(212 days)
BD BACTEC Myco/F Lytic culture medium when used with the BD BACTEC fluorescent series instruments is a nonselective culture medium to be used as an adjunct to aerobic blood culture media for the qualitative culture and recovery of mycobacteria, yeast and fungi from blood. This medium may also be used for the culture of sterile body fluids when veast or fungi are suspected.
BD BACTEC Myco/F Lytic culture medium is a Middlebrook 7H9 and Brain Heart Infusion broth formulation for the recovery of mycobacteria from blood specimens, and yeast and fungi from blood and sterile body fluids. Specific modifications were made to enhance the growth and recovery of mycobacteria, yeast and fungi. These modifications include ferric ammonium citrate to provide an iron source for specific strains of mycobacteria and fungi, the addition of saponin as a blood lysing agent, and the addition of specific proteins and sugars to provide nutritional supplements. Each vial contains a sensor which can detect decreases in oxygen concentration in the vial resulting from microorganism metabolism and growth. The sensor is monitored by the BD BACTEC fluorescent series instrument for increasing fluorescence, which is due to the decrease in oxygen. A positive determination indicates the presumptive presence of viable microorganisms in the vial.
BD BACTEC Myco/F Lytic Culture Vials are supplied in a carton containing 50 vials. It is a nonsterile product.
This document is a 510(k) Substantial Equivalence Determination Decision Summary for the BD BACTEC Myco/F Lytic Culture Vials (plastic). It evaluates the device's performance against a predicate device (BD BACTEC Myco/F Lytic Culture Vials (glass)) to determine if it is substantially equivalent. The studies described are analytical performance comparisons rather than clinical trials with human subjects for diagnostic accuracy.
Here's an analysis of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a bulleted or numbered list with corresponding reported performance values within a formal table. Instead, it presents performance data for the modified (plastic) device compared to the predicate (glass) device across various analytical parameters. The implicit acceptance criteria appear to be substantial equivalence, meaning the performance of the new plastic vial is "equivalent to or better than" the predicate glass vial.
Here's a synthesized table based on the provided data, comparing the plastic device's performance to the predicate:
Table: Summary of Device Performance Compared to Predicate (Implicit Acceptance Criteria: Equivalent to or Better)
| Performance Parameter | Acceptance Criteria (Implied) | Reported Device Performance (Plastic vs. Glass) |
|---|---|---|
| Reproducibility | No statistically significant differences in TTD or % recovery. | Met: No statistically significant differences in organism detection times or percent recovery between three lots for blood and sterile body fluid volumes. |
| Microbial Detection Limit (MDL) - Blood | Equivalent or better performance (ratio of positive yields close to 1 or higher) at low inoculum levels. | Met (mostly): Ratio of positive yields close to 1 or higher for most organisms, except Blastomyces dermatitidis (0.33). This organism's inconsistent growth was noted as a limitation. |
| Microbial Detection Limit (MDL) - Sterile Body Fluid | Equivalent or better performance (ratio of positive yields close to 1 or higher) at low inoculum levels. | Met (mostly): Ratio of positive yields close to 1 or higher for most organisms, except Blastomyces dermatitidis (0.86). This organism's inconsistent growth was noted as a limitation. |
| Delayed Entry in blood (Mycobacteria) | 100% recovery showed in delayed conditions. | Met: 100% recovery for all 8 mycobacterium strains evaluated across various delay times (12-96 hours) and temperatures (20-37.5°C). The Product Insert still recommends prompt placement but provides this information. |
| Time to Detection (TTD) - Blood | Equivalent or better performance (95% CI for median TTD difference contains zero or only negative values for shorter TTD). | Met (mostly): The plastic device performed equivalently to or better than the predicate for most conditions. Exceptions noted were for Dimorphic Fungi (0-1 CFU/vial, 1 mL blood) and Mycobacteria (1-10 CFU/vial, 1mL blood) where median TTD for plastic was longer, but supporting statistical analysis found performance equivalent or better for other conditions. |
| Time to Detection (TTD) - Sterile Body Fluid (SBF) | Equivalent or better performance (95% CI for median TTD difference contains zero or only negative values for shorter TTD). | Met (mostly): The plastic device performed equivalently to or better than the predicate for most conditions. Exceptions noted for Dimorphic Fungi under some test conditions. |
| Percent Recovery (Detection) - Blood (10-100 CFU/vial) | Comparable recovery rates (ratio of positive yields close to 1). | Met: Plastic recovery 99.52% vs. Glass 100%. Ratio of positive yields was 1.00. One instance of negative result only in plastic vial (Blastomyces dermatitidis), noted as a limitation. |
| Percent Recovery (Detection) - SBF (10-100 CFU/vial) | Comparable recovery rates (ratio of positive yields close to 1). | Met: Plastic recovery 100% vs. Glass 99.24%. Ratio of positive yields was 1.01. One instance of negative result only in glass vial (Candida auris). |
| False Positive Rate - Blood | Lower or comparable to predicate. | Met (superior): Plastic: 0.70% (all volumes combined) vs. Glass: 25.87%. Majority of false positives in glass were at higher blood volumes. |
| False Positive Rate - SBF | Lower or comparable to predicate. | Met (lower): Plastic: 0.47% (all SBF types combined) vs. Glass: 0.71%. |
| False Negative Rate - Blood | Comparable rates (not statistically significant difference). | Met: Plastic: 0.65% (4/619) vs. Glass: 0.48% (3/619). Difference not statistically significant (P = 1). |
| False Negative Rate - SBF | Comparable rates (not statistically significant difference). | Met: Plastic: 1.52% (6/396) vs. Glass: 1.01% (4/396). Difference not statistically significant (P = 0.7523). |
| Instrument Compatibility - Blood | Equivalent performance (similar TTD, comparable recovery). | Met: All four instruments (FX, FX-40, 9240, 9050) showed 100% recovery for both plastic and glass vials across organisms and volumes (with one exception for plastic at 5mL on FX-40 (94.44% vs 100% for glass)). TTD results were also comparable with median differences near zero. |
| Instrument Compatibility - SBF | Equivalent performance (similar TTD, comparable recovery). | Met: All four instruments showed 100% recovery for both plastic and glass vials across organisms and SBF volumes. TTD results were also comparable with median differences near zero. |
2. Sample Size Used for the Test Set and Data Provenance
The studies described are analytical performance studies performed in a laboratory setting, rather than clinical studies with patient samples. The samples used are seeded samples (i.e., known microorganisms inoculated into blood or sterile body fluid).
- Test Set (Seeded Samples):
- Reproducibility: Not explicitly stated as a separate "test set" size, but involved testing across three lots of media with varying blood/SBF volumes and inoculum levels.
- Microbial Detection Limit (MDL) - Blood:
- Sample Size: 414 paired vials (plastic vs. glass). 2 pairs discarded due to contamination, resulting in 412 paired vials. (23 organisms x 3 lots x 3 blood vol x 2 inoculum levels x 1 instrument).
- Data Provenance: This is in vitro analytical data obtained from controlled laboratory experiments, not from human patients or a specific country of origin.
- Microbial Detection Limit (MDL) - Sterile Body Fluid (SBF):
- Sample Size: 264 paired vials (plastic vs. glass). (3 organisms x 3 lots x 4 SBF volumes x 2 inoculum levels x 1 instrument x 2 SBF types) + (5 organisms x 3 lots x 4 SBF volumes x 2 inoculum levels x 1 instrument x 1 SBF type).
- Data Provenance: In vitro analytical data.
- Delayed Entry in blood (Mycobacteria):
- Sample Size: Not explicitly stated as a total paired set number, but involved 8 strains of mycobacterium. Total number of vials for each delay condition (e.g., 72/72 for no delay, 70/70 for 12h @ 20-25C, etc.) is provided in Table 7. Each test used 3 lots and 1, 3, or 5 mL human blood.
- Data Provenance: In vitro analytical data using human blood matrix.
- Percent Recovery (Detection) - Blood (10-100 CFU/vial):
- Sample Size: 207 paired sets (plastic vs. glass). (23 organisms x 3 lots x 3 blood volumes x 1 instrument).
- Data Provenance: In vitro analytical data using blood matrix.
- Percent Recovery (Detection) - SBF (10-100 CFU/vial):
- Sample Size: 132 paired sets (plastic vs. glass). (3 organisms x 3 lots x 4 SBF volumes x 1 inoculum level x 1 instrument x 2 SBF types) + (5 organisms x 3 lots x 4 SBF volumes x 1 inoculum level x 1 instrument x 1 SBF type).
- Data Provenance: In vitro analytical data using SBF matrix.
- False Positive Rate - Blood:
- Sample Size: 144 paired sets initially, 143 after contamination exclusion. (8 vials x 3 blood volumes x 3 lots x 2 instruments).
- Data Provenance: In vitro analytical data using fresh blood.
- False Positive Rate - SBF:
- Sample Size: 432 paired sets initially, 425/424 after contamination exclusions. (8 vials x 3 SBF volumes x 3 lots x 2 instruments x 3 SBF types).
- Data Provenance: In vitro analytical data using sterile body fluid.
- False Negative Rate - Blood:
- Sample Size: 619 combined paired sets from Recovery and MDL studies.
- Data Provenance: In vitro analytical data.
- False Negative Rate - SBF:
- Sample Size: 396 combined paired sets from Recovery and MDL studies.
- Data Provenance: In vitro analytical data.
- Instrument Compatibility - Blood:
- Sample Size: 54 paired sets for FX and 9050 each, 53 paired sets for FX-40 and 9240 each (total 214-216 paired sets for blood). (6 organisms x 3 blood volumes x 1 inoculum x 3 lots / 4 instruments).
- Data Provenance: In vitro analytical data.
- Instrument Compatibility - SBF:
- Sample Size: 48 paired sets per instrument (total 192 paired sets for SBF). (4 organisms x 4 SBF volumes x 1 inoculum x 3 lots / 4 instruments).
