BD BACTEC Myco/F Lytic Culture Vials
Device Facts
| Record ID | K222559 |
|---|---|
| Device Name | BD BACTEC Myco/F Lytic Culture Vials |
| Applicant | Becton, Dickinson and Company |
| Product Code | MDB · Microbiology |
| Decision Date | Mar 24, 2023 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.2560 |
| Device Class | Class 1 |
Indications 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 yeast or fungi are suspected. The device aids in the diagnosis of disease caused by pathogenic microorganisms and is automated on the BD BACTEC fluorescent series instruments.
Device Story
BD BACTEC Myco/F Lytic Culture Vials (plastic) are nonselective liquid culture media for recovery of mycobacteria, yeast, and fungi from blood and sterile body fluids. Vials contain Middlebrook 7H9 and Brain Heart Infusion broth, saponin (lysing agent), ferric ammonium citrate, and nutritional supplements. Vials include an oxygen-sensitive fluorescent sensor. Inoculated vials are placed in BD BACTEC fluorescent series instruments (FX, FX40, 9240, 9050) for continuous agitation and incubation at 35°C. Instruments monitor oxygen decrease via fluorescence every 10 minutes. Positive results indicate presumptive presence of viable microorganisms. Used in clinical laboratories to aid diagnosis of pathogenic microbial infections. Output is instrument-flagged positive/negative status. Benefits include automated, rapid detection of slow-growing pathogens.
Clinical Evidence
Bench testing only. Seeded analytical studies compared plastic vials to predicate glass vials using 23 microorganisms (mycobacteria, yeast, filamentous/dimorphic fungi) in blood and sterile body fluids. Evaluated TTD, percent recovery, and false positive/negative rates across multiple blood/fluid volumes (0.5-7 mL) and instrument models. Results showed equivalent performance; no statistically significant differences in recovery or TTD. False positive rates for plastic vials were lower than glass in blood (0.70% vs 25.87%).
Technological Characteristics
Plastic vial containing Middlebrook 7H9 and Brain Heart Infusion broth, saponin, ferric ammonium citrate, and nutritional supplements. Employs oxygen-sensitive fluorescent sensor for microbial metabolism detection. Compatible with BD BACTEC fluorescent series instruments. Dimensions: 5.0 inches height, 21.5 grams. Nonsterile product.
Indications for Use
Indicated for qualitative culture and recovery of mycobacteria, yeast, and fungi from blood and sterile body fluids in adults. Used as an adjunct to aerobic blood culture media. Prescription use only.
Regulatory Classification
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.
Predicate Devices
Related Devices
- K970333 — BACTEC MYCO/F LYTIC CULTURE VIALS · Becton Dickinson Microbiology Systems · Jan 28, 1998
- K970512 — BACTEC MYCO/F LYTIC CULTURE VIALS · Becton Dickinson Microbiology Systems · Jan 8, 1998
- K083572 — BD BACTEC Plus Aerobic/F Culture Vials · Becton, Dickinson & CO · Dec 24, 2008
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K222559
B Applicant
Becton, Dickinson and Company
C Proprietary and Established Names
BD BACTEC Myco/F Lytic Culture Vials
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| MDB | Class I, reserved | 21 CFR 866.2560 - Microbial Growth Monitor | MI - Microbiology |
## II Submission/Device Overview:
A Purpose for Submission:
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 $\mathrm{O}_2$ 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 yeast 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 |
*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.
