(255 days)
BacT/ALERT® PF 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.
The new reagent (BacT/ALERT PF Plus Culture Bottle) is an improvement upon the cleared charcoal formulation reagent (BacT/ALERT PF Culture Bottle). The BacT/ALERT PF 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 PF Culture Bottle contains charcoal, for its antimicrobial neutralization properties, in a complex growth medium. Charcoal is eliminated in the proposed BacT/ALERT PF Plus Culture Bottle, and is replaced with two types of adsorbent resins in a complex growth medium. The proposed BacT/ALERT PF 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 PF 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 (adult and pediatric bottles) or other normally sterile body fluid samples (except urine) (adult bottles only) 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 mefabolize 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 the study information for the BacT/ALERT® PF Plus, as requested:
Acceptance Criteria and Device Performance
| Criteria Category | Acceptance Criteria (Implied/Specific) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity (Growth Performance) | The device must demonstrate effective recovery and detection of a representative panel of aerobic and facultative anaerobic microorganisms (bacteria and yeast) from blood. Implicitly, recovery rates for most common pathogens should be high, ideally 100%. | For most tested microorganisms, 100% recovery was observed. (Table 2):- Staphylococcus aureus: 100.0% (30/30) - Escherichia coli: 100.0% (30/30) - Pseudomonas aeruginosa: 100.0% (12/12) - Klebsiella pneumoniae: 100.0% (12/12) - Candida albicans: 100.0% (30/30) - Streptococcus pneumoniae: 100.0% (30/30) - Staphylococcus epidermidis: 100.0% (12/12) - Enterococcus faecalis: 100.0% (12/12) - Enterococcus faecium: 100.0% (12/12) - Enterobacter cloacae: 100.0% (12/12) - Candida glabrata: 100.0% (12/12) - Haemophilus influenzae: 100.0% (12/12) - Proteus mirabilis: 100.0% (12/12) Less than 100% detection was observed for Capnocytophaga ochracea, Cardiobacterium hominis, Eikenella corrodens, Haemophilus parainfluenzae, Granulicatella adiacens, and Helicobacter cinaedi. |
| Antimicrobial Neutralization | The device should effectively neutralize a broad range of clinically relevant antimicrobials to allow for microbial growth even in the presence of these substances. | Antimicrobials from numerous categories were neutralized. These include penicillins, glycylcyclines, polyenes, macrolides, triazoles, echinocandins, cefazolin, cefoxitin, ceftaroline, aminoglycosides, fluoroquinolones, lincosamides, glycopeptides, and oxazolidinones. Neutralization was not achieved for ceftazidime or cefepime. Less than complete neutralization was observed for ceftotaxime and ceftriaxone (at ranges of 50% PSL to 1-2% PSL depending on microorganism). |
| LoD (Limit of Detection) | The device should reliably detect microorganisms at low concentrations, demonstrating a reproducible Limit of Detection (LoD). Implicitly, at least 95% detection at LoD. | At least 95% detection was achieved at LoD for all tested microorganisms. (Table 3): LoD ranged from 4 CFU/bottle (E. coli, K. pneumoniae, P. aeruginosa) to 8 CFU/bottle (Enterobacter aerogenes). |
| Within-Laboratory Precision (Repeatability) | The device should demonstrate consistent growth performance (percent recovery and time to detection) when tested repeatedly within the same laboratory under various conditions (e.g., multiple lots, operators, instruments). High percent recovery (ideally 100%) and consistent Time to Detection are expected. | High percent recovery and consistent Time to Detection. (Table 4): - C. albicans (Fluconazole): 100.0% recovery across 3 lots, Mean TTD 26.0 hours. - E. coli (Amikacin): 100.0% recovery across 3 lots, Mean TTD 12.0 hours. - K. pneumoniae (Levofloxacin): 100.0% recovery across 3 lots, Mean TTD 13.4 hours. - P. aeruginosa (Piperacillin): 99.1% overall recovery, Mean TTD 19.2 hours. (One lot showed 97.2%) - S. pneumoniae (Penicillin G): 100.0% recovery across 3 lots, Mean TTD 13.2 hours. - S. aureus (Vancomycin): 100.0% recovery across 3 lots, Mean TTD 16.9 hours. |
| Reproducibility | The device should demonstrate consistent growth performance across different testing sites, operators, and days. High overall percent recovery is expected. | Overall reproducibility showed high percent recovery (92.0%). Sites showed varying performance, down to 72.2% for E. aerogenes at Site 2. (Table 5): - Overall % Recovery: 92.0% (698/759) with 95% CI: 89.8%, 93.8%. - Site 1: 95.4% (206/216) - Site 2: 83.5% (213/255) - Site 3: 96.9% (279/288) Excluding laboratory errors, E. aerogenes showed 85.0% recovery, while other organisms achieved 100%. |