- Data Provenance: In vitro analytical data.
All data described is retrospective in the sense that it was collected as part of a pre-market submission process, likely after the plastic vial formulation was developed. It is not prospective clinical data from patient studies. The data provenance is internal laboratory studies, not patient data from a specific country.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for these analytical studies is based on controlled, seeded experiments where the presence and identity of the microorganisms are known.
- The "ground truth" is the known inoculum (CFU/vial) of specific ATCC strains or clinical isolates of mycobacteria, yeast, and fungi.
- Detection by instruments (BD BACTEC fluorescent series instruments) is validated against the known presence/absence of these seeded organisms and further confirmed by subculture for discordant results (e.g., false positives/negatives), which is a standard microbiological method.
- No human experts (like radiologists) are mentioned or typically involved in establishing ground truth for in vitro diagnostic (IVD) culture media performance studies. The ground truth is intrinsically tied to the experimental design – what was precisely inoculated and subsequently confirmed by laboratory methods.
4. Adjudication Method for the Test Set
Adjudication, in the context of IVD performance, would typically involve resolving discrepancies between a device's result and a reference method/truth.
- For these studies, the primary comparison is the Time-to-Detection (TTD) and Percent Recovery of the plastic vial versus the glass predicate vial against the known seeded inoculum.
- For false positive/negative rates, discrepancies between instrument reads and definitive culture (subculture) results are identified. The report explicitly mentions how these were defined:
- False Positive: "instrument positive but subculture negative."
- False Negative: "instrument-negative at the end of protocol yet contains viable organisms upon subculturing onto appropriate culture media."
- There's no mention of a multi-observer or consensus-based adjudication process as one would see in image interpretation studies. The "adjudication" is inherent in the design of comparing instrument readouts to known inputs and standard microbiological subculture confirmation.
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.
- MRMC studies are typically performed for medical imaging devices where human readers interpret images, and the AI's impact on their performance is evaluated.
- This submission concerns an in vitro diagnostic culture medium, which is an automated system for microbial growth detection. The "reader" is the BD BACTEC fluorescent series instrument, not a human.
- Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here. The comparison is between two different types of culture vials (plastic vs. glass), both processed by the same automated instruments.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, in essence, standalone performance was evaluated.
- The device being assessed is the BD BACTEC Myco/F Lytic Culture Vial (plastic), which operates when placed into the BD BACTEC fluorescent series instruments.
- The performance metrics (TTD, Percent Recovery, False Positive/Negative rates) are generated by the instrument's automated detection algorithm based on the changes in fluorescence caused by microbial growth in the vial.
- Humans are involved in inoculating the vials and performing subcultures for confirmation, but the "performance" described is the direct, automated output of the integrated vial-instrument system. It is not an "AI" in the sense of an image interpretation algorithm, but an automated detection system where the organism's metabolism directly causes a measurable signal change detected by the instrument's programming (analogous to an algorithm).
7. The Type of Ground Truth Used
The ground truth used primarily in these analytical studies is an expert-determined, controlled, seeded panel.
- This involves known strains of mycobacteria, yeast, and fungi (e.g., ATCC strains and clinical isolates) at specified inoculum levels (CFU/vial).
- For discordant results (e.g., instrument negative but suspected positive), subculture onto appropriate culture media plates was used to confirm the presence of viable organisms, acting as a definitive microbiological reference method for the seeded content.
- It does not utilize pathology reports (which are for tissue diagnosis) or outcomes data (which would be clinical outcomes in patients).
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" or "training data" in the conventional machine learning sense.
- This is an IVD device validation, not an AI/ML software validation.
- The comparison is between a new device (plastic vial) and a predicate device (glass vial), demonstrating substantial equivalence based on a series of analytical performance studies.
- The "training" of the instrument's underlying detection algorithm (which interprets the fluorescent signals) would have occurred during its initial development and prior regulatory submissions (e.g., for K970333, K970512 for the predicate device). The current submission focuses on demonstrating that the change in vial material (plastic vs. glass) does not adversely affect this established performance.
9. How the Ground Truth for the Training Set Was Established
As noted above, there is no explicitly defined "training set" for the vial in the context of this submission. The ground truth for the instrument's core detection capabilities would have been established historically during its development. This would also involve known, quantifiable microbial cultures and their characteristic growth patterns and metabolic activity in the media over time, likely confirmed by standard agar plate cultures or other gold standard microbiological methods.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and the word "ADMINISTRATION" in a smaller font below.
510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY
I Background Information:
A 510(k) Number
B Applicant
Becton, Dickinson and Company
C Proprietary and Established Names
BD BACTEC Myco/F Lytic Culture Vials
D Regulatory Information
| ProductCode(s) | Classification | RegulationSection | Panel |
|---|---|---|---|
| MDB | Class I, reserved | 21 CFR 866.2560 -Microbial GrowthMonitor | MI - Microbiology |
II Submission/Device Overview:
Purpose for Submission: র
To obtain a substantial equivalence determination for a premarket notification for the BD BACTEC™ Myco F/Lytic Culture Vials (plastic).
B Measurand:
Aerobic microorganisms (mycobacteria, yeast, and fungi) from blood Aerobic microorganisms (yeast, and fungi) from sterile body fluids
C Type of Test:
Liquid culture medium for recovery of microorganisms from blood and sterile body fluids using fluorescent technology to detect decreases in O2 resulting from the metabolism and growth of microorganisms.
III Intended Use/Indications for Use:
A Intended Use(s):
See Indications for Use below.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov
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B Indication(s) for Use:
BD BACTEC Myco/F Lytic culture medium when used with the BD BACTEC fluorescent series instruments is a nonselective culture medium to be used as an adjunct to aerobic blood culture media for the qualitative culture and recovery of mycobacteria, yeast and fungi from blood. This medium may also be used for the culture of sterile body fluids when veast or fungi are suspected.
Additional information
The device aids in the diagnosis of disease caused by pathogenic microorganisms and is automated on the BD BACTEC fluorescent series instruments.
- C Special Conditions for Use Statement(s): Rx - For Prescription Use Only
D Special Instrument Requirements:
BACTEC fluorescent series instruments BACTEC FX, BACTEC FX40, BACTEC 9240 and BACTEC 9050 were evaluated using software versions listed below:
| Instrument | Software Version |
|---|---|
| BACTEC FX | 6.40A or 6.40W* |
| BACTEC 9240 | 4.95A |
| BACTEC 9050 | 2.01A2 |
| BACTEC FX40 | 3.40A |
| STATE A CETT " A " TET" 1 " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " " |
*6.40W is the Window-based version of 6.40A
IV Device/System Characteristics:
A Device Description:
BD BACTEC Myco/F Lytic culture medium is a Middlebrook 7H9 and Brain Heart Infusion broth formulation for the recovery of mycobacteria from blood specimens, and yeast and fungi from blood and sterile body fluids. Specific modifications were made to enhance the growth and recovery of mycobacteria, yeast and fungi. These modifications include ferric ammonium citrate to provide an iron source for specific strains of mycobacteria and fungi, the addition of saponin as a blood lysing agent, and the addition of specific proteins and sugars to provide nutritional supplements. Each vial contains a sensor which can detect decreases in oxygen concentration in the vial resulting from microorganism metabolism and growth. The sensor is monitored by the BD BACTEC fluorescent series instrument for increasing fluorescence, which is due to the decrease in oxygen. A positive determination indicates the presumptive presence of viable microorganisms in the vial.
BD BACTEC Myco/F Lytic Culture Vials are supplied in a carton containing 50 vials. It is a nonsterile product.
Principle of Operation: B
The BD BACTEC Myco/F Lytic Culture Vial is designed for the rapid detection of mycobacteria in blood, and yeast and fungi in blood and sterile body fluids. Specimens are inoculated into the BD BACTEC Myco/F Lytic vial either with a syringe or direct draw with a needle and tubing. The vial is placed into the BD BACTEC fluorescent series instrument and is continuously
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agitated and incubated at 35°C for maximum recovery. The default testing protocol is 42 days. The recommended testing protocols for the following organisms are: 7 days for yeast, 30 days for filamentous fungi, and 42 days for mycobacteria and dimorphic fungi. Each vial contains a sensor which can detect decreases in oxygen concentration in the vial resulting from microorganism metabolism and growth. The sensor is monitored by the BD BACTEC fluorescent series instrument every ten minutes. Analysis of the rate of oxygen decrease as measured by increasing fluorescence enables the BD BACTEC fluorescent series instrument to determine if the vial is instrument positive determination indicates the presumptive presence of viable microorganisms in the vial. Detection is limited to microorganisms that will grow in the medium at 35 ℃. The medium is not selective and will support the growth of other aerobic organisms including bacteria which may interfere, if present, with the recovery of slower growing mycobacteria, yeast and fungi. Culture vials which remain negative after the completion of protocol, and which show no visible sign of positivity are removed from the instrument and sterilized prior to discarding. This qualitative culture functions as an aid to diagnosis and is automated on the BD BACTEC fluorescent series instrument.