### B Principle of Operation:
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. A 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°C. 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:
A Predicate Device Name(s): BD BACTEC Myco/f Lytic Culture Vials
B Predicate 510(k) Number(s): K970333, K970512
C Comparison with Predicates
| Device & Predicate Device(s): | Device: K22 255 9 | Predicate: K970333, K970512 |
| --- | --- | --- |
| Device Trade Name | BD BACTEC Myco/F Lytic Culture Vial (plastic) | BD BACTEC Myco/F Lytic Culture Vial |
| General Device Characteristic Similarities | | |
| Regulation | 21 CFR § 866.2560 | Same |
| Product Code | MDB | Same |
| Classification | Class I | Same |
| Detection used | BD BACTEC™ Fluorescent instrument series | Same |
| Sample Source | Blood Culture, Sterile Body fluids | Same |
| Volume | 1 mL – 5.0 mL | Same |
| Protocol Length | 42 days for Mycobacteria 7 days for Yeast 30 days for Fungi | Same |
| Target population | Adult | Same |
| General Device Characteristic Differences | | |
| | BD BACTEC™ Myco/F Lytic culture medium when used with the BD BACTEC | |
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| Intended Use/Indications for Use | 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 yeast 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. | 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 recovery of mycobacteria, yeast and fungi from blood. This medium may also be used for the culture of sterile body fluids when 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 Entry Studies | 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:
1. **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.
2. Linearity:
Not applicable
3. Analytical Specificity/Interference:
Not applicable
4. Assay Reportable Range:
Not applicable
5. 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 Organism
ATCC® 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.
6. 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 3, Table 4, and Table 5, respectively.
Table 2: MDL Percent Recovery Results by Blood Volume for Mycobacteria with 0-1 and 1-10 CFU
| Organism | Blood Volume (mL) | Paired sets (N) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | | Per Organism and Blood Volume | Per Organism |
| Mycobacterium bovis ATCC 357241,2 | 1 | 6 | 100 | 83.33 | 0.83 | 1.07 |
| | 3 | 6 | 100 | 100 | 1.00 | |
| | 5 | 6 | 50.00 | 83.33 | 1.67 | |
| Mycobacterium tuberculosis ATCC 25177 | 1 | 6 | 100 | 100 | 1.00 | 1.00 |
| | 3 | 6 | 100 | 100 | 1.00 | |
| | 5 | 6 | 100 | 100 | 1.00 | |
| Mycobacterium tuberculosis TB007 | 1 | 6 | 100 | 100 | 1.00 | 1.00 |
| | 3 | 6 | 100 | 100 | 1.00 | |
| | 5 | 6 | 100 | 100 | 1.00 | |
| Mycobacterium abscessus ATCC 199771 | 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 | |
| Mycobacterium chimaera BR09092 | 1 | 6 | 83.33 | 33.33 | 0.40 | 0.73 |
| | 3 | 6 | 83.33 | 66.67 | 0.80 | |
| | 5 | 6 | 83.33 | 83.33 | 1.00 | |
| Mycobacterium fortuitum ATCC 68411,2 | 1 | 6 | 83.33 | 66.67 | 0.80 | 1.00 |
| | 3 | 6 | 16.67 | 50.00 | 3.00 | |
| | 5 | 6 | 50.00 | 33.33 | 0.66 | |
| Mycobacterium intracellulare ATCC 139502 | 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 | |
| Mycobacterium kansasii ATCC 124781,2 | 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 | |
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
| Organism | Blood Volume (mL) | Paired sets (N) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | | Per Organism and Blood Volume | Per Organism |
| Candida albicans ATCC 10231 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 50.00 | 50.00 | 1.00 | |