| Delayed Entry | The device should maintain effective microbial recovery even after delays in loading into the instrument, under various temperature conditions. A cautionary note is expected if performance is significantly degraded under certain conditions. | High recovery across most delayed entry conditions, with one critical caution. (Table 6): - Control (No delay): 100.0% recovery. - 2-8°C, 48 hours hold: 98.6% recovery. - 20-25°C, 24 hours hold: 98.0% recovery. - 20-25°C, 36 hours hold: 91.9% recovery. - 35-37°C, 8 hours hold: 98.9% recovery. - 35-37°C, 24 hours hold: 56.6% recovery. CAUTIONARY NOTE issued for this condition. False positive rate for negative controls was 0.5% (1/221). |
| Clinical Study Performance (Blood Cultures) | The device (PF Plus) should demonstrate comparable or improved performance compared to the predicate device (PF) in a clinical setting for the recovery of microorganisms from blood. | BacT/ALERT PF Plus demonstrated improved or comparable clinical performance over the predicate PF bottle. (Table 7): - Ratio of True Positives for Significant isolates: 1.182 (PF Plus detected 91 vs PF detected 77). - Ratio of True Positives for Contaminant isolates: 0.828 (PF Plus detected 24 vs PF detected 29). - Ratio of True Positives for Unknown isolates: 1.136 (PF Plus detected 25 vs PF detected 22). - Overall Ratio of True Positives: 1.094 (140/128) with a 95% Cl of (0.954, 1.234). - 44 isolates detected only by PF Plus vs 32 isolates detected only by PF. False positive rate: 0.05% (1/2215) in the clinical study population. |
| Interfering Substances | Potential interfering substances (plasma, blood, blood clots, WBCs) should not interfere with microorganism recovery and detection, nor should they generate false positive results. | No interference or false positives were observed. Plasma, blood, blood clots, and white blood cells (at concentrations relevant to bacteremia) neither interfered with recovery and detection of organisms nor generated false positive results in the absence of organisms. |
Study Details
2. Sample Size and Data Provenance (Test Set)
- Analytical Sensitivity (Growth Performance):
- Sample Size: Varies by microorganism. For most listed, 30 replicates (e.g., 30/30) were tested. For others, 12 replicates (e.g., 12/12) were used.
- Data Provenance: In-house seeded studies with blood obtained from healthy human volunteers. This is a prospective study design using controlled laboratory conditions.
- Limit of Detection (LoD):
- Sample Size: A minimum of 30 replicates were tested per species.
- Data Provenance: In-house seeded studies. Bottles at end of shelf life were used, and H. influenzae testing included 4 ml pooled human blood supplementation. This is a prospective study design using controlled laboratory conditions.
- Within-Laboratory Precision (Repeatability):
- Sample Size: A minimum of 108 replicates were tested for each organism/antimicrobial combination.
- Data Provenance: In-house seeded studies over 12 days on multiple instruments by multiple operators. Organisms grown in the presence of clinically relevant antimicrobial concentrations. This is a prospective study design using controlled laboratory conditions.
- Reproducibility:
- Sample Size: Target of 162 replicates per site for 9 organisms, conducted over 3 days. Total replicates across sites varied per organism, e.g., 72 for S. aureus, 87 for C. albicans, 123 for E. aerogenes.
- Data Provenance: Seeded studies conducted at three sites. This is a prospective multi-site laboratory study.
- Delayed Entry:
- Sample Size: For inoculated test bottles, a total of 459 to 458 bottles across various conditions. For negative controls, 221 bottles. Eleven species were tested, with an acceptable range of 30 to 300 CFU per bottle.
- Data Provenance: Seeded studies generated at three sites using human blood from healthy volunteers. This is a prospective multi-site laboratory study.
- Clinical Study Results (Blood Cultures):
- Sample Size: 2188 bottle pairs (4376 bottles total) from 1086 pediatric patients. The total reported population for analysis was 2215 results (172 isolates from positive pairs and 2043 negative pairs).
- Data Provenance: Multi-center clinical study conducted at three different geographic sites in the U.S. This is a prospective clinical study with real patient samples.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Analytical, LoD, Repeatability, Reproducibility, Delayed Entry Studies: These were seeded studies with known microorganisms and inoculum levels, so the "ground truth" was inherently defined by the experimental setup. No independent experts were needed to establish the ground truth for microbial identity or presence.
