(53 days)
MYCO/F-Sputa culture media BACTEC Supplement /F when used with the BACTEC Brand 9000MB fluorescent series instrument is a qualitative procedure for the in vitro culture and recovery of mycobacteria from digested decontaminated clinical specimens and sterile body fluids other than blood.
MYCO/F-Sputa culture media with the addition of BACTEC Supplement/F when used with the BACTEC Brand 9000MB fluorescent series instrument is a qualitative test for the in-vitro culture and recovery of mycobacteria from digested decontaminated clinical specimens and sterile body fluids other than blood from patients suspected of pulmonary or disseminated mycobacterial infection.
BACTEC® MYCO/F-Sputa Culture Vials containing 7H9 Middlebrook broth base with nutrient additives and antimicrobial supplement (Polymyxin B, amphotericin B, nalidixic acid, trimethoprim & azlocillin (PANTA)). Growth detection is by fluorescent detection of O₂ consumption by mycobacterial growth using the BACTEC® 9000MB automated system.
Here's the analysis of the provided text regarding the BACTEC® MYCO/F-Sputa Culture Vials, structured according to your request:
Acceptance Criteria and Study Performance for BACTEC® MYCO/F-Sputa Culture Vials
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by comparing the new device against two predicate devices: BACTEC 12B Culture Vials (using the BACTEC 460TB system) and Conventional Media (Lowenstein-Jensen agar slants). The study aims to demonstrate "equivalence of mycobacterial growth detection methods".
| Acceptance Criterion (Implicit) | Predicate 1: BACTEC 460TB System | Predicate 2: Conventional Media (Lowenstein-Jensen) | BACTEC® MYCO/F-Sputa Culture Vials Performance | Device Meets Criterion? |
|---|---|---|---|---|
| Time to Detection (Overall All Isolates) | 13.3 days | 24.3 days | 12.2 days | Yes (No significant difference vs. BACTEC 460TB, statistically significantly faster than Conventional Media) |
| Time to Detection (MTB Complex) | 17.2 days | 22.1 days | 18.4 days | Yes |
| Time to Detection (M Avium Complex) | 10.2 days | 28.3 days | 7.9 days | Yes |
| Mycobacterial Recovery (Pathogenic Isolates) | 30 (78.9%) of 38 total | 24 (63.2%) of 38 total | 29 (76.3%) of 38 total | Yes (No statistical difference vs. either predicate) |
| Combined Recovery (New Device + Conventional Media) | Not applicable | Not applicable | 89.5% of total pathogenic isolates | N/A (reported, but not a direct comparison for equivalence) |
| False Positive Rate | Not explicitly stated for predicates, but generally accepted to be low for equivalent predicate systems | Not explicitly stated, but generally accepted to be low for equivalent predicate systems | 5.0% (Overall for the BACTEC 9000MB system) | Yes (Reported, and context implies acceptance despite variation from respiratory specimens) |
| Breakthrough Contamination Rate (Norm. Sterile Specimens) | Not explicitly stated for predicates | Not explicitly stated for predicates | 4.7% - 18.9% | Yes (Reported, acceptance implied through clearance) |
| Breakthrough Contamination Rate (Non-sterile Specimens) | Not explicitly stated for predicates | Not explicitly stated for predicates | 8.2% - 73.9% | Yes (Reported, acceptance implied through clearance) |
| Overall Breakthrough Contamination Rate | Not explicitly stated for predicates | Not explicitly stated for predicates | 14.9% | Yes (Reported, acceptance implied through clearance) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Time to Detection Study: The document mentions "Paired t-tests were performed to compare time to detection...". It does not explicitly state the total number of positive cultures included in these specific analyses, but it does provide overall average detection times.
- Recovery Performance Study: 803 non-respiratory specimens were tested. From these, 38 pathogenic mycobacteria positive isolates were recovered.
- Data Provenance: The recovery performance study was conducted "at a large tertiary care teaching hospital". This suggests a real-world clinical setting. The document does not specify the country of origin, but given the FDA 510(k) submission, it is highly likely to be U.S.-based. The study appears to be prospective in nature, as it describes a controlled comparison of testing methods on collected specimens.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not specify the number of experts or their qualifications for establishing the ground truth. However, for mycobacterial culture and identification, ground truth is typically established by:
- Standard microbiological culture techniques and subsequent identification methods (e.g., biochemical tests, genetic probes).
- Clinician's diagnosis and patient outcomes.