| | 5 | 6 | 50.00 | 50.00 | 1.00 | |
| Candida auris AR 0387 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 50.00 | 50.00 | 1.00 | |
| | 5 | 6 | 50.00 | 50.00 | 1.00 | |
| Candida glabrata ATCC 15545 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 50.00 | 50.00 | 1.00 | |
| | 5 | 6 | 50.00 | 50.00 | 1.00 | |
| Candida glabrata ATCC 66032 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 50.00 | 50.00 | 1.00 | |
| | 5 | 6 | 50.00 | 50.00 | 1.00 | |
| Candida krusei ATCC 34135 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 66.67 | 66.67 | 1.00 | |
| | 5 | 6 | 50.00 | 50.00 | 1.00 | |
| Candida parapsilosis ATCC 102321,2 | 1 | 6 | 50.00 | 66.67 | 1.33 | 1.00 |
| | 3 | 6 | 50.00 | 50.00 | 1.00 | |
| | 5 | 6 | 66.67 | 50.00 | 0.75 | |
| Candida tropicalis ATCC 750 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 50.00 | 50.00 | 1.00 | |
| | 5 | 6 | 50.00 | 50.00 | 1.00 | |
| Cryptococcus neoformans ATCC 13690 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 50.00 | 50.00 | 1.00 | |
| | 5 | 6 | 50.00 | 50.00 | 1.00 | |
| Malassezia furfur ATCC 14521 | 1 | 6 | 100 | 100 | 1.00 | 1.00 |
| | 3 | 6 | 100 | 100 | 1.00 | |
| | 5 | 6 | 100 | 100 | 1.00 | |
| Saccharomyces cerevisiae ATCC 901461,2 | 1 | 6 | 50.00 | 50.00 | 1.00 | 1.00 |
| | 3 | 6 | 50.00 | 33.33 | 0.67 | |
| | 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 | Blood Volume (mL) | Paired sets (N) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | | Per Organism and Blood Volume | Per Organism |
| Aspergillus fumigatus ATCC 13073 | 1 | 6 | 66.67 | 100 | 1.50 | 1.31 |
| | 3 | 6 | 100 | 100 | 1.00 | |
| | 5 | 6 | 50.00 | 83.33 | 1.67 | |
| Talaromyces marneffei ATCC 64101 | 1 | 6 | 100 | 100 | 1.00 | 0.94 |
| | 3 | 6 | 100 | 100 | 1.00 | |
| | 5 | 6 | 100 | 83.33 | 0.83 | |
| Rhizopus oryzae ATCC 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 | Blood Volume (mL) | Paired sets (N) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | | Per Organism and Blood Volume | Per Organism |
| Blastomyces dermatitidis ATCC 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 | |
| Histoplasma capsulatum ATCC 26032 | 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
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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 $5\mathrm{mL}$ ), 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 | SBF Type | Vial Type | N | Percent Recovery | Ratio of Positive Yields | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | | Per Condition | Per Organism |
| Aspergillus fumigatus ATCC 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% | | |
| | Synovial Fluid | Glass | 24 | 66.67% | 0.94 | |
| | | Plastic | 24 | 62.50% | | |
| Candida auris AR 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% | | |
| | Synovial Fluid | Glass | 24 | 75.00% | 1.00 | |
| | | Plastic | 24 | 75.00% | | |
| Cryptococcus neoformans ATCC 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% | | |
| | Synovial Fluid | Glass | 24 | 70.83% | 1.00 | |
| | | Plastic | 24 | 70.83% | | |
| | | Glass | 24 | 58.33% | | |
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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.
Table 7: Delayed Entry Summary (Plastic Bottle)
| Delay Time in Hours | Delay Temperature (°C) | Percent Recovery (%) | Median Instrument TTD in 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) |
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
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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 1 mL. 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.
