluding lab errors: 100% recovery except for E. aerogenes (85.0%). |
| Delayed Entry (Holds): | High % Recovery within specified hold times | Control: 100% (no delay). 2-8°C/48h: 98.6%. 20-25°C/24h: 98.0%. 20-25°C/36h: 91.9%. 35-37°C/8h: 98.9%. CAUTION: 35-37°C/24h: 56.6%. |
| Minimal false positives | 0.5% (1/221) false positive in negative controls. | |
| Clinical Study (Blood): | Ratio of FA Plus to FA True Positives ≥ 1 for significant isolates | Ratio of 1.178 for significant isolates (159 FA Plus vs. 135 FA). Total ratio 1.072 (208 FA Plus vs. 194 FA). |
| Minimal false positives | 0.30% (5/1685) false positives. | |
| Clinical Study (SBF): | Ratio of FA Plus to FA True Positives ≥ 1 for significant isolates | Ratio of 1.102 for significant isolates (65 FA Plus vs. 59 FA). Total ratio 1.269 (85 FA Plus vs. 67 FA). |
| Minimal false positives | 0% (0/421) false positives. |
2. Sample Sizes and Data Provenance
- Analytical Sensitivity (Growth Performance):
- Test Set Sample Size: Varies by microorganism (e.g., 33/33, 15/15), generally small per species, but covering n replicates.
- Data Provenance: In-house seeded studies. Blood obtained from healthy human volunteers.
- Limit of Detection (LoD):
- Test Set Sample Size: Minimum of 30 replicates per species.
- Data Provenance: In-house seeded studies, using bottles at end of shelf life.
- Within-Laboratory Precision (Repeatability):
- Test Set Sample Size: Minimum of 108 replicates (organism/antimicrobial combination) over 12 days.
- Data Provenance: In-house seeded studies
- Reproducibility:
- Test Set Sample Size: Target of 162 replicates per site across 3 sites (total of 486).
- Data Provenance: Seeded studies at three sites (implicitly internal or contract labs).
- Delayed Entry:
- Test Set Sample Size: Target concentrations of 100 CFU per bottle (35 to 290 CFU/bottle actual inoculum). At least 11 species. Control: 459 bottles. Held conditions: ~296-459 bottles per condition.
- Data Provenance: Seeded studies at three sites. Human blood from healthy volunteers.
- Clinical Study (Blood Cultures):
- Test Set Sample Size: 1656 bottle pairs (from 728 adult patients). Total 1685 results (267 isolates + 1418 negative pairs).
- Data Provenance: Multi-center clinical study at three different geographic sites in the U.S. Prospective (implied, as it compares performance).
- Clinical Study (Sterile Body Fluid Cultures):
- Test Set Sample Size: 404 bottle pairs (from 369 adult patients). Total 421 results (92 isolates + 329 negative pairs).
- Data Provenance: Multi-center clinical study at four different geographic sites in the U.S. and Canada. Prospective (implied).
3. Number of Experts and Qualifications for Ground Truth
- For all seeded studies (Analytical Sensitivity, LoD, Repeatability, Reproducibility, Delayed Entry), the ground truth is established by the known inoculum of microorganisms and subsequent culture confirmation/gram stain. No external experts are mentioned for these in-vitro studies beyond the internal study design and execution.
- For Clinical Studies (Blood and SBF Cultures):
- Number of Experts: Not explicitly stated.
- Qualifications of Experts: The text states, "Clinical isolates recovered were classified as significant, contaminant, or unknown based on determination by the clinical trial sites." This implies clinical microbiologists, infectious disease physicians, or other qualified laboratory personnel at the participating clinical sites were responsible for this determination. Specific qualifications (e.g., years of experience) are not provided.
4. Adjudication Method for the Test Set
- For seeded studies, adjudication is not typically performed in the same way as clinical imaging studies. The "ground truth" is directly controlled by the known seeded organisms and concentrations, and confirmed by lab methods (subculture, Gram stain).