- Clinical Study: The document states, "Clinical isolates recovered were classified as significant, contaminant, or unknown based on determination by the clinical trial sites." This implies a judgment by clinical laboratory personnel or clinicians at the three study sites. Specific numbers or qualifications (e.g., "radiologist with 10 years of experience") are not provided in the document. It can be inferred that these would be licensed medical professionals (e.g., clinical microbiologists, infectious disease physicians) involved in patient care and laboratory diagnostics.
4. Adjudication Method for the Test Set
- Analytical, LoD, Repeatability, Reproducibility, Delayed Entry Studies: Not applicable, as these were seeded studies where the "ground truth" (presence and identity of microorganisms) was controlled by the experimental design. Detection was based on instrument flagging and confirmation by subculture/Gram stain.
- Clinical Study: The document specifies: "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 PF Plus or PF bottle was positive." This indicates a comparative approach where confirmation by subculture was the primary adjudication for a positive result from the instrument, and then classification (significant, contaminant, unknown) was determined by individuals at the clinical trial sites. No explicit mention of an "adjudication panel" or specific consensus method like 2+1 or 3+1 is provided for the final classification of clinical significance.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
- No, an MRMC comparative effectiveness study was not done in the context of human readers improving with or without AI assistance. This device is a diagnostic instrument (culture bottle and detection system) for microbial growth, not an AI-assisted diagnostic imaging tool for human interpretation. The "comparison" in the clinical study was between two different culture bottle formulations (PF Plus vs. PF) as standalone detection systems.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance study was done. The entire analytical and clinical evaluation focuses on the performance of the BacT/ALERT® PF Plus culture bottles when used with the BacT/ALERT® Microbial Detection System as a standalone system. The system automatically monitors for growth, flags positive bottles, and then subculture/Gram stain is performed to identify the organism. The reported "percent recovery" and "time to detection" are purely instrumental/algorithmic outputs, confirmed by microbiological methods. There is no human-in-the-loop interpretative step being evaluated for the device's primary function (detection of microbial growth) itself.
7. The Type of Ground Truth Used (Test Set)
- Analytical Sensitivity, LoD, Repeatability, Reproducibility, Delayed Entry:
- Expert Consensus / Microbiological Confirmation: For these in vitro seeded studies, the ground truth was established by known inoculum concentrations of specific microorganisms confirmed by traditional microbiological techniques (e.g., viable plate counts for inoculum, subculture, and Gram stain for confirmation of instrument-flagged bottles).
- Clinical Study:
- Microbiological Confirmation & Clinical Judgment:
- The fact that a sample contained a microorganism was established by subculture of instrument-flagged positive bottles.
- The significance of the recovered isolates (significant, contaminant, or unknown) was based on clinical determination by the clinical trial sites, which combines microbiological results with patient clinical context.
- Microbiological Confirmation & Clinical Judgment:
8. The Sample Size for the Training Set
- The document describes performance testing for a device (culture bottle), not an AI/ML algorithm that would typically have a distinct "training set." The "knowledge base specifications utilized by the firmware included changes to the initial value threshold variables used by the firmware algorithm." This suggests that the algorithm itself undergoes adjustments or training, but no specific "training set" sample size is provided in the document. The data presented are for validation/verification (test sets).
9. How the Ground Truth for the Training Set Was Established
- As mentioned above, the document does not explicitly describe a "training set" or how its ground truth was established. It states that "changes to the initial value threshold variables used by the firmware algorithm" were made. This implies an iterative development process where internal data (likely similar to the analytical studies presented, but not explicitly labeled as "training") would be used to optimize these thresholds. The specific data, methods, or ground truth establishment for this firmware adjustment/training are not detailed in this 510(k) summary.
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KI21446
510(k) SUMMARY
JAN 2 5 2013
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® PF Plus
Device Identification
Trade Name: BacT/ALERT® PF 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: | bioMérieux, Inc. |
|---|---|
| Company Address: | 100 Rodolphe StreetDurham, NC 27712 |
| Contact: | Elizabeth Landon, Staff Regulatory Affairs Specialist |
| Telephone #: | 919-620-2329 |
| FAX #: | 919-620-2548 |
| Alternate Contact: | Jocelyn Jennings, Senior Manager, Regulatory Affairs |
| Telephone #: | 919-620-2894 |
| FAX #: | 919-620-2548 |
| Preparation Date: | May 11, 2012 |
Intended Use of the Device
BacT/ALERT® PF 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.
Description of the Device
The new reagent (BacT/ALERT PF Plus Culture Bottle) is an improvement upon the cleared charcoal formulation reagent (BacT/ALERT PF Culture Bottle). The BacT/ALERT PF Culture Bottles are used with the BacT/ALERT Microbial Detection Systems in qualitative procedures for recovery and detection of microorganisms from blood.