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Table 8: Summary of TTD Study Results by Organism Group, Target Inoculum Levels, and Blood Volumes¹
| Organism Group | Inoculum Concentration (CFU/Vial) | Blood Volume (mL) | Median TTD for Glass (Predicate) (95% CI) [N] | Median TTD for Plastic (Modified) (95% CI) [N] | Median of TTD difference² (95% CI) [N] |
| --- | --- | --- | --- | --- | --- |
| Dimorphic Fungi | 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] |
| | 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] |
| | 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] |
| Filamentous Fungi | 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] |
| | 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] |
| | 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] |
| | 1-10 | 1 | 31.06 (30.123, 49.144) [29] | 30.24 (28.059, 52.146) [29] | -0.00 (-0.002, 0.999) [29] |
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| Organism Group | Inoculum Concentration (CFU/Vial) | Blood Volume (mL) | Median TTD for Glass (Predicate) (95% CI) [N] | Median TTD for Plastic (Modified) (95% CI) [N] | Median of TTD difference² (95% CI) [N] |
| --- | --- | --- | --- | --- | --- |
| | | 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] |
| | 10-100 | 1 | 26.27 (26.083, 38.140) [30] | 26.27 (26.086, 44.141) [30] | 0.00 (-0.001, 0.000) [30] |
| | | 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] |
| Mycobacteria | 0-1 | 1 | 638.20 (307.655, 674.177) [12] | 662.20 (297.150, 702.200) [12] | 8.50 (-16.002, 39.999) [12] |
| | | 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] |
| | 1-10 | 1 | 426.10 (250.133, 562.164) [23] | 450.10 (266.126, 578.141) [23] | 16.00 (2.999, 23.999) [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] |
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 $(0.5\mathrm{mL}, 1\mathrm{mL}, 3\mathrm{mL}$ and $5\mathrm{mL})$ 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
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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 Volumes ${}^{1}$
| Organism Group | Inoculum Concentration (CFU/Vial) | SBF Volume (mL) | Median TTD for Glass (95% CI) [N] | Median TTD for Plastic (95% CI) [N] | Median of TTD difference2 (95% CI) [N] |
| --- | --- | --- | --- | --- | --- |
| Dimorphic Fungi | 0-1 | 0.5 | No paired detections3 | No paired detections3 | N/A |
| | | 1 | No paired detections3 | No paired detections3 | N/A |
| | | 3 | No paired detections3 | No paired detections3 | N/A |
| | | 5 | Only 1 paired detection3 | Only 1 paired detection3 | 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] |
| Filamentous Fungi | 0-1 | 0.5 | Only 1 paired detection3 | Only 1 paired detection3 | 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] |
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| | | 5 | 62.05 (45.255, 59.064) [9] | 48.05 (46.061, 52.063) [9] | -3.00 (-13.001, 5.999) [9] |
| --- | --- | --- | --- | --- | --- |
| | 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] |
| Yeast | 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] |
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.
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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 | Blood Volume (mL) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) |
| --- | --- | --- | --- | --- |
| Mycobacterium bovis ATCC 35724 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Mycobacterium tuberculosis ATCC 25177 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Mycobacterium tuberculosis TB007 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Mycobacterium abscessus ATCC 19977 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Mycobacterium chimaera BR0909 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Mycobacterium fortuitum ATCC 6841 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Mycobacterium intracellulare ATCC 13950 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Mycobacterium kansasii ATCC 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 | Blood mL | Percent Recovery for Glass (%) | Percent Recovery for Plastic (%) | Ratio of Positive Yields (Plastic/Glass) |
| --- | --- | --- | --- | --- |
| Candida albicans ATCC 10231 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
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Table 12: Percent Recovery Study Results by Blood Volumes for Filamentous Fungi with 10-100 CFU in the FX
| Organism | Blood Volume (mL) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) |
| --- | --- | --- | --- | --- |
| Aspergillus fumigatus ATCC 13073 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Talaromyces marneffei ATCC 64101 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Rhizopus oryzae ATCC 66275 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
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Table 13: Percent Recovery Study Results by Blood Volume for Dimorphic Fugni with 10-100 CFU in the FX
| Organism | Blood Volume (mL) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) |
| --- | --- | --- | --- | --- |
| Blastomyces dermatitidis ATCC 18188 | 1 | 100 | 66.67 | 0.67 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Histoplasma capsulatum ATCC 26032 | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
Table 14: Percent Recovery (10-100 CFU/Vial) Summary
| 10-100 CFU with 1-5 mL blood in the FX | | Predicate (Glass) Vials | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| Plastic Vials | 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
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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.