Given the context of an in vitro diagnostic device for culture and recovery, the "ground truth" for recovery and time to detection would be based on the established gold standard methods for mycobacterial identification. It's implied that the results from the predicate devices (BACTEC 460TB and Conventional Media) served as reference points or "ground truth comparators" for the new device.
4. Adjudication Method for the Test Set
The document does not describe a formal "adjudication method" in the sense of multiple independent reviewers resolving discrepancies. The comparison is between the performance metrics of the BACTEC MYCO/F-Sputa culture vials and the predicate devices (BACTEC 12B and Conventional Media). Statistical tests (paired t-tests and McNemar's paired comparison) were used to determine the significance of observed differences, which is a form of objective comparison rather than expert adjudication of individual case disagreement.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Readers Improvement with AI vs. Without AI Assistance
This question is not applicable. The device described (BACTEC® MYCO/F-Sputa Culture Vials) is an in vitro diagnostic device for laboratory use to detect microbial growth. It is not an AI-assisted diagnostic tool that directly aids human readers in interpreting medical images or other complex data. Therefore, an MRMC study and effects on human reader performance with AI assistance are outside the scope of this device.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies described are essentially "standalone" performance evaluations of the device. The BACTEC® 9000MB system automates the incubation, agitation, and fluorescent detection of oxygen consumption, indicating mycobacterial growth. The reported time to detection and recovery rates are inherent to the device and system, operating without direct human interpretation of a reading (other than setting up the culture and interpreting the system's output). The "human-in-the-loop" component primarily involves collecting and processing the specimen, loading it into the system, and then acting on the system's results.
7. The Type of Ground Truth Used
The ground truth used for these studies is based on:
- Microbial Culture and Identification: The actual recovery and identification of mycobacteria from clinical specimens by established laboratory methods, including conventional culture and the predicate BACTEC 12B system. The "total pathogenic mycobacteria positive isolates" (38 cases) serves as the reference for recovery studies. The time until growth is detected by these established methods serves as the ground truth for time to detection.
8. The Sample Size for the Training Set
The document does not explicitly state a sample size for a "training set." This is because the BACTEC® MYCO/F-Sputa Culture Vials are a culture medium used with an instrument, not a machine learning or AI algorithm that requires a distinct training phase. The development of the medium and the BACTEC 9000MB system would have involved extensive R&D, but not a "training set" in the context of AI. The described studies are performance validation studies.
9. How the Ground Truth for the Training Set Was Established
As there is no distinct "training set" in the AI sense for this type of device, this question is not applicable. The development of the culture medium would have been guided by traditional microbiological principles and established methods for optimizing microbial growth and detection.
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AUG - 8 1997
June 13, 1997
SUMMARY OF SAFETY AND EFFECTIVENESS
SUBMITTED BY:
Colleen A. Rohrbeck Becton Dickinson Microbiology Systems 250 Schilling Circle Cockeysville, MD 21030-0243
NAME OF DEVICE:
Trade Name:
Common Name:
Microbial Growth Monitor
BACTEC® MYCO/F-Sputa Culture Vials
PREDICATE DEVICES:
BACTEC® 460TB System Conventional Media
INTENDED USE:
MYCO/F-Sputa culture media BACTEC Supplement /F when used with the BACTEC Brand 9000MB fluorescent series instrument is a qualitative procedure for the in vitro culture and recovery of mycobacteria from digested decontaminated clinical specimens and sterile body fluids other than blood.
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DEVICE COMPARISON:
The BACTEC® MYCO/F-Sputa culture vials will be compared to the BACTEC 12B culture vials and conventional medium (Lowenstein-Jensen agar slants) for purposes of evaluating equivalence of mycobacterial growth detection methods in non-respiratory specimens.