- For Clinical Studies (Blood and SBF Cultures):
- "A pair of bottles was determined to have a positive status if the subculture of either the FA Plus or FA bottle was positive."
- "A culture bottle was determined to be a 'True Positive' if the culture was flagged positive by the BacT/ALERT System and resulted in growth of the isolate upon subculture of this bottle."
- "Clinical isolates recovered were classified as significant, contaminant, or unknown based on determination by the clinical trial sites."
- This indicates that subcultures and expert determination at the clinical sites served as the primary adjudication method for classifying positive results and the significance of isolates. No explicit 2+1 or 3+1 "expert consensus" model is described beyond the site-level determination.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC study was performed in the context of human readers improving with AI assistance. This device is a microbial detection system, not an AI diagnostic imaging tool that assists human readers.
- The clinical studies performed compare the performance of the new BacT/ALERT® FA Plus Culture Bottle to the predicate BacT/ALERT® FA Culture Bottle in a "bottle pair" design, which is a comparative effectiveness study of two devices, not human-AI interaction.
- The "effect size" mentioned, such as the ratio of true positives (e.g., 1.178 for significant blood isolates), represents the improved detection by the new bottle type compared to the previous one, not human reader improvement with AI.
6. Standalone Performance Study
- Yes, the device's performance, as measured by its ability to recover and detect microorganisms, is evaluated in a standalone manner. All the analytical (seeded) studies (Analytical Sensitivity, LoD, Repeatability, Reproducibility, Delayed Entry) are assessments of the algorithm/device performance without human-in-the-loop directly influencing the detection flagging.
- The clinical studies also report the device's performance (true positives, false positives) based solely on its output and subsequent lab confirmation, demonstrating its standalone effectiveness in a clinical setting.
7. Type of Ground Truth Used
- For all seeded studies: The ground truth is the known identity and concentration of the microorganisms inoculated into the bottles, confirmed by post-detection laboratory methods (e.g., Gram stain, subculture).
- For clinical studies: The ground truth is established through subculture of flagged positive bottles and subsequent determination of isolate significance (significant, contaminant, unknown) by the clinical trial sites. This combines direct microbiological evidence with clinical judgment.
8. Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning or AI model development. This device is a culture medium and detection system, not a software algorithm that learns from a training dataset in the typical AI sense.
- The mention of "knowledge base specifications utilized by the firmware included changes to the initial value threshold variables" suggests that some parameters of the detection algorithm were likely tuned or established based on internal development data, but this is not described as a formal "training set" with separate validation.
9. How Ground Truth for Training Set was Established
- As mentioned above, there is no explicit "training set" described for an AI model. The system relies on chemical reactions (CO2 production changing sensor color) and firmware interpreting these changes, with threshold adjustments.
- Any ground truth used to optimize these firmware thresholds would have likely come from internal R&D studies, similar to the "in-house seeded studies" described for performance testing, where the presence and growth of organisms are known and confirmed microbiologically.
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BacT/ALERT® FA Plus Culture Bottle
JAN 2 2 2013
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
Name of device
BacT/ALERT® FA Plus
Device Identification
Trade Name: BacT/ALERT® FA Plus Culture Bottle Classification Name: Blood Culturing System, Microbiology Product Code: MDB Regulation: 21CFR866.2560, microbial growth monitor Device Class: Class 1, not exempt from premarket notification per 21CFR807.81
Premarket Notification Submitter
| Company Name:Company Address: | bioMérieux, Inc.100 Rodolphe StreetDurham, NC 27712 |
|---|---|
| Contact:Telephone #:FAX #: | Jocelyn Jennings, Senior Manager, Regulatory Affairs919-620-2894919-620-2548 |
| Preparation Date: | May 16, 2012 |
Intended Use of the Device
BacT/ALERT® FA Plus Culture Bottles are used with the BacT/ALERT® Microbial Detection System in qualitative procedures for enhanced recovery and detection of aerobic and facultative anaerobic microorganisms (bacteria and yeast) from blood and other normally sterile body fluids.