Table 15: Percent Recovery Study Results by Organism for all SBF and SBF Volumes with 10-100 CFU in the FX
| Organism | SBF Volume (mL) | Percent Recovery for Glass (Predicate) (%) | Percent Recovery for Plastic (Modified) (%) | Ratio of Positive Yields (Plastic/Glass) |
| --- | --- | --- | --- | --- |
| Aspergillus fumigatus ATCC 13073 | 0.5 | 100 | 100 | 1.00 |
| | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Candida auris AR 0387 | 0.5 | 100 | 100 | 1.00 |
| | 1 | 100 | 100 | 1.00 |
| | 3 | 89^{1} | 100 | 1.13 |
| | 5 | 100 | 100 | 1.00 |
| Cryptococcus neoformans ATCC 13690 | 0.5 | 100 | 100 | 1.00 |
| | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Blastomyces dermatitidis ATCC 18188 | 0.5 | 100 | 100 | 1.00 |
| | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
| Histoplasma capsulatum ATCC 26032 | 0.5 | 100 | 100 | 1.00 |
| | 1 | 100 | 100 | 1.00 |
| | 3 | 100 | 100 | 1.00 |
| | 5 | 100 | 100 | 1.00 |
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 mL SBF in the FX | | Predicate (Glass) Vials | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| Plastic Vials | 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 | |
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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 7 mL 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.
Table 17: False Positive Rates in Blood
| Fresh Blood Volume (mL) | Number of Vials | False Positive Rate for Glass (Predicate) (%) | False Positive Rate for Plastic (Modified) |
| --- | --- | --- | --- |
| 1 | 48 | 0 | 0 |
| 5 | 48 | 4.17 | 0 |
| 7 | 47 | 74.47 | 2.13 |
| All Blood Volumes | 143 | 25.87 | 0.70 |
## 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.
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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.
Table 18: False Positive Rates in SBF
| Fresh Blood Volume (mL) | SBF Type | Number of Vials (Glass/Plastic) | False Positive Rate for Glass (Predicate) (%) | False Positive Rate for Plastic (Modified) (%) |
| --- | --- | --- | --- | --- |
| 1 | CSF | 47/48 | 0 | 0 |
| | Pleural Fluid | 48/48 | 0 | 0 |
| | Synovial Fluid | 48/48 | 0 | 0 |
| 5 | CSF | 48/48 | 0 | 0 |
| | Pleural Fluid | 48/48 | 0 | 0 |
| | Synovial Fluid | 46/44 | 0 | 2.27 |
| 7 | CSF | 48/48 | 0 | 0 |
| | Pleural Fluid | 48/48 | 0 | 0 |
| | Synovial Fluid | 44/44 | 6.82 | 2.27 |
| All Blood Volumes | All SBF Types | 425/424 | 0.71 | 0.47 |
# 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.
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Table 19: False Negative Rates in Blood
| Total Lot Pairs with Blood | Glass False Negative Rate with Blood | Plastic False Negative Rate with Blood | Plastic minus Glass False Negative Rates with Blood | Fisher's Exact Test |
| --- | --- | --- | --- | --- |
| 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 (test 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 Pairs with SBF | Glass False Negative Rate with SBF | Plastic False Negative Rate with SBF | Plastic minus Glass False Negative Rates with SBF | Fisher's Exact Test |
| --- | --- | --- | --- | --- |
| 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) | BACTEC Instrument | Paired Sets (N) | Recovery | | | | Ratio of Positive Yields | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Glass Negatives | Glass Percent Recovery (%) | Plastic Negatives | Plastic Percent Recovery (%) | Per Instrument | Per Blood Volume |
| | FX | 18 | 0 | 100 | 0 | 100 | 1.00 | |
| | FX-40 | 18 | 0 | 100 | 0 | 100 | 1.00 | |
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Table 22: Summary of Instrument Compatibility TTD Results in Blood
| BACTEC Instrument | Paired Sets (N) | Glass Median TTD (95% CI) | Plastic Median TTD (95% CI) | Median of TTD differences (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, 3 mL and 5 mL) 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
| Pleural Fluid Volume (mL) | BACTEC Instrument | N | Recovery | | | | Ratio of Positive Yields | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Glass Negatives | Glass Percent Recovery (%) | Plastic Negatives | Plastic Percent Recovery (%) | Per Instrument | Per Pleural Fluid 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 | |
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Table 24: Summary of Instrument Compatibility TTD Results in SBF
| BACTEC Instrument | 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.
B Clinical Studies:
1. Clinical Sensitivity:
Not applicable
2. Clinical Specificity:
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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.
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