V Substantial Equivalence Information:
Predicate Device Name(s): A
BD BACTEC Myco/f Lytic Culture Vials
C Comparison with Predicates
| Device & PredicateDevice(s): | Device: | Predicate: K970333,K970512 |
|---|---|---|
| K222559 | ||
| Device Trade Name | BD BACTEC Myco/F Lytic Culture Vial(plastic) | BD BACTEC Myco/F Lytic CultureVial |
| General DeviceCharacteristicSimilarities | ||
| Regulation | 21 CFR § 866.2560 | Same |
| Product Code | MDB | Same |
| Classification | Class I | Same |
| Detection used | BD BACTEC™ Fluorescent instrumentseries | Same |
| Sample Source | Blood Culture, Sterile Body fluids | Same |
| Volume | 1 mL - 5.0 mL | Same |
| Protocol Length | 42 days forMycobacteria 7days for Yeast30 days for Fungi | Same |
| Target population | Adult | Same |
| General DeviceCharacteristicDifferences | ||
| BD BACTEC™ Myco/F Lytic culturemedium when used with the BD BACTEC |
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| Intended Use/Indicationsfor Use | fluorescent series instruments is anonselective culture medium to be used asan adjunct to aerobic blood culture mediafor the qualitative culture and recovery ofmycobacteria, yeast and fungi from blood.This medium may also be used for theculture of sterile body fluids when yeast orfungi are suspected.Additional informationThe device aids in the diagnosis of diseasecaused by pathogenic microorganisms andisautomated on the BD BACTEC™fluorescentseries instruments. | BD BACTEC™ Myco/F Lytic culturemedium when used with the BD BACTECfluorescent series instruments is anonselective culture medium to be used as anadjunct to aerobic blood culture media forthe recovery of mycobacteria, yeast andfungi from blood. This medium may also beused for the culture of sterile body fluidswhen yeast or fungi are suspected. |
|---|---|---|
| Vial Material | Plastic | Glass |
| Vial Weight | 21.5 grams | 102.05 grams |
| Vial Height | 5.0 inches | 5.6 inches |
| Delayed Vial EntryStudies | Included | Not Included |
VI Standards/Guidance Documents Referenced:
CLSI. Principles and Procedures for Blood Cultures. 2nd ed. CLSI guideline M47. Clinical and Laboratory Standards Institute; 2022.
VII Performance Characteristics (if/when applicable):
A Analytical Performance:
-
- Precision/Reproducibility:
Blood Volumes
The BACTEC Myco/F Lytic (plastic) vial was evaluated at three different blood volumes (1mL, 3mL, 5mL) across three lots in Time-To- Detection (TTD) and Percent Recovery studies. Different lots of key raw materials were used to manufacture each lot of culture media. Inoculum levels of 0-1, 1-10, and 10-100 CFU were used in the analysis. Results of the reproducibility study demonstrated no statistically significant differences in organism detection times or percent recovery with blood specimens between the three different lots of BACTEC Myco/F Lytic (plastic) vials.
Sterile Body Fluid Volumes
The BACTEC Myco/F Lytic (plastic) vial was evaluated at three different sterile body fluid types (pleural, synovial, and cerebrospinal), four different volumes (0.5mL, 1mL, 3mL, 5mL) across three lots in Time-To- Detection (TTD) and Percent Recovery studies. Different lots of key raw materials were used to manufacture each lot of culture media. Inoculum levels of 0-1, 1-10, and 10-100 CFU were used in the analysis. Results of the reproducibility study demonstrated no statistically significant differences in organism
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detection times or percent recovery with sterile body fluid specimens between the three different lots of BACTEC Myco/F Lytic (plastic) vials.
-
- Linearity:
Not applicable
- Linearity:
-
- Analytical Specificity/Interference:
Not applicable
- Analytical Specificity/Interference:
-
- Assay Reportable Range:
Not applicable
- Assay Reportable Range:
-
- Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Quality Control
An internal validation study across three lots with a target inoculum level of 10-100 CFU per vial was conducted using organisms listed below:
Table 1: Quality Control Organism and TTD Range
| QC OrganismATCC® Strain | Time-To-Detection (TTD)(Days) |
|---|---|
| Candida glabrata ATCC 15545 | <3 |
| Cryptococcus neoformans, ATCC 13690 | <3 |
| Mycobacterium fortuitum, ATCC 6841 | ≤21 |
| Mycobacterium intracellulare, ATCC 13950 | 8-16 |
| Mycobacterium kansasii, ATCC 12478 | ≤21 |
| Mycobacterium tuberculosis ATCC 25177 (H37Ra) | ≤21 |
There were a total of 240 replicates of these six QC organisms for the study. Each organism was tested for either 36 (12 replicates x 3 lots) or 60 (20 replicates x 3 lots) replicates. All organisms were detected within the associated duration captured in Table 1.
-
- Detection Limit:
Blood Volumes
Microbial Detection Limit (MDL, target inoculum level 0-1, 1-10 CFU/vial) in blood
The microbial detection limit study was conducted to assess the capability of the culture media to detect low numbers of organisms (expected target level of 0-1 and 1- 10 CFU/vial) when present in blood. The study included 23 organisms (8 mycobacteria, 10 yeast, 3 filamentous fungi, and 2 dimorphic fungi strains) tested at three blood volumes (1, 3 and 5 mL), each with two inoculum levels of 0-1 and 1-10 CFU/vial and across three lots by one instrument (BACTEC FX):
23 orgs x 3 lots x 3 blood vol x 2 inoculum levels x 1 instrument= 414* paired vials
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*Note: Two pairs were discarded due to contamination resulting in 412 paired vials.
The ratio of positive yields was calculated. The combined performance results of 0-1 and 1-10 CFU/vial for each organism type (mycobacteria, yeast, filamentous fungi, and dimorphic fungi) are provided in Table 2, Table 4, and Table 5, respectively.
| BloodVolume(mL) | Pairedsets(N) | PercentRecoveryfor Glass(Predicate)(%) | PercentRecoveryfor Plastic(Modified)(%) | Ratio of Positive Yields(Plastic/Glass) | ||
|---|---|---|---|---|---|---|
| Organism | Per Organism andBlood Volume | PerOrganism | ||||
| Mycobacterium bovisATCC 357241,2 | 1 | 6 | 100 | 83.33 | 0.83 | |
| 3 | 6 | 100 | 100 | 1.00 | 1.07 | |
| 5 | 6 | 50.00 | 83.33 | 1.67 | ||
| Mycobacteriumtuberculosis ATCC25177 | 1 | 6 | 100 | 100 | 1.00 | |
| 3 | 6 | 100 | 100 | 1.00 | 1.00 | |
| 5 | 6 | 100 | 100 | 1.00 | ||
| Mycobacteriumtuberculosis TB007 | 1 | 6 | 100 | 100 | 1.00 | |
| 3 | 6 | 100 | 100 | 1.00 | 1.00 | |
| 5 | 6 | 100 | 100 | 1.00 | ||
| Mycobacteriumabscessus ATCC199771 | 1 | 6 | 83.33 | 83.33 | 1.00 | 1.08 |
| 3 | 6 | 66.67 | 83.33 | 1.25 | ||
| 5 | 6 | 66.67 | 66.67 | 1.00 | ||
| Mycobacteriumchimaera BR09092 | 1 | 6 | 83.33 | 33.33 | 0.40 | |
| 3 | 6 | 83.33 | 66.67 | 0.80 | 0.73 | |
| 5 | 6 | 83.33 | 83.33 | 1.00 | ||
| Mycobacteriumfortuitum ATCC68411,2 | 1 | 6 | 83.33 | 66.67 | 0.80 | |
| 3 | 6 | 16.67 | 50.00 | 3.00 | 1.00 | |
| 5 | 6 | 50.00 | 33.33 | 0.66 | ||
| Mycobacteriumintracellulare ATCC139502 | 1 | 6 | 66.67 | 50.00 | 0.75 | 0.83 |
| 3 | 4 | 50.00 | 25.00 | 0.50 | ||
| 5 | 6 | 66.67 | 66.67 | 1.00 | ||
| Mycobacteriumkansasii ATCC124781,2 | 1 | 6 | 83.33 | 83.33 | 1.00 | 1.00 |
| 3 | 6 | 50.00 | 66.67 | 1.33 | ||
| 5 | 6 | 66.67 | 50.00 | 0.75 |
Table 2: MDL Percent Recovery Results by Blood Volume for Mycobacteria with 0-1 and 1-10 CFU
1 The percent recovery of these pathogens at some low inoculum levels and blood volume test conditions and test strains were higher with this device compared to the predicate. However, these differences are not statistically significant.
2 The percent recovery of these pathogens at some low inoculum levels and blood volume test conditions and test strains were lower in the candidate device compared to the predicate device. However, these differences are not statistically significant.
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Table 3: MDL Percent Recovery Results by Blood Volume for Yeast with 0-1 and 1-10 CFU in the FX
| BloodVolume(mL) | Pairedsets(N) | PercentRecovery forGlass(Predicate)(%) | Percent Recoveryfor Plastic(Modified)(%) | Ratio of Positive Yields(Plastic/Glass) | ||
|---|---|---|---|---|---|---|
| Organism | Per Organismand BloodVolume | PerOrganism | ||||
| Candida albicansATCC 10231 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 50.00 | 50.00 | 1.00 | 1.00 | |
| 5 | 6 | 50.00 | 50.00 | 1.00 | ||
| Candida auris AR0387 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 50.00 | 50.00 | 1.00 | 1.00 | |
| 5 | 6 | 50.00 | 50.00 | 1.00 | ||
| Candida glabrataATCC 15545 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 50.00 | 50.00 | 1.00 | 1.00 | |
| 5 | 6 | 50.00 | 50.00 | 1.00 | ||
| Candida glabrataATCC 66032 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 50.00 | 50.00 | 1.00 | 1.00 | |
| 5 | 6 | 50.00 | 50.00 | 1.00 | ||
| Candida kruseiATCC 34135 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 66.67 | 66.67 | 1.00 | 1.00 | |
| 5 | 6 | 50.00 | 50.00 | 1.00 | ||
| CandidaparapsilosisATCC 102321,2 | 1 | 6 | 50.00 | 66.67 | 1.33 | |
| 3 | 6 | 50.00 | 50.00 | 1.00 | 1.00 | |
| 5 | 6 | 66.67 | 50.00 | 0.75 | ||
| Candida tropicalisATCC 750 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 50.00 | 50.00 | 1.00 | 1.00 | |
| 5 | 6 | 50.00 | 50.00 | 1.00 | ||
| Cryptococcusneoformans ATCC13690 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 50.00 | 50.00 | 1.00 | 1.00 | |
| 5 | 6 | 50.00 | 50.00 | 1.00 | ||
| Malassezia furfurATCC 14521 | 1 | 6 | 100 | 100 | 1.00 | |
| 3 | 6 | 100 | 100 | 1.00 | 1.00 | |
| 5 | 6 | 100 | 100 | 1.00 | ||
| Saccharomycescerevisiae ATCC901461,2 | 1 | 6 | 50.00 | 50.00 | 1.00 | |
| 3 | 6 | 50.00 | 33.33 | 0.67 | 1.00 | |
| 5 | 6 | 33.33 | 50.00 | 1.50 |
1 The percent recovery of these pathogens at some low inoculum levels and blood volume test conditions and test strains were higher with this device compared to the predicate. However, these differences are not statistically significant.