Description of the Device
The new reagent (BacT/ALERT FA Plus Culture Bottle) is an improvement upon the cleared charcoal formulation reagent (BacT/ALERT FA Culture Bottle). The BacT/ALERT FA Culture Bottles are used with the BacT/ALERT Microbial Detection Systems in qualitative procedures for recovery and detection of microorganisms from blood.
The predicate BacT/ALERT FA Culture Bottle contains charcoal, for its antimicrobial neutralization properties, in a complex growth medium. Charcoal
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is eliminated in the proposed BacT/ALERT FA Plus Culture Bottle, and is replaced with two types of adsorbent resins in a complex growth medium. The proposed BacT/ALERT FA Plus Culture Bottle is optimized to increase antimicrobial neutralization properties, and to increase the clarity of Gram stains in comparison to the predicate BacT/ALERT FA Culture Bottle.
The BacT/ALERT Microbial Detection System provides both a microbial detection system and a culture medium bottle with suitable nutritional and environmental conditions for microorganisms commonly encountered in blood or other normally sterile body fluid samples (except urine) taken from a patient suspected of having bacteremia/fungemia. An inoculated bottle is placed into the instrument where it is incubated and continuously monitored for the presence of microorganisms that will grow in the BacT/ALERT bottles.
The BacT/ALERT Microbial Detection System utilizes a colorimetric sensor and reflected light to monitor the presence and production of carbon dioxide (CO2) that is dissolved in the culture medium. If microorganisms are present in the test sample, carbon dioxide is produced as the microorganisms metabolize the substrates in the culture medium. When growth of the microorganisms produces CO2, the color of the gas-permeable sensor installed in the bottom of each culture bottle changes from blue-green to vellow. The lighter color results in an increase of reflectance units monitored by the system. Bottle reflectance is monitored and recorded by the instrument every 10 minutes.
SUBSTANTIAL EQUIVALENCE INFORMATION
Predicate device name(s): BacT/ALERT® FA Culture Bottle
Predicate device 510(k) number(s) K020813
Comparison with predicate
The BacT/ALERT FA Plus Culture Bottle is claimed substantially equivalent to the BacT/ALERT FA Culture Bottle (K020813).
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Table 1. Similarities and differences between the tests are outlined below:
| Culture Bottle Characteristics: Changes versus K020813 | |
|---|---|
| Specimen Sampling andHandling | unchanged |
| Assay Types | unchanged |
| Reaction Types | unchanged |
| Calibration | unchanged |
| Quality Control (by Operator) | unchanged |
| Principles of Operation | unchanged |
| Firmware | No changes to firmware code occurred.The structure of the firmware algorithm remain unchanged.The knowledge base specifications utilized by the firmware includedchanges to the initial value threshold variables used by the firmwarealgorithm.Variables related to controlling barcode recognition were adjusted toenable recognition of the new bottle type. |
Performance Characteristics
Analytical Testing
Analytical Sensitivity: Growth Performance
Data represent results from in-house seeded studies with and without blood obtained from healthy human volunteers. Multiple strains were tested for each i species at target inoculum levels of 125 CFU per bottle. The species listed are representatives of clinically prevalent organisms in blood cultures and sterile body fluids.