| BACTEC MYCO/F-SputaCulture Vials | BACTEC 12 BCulture Vials | |
|---|---|---|
| Intended Use | Qualitative culture andrecovery of mycobacteria fromclinical specimens | Qualitative culture andrecovery of mycobacteriafrom clinical specimens |
| Sample type | Sterile body fluids other thanblood and digesteddecontaminated clinicalspecimens | Clinical specimens,sputum, gastric, urine,tissue, mucopurulentspecimens, other bodyfluids and otherrespiratory secretions |
| Sample volume | 0.5mL | 0.5 - 1.0 mL |
| Growth medium | 7H9 Middlebrook broth basewith nutrient additives | Enriched 7H9Middlebrook broth base |
| Reactive IngredientConcentration | ||
| Processed Water7H9 Broth BaseCasein HydrolysateSupplement H*GlycerolAmmonium SulfateFerric Ammonium CitratePolysorbate 80HeminBovine Serum AlbuminCatalase14C-substrate | 40 ml0.47% w/v0.10% w/v0.30% w/v0.10% w/v0.05% w/v0.006% w/v0.0025% w/v0.0005% w/v--------- | 4 ml4.7 g/L1.0g/L------------------5.0g/L48,000 units/L1,000 $\mu$ Ci/L |
| Table 1: | BACTEC MYCO/F-Sputa Culture Vials versus BACTEC 12B Culture Vial |
|---|---|
| ---------- | ------------------------------------------------------------------ |
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| BACTEC MYCO/F-SputaCulture Vials | BACTEC 12 BCulture Vials | |
|---|---|---|
| Antimicrobial Supplement | Polymyxin B, amphotericin B,nalidixic acid, trimethoprim &azlocillin (PANTA) | Polymyxin B,amphotericin B, nalidixicacid, trimethoprim &azlocillin (PANTA) |
| Growth Detection | Fluorescent detection of O₂consumption by mycobacterialgrowth | Radiometric detection ofCO₂ liberated bymycobacterial growth |
| Incubation temperature/mixing | On-board incubation at 37°C±1.5°C; internal instrumentagitation every 10 minutes | External incubation at37°C ± 1.0°C. Noagitation in instrument |
| Automated System Usedfor Detection | BACTEC® 9000MB | BACTEC® 460TB |
- L-asparagine
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Device Comparison (cont.)
| Table 2: | |||
|---|---|---|---|
| -- | -- | -- | ---------- |
| BACTEC MYCO/F-SputaCulture Media | CONVENTIONALMEDIUM¹ | |
|---|---|---|
| Intended Use | Qualitative culture andrecovery of mycobacteria fromclinical specimens | Qualitative culture andrecovery of mycobacteriafrom clinical specimens |
| Sample type | Sterile body fluids other thanblood and digesteddecontaminated clinicalspecimens | Primary specimens type -respiratory; other bodyfluids (including blood)acceptable |
| Sample volume | 0.5mL | 0.1 - 0.5 mL |
| Growth medium | 7H9 Middlebrook broth basewith nutrient additives | Lowenstein-Jensenmedium; Egg enrichedagar base with nutrientadditives |
| Reactive IngredientConcentration | ||
| Processed Water | 40 ml | 8 ml |
| 7H9 Broth Base | 0.47% w/v | --- |
| Casein Hydrolysate | 0.10% w/v | --- |
| Supplement H* | 0.30% w/v | 0.22% w/v |
| Glycerol | 0.10% w/v | 0.74% v/v |
| Ammonium Sulfate | 0.05% w/v | --- |
| Ferric Ammonium Citrate | 0.006% w/v | --- |
| Polysorbate 80 | 0.0025% w/v | --- |
| Hemin | 0.0005% w/v | --- |
| Monopotassium Phosphate | --- | 0.15% w/v |
| Magnesium Sulfate | --- | 0.014% w/v |
| Sodium Citrate | --- | 0.037% w/v |
| Potato Flour | --- | 1.86% w/v |
| Whole Egg | --- | 62% v/v |
| Malachite Green | --- | 0.024% w/v |
| Antimicrobial Supplement | Polymyxin B, amphotericin B,nalidixic acid, trimethoprim &azlocillin (PANTA) | None |
:
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| BACTEC MYCO/F-SputaCulture Media | CONVENTIONALMEDIUM1 | |
|---|---|---|
| Growth Detection | Fluorescent detection of O2consumption by mycobacterialgrowth | Macroscopic observanceof growth of media surface |
| Incubation temperaturemixing | On-board incubation at 37°C$\pm$ 1.5°C; internal instrumentagitation every 10 minutes | 35°C to 38°C2Manual manipulation ofmedia |
| Automated System Usedfor Detection | BACTEC® 9000MB | None Required |
1- CONVENTIONAL MEDIA - Lowenstein-Jensen agar slants
2- CDC recommendations
- L-asparagine
TIME TO DETECTION:
Table 3 shows the overall average times to detection of positive mycobacterial cultures for the BACTEC® MYCO/F-Sputa culture vials, BACTEC 12B culture vials, and conventional media.
| Table 3: | Overall Average Times to Detection for Non-Respiratory Specimens |
|---|---|
| ---------- | ------------------------------------------------------------------ |
| ISOLATE GROUP | BACTEC 9000MB | BACTEC 460TB | CONVENTIONAL LJ |
|---|---|---|---|
| ALL MYCOBACTERIALISOLATES | 12.2 days | 13.3 days | 24.3 days |
| MTB COMPLEX | 18.4 days | 17.2 days | 22.1 days |
| M AVIUM COMPLEX | 7.9 days | 10.2 days | 28.3 days |
Paired t-tests were performed to compare time to detection in the BACTEC MYCO/F-Sputa culture vials to each of the reference systems, BACTEC 460TB and conventional media (Lowenstein-Jensen), for digested decontaminated clinical specimens and sterile body fluids other than blood. Both tests were performed at the 5% significance level.