2 The percent recovery of these pathogens at some low inoculum levels and blood volume test conditions and test strains were lower in the candidate device compared to the predicate device. However, these differences are not statistically significant.
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Table 4: MDL Percent Recovery Results by Blood Volume for Filamentous Fungi with 0-1 and 1-10 CFU
| Organism | BloodVolume(mL) | Pairedsets(N) | PercentRecoveryfor Glass(Predicate)(%) | PercentRecovery forPlastic(Modified)(%) | Ratio of Positive Yields(Plastic/Glass) | |
|---|---|---|---|---|---|---|
| Per Organismand BloodVolume | PerOrganism | |||||
| AspergillusfumigatusATCC 13073 | 1 | 6 | 66.67 | 100 | 1.50 | 1.31 |
| 3 | 6 | 100 | 100 | 1.00 | ||
| 5 | 6 | 50.00 | 83.33 | 1.67 | ||
| TalaromycesmarneffeiATCC 64101 | 1 | 6 | 100 | 100 | 1.00 | 0.94 |
| 3 | 6 | 100 | 100 | 1.00 | ||
| 5 | 6 | 100 | 83.33 | 0.83 | ||
| Rhizopus oryzaeATCC 66275 | 1 | 6 | 100 | 100 | 1.00 | 1.00 |
| 3 | 6 | 100 | 100 | 1.00 | ||
| 5 | 6 | 100 | 100 | 1.00 |
Table 5: MDL Percent Recovery Results by Blood Volume for Dimorphic Fungi with 0-1 and 1-10 CFU in the FX
| Organism | BloodVolume(mL) | Pairedsets(N) | Percent Recoveryfor Glass(Predicate)(%) | Percent Recoveryfor Plastic(Modified)(%) | Ratio of Positive Yields(Plastic/Glass) | |
|---|---|---|---|---|---|---|
| Per Organism andBlood Volume | PerOrganism | |||||
| BlastomycesdermatitidisATCC 18188 | 1 | 6 | 16.67 | 0 | 0.00 | 0.33 |
| 3 | 6 | 16.67 | 0 | 0.00 | ||
| 5 | 6 | 66.67 | 33.33 | 0.50 | ||
| Histoplasmacapsulatum ATCC26032 | 1 | 6 | 100 | 83.33 | 0.83 | 0.94 |
| 3 | 6 | 100 | 100 | 1.00 | ||
| 5 | 6 | 100 | 100 | 1.00 |
The MDL study with blood demonstrated that the plastic device performed equivalently based on a value of close to 1 or higher when compared to the predicate glass device at low target inoculum levels for all organisms with the exception of Blastomyces dermatitidis. The Blastomyces dermatitidis resulted in a ratio of positive yields of 0.33. The culture medium of BD BACTEC Myco/F Lytic displays inconsistent growth of Blastomyces dermatitidis. Information about this organism was noted as a limitation in the product insert.
Sterile Body Fluid Volumes
Microbial Detection Limit (MDL, target inoculum level 0-1, 1-10 CFU/vial) with Sterile Body Fluid (SBF)
The microbial detection limit study was conducted to assess the capability of the culture
{8}------------------------------------------------
media to detect low numbers of organisms (expected target level of 0-1 and 1- 10 CFU/vial) when present in sterile body fluid (pleural, synovial, and cerebrospinal). Five organisms (1 filamentous fungi, 2 yeast, and 2 dimorphic fungi strains) were tested with cerebrospinal fluid (CSF) and three organisms (1 filamentous fungi and 2 yeast strains) were tested with pleural and synovial fluid at four sterile body fluid volumes (0.5, 1, 3 and 5 mL), each with two inoculum levels of 0-1 and 1-10 CFU/vial and across three lots by one instrument (BACTEC FX).
3 organisms x 3 lots x 4 SBF volumes x 2 inoculum levels x 1 instrument x 2 SBF (pleural & synovial fluid) = 144 paired vials
5 organisms x 3 lots x 4 SBF volumes x 2 inoculum levels x 1 instrument x 1 SBF (cerebrospinal fluid) = 120 paired vials
Total =264 paired vials
The ratio of positive yields was calculated to assess performance. The detection results of 0-1 and 1-10 CFU/vial were evaluated for each organism and organism group (mycobacteria, yeast, filamentous fungi, and dimorphic fungi), as shown in Table 6.
| Table 6: MDL Percent Recovery Results by Organisms at Target Inoculum 0-1 and 1-10 CFU in | ||
|---|---|---|
| SBF |
| Organism | SBFType | VialType | N | PercentRecovery | Ratio of Positive Yields | |
|---|---|---|---|---|---|---|
| Per Condition | Per Organism | |||||
| AspergillusfumigatusATCC 13073 | CSF | Glass | 24 | 79.17% | 1.05 | 1.00 |
| Plastic | 24 | 83.33% | ||||
| Pleural Fluid | Glass | 24 | 75.00% | 1.00 | ||
| Plastic | 24 | 75.00% | ||||
| SynovialFluid | Glass | 24 | 66.67% | 0.94 | ||
| Plastic | 24 | 62.50% | ||||
| Candida aurisAR 0387 | CSF | Glass | 24 | 75.00% | 1.00 | 1.04 |
| Plastic | 24 | 75.00% | ||||
| Pleural Fluid | Glass | 24 | 70.83% | 1.12 | ||
| Plastic | 24 | 79.17% | ||||
| SynovialFluid | Glass | 24 | 75.00% | 1.00 | ||
| Plastic | 24 | 75.00% | ||||
| CryptococcusneoformansATCC 13690 | CSF | Glass | 24 | 54.17% | 1.31 | 1.18 |
| Plastic | 24 | 70.83% | ||||
| Pleural Fluid | Glass | 24 | 58.33% | 1.29 | ||
| Plastic | 24 | 75.00% | ||||
| SynovialFluid | Glass | 24 | 70.83% | 1.00 | ||
| Plastic | 24 | 70.83% | ||||
| Glass | 24 | 58.33% |
{9}------------------------------------------------
| BlastomycesdermatitidisATCC 18188 | CSF | Plastic | 24 | 50.00% | 0.86 | 0.86 |
|---|---|---|---|---|---|---|
| HistoplasmacapsulatumATCC 18188 | CSF | GlassPlastic | 24 | 54.17%58.33% | 1.08 | 1.08 |
The MDL study with sterile body fluid demonstrated that the modified plastic device performed equivalently based on a value of 1 or higher when compared to the predicate glass device at low target inoculum levels for all organisms with the exception of Blastomyces dermatitidis. The Blastomyces dermatitidis resulted in a ratio of positive yields of 0.86. The culture medium of BD BACTEC Myco/F Lytic displays inconsistent growth of Blastomyces dermatitidis at low target inoculum of 0-1 or 1-10 CFU/vial. Information about this organism was noted as a limitation in the product insert.
7. Assay cut-off
Not applicable
8. Delayed Entry in blood for Mycobacteria
As a way to assess the potential effects from delay which may occur in practice, an internal study was conducted to evaluate the effect of recovery, from the time the plastic Myco/F Lytic culture vial was inoculated, to the time the vial was placed on the instrument. This seeded study was conducted using three lots of the plastic Myco/ F Lytic culture vials. The delayed vial entry study was conducted using the following mycobacterium at target concentrations of 10-100 CFU/vial: Mycobacterium abscessus, Mycobacterium bovis, Mycobacterium chimaera, Mycobacterium fortuitum, Mycobacterium intracellulare, Mycobacterium kansasii, and 2 strains of Mycobacterium tuberculosis. Vials were prepared in 1-, 3-, and 5-mL human blood. All samples were held at the specified temperatures and times prior to loading into the BD BACTEC fluorescent instrument. Percent recovery and Time-To-Detection reflects time to positive flagged by the instrument. The study demonstrated that all delayed entry conditions showed 100% percent recovery of the 8 strains of mycobacterium evaluated. These results are acceptable. Study results are presented in Table 7 below.
| Delay Time inHours | DelayTemperature(°C) | PercentRecovery (%) | Median Instrument TTDin Hours (Range) |
|---|---|---|---|
| No Delay | Control | 100 (72/72) | 370.2 (71.1-650.2) |
| 12 | 34.5-37.5 | 100 (72/72) | 346.3 (58.2-642.4) |
| 12 | 20-25 | 100 (70/70) | 370.4 (63.2-642.3) |
| 24 | 20-25 | 100 (72/72) | 362.2 (55.1-706.4) |
| 48 | 20-25 | 100 (71/71) | 346.2 (42.1-732.4) |
| 72 | 20-25 | 100 (71/71) | 338.2 (32.1-618.4) |
| 96 | 20-25 | 100 (72/72) | 330.2 (21.2-610.2) |
Table 7: Delayed Entry Summary (Plastic Bottle)
The Product Insert recommends that the inoculated culture bottles are placed in the BD BACTEC fluorescent series instrument as soon as possible after collection: "BD recommends that inoculated culture bottles be placed into the BD BACTEC fluorescent series instruments
{10}------------------------------------------------
as soon as possible after collection. But, in the unavoidable cases when there is a delay in bottle receipt by the laboratory, delayed entry information is provided from seeded studies for mycobacterium in the 'Expected Values and Specific Performance Characteristics (Blood Cultures)' section. Medium has not been evaluated for delayed vial entry for yeast, fungi, or sterile body fluids."