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The predicate BacT/ALERT PF Culture Bottle contains charcoal, for its antimicrobial neutralization properties, in a complex growth medium. Charcoal is eliminated in the proposed BacT/ALERT PF Plus Culture Bottle, and is replaced with two types of adsorbent resins in a complex growth medium. The proposed BacT/ALERT PF 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 PF 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 (adult and pediatric bottles) or other normally sterile body fluid samples (except urine) (adult bottles only) 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 mefabolize 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.
SUBSTANTIAL EQUIVALENCE INFORMATION
Predicate device name(s)
BacT/ALERT® PF Culture Bottle
Predicate device 510(k) number(s) K020923
Comparison with predicate
The BacT/ALERT PF Plus Culture Bottle is claimed substantially equivalent to the BacT/ALERT PF Culture Bottle (K020923).
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Image /page/2/Picture/0 description: The image shows the logo for BIOMÉRIEUX. The logo consists of the word "BIOMÉRIEUX" in a stylized font, with a circle above the text. A line extends vertically through the center of the circle and text.
| Table 1. Similarities and differences between the tests are outlined below: | ||
|---|---|---|
| -- | -- | ----------------------------------------------------------------------------- |
| Culture Bottle Characteristics: Changes versus K020923 | |
|---|---|
| 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 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 blood obtained from healthy human volunteers. Multiple strains were tested for each species at target inoculum levels of 125 CFU per bottle. The species listed are representatives of clinically prevalent organisms in blood cultures.
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| Blood | ||||
|---|---|---|---|---|
| Microorganism | % Recovery (n) | Range CFU/bottle | Time to Detection (hours) Mean | Range |
| Staphylococcus aureus | 100.0 (30/30) | 54 - 150 | 13.3 | 12.2 - 15.2 |
| Escherichia coli | 100.0 (30/30) | 71 - 254 | 11.2 | 10.3 - 11.7 |
| Pseudomonas aeruginosa | 100.0 (12/12) | 74 - 148 | 15.7 | 13.7 - 17.8 |
| Klebsiella pneumoniae | 100.0 (12/12) | 89 - 123 | 11.3 | 10.6 - 12.3 |
| Candida albicans | 100.0 (30/30) | 88 - 298 | 29.0 | 19.2 - 52.8 |
| Streptococcus pneumoniae | 100.0 (30/30) | 3 - 260 | 13.8 | 10.8 - 16.5 |
| Staphylococcus epidermidis | 100.0 (12/12) | 44 - 135 | 17.6 | 14.3 - 18.8 |
| Enterococcus faecalis | 100.0 (12/12) | 63 - 259 | 11.6 | 11.0 - 12.2 |
| Enterococcus faecium | 100.0 (12/12) | 25 - 120 | 12.8 | 11.3 - 14.4 |
| Enterobacter cloacae . | 100.0 (12/12) | 111 - 200 | 11.6 | 10.8 - 12.5 |
| Candida glabrata | 100.0 (12/12) | 118 - 281 | 43.5 | 27.3 - 64.8 |
| Haemophilus influenzae | 100.0 (12/12) | 105 - 266 | 14.4 | 12.0 - 16.8 |
| Proteus mirabilis | 100.0 (12/12) | 36 - 213 | 12.5 | 11.3 - 14.6 |
Table 2. Growth Performance Results
Less than 100% detection was observed for some microorganisms, to include Capnocytophaga ochracea, Cardiobacterium hominis, Eikenella corrodens, Haemophilus parainfluenzae, Granulicatella adiacens, and Helicobacter cinaedi
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 PF 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 categories were neutralized by the medium: penicillins, glycylcyclines, polyenes, macrolides, triazoles, echinocandins, cefazolin, cefoxitin, ceftaroline, aminoglycosides, fluoroquinolones, lincosamides, glycopeptides, and oxazolidinones. Antimicrobial neutralization was not achieved for ceftazidime or cefepime.
Less than complete neutralization was observed for ceftotaxime and ceftriaxone. Cefotaxime was neutralized at ranges of 50% peak serum level (PSL) to 2% PSL depending on the microorganism. Ceftriaxone was neutralized at ranges of 50% PSL to 1% PSL depending on the organism.
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Potentially Interfering Substances
In-house seeded studies were conducted with plasma, blood, and blood clots. Aliquots of each of these fluids also received white blood cells at concentrations relevant to bacteremia in blood. 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.