No significant difference in time to detection was seen between the BACTEC MYCO/F-Sputa culture vials and the BACTEC 460TB system. A statistically significant difference in time to detection was seen between the BACTEC MYCO/F-Sputa culture vials and conventional media.
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RECOVERY PERFORMANCE:
In a separate study at a large tertiary care teaching hospital. 803 non-respiratory specimens were tested with the BACTEC MYCO/F-Sputa culture medium, BACTEC 12B culture medium, and conventional medium (Lowenstein-Jensen). The total number of pathogenic mycobacteria positive isolates recovered in the study was 38. Of these positive isolates, the BACTEC 9000MB system recovered 29 (76.3%), 30 (78.9%) were recovered in the BACTEC 460TB system, and 24 (63.2%) were recovered by conventional medium (Lowenstein-Jensen). The BACTEC 9000MB system and solid media combined recovered 89.5% of the total pathogenic isolates. Total positive specimens (pathogenic and non-pathogenic mycobacteria) were distributed among the following sources: gastric (5.1%), sterile body fluids other than blood (17.9%), stool (10.3%), superficial skin/wound drainage (5.1%), tissue (53.8%), and urine (7.7%). The following isolates were detected as positive in the BACTEC 9000MB system using MYCO/F-Sputa during this clinical trial: M. tuberculosis, M. avium complex, M. chelonae, M. fortuitum, and M. bovis.
A McNemar's paired comparison (modified chi-square test) was conducted to determine the significance of differences in total recovery between BACTEC MYCO/F-Sputa culture vials and the BACTEC 460TB system, as well as between the BACTEC MYCO/F-Sputa culture vials and conventional (Lowenstein Jensen) media. Both tests were performed at the 5% significance level.
No statistical difference in recovery was seen between the BACTEC MYCO/F-Sputa culture vials and the BACTEC 460TB system. No statistical difference in recovery was seen between the BACTEC MYCO/F-Sputa culture vials and conventional media. Therefore, recovery of mycobacteria from digested decontaminated clinical specimens and sterile body fluids other than blood was not found to be different in the BACTEC MYCO/F-Sputa culture vials when compared to either the BACTEC 460TB system or conventional media.
The overall false positive rate (instrument-positive, smear and/or subculture negative) was 5.0%. Due to the variety of specimens collected and tested. the false positive rate varied significantly from the rate previously reported for respiratory specimens.
The breakthrough contamination rate for normally sterile specimens (i.e. tissue and sterile body fluids other than blood) ranged from 4.7% - 18.9%; non-sterile specimens (i.e. gastric, stool, urine, superficial skin/wound drainage) ranged from 8.2% - 73.9%. The overall breakthrough contamination rate was 14.9%.
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Image /page/6/Picture/0 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of an eagle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Colleen Rohrbeck Regulatory Affairs Associate Becton Dickinson Microbiology Systems 250 Schilling Circle Cockeysville, Maryland 21030-0243 ······
AUG - 8 1997
Re : K972758 Trade Name: BACTEC® MYCO/F-Sputa Culture Vials Requlatory Class: I Product Code: MDB Dated: June 13, 1997 Received: June 16, 1997
Dear Ms. Rohrbeck:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Flease note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.
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Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INDICATIONS STATEMENT
K940268 K972758 510(k) Number (if known):
Device Name:
-- BACTEC® MYCO/F - Sputa Culture Vials -----
Indications for Use:
MYCO/F-Sputa culture media with the addition of BACTEC Supplement/F when used with the BACTEC Brand 9000MB fluorescent series instrument is a qualitative test for the in-vitro culture and recovery of mycobacteria from digested decontaminated clinical specimens and sterile body fluids other than blood from patients suspected of pulmonary or disseminated mycobacterial infection.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Re Ps
(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number
510(k) Number
K972758
Prescription Use
(Per 21 CFR 801.109)
OR
Over-the-Counter-Use
A;\indicat.stm
§ 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.