B Comparison Studies:
Performance of the BD BACTEC Myco/F Lytic Culture Vial (plastic) was evaluated in seeded internal analytical studies to demonstrate comparable performance to the predicate device, the BD BACTEC Myco/F Lytic Culture Vial (glass). Comparison results were acceptable. The comparisons were made using the following parameters: time to detection, percent recovery, false negative rate, and false positive rate.
1. Method Comparison with Predicate Device:
Instrument Time to Detection (TTD) study in blood
The TTD (in hours) was recorded as part of the combined Percent Recovery and the Microbial Detection Limit studies using the BD BACTEC FX at three inoculum levels, across three blood volumes (1 mL, 3 mL and 5 mL) over three media lots. The Percent Recovery study represented by the standard inoculum of 10 to 100 CFU per vial and the Microbial Detection Limit study represented by the challenge inoculum levels of 0 to 1 and 1 to 10 CFU per vial.
The data was analyzed using the 95% confidence interval with the bootstrap method. The TTD data was stratified by organism group, target inoculum level, and blood volume. The results are shown in Table 8.
The TTD study demonstrated that the plastic device performed equivalently when compared to the predicate glass device when stratified by organism group (Dimorphic Fungi, Filamentous, Fungi, Yeast and Mycobacteria), inoculum concentration (0-1, 1-10, 10-100), and blood volume (1 mL, 3 mL and 5 mL). The results show that the test vial performed equivalently to or better than the predicate vial for all conditions, with the exception of Dimorphic Fungi at an inoculum concentration of 0-1 CFU/vial at 1 mL blood volume and Mycobacteria at an inoculum concentration of 1-10 CFU/vial and blood volume of 1mL. The data was statistically analyzed by means of 95% CI with the bootstrap method, where the 95% CI for equivalent median detection times versus the predicate vial contains zero and the 95% CI for median detection times shorter than the predicate contains only negative values.
{11}------------------------------------------------
Table 8: Summary of TTD Study Results by Organism Group, Target Inoculum Levels, and Blood Volumes¹
| OrganismGroup | InoculumConcentration(CFU/Vial) | BloodVolume(mL) | Median TTD forGlass (Predicate)(95% CI) [N] | Median TTD forPlastic (Modified)(95% CI) [N] | Median of TTDdifference²(95% CI) [N] |
|---|---|---|---|---|---|
| DimorphicFungi | 0-1 | 1 | 820.10 (722.121,918.132) [2] | 960.15 (954.154,966.151) [2] | 140.00 (36.021,244.029) [2] |
| 3 | 490.00 (458.100,930.150) [3] | 698.10 (482.130,754.140) [3] | 24.00 (-176.01, 208.01)[3] | ||
| 5 | 442.10 (442.112,514.146) [3] | 418.10 (394.111,458.116) [3] | -48.00 (-96.036,16.002) [3] | ||
| DimorphicFungi | 1-10 | 1 | 514.30 (514.091,602.092) [3] | 578.10 (530.090,642.258) [3] | 64.00 (-72.002,129.006) [3] |
| 3 | 370.06 (354.054,386.061) [3] | 338.10 (322.054,418.064) [3] | -32.00 (-32.000,32.003) [3] | ||
| 5 | 370.10 (314.064,462.163) [5] | 362.00 (338.070,866.230) [5] | 40.10 (-24.000,404.070) [5] | ||
| DimorphicFungi | 10-100 | 1 | 354.00 (338.140,858.230) [5] | 450.10 (330.140,754.227) [5] | -8.00 (-376.016,112.005) [5] |
| 3 | 450.00 (262.150,850.300) [6] | 282.10 (262.148,538.169) [6] | -104.10 (-384.080,8.000) [6] | ||
| 5 | 258.10 (250.159,318.114) [6] | 266.10 (258.159,374.116) [6] | 8.00 (-24.001, 88.002)[6] | ||
| FilamentousFungi | 0-1 | 1 | 80.00 (26.08,514.30) [7] | 57.00 (26.08,530.30) [7] | -3.00 (-32.006, 1.999)[7] |
| 3 | 82.20 (26.069,410.246) [9] | 74.20 (26.066,314.236) [9] | -2.00 (-96.010, 17.015)[9] | ||
| 5 | 32.10 (25.054,234.214) 95] | 26.10 (25.053,290.220) [5] | -1.00 (-16.054, 72.061)[5] | ||
| FilamentousFungi | 1-10 | 1 | 53.10 (23.085,162.201) [9] | 53.20 (22.084,202.176) [9] | -0.00 (-5.001, 31.999)[9] |
| 3 | 52.10 (22.075,218.167) [9] | 57.10 (22.072,138.165) [9] | -1.00 (-24.001, 4.999)[9] | ||
| 5 | 52.10 (23.061,114.151) [9] | 44.10 (23.057,114.152) [9] | -1.00 (-10.001, -0.001)[9] | ||
| FilamentousFungi | 10-100 | 1 | 37.10 (19.126,106.140) [9] | 36.10 (19.125,106.141) [9] | -0.00 (-1.001, -0.001)[9] |
| 3 | 37.10 (19.119,98.133) [9] | 37.10 (19.119,98.132) [9] | -0.00 (-1.001, -0.001)[9] | ||
| 5 | 37.10 (19.113,98.124) [9] | 36.10 (19.112,98.125) [9] | -0.00 (-1.001, 0.999) [9] | ||
| Yeast | 0-1 | 1 | 70.12 (70.120,73.131) [3] | 70.12 (70.121,72.126) [3] | -0.00 (-3.008, 2.006) [3] |
| 3 | 64.10 (61.107,65.109) [3] | 66.10 (64.108,67.106) [3] | 2.00 (-1.001, 5.999) [3] | ||
| 5 | 62.10 (61.094,65.092) [3] | 63.09 (61.095,65.091) [3] | -0.00 (-1.001, 1.999) [3] | ||
| Yeast | 1-10 | 1 | 31.06 (30.123,49.144) [29] | 30.24 (28.059,52.146) [29] | -0.00 (-0.002, 0.999)[29] |
| OrganismGroup | InoculumConcentration(CFU/Vial) | BloodVolume(mL) | Median TTD forGlass (Predicate)(95% CI) [N] | Median TTD forPlastic (Modified)(95% CI) [N] | Median of TTDdifference²(95% CI) [N] |
| 10-100 | 3 | 30.11 (29.111,33.123) [29] | 30.11 (29.065,35.121) [29] | -0.00 (-0.002, 0.999)[29] | |
| 5 | 30.05 (27.102,31.114) [29] | 30.22 (28.103,32.051) [29] | -0.00 (-0.001, -0.001)[29] | ||
| 1 | 26.27 (26.083,38.140) [30] | 26.27 (26.086,44.141) [30] | 0.00 (-0.001, 0.000)[30] | ||
| 10-100 | 3 | 26.67 (25.079,30.150) [30] | 26.17 (24.086,31.648) [30] | -0.00 (-0.001, -0.001)[30] | |
| 5 | 26.66 (24.075,28.111) [30] | 26.66 (25.073,29.143) [30] | -0.00 (-0.001, -0.001)[30] | ||
| 1 | 638.20 (307.655,674.177) [12] | 662.20 (297.150,702.200) [12] | 8.50 (-16.002, 39.999)[12] | ||
| 0-1 | 3 | 698.20 (626.208,722.163) [11] | 682.20 (642.207,714.166) [11] | -16.00 (-40.001,15.999) [11] | |
| 5 | 554.10 (338.130,642.126) [9] | 610.20 (338.134,650.191) [9] | 56.00 (-32.002, 79.974)[9] | ||
| Mycobacteria | 1-10 | 1 | 426.10 (250.133,562.164) [23] | ||
| 3 | 562.20 (378.128,594.186) [20] | 79.10 (418.126,602.142) [20] | 8.00 (-11.001, 28.000)[20] | ||
| 5 | 394.10 (306.137,522.158) [23] | 434.10 (314.131,546.140) [23] | 8.00 (-4.001, 31.998)[23] | ||
| 10-100 | 1 | 414.10 (226.163,482.089) [24] | 410.10 (242.162,498.164) [24] | 12.00 (-0.001, 23.999)[24] | |
| 3 | 390.10 (234.167,506.158) [24] | 370.20 (250.155,474.121) [24] | 8.00 (-2.001, 11.999)[24] | ||
| 5 | 346.20 (290.092,426.111) [24] | 330.20 (290.091,450.109) [24] | 1.00 (-0.001, 15.999)[24] | ||
| OrganismGroup | InoculumConcentration(CFU/Vial) | SBFVolume(mL) | Median TTD forGlass(95% CI) [N] | Median TTD forPlastic(95% CI) [N] | Median of TTDdifference²(95% CI) [N] |
| DimorphicFungi | 0-1 | 0.5 | No paireddetections³ | No paired detections³ | N/A |
| 1 | No paireddetections³ | No paired detections³ | N/A | ||
| 3 | No paireddetections³ | No paired detections³ | N/A | ||
| 5 | Only 1 paireddetection³ | Only 1 paireddetection³ | N/A | ||
| 1-10 | 0.5 | 656.20 (414.218,726.233) [6] | 677.20 (614.251,816.239) [6] | 117.00 (-50.002,244.036) [6] | |
| 1 | 607.20 (442.18,726.240) [6] | 680.20 (502.224,798.242) [6] | 53.00 (10.000, 142.034)[6] | ||
| 3 | 786.00 (538.26,924.26) [3] | 720.00 (378.20,816.25) [3] | -108.00 (-160.063, -66.001) [3] | ||
| 5 | 645.00 (426.18,990.44) [4] | 626.20 (466.185,840.263) [4] | 29.00 (-404.19, 198.06)[4] | ||
| 10-100 | 0.5 | 318.10 (250.132,546.184) [6] | 522.20 (382.134,633.189) [6] | 142.00 (17.001, 264.075)[6] | |
| 1 | 394.10 (218.116,509.180) [6] | 605.20 (450.157,636.201) [6] | 210.00 (108.004,252.075) [6] | ||
| 3 | 533.20 (390.104,603.214) [6] | 506.20 (474.193,589.196) [6] | 48.00 (-129.021,124.070) [6] | ||
| 5 | 558.20 (434.134,649.223) [6] | 485.20 (373.098,570.220) [6] | -72.00 (-156.039, 15.000)[6] | ||
| FilamentousFungi | 0-1 | 0.5 | Only 1 paireddetection³ | Only 1 paireddetection³ | N/A |
| 1 | 82.09 (80.088,84.094) [2] | 70.59 (69.093,72.087) [2] | -11.50 (-15.001, -8.001)[2] | ||
| 3 | 81.07 (73.195,83.077) [3] | 65.07 (58.194,72.075) [3] | -15.00 (-16.001, -11.001)[3] | ||
| 5 | 72.56 (61.056,98.063) [4] | 64.56 (54.057,82.055) [4] | -12.00 (-36.001, 21.000)[4] | ||
| 1-10 | 0.5 | 60.07 (49.289,64.075) [9] | 49.08 (48.074,54.072) [9] | -8.00 (-14.999, 1.999) [9] | |
| 1 | 54.06 (51.275,59.068) [9] | 49.06 (47.065,62.069) [9] | -2.00 (-8.999, 5.999) [9] | ||
| 3 | 51.06 (47.068,61.052) [9] | 52.05 (47.264,59.070) [9] | -0.00 (-7.001, 10.999) [9] | ||
| 5 | 62.05 (45.255, 59.064) [9] | 48.05 (46.061, 52.063) [9] | -3.00 (-13.001, 5.999) [9] | ||
| Yeast | 10-100 | 0.5 | 41.11 (39.078, 44.108) [9] | 38.074 (36.079, 38.176) [9] | -4.00 (-6.002, -2.001) [9] |
| 1 | 40.07 (35.145, 43.106) [9] | 37.07 (35.146, 38.102) [9] | -3.00 (-6.001, 0.999) [9] | ||
| 3 | 37.06 (33.137, 41.096) [9] | 36.13 (34.059, 38.097) [9] | -1.00 (-3.001, 0.999) [9] | ||