| Blood | No Blood | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Microorganism | %Recovery(n) | RangeCFU/bottle | Time to Detection(hours) | %Recovery*(n=3) | RangeCFU/bottle | Time to Detection(hours) | |||
| Mean | Range | Mean | Range | ||||||
| Staphylococcusaureus | 100.0(33/33) | 54 - 150 | 13.4 | 12.2 -15.6 | 100 | 116 - 150 | 16.7 | 14.6 -18.2 | |
| Escherichia coli | 100.0(33/33) | 71 - 254 | 11.3 | 10.3 -12.4 | 100 | 73 - 176 | 11.4 | 10.6 -11.9 | |
| Pseudomonasaeruginosa | 100.0(15/15) | 74 - 148 | 16 | 13.7 -18.6 | 100 | 74 - 148 | 20.8 | 17.8 -25.6 | |
| Klebsiella pneumoniae | 100.0(15/15) | 89 - 123 | 11.3 | 10.6 -12.3 | 100 | 95 - 123 | 12 | 11.6 -12.4 | |
| Candida albicans | 100.0(38/38) | 88 - 298 | 28.9 | 19.2 -52.8 | 100 | 88 - 298 | 27.1 | 22.1 -30.1 | |
| Streptococcuspneumoniae | 100.0(33/33) | 3 - 260 | 13.9 | 10.8 -16.5 | 100 | 4 - 25 | 14.3 | 13.01 -16.3 |
Table 2. Growth Performance Results
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| Blood | No Blood | |||||||
|---|---|---|---|---|---|---|---|---|
| Microorganism | % | Range | Time to Detection(hours) | % | Range | Time to Detection(hours) | ||
| Recovery(n) | CFU/bottle | Mean | Range | Recovery*(n=3) | CFU/bottle | Mean | Range | |
| Staphylococcusepidermidis | 100.0(15/15) | 44 - 135 | 17.6 | 14.3 -36.0 | 100 | 45 - 105 | 21.4 | 19.0 -24.8 |
| Enterococcus faecalis | 100.0(15/15) | 63 - 259 | 11.6 | 11.0 -12.3 | 100 | 71 - 169 | 12.3 | 11.8 -12.7 |
| Enterococcus faecium | 100.0(15/15) | 25 - 120 | 12.6 | 11.3 -14.4 | 100 | 25 - 120 | 15.5 | 14.0 -17.5 |
| Enterobacter cloacae | 100.0(15/15) | 111 - 200 | 12 | 10.8 -15.7 | 100 | 111 - 185 | 11.7 | 11.3 -12.0 |
| Candida glabrata | 100.0(15/15) | 118 - 281 | 44.8 | 27.3 -64.8 | 100 | 118 - 194 | 39.9 | 30.9 -50.4 |
| Haemophilusinfluenzae | 100.0(15/15) | 105 - 266 | 14.4 | 12.1 -16.8 | 0 | - | - | - |
| Proteus mirabilis | 100.0(15/15) | 36 - 213 | 12.9 | 11.3 -16.3 | 100 | 36 - 213 | 12.5 | 11.3 -13.6 |
Bac T/ALERT TA Phis Culture Bottle
*In case of less than 100% recovery, it is recommended to add blood such as sterile defibrinated horse blood (10% v/v). *
Antimicrobial Neutralization
Neutralization of antimicrobials by adsorbent polymeric beads varies depending upon dosage level and timing of specimen collection. Internal studies have demonstrated that antimicrobials are effectively neutralized by the BacT/ALERT FA Plus medium. In these tests, antimicrobials were added in clinically relevant concentrations directly to culture bottles during inoculation with susceptible strains. The effectiveness of the antimicrobials was confirmed by parallel testing using a non-neutralizing medium as a control. Antimicrobials from the following antimicrobial/antimicrobial categories were neutralized by the medium: penicillins, glycycyclines, polyenes, macrolides, triazoles, echinocandins, cefazolin, cefoxitin, cefotaxime, ceftaroline , aminoglycosides, fluoroquinolones, lincosamides, glycopeptides, and oxazolidinones.
Antimicrobial neutralization was not achieved for ceftazidime or cefepime.
Less than complete neutralization was observed for cefotaxime and ceftriaxone. Cefotaxime was neutralized at ranges of 50% PSL to 2% PSL depending on the microorganism. Ceftriaxone was neutralized at ranges of 50% PSL to 1% PSL depending on the organism. For additional information on antimicrobial agents neutralized by FA Plus bottles, contact your local bioMerieux representative.
Potentially Interfering Substances
In-house seeded studies were conducted with cerebrospinal fluid, pleural fluid, synovial fluid, plasma, blood, and blood clots. Aliquots of each of these fluids also received white blood cells at concentrations relevant to bacteremia in each given body fluid. Testing was conducted with and without microorganisms. These substances neither interfered with recovery and detection of organisms, nor did they generate false positive results in the absence of organisms.