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 |
| Pseudomonas aeruginosa | NCTC 12924 | 4 |
| Salmonella enterica | ATCC 14028 | 5 |
| Staphylococcus aureus | NCTC 10788 | 5 |
| Streptococcus pneumoniae | ATCC 6305 | 6 |
Table 3. Summary of LoD Data
NOTE: 96.7% of the bottles were subcultured within 30 minutes of being declared positive. STL 104016 was sourced from internal culture collection.
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 PF 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.
| 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 |
Table 4. Summary of the Within-Laboratory Precision Data
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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 PF Plus bottle, at a target inoculum of 100 CFU/bottle, with an acceptable range of 30-300 CFU/bottle and the other 7 organisms at a target range of 1-17 CFU/bottle. 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, gram stain/subculture consistent with the seeded organisms.
| 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
*Plate count of 270 CFU/bottle was arrived at by serial dilution.
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%
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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, gram stain/subculture consistent with the seeded organisms.
| Sample Input | IncubationTemperature (°C) | Hold Time(hours) | % Recovery | Time to Detection from SampleInoculation(Hold Time + Instrument TTD inhours) | |
|---|---|---|---|---|---|
| Mean | Range | ||||
| Inoculated TestBottles | 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 | |
| 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 krusei, Eschenchia coli, Klebsiella pneumoniae, Acinetobacter baumannii. Pseudomonas aeruginosa. Streptococcus pneumoniae. Enterococus faecium. Haemophilus 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 PF Plus and PF blood culture bottles for pediatric culture pairs that received blood volumes between 0.1 ml and 4 ml (compliant pairs). A total of 2188 bottle pairs were obtained from 1086 pediatric patients suspected of blood stream bacterial/veast 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 PF Plus or PF 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 PF Plus and PF culture bottles, and the ratio of PF Plus true positives to PF 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.
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BIOMÉRIEUX
A total of 172 isolates were recovered from all compliant pediatric blood culture pairs with a positive status. There were a total of 145 bottle pairs that recovered at least 1 isolate by subculture of PF Plus or PF bottles. A total of 126 bottle pairs recovered a single isolate, 12 bottle pairs recovered two isolates, 6 bottle pairs recovered 3 isolates, and 1 bottle pair recovered 4 isolates. The total population reported in Table 7 comprises the 172 isolates recovered from positive bottle pairs and 2043 negative bottle pairs for a total of 2215 results. The BacT/ALERT PF Plus bottle detected a total of 140 isolates compared to the BacT/ALERT PF bottle that detected 128 isolates. Of the significant isolates, the BacT/ALERT PF Plus bottle detected a total of 91 isolates compared to the BacT/ALERT PF bottle that detected 77 isolates. One (1) false positive was identified by subculture of a positive BacT/ALERT PF Plus bottle and comprised 0.05% (1/2215) of the study population.
| Clinical IsolateDetermination | BacT/ALERTPF Plus TruePositives | % of BacT/ALERT PFPlusTrue Positives inPopulation | BacT/ALERT PFTruePositives | % of BacT/ALERT PFTruePositives InPopulation | Ratio of TruePositives* |
|---|---|---|---|---|---|
| Significant | 91 | 4.1% (91/2215) | 77 | 3.5% (77/2215) | 1.182 |
| Contaminant | 24 | 1.1% (24/2215) | 29 | 1.3% (29/2215) | 0.828 |
| Unknown | 25 | 1.1% (25/2215) | 22 | 1.0% (22/2215) | 1.136 |
| Total | 140 | 6.3% (140/2215) | 128 | 5.8% (128/2215) | 1.094 |
Table 7. All Compliant Pairs with Single and Multiple Isolates Combined (Blood Cultures)
*Ninety six (96) isolates were detected by both PF Plus and PF, 44 isolates were detected only by PF Plus and 32 isolates were detected only by PF. The ratio of true positive rates for overall isolates was 1.094 (140/128) with a 95% Cl of (0.954,1.234).
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
JAN 2 5 2013
bioMérieux, Inc C/O Ms. Elizabeth Landon Staff Regulatory Affairs Specialist 100 Rodolphe Street Durham, NC 27712
Re: K121446
Trade/Device Name: BacT/ALERT PF Plus Culture Bottle Regulation Number: 21 CFR 2560 Regulation Name: Microbial Growth Monitor Regulatory Class: Class I Product Code: MDB Dated: January 14, 2013 Received: January 15, 2013
Dear Ms. Landon:
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
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Page 2 - Ms. Landon
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.
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): K121446
Device Name: BacT/ALERT® PF Plus Culture Bottles
Intended Use:
BacT/ALERT® PF 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.
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)
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510(k) K121446
§ 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.