| 5 | 36.05 (33.114, 39.083) [9] | 35.09 (34.111, 38.085) [9] | -0.00 (-2.001, 0.999) [9] | ||
| 0-1 | 0.5 | 29.10 (28.081, 77.111) [5] | 28.10 (28.079, 73.112) [5] | -1.00 (-4.001, 0.001) [5] | |
| 1 | 30.60 (29.099, 81.119) [4] | 29.60 (28.117, 83.120) [4] | -0.50 (-2.000, 2.001) [4] | ||
| 3 | Only 1 paired detection³ | Only 1 paired detection³ | N/A | ||
| 5 | 29.09 (29.091, 29.095) [2] | 28.09 (28.091, 28.094) [2] | -1.00 (-1.001, -1.001) [2] | ||
| 1-10 | 0.5 | 45.87 (27.273, 66.215) [18] | 47.29 (26.772, 69.711) [18] | 0.00 (-1.501, 2.001) [18] | |
| 1 | 28.13 (27.092, 71.117) [17] | 28.42 (27.093, 70.120) [17] | -0.00 (-1.002, 1.001) [17] | ||
| 3 | 46.68 (27.587, 72.113) [18] | 46.68 (27.085, 70.607) [18] | -1.00 (-1.998, -0.001) [18] | ||
| 5 | 45.60 (27.569, 70.616) [18] | 47.11 (27.076, 72.596) [18] | -0.00 (-1.001, 0.001) [18] | ||
| 10-100 | 0.5 | 40.12 (24.088, 59.156) [18] | 40.12 (24.089, 58.639) [18] | 0.00 (-0.002, 0.001) [18] | |
| 1 | 41.13 (24.110, 59.150) [18] | 40.63 (24.104, 58.649) [18] | -0.50 (-1.001, 0.001) [18] | ||
| 3 | 61.17 (24.121, 62.164) [17] | 58.17 (24.120, 61.164) [17] | -1.00 (-2.001, 0.001) [17] | ||
| 5 | 42.63 (24.133, 63.144) [18] | 42.16 (24.133, 62.130) [18] | -0.00 (-1.001, 0.001) [18] |
{12}------------------------------------------------
¹ All lots combined.
2 Median of the difference between Glass (Predicate) and Plastic (Modified) devices.
Instrument Time to Detection (TTD) study in SBF
The TTD (in hours) was recorded as part of the combined Percent Recovery and the Microbial Detection Limit studies using the BD BACTEC FX at three inoculum levels, three sterile body fluid types (pleural, synovial, and cerebrospinal) across four sterile body fluid volumes (0.5 mL, 1 mL, 3 mL and 5 mL) over three media lots. The Percent Recovery study represented by the standard inoculum of 10 to 100 CFU per vial and the Microbial Detection Limit study represented by the challenge inoculum levels of 0 to 1 and 1 to 10 CFU per vial.
The data was analyzed using the 95% confidence interval with the bootstrap method. The TTD data was stratified by target inoculum level, sterile body fluid volume or organism. The results are shown in Table 9.
The TTD study demonstrated that the plastic device performed equivalently when compared to the predicate glass device when stratified by organism group (Dimorphic Fungi, Filamentous, Fungi, and Yeast), inoculum concentration (0-1, 1-10, 10-100), and sterile body
{13}------------------------------------------------
fluid volume (0.5 mL, 1 mL, 3 mL and 5 mL). The results show that the test vial performed equivalently to or better than the predicate vial for all conditions, with the exception of Dimorphic Fungi under some test conditions. The data was statistically analyzed by means of 95% CI with the bootstrap method, where the 95% CI for equivalent median detection times versus the predicate vial contains zero and the 95% CI for the median detection times shorter than the predicate contains only negative values.
Table 9: Summary of TTD Study Results by Organism Group, Target Inoculum Levels, and SBF Volumes1
{14}------------------------------------------------
1 All lots combined.
2 Median of the difference between Glass (Predicate) and Plastic (Modified) devices
3 At least two distinct values are required to generate a confidence interval
Percent Recovery (Detection) Study in Blood
The percent recovery (detection) was evaluated in a study of 207 paired sets at the standard inoculum level of 10 to 100 CFU/vial on one instrument across three lots using a diverse set of microorganisms frequently isolated in blood. The study included 23 microorganisms (8 mycobacteria, 10 yeast, 3 filamentous fungi, and 2 dimorphic fungi strains) tested at three blood volumes (1, 3 and 5 mL).
23 organisms x 3 lots x 3 blood volumes x 1 instrument= 207 paired sets
The performance of each organism type (mycobacteria, yeast, filamentous fungi, and dimorphic fungi) at inoculum of 10 to 100 CFU per vial are shown in Table 10 - Table 13.
{15}------------------------------------------------
The results for all data combined are shown in Table 14.
Table 10: Percent Recovery Study Results by Blood Volume for Mycobacteria with 10-100 CFU in the FX
| Organism | BloodVolume(mL) | PercentRecovery forGlass(Predicate)(%) | PercentRecovery forPlastic(Modified)(%) | Ratio of PositiveYields(Plastic/Glass) |
|---|---|---|---|---|
| Mycobacterium bovisATCC 35724 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| Mycobacteriumtuberculosis ATCC25177 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| Mycobacterium tuberculosisTB007 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| MycobacteriumabscessusATCC 19977 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| MycobacteriumchimaeraBR0909 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| MycobacteriumfortuitumATCC 6841 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| MycobacteriumintracellulareATCC 13950 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| MycobacteriumkansasiiATCC 12478 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 |
Table 11: Percent Recovery Study Results by Blood Volume for Yeast with 10-100 CFU in the FX
| Organism | BloodmL | PercentRecovery forGlass (%) | PercentRecovery forPlastic (%) | Ratio of PositiveYields(Plastic/Glass) |
|---|---|---|---|---|
| Candida albicansATCC 10231 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 |
{16}------------------------------------------------
| 1 | 100 | 100 | 1.00 | |
|---|---|---|---|---|
| Candida auris AR | 3 | 100 | 100 | 1.00 |
| 0387 | 5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| Candida glabrata | 3 | 100 | 100 | 1.00 |
| ATCC 15545 | 5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| Candida glabrata | 3 | 100 | 100 | 1.00 |
| ATCC 66032 | 5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| Candida krusei | 3 | 100 | 100 | 1.00 |
| ATCC 34135 | 5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| CandidaparapsilosisATCC 10232 | 3 | 100 | 100 | 1.00 |
| 5 | 100 | 100 | 1.00 | |
| 1 | 100 | 100 | ||
| Candida tropicalis | 3 | 100 | 100 | 1.00 |
| ATCC 750 | 5 | 100 | 100 | 1.00 |
| Cryptococcus | 1 | 100 | 100 | 1.00 |
| neoformans ATCC | 3 | 100 | 100 | 1.00 |
| 13690 | 5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| Malassezia furfurATCC 14521 | 3 | 100 | 100 | 1.00 |
| 5 | 100 | 100 | 1.00 | |
| Saccharomyces | 1 | 100 | 100 | |
| cerevisiae | 3 | 100 | 100 | 1.00 |
| ATCC 90146 | 5 | 100 | 100 | 1.00 |
Table 12: Percent Recovery Study Results by Blood Volumes for Filamentous Fungi with 10-100 CFU in the FX
| Organism | BloodVolume(mL) | PercentRecoveryfor Glass(Predicate)(%) | PercentRecovery forPlastic(Modified)(%) | Ratio of PositiveYields(Plastic/Glass) |
|---|---|---|---|---|
| AspergillusfumigatusATCC 13073 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| TalaromycesmarneffeiATCC 64101 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| Rhizopus oryzaeATCC 66275 | 1 | 100 | 100 | 1.00 |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 |
{17}------------------------------------------------
Table 13: Percent Recovery Study Results by Blood Volume for Dimorphic Fugni with 10-100 CFU in the FX
| Organism | BloodVolume(mL) | PercentRecoveryfor Glass(Predicate)(%) | PercentRecovery forPlastic(Modified)(%) | Ratio of PositiveYields (Plastic/Glass) |
|---|---|---|---|---|
| BlastomycesdermatitidisATCC 18188 | 1 | 100 | 66.67 | 0.67 |
| BlastomycesdermatitidisATCC 18188 | 3 | 100 | 100 | 1.00 |
| BlastomycesdermatitidisATCC 18188 | 5 | 100 | 100 | 1.00 |
| HistoplasmacapsulatumATCC 26032 | 1 | 100 | 100 | 1.00 |
| HistoplasmacapsulatumATCC 26032 | 3 | 100 | 100 | 1.00 |
| HistoplasmacapsulatumATCC 26032 | 5 | 100 | 100 | 1.00 |
Table 14: Percent Recoverv (10-100 CFU/Vial) Summarv
| 10-100 CFU with 1-5 mL blood in the FX | Predicate (Glass) Vials | ||||
|---|---|---|---|---|---|
| Positive | Negative | Total | |||
| PlasticVials | Positive | 206 | 0 | 206 | |
| Negative | 1 | 0 | 1 | ||
| Total | 207 | 0 | 207 | ||
| % Glass recovery: | 100% | ||||
| % Plastic recovery: | 99.52% | ||||
| Ratio of positive yields: | 1.00 |
Of the 207 paired sets, 206 sets recovered organisms in both the plastic vial and the predicate glass vial. In only one paired set was there a single negative result between the plastic vial and predicate glass vial. The single negative result was in the plastic vial inoculated with Blastomyces dermatitidis with 1 mL blood. The culture medium of BD BACTEC Myco/F Lytic displays inconsistent growth of Blastomyces dermatitidis. Information about this organism was noted as a limitation in the product insert.