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Limit of Detection (LoD)
Data shows results from in-house seeded studies. A minimum of 30 replicates were tested per species. The data was generated using bottles at end of shelf life. Bottles inoculated with H. influenzae received 4 ml pooled human blood supplementation. At least 95% detection was achieved at LoD.
| Microorganism | Strain ID | LoD (CFU/bottle) |
|---|---|---|
| Candida albicans | ATCC 14053 | 6 |
| Enterobacter aerogenes | ATCC 13048 | 8 |
| Enterococcus faecalis | NCTC 12697 | 5 |
| Escherichia coli | NCTC 12923 | 4 |
| Haemophilus influenzae | ATCC 10211 | 6 |
| Klebsiella pneumoniae | STL 104016 | 4 |
| Listeria monocytogenes | ATCC 15313 | 6 |
| Pseudomonasaeruginosa | NCTC 12924 | 4 |
| Salmonella enterica | ATCC 14028 | 5 |
| Staphylococcus aureus | NCTC 10788 | 5 |
| Streptococcuspneumoniae | ATCC 6305 | 6 |
Table 3. Table 2 Summary of LoD Data
Within-Laboratory Precision (Repeatability)
Data represents results from in-house seeded studies conducted on 12 days on multiple instruments by multiple operators. Organisms were grown in the presence of clinically relevant concentrations of antimicrobials to which they are susceptible. In this seeded study BacT/ALERT FA Plus bottles were subcultured at least 24 hours after being flagged positive by the instrument. A minimum of 108 replicates were tested for each organism/antimicrobial combination.
| Table 4. Summary of the Within-Laboratory Precision Data | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| -- | -- | -- | -- | -- | -- | -- | -- | -- | ---------------------------------------------------------- | -- |
| Sample Input | CFU/bottle (range) | % Recovery | Time to Detection (hours) | |||||
|---|---|---|---|---|---|---|---|---|
| Organism | Antimicrobial | Lot 1 | Lot 2 | Lot 3 | Overall | Mean | Range | |
| C. albicans | Fluconazole | 140 - 364 | 100.0 | 100.0 | 100.0 | 100.0 | 26.0 | 22.8 - 31.3 |
| E. coli | Amikacin | 26 - 156 | 100.0 | 100.0 | 100.0 | 100.0 | 12.0 | 11.2 - 13.0 |
| K. pneumoniae | Levofloxacin | 108 - 170 | 100.0 | 100.0 | 100.0 | 100.0 | 13.4 | 11.7 - 15.2 |
| P. aeruginosa | Piperacillin | 80 - 148 | 100.0 | 97.2 | 100.0 | 99.1 | 19.2 | 17.4 - 24.1 |
| S. pneumoniae | Penicillin G | 9 - 505 | 100.0 | 100.0 | 100.0 | 100.0 | 13.2 | 11.6 - 15.5 |
| S. aureus | Vancomycin | 94 - 158 | 100.0 | 100.0 | 100.0 | 100.0 | 16.9 | 14.6 - 20.3 |
Reproducibility .
Data represents results from seeded studies conducted at three sites using a target of 162 replicates per site on 3 days with a minimum of two operators per site. Reproducibility was evaluated on each of 9 organisms. Two organisms (C. albicans and S .pneumoniae) were prepared via serial dilution and the other 7 organisms were prepared using BioBalls. C. albicans and S. pneumoniae were seeded into the FA Plus bottle, at a target inoculum of 100 CFU/bottle, with an
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BacT/ALERT® FA Plus Culture Bottle
acceptable range of 30-300 CFU/bottle and the other 7 organisms at a target range of 1-17 CFU/bottle. The actual inoculum ranged from 6 CFU/bottle to 700 CFU/bottle for the 30-300 CFU/bottle range, and from 1 CFU/bottle to 270 CFU/bottle for the 1-17 CFU/bottle range. Percent recovery reflects positive flag by the instrument and Gram-stain/subculture consistent with the seeded organism.
| Sample Input | % Recovery | Time toDetection | InoculumRanges(CFU/Bottle) | ||||
|---|---|---|---|---|---|---|---|
| Site 1 | Site 2 | Site 3 | Overall | Mean | Range | ||
| S. aureus | 100.0%(18/18) | 87.5%(21/24) | 100.0%(30/30) | 95.8%(69/72) | 15.6 | 14.6-16.7 | 2-11 |
| C. albicans | 100.0%(18/18) | 83.3%(30/36) | 100.0%(33/33) | 93.1%(81/87) | 36.6 | 24.6-76.8 | 14-700 |
| E. coli | 100.0%(27/27) | 77.8%(21/27) | 100.0%(30/30) | 92.9%(78/84) | 12.8 | 11.8-14.1 | 1-38 |
| P. aeruginosa | 100.0%(24/24) | 75.0%(18/24) | 97.0%(32/33) | 91.4%(74/81) | 18.4 | 17.1-21.1 | 1-11 |
| E. faecalis | 100.0%(18/18) | 79.2%(19/24) | 96.7%(29/30) | 91.7%(66/72) | 13.9 | 12.6-15.3 | 1-15 |
| E. aerogenes | 74.4%(29/39) | 72.2%(26/36) | 85.4%.(41/48) | 78.1%(96/123) | 14.9 | 11.7-20.8 | 1-270 |
| L.monocytogenes | 100.0%(18/18) | 100.0%(24/24) | 100.0%(30/30) | 100.0%(72/72) | 24.1 | 20.4-36.4 | 1-14 |
| S. enterica | 100.0%(24/24) | 75.0%(18/24) | 100.0%(33/33) | 92.6%(75/81) | 13.5 | 2.3-14.8 | 1-13 |
| S. pneumoniae | 100.0%(30/30) | 100.0%(36/36) | 100.0%(21/21) | 100.0%(87/87) | 14.2 | 11.6-18.9 | 6-500 |
| Overall | 95.4%(206/216)95% CI:91.7%,97.8% | 83.5%(213/255)95% CI:78.4%,87.9% | 96.9%(279/288)95% CI:94.2%,98.6% | 92.0%(698/759)95% CI:89.8%,93.8% |
Table 5. Summary of Reproducibility Data
The above data includes repeat testing performed as a result of laboratory errors at a single site (i.e. contaminated bottles/reagents, colony counts out of range, and site failure to change bottle status after positive instrument signal and positive subculture). Data excluding the laboratory errors demonstrated 100% recovery with the exception of E. aerogenes, which exhibited 85.0% recovery for all sites combined.
Delayed Entry
Results from seeded studies using 11 species* at target concentrations 100 CFU per bottle (acceptable range of 30 to 300 CFU per bottle) were generated at three sites. Actual inoculum levels ranged from 35 CFU/bottle to 290 CFU/bottle. All bottles contained human blood from healthy volunteers and were held at specified temperatures and times prior to loading into the BacT/ALERT instrument. Percent recovery reflects positive flag by the instrument and Gram stain/subculture consistent with the seeded organism.
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BacT/ALERT® FA Plus Culture Bottle
| Sample Input | IncubationTemperature (°C) | Hold Time(hours) | % Recovery | Time to Detection from SampleInoculation(Hold Time + Instrument TTD Inhours) | |
|---|---|---|---|---|---|
| Mean | Range | ||||
| Control | No delay | 100.0% (459/459) | 14.3 | 8.5 - 84.0 | |
| 2-8 | 48 | 98.6%(292/296) | 63.7 | 57.5 - 103.2 | |
| Inoculated TestBottles | 20-25 | 24 | 98.0%(291/297) | 31.8 | 26.2 - 74.4 |
| 20-25 | 36 | 91.9%(272/296) | 41.8 | 38.0 - 70.5 | |
| 35-37 | 8 | 98.9%(454/459) | 16.1 | 10.2 - 53.8 | |
| 35-37 | 24 | 56.6% ***(259/458) | 28.3 | 26.0 - 74.4 | |
| NegativeControls | All conditions | 0.5% (1/221)** | - | - |
Table 6. Summary of Delayed Entry Data
*Staphylococcus aureus, Candida albicans, Candida krusei, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Streptococus pneumoniae, Enterococus faecium, Haemophius influenzae, Neisseria meningitidis
**False positive observed during seeded study (1/221)
** CAUTION: Culture bottles held at 35 to 37°C for 24 hours or longer before loading may not detect microorganisms and should be subcultured.