Percent Recovery (Detection) Study in SBF
The percent recovery (detection) was evaluated in a study of 207 paired sets at the standard inoculum level of 10 to 100 CFU/vial on one instrument across three lots using microorganisms frequently isolated in sterile body fluid. Five microorganisms (1 filamentous fungi, 2 yeast, and 2 dimorphic fungi strains) were tested with cerebrospinal fluid and three organisms (1 filamentous fungi, and 2 yeast strains) were tested with pleural and synovial fluid at four sterile body fluid volumes (0.5, 1, 3 and 5 mL).
3 organisms x 3 lots x 4 SBF volumes x 1 inoculum level x 1 instrument x 2 SBF Types = 72
5 organisms x 3 lots x 4 SBF volumes x 1 inoculum level x 1 instrument x 1 SBF Type = 60 Total =132 paired sets
{18}------------------------------------------------
The performance of each organism type (filamentous fungi, yeast and dimorphic fungi) at inoculum of 10 to 100 CFU per vial are shown in Table 15. The results for all data combined are shown in Table 16.
| Organism | SBFVolume(mL) | Percent Recovery forGlass (Predicate)(%) | Percent Recovery forPlastic (Modified)(%) | Ratio of PositiveYields (Plastic/Glass) |
|---|---|---|---|---|
| AspergillusfumigatusATCC 13073 | 0.5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| Candida aurisAR 0387 | 0.5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| 3 | 891 | 100 | 1.13 | |
| 5 | 100 | 100 | 1.00 | |
| CryptococcusneoformansATCC 13690 | 0.5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| BlastomycesdermatitidisATCC 18188 | 0.5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 | |
| HistoplasmacapsulatumATCC 26032 | 0.5 | 100 | 100 | 1.00 |
| 1 | 100 | 100 | 1.00 | |
| 3 | 100 | 100 | 1.00 | |
| 5 | 100 | 100 | 1.00 |
Table 15: Percent Recovery Study Results by Organism for all SBF Volumes with 10-100 CFU in the FX
1 The one (1) bottle that did not detect was C. auris AR0387 with 3 mL of synovial fluid.
Table 16: Percent Recovery (10-100 CFU/Vial) Summary
| 10-100 CFU with 0.5-5 mLSBF in the FX | Predicate (Glass) Vials | ||||
|---|---|---|---|---|---|
| PlasticVials | Positive | Positive | Negative | Total | |
| Positive | 131 | 1 | 132 | ||
| Negative | 0 | 0 | 0 | ||
| Total | 131 | 1 | 132 | ||
| % Glass recovery: | 99.24% | ||||
| % Plastic recovery: | 100% | ||||
| Ratio of positive yields: | 1.01 |
{19}------------------------------------------------
Of the 132 paired sets, 131 sets recovered organisms in both the plastic vial and the predicate glass vial. In only one paired set was there a single negative result between the plastic vial and predicate glass vial. The single negative result was in the glass vial inoculated with Candida auris.
False Positive Rate (Instrument-positive, subculture-negative) in Blood
False positive was defined as instrument positive but subculture negative in the evaluation. False positivity was assessed with vials inoculated with fresh blood of 3, 5, and 7 mL, but no organisms were added to the vials. There were a total of 144 paired sets across three lots using BACTEC FX and BACTEC 9240 and completed at the default 42-day protocol.
8 vials x 3 blood volumes x 3 lots x 2 instruments= 144* paired sets
*Note: One lot pair with 7mL blood was excluded due to contamination resulting in 143 paired vials.
There were no false positives observed for the plastic vials with 1 mL and 5 mL fresh blood. There was one false positive observed for the plastic vials with 7 mL fresh blood. There were no false positives observed for the predicate (glass) vial in 1 mL fresh blood. There were two false positives observed for the predicate (glass) vial in 5 mL of fresh blood and thirty-five observed in 7 mL of fresh blood. Majority of the false positives were observed in the higher blood volumes. The false positive rate for the plastic vial for all fresh blood volume combined was 0.70%, which is lower than the 25.87% for the predicate vials (glass). The Myco/F Lytic plastic vials (test) therefore met the threshold of equivalent to or better than Myco/F Lytic glass vials (predicate) performance. The Myco/F Lytic glass product insert includes the following statement "false positivity most likely will increase when the blood volume is above 5 mL" to address the high false positive rate at higher volume. This limitation is also included in the plastic labeling. The False Positive Rates stratified by blood volume is presented in Table 17.
| Fresh Blood Volume(mL) | Number ofVials | False Positive Rate forGlass (Predicate)(%) | False Positive Rate forPlastic(Modified) |
|---|---|---|---|
| 1 | 48 | 0 | 0 |
| 5 | 48 | 4.17 | 0 |
| 7 | 47 | 74.47 | 2.13 |
| All Blood Volumes | 143 | 25.87 | 0.70 |
Table 17: False Positive Rates in Blood
False Positive Rates (Instrument-positive, subculture-negative) in Sterile Body Fluid
False positive was defined as instrument positive but subculture negative in the evaluation. False positivity was assessed with vials inoculated with sterile body fluid of 0.5, 5, and 7 mL, but no organisms were added to the vials. There were a total of 432 pair sets across three lots using BACTEC FX and BACTEC 9240 and completed at the default 42-day protocol.
8 vials x 3 SBF volumes x 3 lots x 2 instruments* 3 SBF types= 432* paired sets
*Note: 15 vials (7 glass and 8 plastic) were excluded due to contamination resulting in 425/424 paired vials.
{20}------------------------------------------------
A total of 432 vial pairs were inoculated with sterile body fluid. Fifteen vials were excluded due to contamination. No false positives occurred in the test vial (plastic) or predicate vial (glass) with 0.5 mL of any sterile body fluid. At the 5-mL sterile body fluid level there was only a single false positive with synovial fluid in the predicate vial (glass). The 7-mL overfill level produced four false positives, all with synovial fluid, three in the test vial (plastic) and one in the predicate vial (glass). The false positive rate for all sterile body fluids combined was 0.71% in the predicate vial (glass) and 0.47% in the test vial (plastic). The False Positive Rates stratified by blood sterile body fluid volume and SBF type is presented in Table 18.
| Fresh Blood Volume(mL) | SBF Type | Number of Vials(Glass/Plastic) | False Positive Ratefor Glass (Predicate)(%) | False Positive Ratefor Plastic(Modified)(%) |
|---|---|---|---|---|
| 1 | CSF | 47/48 | 0 | 0 |
| 1 | Pleural Fluid | 48/48 | 0 | 0 |
| 1 | Synovial Fluid | 48/48 | 0 | 0 |
| 5 | CSF | 48/48 | 0 | 0 |
| 5 | Pleural Fluid | 48/48 | 0 | 0 |
| 5 | Synovial Fluid | 46/44 | 0 | 2.27 |
| 7 | CSF | 48/48 | 0 | 0 |
| 7 | Pleural Fluid | 48/48 | 0 | 0 |
| 7 | Synovial Fluid | 44/44 | 6.82 | 2.27 |
| All Blood Volumes | All SBF Types | 425/424 | 0.71 | 0.47 |
Table 18: False Positive Rates in SBF
False Negative Rates (Instrument-negative, subculture-positive) in Blood
All inoculated paired sets (414 from the Recovery study + 205 from the Microbial Detection Limit study =619 paired sets) that were instrument negative at the end of default protocol (42 days) were subcultured onto appropriate culture media plates. This combined data set was evaluated for the false negative rates. A false negative is a vial that was instrument-negative at the end of protocol yet contains viable organisms upon subculturing onto appropriate culture media. A total of seven false negatives were identified from growth on sub-culture of terminal negatives. Four were Blastomyces dermatitidis across a range of inoculum levels and blood volumes, one in the predicate (glass) vial and three in the plastic vials. The remaining three were Mycobacterium bovis at the 0-1 CFU target inoculum with 5 mL blood, two in the predicate (glass) and one in the plastic vials. False negative rates for the predicate (glass) vial and plastic vial were low and comparable based on a rate of 0.48% (3/619) and 0.65% (4/619), respectively. The difference in false negative rates for Myco/F Lytic glass (predicate vial) and Myco/F Lytic plastic vial (test vial) were not statistically significant. The False Negative Rates for each vial type is presented in Table 19.
{21}------------------------------------------------
| Total LotPairs withBlood | Glass FalseNegative Rate withBlood | Plastic FalseNegative Rate withBlood | Plastic minus GlassFalse NegativeRates with Blood | Fisher's ExactTest |
|---|---|---|---|---|
| 619 | 0.48% (3/619) | 0.65% (4/619) | 0.17% | P = 1 |
False Negative Rates (Instrument-negative, subculture positive) in Sterile Body Fluid
All inoculated paired sets (132 from the Recovery study + 264 from the Microbial Detection Limit study =396 paired sets) that were instrument negative at the end of the default protocol (42 days) were subcultured onto appropriate culture media plates. This combined data set was evaluated for the false negative rates. A false negative is a vial that was instrument-negative at the end of protocol yet contains viable organisms upon subculturing onto appropriate culture media. A total of ten false negatives were identified from growth on sub-culture of terminal negatives. All ten false negatives were dimorphic fungi (9 were H. capsulatum and one Blastomyces dermatitidis) at the lower inoculum levels (0-1 or 1-10 CFU). False negative rates for the predicate (glass) vial and plastic vial were comparable based on a rate of 1.01% (4/396) and 1.52% (6/396), respectively. The difference in false negative rates for Myco/F Lytic glass (predicate vial) and Myco/F Lytic plastic vial) were not statistically significant. The False Negative Rates for each vial type is presented in Table 20.
Table 20: False Negative Rates in Sterile Body Fluid
| Total Lot Pairswith SBF | Glass FalseNegative Ratewith SBF | Plastic FalseNegative Ratewith SBF | Plastic minus GlassFalse Negative Rateswith SBF | Fisher's ExactTest |
|---|---|---|---|---|
| 396 | 1.01% (4/396) | 1.52% (6/396) | 0.51% | P = 0.7523 |
BD BACTEC Instrument Compatibility Study
The BD BACTEC instrument compatibility study evaluated three lots of BD BACTEC Myco/F Lytic Culture Vials (plastic) and three lots of BD BACTEC Myco/F Lytic Culture Vials (glass) using four of the BACTEC fluorescent instruments (FX, FX-40, 9240, and 9050). A total of 6 organisms (Mycobacterium tuberculosis, Mycobacterium fortuitum, Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus) were evaluated at three different blood volumes (1 mL, 3mL and 5mL) and one target inoculum concentration (10-100). The BACTEC instrument compatibility study Percent Recovery results are shown in Table 21 and the Time-To-Detection results are shown in Table 22.
Table 21: Summary of Instrument Compatibility Percent Recovery Results in Blood
| Blood(mL) | BACTECInstrument | PairedSets(N) | Recovery | Ratio of Positive Yields | ||||
|---|---|---|---|---|---|---|---|---|
| GlassNegatives | GlassPercentRecovery(%) | PlasticNegatives | PlasticPercentRecovery(%) | PerInstrument | Per BloodVolume | |||
| FX | 18 | 0 | 100 | 0 | 100 | 1.00 | ||
| FX-40 | 18 | 0 | 100 | 0 | 100 | 1.00 |
{22}------------------------------------------------
| 1 | 9240 | 18 | 0 | 100 | 0 | 100 | 1.00 | 1.00 |
|---|---|---|---|---|---|---|---|---|
| 9050 | 18 | 0 | 100 | 0 | 100 | 1.00 | ||
| 3 | FX | 18 | 0 | 100 | 0 | 100 | 1.00 | 1.00 |
| FX-40 | 18 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9240 | 18 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9050 | 18 | 0 | 100 | 0 | 100 | 1.00 | ||
| 5 | FX | 18 | 0 | 100 | 0 | 100 | 1.00 | 0.99 |
| FX-40 | 18 | 0 | 100 | 1 | 94.44 | 0.94 | ||
| 9240 | 17 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9050 | 18 | 0 | 100 | 0 | 100 | 1.00 |
Table 22: Summary of Instrument Compatibility TTD Results in Blood
| BACTECInstrument | PairedSets(N) | Glass Median TTD(95% CI) | Plastic Median TTD(95% CI) | Median of TTDdifferences (95% CI) |
|---|---|---|---|---|
| FX | 54 | 45.1 (36.61, 52.57) | 44.1 (36.10, 51.65) | -0.00 (-0.584, 0.999) |
| FX-40 | 53 | 50.6 (35.17, 53.62) | 50.1 (35.16, 53.06) | -0.00 (-0.011, -0.001) |
| 9240 | 53 | 49.0 (36.01, 53.05) | 48.0 (35.01, 53.05) | 0.00 (-1.000, 0.000) |
| 9050 | 54 | 49.7 (44.50, 52.33) | 50.8 (44.50, 57.50) | 0.00 (0.00, 0.916) |
The study demonstrated that the four instruments performed equivalently, and they are compatible with the BD BACTEC Myco/F Lytic culture medium in plastic vials.
BD BACTEC Instrument Compatibility Study with Sterile Body Fluids
The BD BACTEC instrument compatibility study evaluated three lots of BD BACTEC Myco/F Lytic Culture Vials (plastic) and three lots of BD BACTEC Myco/F Lytic Culture Vials (glass) using four of the BACTEC fluorescent instruments (FX, FX40, 9240, and 9050). A total of 4 organisms (Candida glabrata, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus) were evaluated at four different sterile body fluid volumes (0.5, 1 mL, 3mL and 5mL) and one target inoculum concentration (10-100). The BACTEC instrument compatibility study Percent Recovery results are shown in Table 23 and the Time-To-Detection results are shown in Table 24.
Table 23: Summary of Instrument Compatibility Percent Recovery Results in SBF
| PleuralFluidVolume(mL) | BACTECInstrument | N | Recovery | Ratio of Positive Yields | ||||
|---|---|---|---|---|---|---|---|---|
| GlassNegatives | GlassPercentRecovery(%) | PlasticNegatives | PlasticPercentRecovery(%) | PerInstrument | Per PleuralFluid Volume | |||
| 0.5 | FX | 12 | 0 | 100 | 0 | 100 | 1.00 | 1.00 |
| FX-40 | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9240 | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9050 | 12 | 0 | 100 | 0 | 100 | 1.00 |
{23}------------------------------------------------
| FX | 12 | 0 | 100 | 0 | 100 | 1.00 | 1.00 | |
|---|---|---|---|---|---|---|---|---|
| 1 | FX-40 | 12 | 0 | 100 | 0 | 100 | 1.00 | |
| 9240 | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9050 | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| FX | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| 3 | FX-40 | 12 | 0 | 100 | 0 | 100 | 1.00 | |
| 9240 | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9050 | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| FX | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| 5 | FX-40 | 12 | 0 | 100 | 0 | 100 | 1.00 | |
| 9240 | 12 | 0 | 100 | 0 | 100 | 1.00 | ||
| 9050 | 12 | 0 | 100 | 0 | 100 | 1.00 |
Table 24: Summary of Instrument Compatibility TTD Results in SBF
| BACTECInstrument | N | Glass Median dTTD(95% CI) | Plastic Median dTTD(95% CI) | Median of TTD differences(95% CI) |
|---|---|---|---|---|
| FX | 48 | 30.70(25.317, 38.066) | 30.18(25.321, 36.079) | -0.001(-1.001, -0.001) |
| FX-40 | 48 | 30.13(24.443, 38.200) | 29.14(24.674, 38.199) | -0.002(-1.001, -0.002) |
| 9240 | 48 | 30.50(23.003, 43.005) | 30.00(23.003, 38.005) | -1.000(-1.500, -1.000) |
| 9050 | 48 | 32.25(23.834, 53.167) | 32.25(23.822, 54.167) | 0.000(-1.000, 0.000) |
The study demonstrated that the four instruments performed equivalently, and they are compatible with the BD BACTEC Myco/F Lytic culture medium in plastic vials.
7. Matrix Comparison:
Testing with Blood
In seeded analytical studies, the performance of BD BACTEC Myco/F Lytic culture medium in plastic vial was compared to that in glass vial, with three human blood volumes, 8 mycobacteria, 10 yeasts and 5 dimorphic fungi across four fluorescent series instruments: BACTEC FX, FX40, BACTEC 9240, and BACTEC 9050.
Testing with Sterile Body Fluid (SBF)
In seeded analytical studies, the performance of BD BACTEC Myco/F Lytic culture medium in plastic vial was compared to that in glass vial, with four sterile body fluid volumes, 3 yeasts and 3 dimorphic fungi using the BD BACTEC fluorescent series instruments.
Clinical Studies: B
-
- Clinical Sensitivity:
Not applicable
- Clinical Sensitivity:
-
- Clinical Specificity:
{24}------------------------------------------------
Not applicable
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable
C Clinical Cut-Off:
Not applicable
D Expected Values/Reference Range:
Seeded analytical studies demonstrated equivalent performance of the BD BACTEC Myco/F Lytic (plastic) blood culture medium when compared to the BD BACTEC Myco/F Lytic (glass) blood culture medium.
VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
§ 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.