Clinical Study Results (Blood Cultures)
A multi-center clinical study was conducted at three different geographic sites in the U.S. comparing the performance of the FA Plus and FA blood culture bottles for aerobic culture pairs that received blood volumes between 6 ml and 10 ml (compliant pairs). A total of 1656 bottle pairs were obtained from 728 adult patients suspected of blood stream bacterial/yeast infections. Subcultures of both bottles were performed when either bottle in the set was determined to be positive by the BacT/ALERT system. A pair of bottles was determined to have a positive status if the subculture of either the FA Plus or FA bottle was positive. A culture bottle was determined to be a "True Positive" if the culture was flagged positive by the BacT/ALERT System and resulted in growth of the isolate upon subculture of this bottle. True positive rates were calculated for the FA Plus and FA culture bottles, and the ratio of FA Plus true positives to FA true positives was calculated to compare performance. Clinical isolates recovered were classified as significant, contaminant, or unknown based on determination by the clinical trial sites.
A total of 267 isolates were recovered from all compliant aerobic culture pairs with a positive status. There were a total of 238 bottle pairs that recovered at least 1 isolate by subculture of FA Plus or FA bottles. A total of 214 bottle pairs recovered a single isolate, 19 bottle pairs recovered two isolates, and 5 bottle pairs recovered 3 isolates. The total population reported in table below comprises the 267 isolates recovered from positive bottle pairs and 1418 negative bottle pairs for a total of 1685 results.
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BacT/ALERT® FA Plus Culture Bottle The BacT/ALERT FA Plus bottle detected a total of 208 isolates compared to the BacT/ALERT FA bottle that detected 194 isolates. Of the significant isolates, the BacT/ALERT FA Plus bottle detected a total of 159 isolates compared to the BacT/ALERT FA bottle that detected 135 isolates. Five false positives were identified by subculture of positive BacT/ALERT FA Plus bottles and comprised 0.30% (5/1685) of the study population.
| Clinical IsolateDetermination | BacT/ALERTFA Plus TruePositives | % of BacT/ALERT FAPlusTrue Positives inPopulation | BacT/ALERT FATruePositives | % of BacT/ALERT FATruePositives inPopulation | Ratio of TruePositives* |
|---|---|---|---|---|---|
| Significant | 159 | 9.4%(159/1685) | 135 | 8.0%(135/1685) | 1.178 |
| Contaminant | 36 | 2.1%(36/1685) | 47 | 2.8% (47/1685) | 0.766 |
| Unknown | 13 | 0.8%(13/1685) | 12 | 0.7% (12/1685) | 1.083 |
| Total | 208 | 12.3%(208/1685) | 194 | 11.5%(194/1685) | 1.072 |
Table 7. All Compliant Pairs with Single and Multiple Isolates Combined (Blood Cultures)
*Sixty (60) isolates were detected by both FA Plus and FA, 25 isolates were detected only by FA Plus and 7 isolates were detected only by FA. The ratio of true positive rates for overall isolates was 1.072 (208/194) with a 95% Cl of (0.952, 1.193).
Clinical Study Results (Sterile Body Fluid Cultures)
A multi-center clinical study was conducted at four different geographic sites in the U.S. and Canada comparing the performance of the FA Plus and FA culture bottles with sterile body fluid specimens (SBF). A total of 404 bottle pairs were obtained from 369 adult patients suspected of SBF bacterial/yeast infections. Sterile body fluid types evaluated were amniotic fluid, continuous ambulatory peritoneal dialysis (CAPD) fluid, cerebrospinal fluid (CSF), peritoneal fluid, pleural fluid, and synovial fluid. Clinical isolates recovered were classified as significant, contaminant, or unknown based on determination by the clinical trial sites.
A total of 92 isolates were recovered from all aerobic SBF culture pairs with a positive status. There were a total of 75 bottle pairs that recovered at least 1 isolate by subculture of FA Plus or FA bottles. A total of 62 bottle pairs recovered a single isolate, 9 bottle pairs recovered two isolates, and 4 bottle pairs recovered 3 isolates. The total population reported in table below comprises the 92 isolates recovered from positive bottle pairs and 329 negative bottle pairs for a total of 421 results. The FA Plus bottle detected a total of 85 isolates compared to the FA bottle that detected 67 isolates. Of the significant isolates, the FA Plus bottle detected a total of 65 isolates compared to the FA bottle that detected 59 isolates. No false positives were observed for the FA Plus bottle from the study population (0/421).
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BacT/ALER'1®FA Plus Culture Boulle Table 8. All Pairs with Single and Multiple Isolates Combined (Sterile Body Fluids)
| Clinical IsolateDetermination | BacT/ALERTFA Plus TruePositives | % of BacT/ALERT FAPlusTrue Positives inPopulation | BacT/ALERT FATruePositives | % of BacT/ALERT FATruePositives inPopulation | Ratio of TruePositives* |
|---|---|---|---|---|---|
| Significant | 65 | 15.4%(65/421) | 59 | 14.0%(59/421) | 1.102 |
| Contaminant | 13 | 3.1%(13/421) | 2 | 0.5%(2/421) | 6.500 |
| Unknown | 7 | 1.7%(7/421) | 6 | 1.4%(6/421) | 1.167 |
| Total | 85 | 20.2%(85/421) | 67 | 15.9%(67/421) | 1.269 |
*Sixty (60) isolates were detected by both FA Plus and FA, 25 isolates were detected only by FA Plus and 7 isolates were detected by only FA. The ratio of true positive rates for overall isolates was 1.269 (85/69) with a 95% Cl of (1.083, 1.455).
Proposed labeling
The proposed labeling is complete.
Conclusion
The information in this premarket notification is complete and supports a substantial equivalence decision.
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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 20993-002
bioMerieux Inc. C/O Jocelyn Jennings Senior Manager, Regulatory Affairs 100 Rodolphe Street Durham; NC 27712
Re: K121461
Trade/Device Name: BacT/Alert FA Plus Culture Bottle Regulation Number: 21 CFR 866.2560 Regulation Name: Microbial Growth Monitor Regulatory Class: Class I Product Code: MDB Dated: January 14, 2013 Received: January 15, 2013
Dear Ms. Jennings:
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 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); 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.
JAN 2 2 2013
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If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/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/cdrh/industry/support/index.html.
Sincerely yours,
Sally A. Hojvat
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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INTENDED USE STATEMENT
510(k) Number (if known): K121461
Device Name: BacT/ALERT® FA Plus Culture Bottles
Intended Use:
BacT/ALERT® FA Plus Culture Bottles are used with the BacT/ALERT® Microbial Detection System in qualitative procedures for recovery and detection of aerobic and facultative anaerobic microorganisms (bacteria and yeast) from blood and other normally sterile body fluids.
Prescription Use X (Part 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 OF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
SalyaAmur
Division Sign-Off
Division Sign-Off
Office of In Vitro Diagnostics and Radiological Haalth
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1121461 510(k)
§ 866.2560 Microbial growth monitor.
(a)
Identification. A microbial growth monitor is a device intended for medical purposes that measures the concentration of bacteria suspended in a liquid medium by measuring changes in light scattering properties, optical density, electrical impedance, or by making direct bacterial counts. The device aids in the diagnosis of disease caused by pathogenic microorganisms.(b)
Classification. Class I. With the exception of automated blood culturing system devices that are used in testing for bacteria, fungi, and other microorganisms in blood and other normally sterile body fluids, this device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter.