(90 days)
Not Found
No
The device description and performance studies focus on the physical properties of the disc and traditional AST methods, with no mention of AI/ML.
No
The device is an in vitro diagnostic (IVD) test used to determine the susceptibility of bacteria to an antimicrobial agent, rather than a device for directly treating a condition or disease in a patient.
Yes
This device is used for in vitro susceptibility testing to determine if specific bacteria are susceptible to Lefamulin, which is a diagnostic purpose to guide treatment decisions.
No
The device description clearly states it is a physical disc made of absorbent paper impregnated with a drug, and it is used in a semi-quantitative agar diffusion test method. This is a hardware component, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is used for "in vitro susceptibility testing." This is a key characteristic of an IVD, as it's used to test samples outside of the body to provide information about a patient's health or condition.
- Device Description: The description details a physical product (discs impregnated with a substance) used in a laboratory setting for testing.
- Performance Studies: The document describes clinical and challenge testing performed on bacterial isolates, which are samples tested in vitro. The results are presented in terms of "Category Agreement," "major errors," and "very major errors," which are metrics relevant to the performance of an IVD in determining antimicrobial susceptibility.
- Predicate Device: The mention of a "Predicate Device" (HardyDisk AST Lefamulin 20μg (LMU20)) with a K number (K192326) indicates that this device is being compared to another legally marketed IVD.
The entire context of the document points to this device being used in a laboratory setting to perform diagnostic testing on biological samples (bacterial isolates) to determine their susceptibility to an antimicrobial agent. This aligns perfectly with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
BD BBL Sensi-Disc Antimicrobial Susceptibility Test (AST) Discs are used in the semi-quantitative agar diffusion test method for in vitro susceptibility testing.
BD BBL Sensi-Disc Lefamulin Disc 20 µg (LMU-20) can be used to determine susceptibility to Lefamulin against the following bacteria, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in Clinical Infections Against:
Gram-positive Bacteria Streptococcus pneumoniae Staphylococcus aureus (methicillin-susceptible isolates)
Gram-negative Bacteria Haemophilus influenzae
Product codes
JTN
Device Description
The BD BBL Sensi-Disc Lefamulin 20 µg (LMU-20) device is a 6 mm disc prepared by impregnating high quality absorbent paper with accurately determined amounts of Lefamulin. Discs are clearly marked on both sides with the code LMU-20. The code designates the agent Lefamulin (LMU) and the drug content (20 ug).
BD BBL Sensi-Disc Antimicrobial Susceptibility Test Discs are furnished in cartridges containing 50 discs each. The last disc in each cartridge is marked "X" and contains the drug as coded. BD BBL Sensi-Disc Antimicrobial Susceptibility Test Discs can be dispensed using a BD BBL Sensi-Disc Dispenser.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Study Type: Analytical Performance - Precision/Reproducibility
Sample Size: 15 organisms (5 Haemophilus influenzae, 5 Staphylococcus aureus, 5 Streptococcus pneumoniae) tested in triplicate with two disc lots on three separate days, read by three independent readers. Total 270 data points for evaluation.
Key Results: Reproducibility performance between disc lots and across readers is >95% (100% for between disc lots, 98.89% for across readers) and meets the acceptance criteria.
Study Type: Analytical Performance - Quality Control (QC) Testing
Sample Size: CLSI-recommended QC isolates: Haemophilus influenzae (ATCC 49247), Staphylococcus aureus (ATCC 25923), and Streptococcus pneumoniae (ATCC 49619). Tested a minimum of 20 replicates per lot per reader. One Comparator disk lot and two BD disc lots were used. Visually read by three independent readers. Total 129 data points for BD lots (69 for Lot A, 60 for Lot B) and 69 for Comparator disk.
Key Results: The BD disc QC performance is > 95% and is acceptable.
Study Type: Analytical Performance - Inoculum Density Check
Sample Size: All QC and reproducibility isolates, as well as 14.0% of clinical isolates.
Key Results: All were within the expected range.
Study Type: Method Comparison with Predicate Device - Clinical Testing
Sample Size: 270 clinical isolates (90 Haemophilus influenzae, 90 Staphylococcus aureus (methicillin-susceptible isolates), and 90 Streptococcus pneumoniae).
Key Results:
- Haemophilus influenzae: 98.9% CA (89/90)
- Staphylococcus aureus (methicillin-susceptible isolates): 100.0% CA (90/90)
- Streptococcus pneumoniae: 98.9% CA (89/90)
- Overall Clinical: 99.3% CA (268/270)
Study Type: Method Comparison with Predicate Device - Challenge Testing
Sample Size: 66 challenge isolates (22 Haemophilus influenzae, 22 Staphylococcus aureus (methicillin-susceptible isolates), and 22 Streptococcus pneumoniae).
Key Results:
- Haemophilus influenzae: 86.4% CA (19/22)
- Staphylococcus aureus (methicillin-susceptible isolates): 100.0% CA (22/22)
- Streptococcus pneumoniae: 100.0% CA (22/22)
- Overall Challenge: 95.5% CA (63/66)
Study Type: Method Comparison with Predicate Device - Combined Clinical and Challenge
Sample Size: 336 total isolates.
Key Results:
- Overall Combined: 98.5% CA (331/336).
- Haemophilus influenzae: 96.4% CA (108/112), with 3 very major errors and 1 major error.
- Staphylococcus aureus (methicillin-susceptible isolates): 100.0% CA (112/112), with no very major or major errors.
- Streptococcus pneumoniae: 99.1% CA (111/112), with 1 very major error and no major errors.
- The adjusted potential VMJ error rate is 0%.
- A limitation was added to labeling due to insufficient resistant isolates: "The current absence of resistant isolates precludes defining any results other than "Susceptible." Isolates yielding results other than "Susceptible" should be submitted to a reference laboratory for further testing."
Key Metrics
- Reproducibility: >95%
- Quality Control (QC) performance: >95%
- Category Agreement (CA):
- Clinical: 99.3% (268/270)
- Challenge: 95.5% (63/66)
- Combined: 98.5% (331/336)
- Very Major Errors (VMJ):
- Haemophilus influenzae Combined: 3
- Streptococcus pneumoniae Combined: 1
- Overall Combined: 4 (adjusted potential VMJ error rate is 0%)
- Major Errors (MAJ):
- Haemophilus influenzae Combined: 1
- Overall Combined: 1
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
This submission included a breakpoint change protocol that was reviewed and accepted by FDA. This protocol addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/drugs/developmentresources/antibacterial-susceptibility-test-interpretive-criteria). The protocol outlined the specific procedures and acceptance criteria that Becton, Dickinson, and Company (BD Diagnostic Systems) intends to use to evaluate the BD BBL Sensi-Disc Lefamulin 20ug (LMU-20) when revised breakpoints for Lefamulin are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, BD Diagnostic Systems will update the Lefamulin 20ug device label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation.
§ 866.1620 Antimicrobial susceptibility test disc.
(a)
Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).
0
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June 7, 2023
Becton, Dickinson and Company Katherine Cicala Regulatory Affairs Specialist 7 Loveton Circle Sparks, Maryland 21152-0999
Re: K230651
Trade/Device Name: BD BBL Sensi-Disc Lefamulin 20μg (LMU-20) Regulation Number: 21 CFR 866.1620 Regulation Name: Antimicrobial Susceptibility Test Disc Regulatory Class: Class II Product Code: JTN Dated: March 8, 2023 Received: March 9, 2023
Dear Katherine Cicala:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar -S
Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K230651
Device Name BD BBL Sensi-Disc Lefamulin 20ug (LMU-20)
Indications for Use (Describe)
BD BBL Sensi-Disc Antimicrobial Susceptibility Test (AST) Discs are used in the semi-quantitative agar diffusion test method for in vitro susceptibility testing.
BD BBL Sensi-Disc Lefamulin Disc 20 µg (LMU-20) can be used to determine susceptibility to Lefamulin against the following bacteria, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in Clinical Infections Against: Gram-positive Bacteria Streptococcus pneumoniae Staphylococcus aureus (methicillin-susceptible isolates)
Gram-negative Bacteria Haemophilus influenzae
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) Summary
Summary Preparation Date: June 06, 2023
I Background Information
A 510(k) Number
B Applicant
BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, Maryland 21152 Establishment Registration Number: 1119779
C Proprietary and Established Name
BD BBL Sensi-Disc Lefamulin 20 ug (LMU-20)
D Regulatory Information
| Product Code | Classification | Regulation Section | Panel |
|---|---|---|---|
| JTN | Class II | 21 CFR 866.1620 - | |
| Antimicrobial Susceptibility | |||
| Test Disc | MI - Microbiology |
II Submission/Device Overview:
A Purpose for Submission:
To obtain substantial equivalence determination for Lefamulin Antimicrobial Susceptibility Test Disc.
B Measurand:
Lefamulin Disc 20 µg (LMU-20)
C Type of Test:
Antimicrobial Susceptibility Test Disc
III Intended Use/Indications for Use:
A Intended Use(s):
See Indications for Use below.
4
B Indication(s) for Use:
BD BBL Sensi-Disc Antimicrobial Susceptibility Test (AST) Discs are used in the semiquantitative agar diffusion test method for in vitro susceptibility testing.
BD BBL Sensi-Disc Lefamulin Disc 20 µg (LMU-20) can be used to determine susceptibility to Lefamulin against the following bacteria, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in Clinical Infections Against:
Gram-positive Bacteria Streptococcus pneumoniae Staphylococcus aureus (methicillin-susceptible isolates)
Gram-negative Bacteria Haemophilus influenzae
C Special Conditions for Use Statement(s):
- . Rx - For Prescription Use Only
- Per the FDA-Recognized Susceptibility Test Interpretive Criteria website, the safety and . efficacy of antimicrobial drugs, for which antimicrobial susceptibility is tested by this AST device, may or may not have been established in adequate and well-controlled clinical trials for treating clinical infections due to microorganisms outside of those found in the indications and usage in the drug label. The clinical significance of susceptibility information in those instances is unknown. The approved labeling for specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved.
- Limitations
- The current absence of resistant isolates precludes defining any results other than ● "Susceptible." Isolates yielding results other than "Susceptible" should be submitted to a reference laboratory for further testing.
D Special Instrument Requirements:
Not applicable.
IV Device/System Characteristics:
A Device Description:
The BD BBL Sensi-Disc Lefamulin 20 µg (LMU-20) device is a 6 mm disc prepared by impregnating high quality absorbent paper with accurately determined amounts of Lefamulin. Discs are clearly marked on both sides with the code LMU-20. The code designates the agent Lefamulin (LMU) and the drug content (20 ug).
BD BBL Sensi-Disc Antimicrobial Susceptibility Test Discs are furnished in cartridges containing 50 discs each. The last disc in each cartridge is marked "X" and contains the drug as coded. BD BBL Sensi-Disc Antimicrobial Susceptibility Test Discs can be dispensed using a BD BBL Sensi-Disc Dispenser.
5
B Principle of Operation:
A suitable therapeutic agent can be determined using filter paper discs impregnated with specified concentrations of antimicrobial agents placed on the surface of a suitable test medium. The test is performed by inoculating pure cultures of clinical isolates onto the test medium and placing the AST disc on the surface of the medium. The antibiotic within the disc diffuses into the agar. After incubation, the zones of inhibition around the discs are measured and compared against recognized zone diameter ranges for the specific antimicrobial agent/organism combinations being tested.
V Substantial Equivalence Information:
A Predicate Device Name:
HardyDisk AST Lefamulin 20μg (LMU20)
B Predicate 510(k) Number:
C Comparison with Predicate:
| Device &
Predicate Device: | Device:
K230651 | Predicate:
K192326 |
|-------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Trade | BD BBL Sensi-Disc Lefamulin | HardyDisk AST Lefamulin 20 |
| Name | 20 µg (LMU-20) | ug (LMU20) |
| | General Device Characteristic Similarities | |
| Regulation | 866.1620 | Same |
| Product Code | JTN | Same |
| Intended Use | See Indications for Use below. | HardyDisk AST Disks are used
for semi-quantitative in vitro
susceptibility testing by the agar
diffusion test procedure (Kirby-
Bauer) of rapidly growing and
certain fastidious bacterial
pathogens. Standardized methods
for agar diffusion testing have
been described for
Enterobacteriaceae,
Staphylococcus spp.,
Pseudomonas spp.,
Acinetobacter spp., Listeria
monocytogenes, Enterococcus
spp., and by modified
procedures, Haemophilus spp.,
Neisseria gonorrhoeae, N.
meningitidis and Streptococcus
spp., including Streptococcus
pneumoniae. |
| Device & | Device: | Predicate: |
| Predicate Device: | K230651 | K192326 |
| Indications for Use | BD BBL Sensi-Disc
Antimicrobial Susceptibility
Test (AST) Discs are used in
the semi-quantitative agar
diffusion test method for in
vitro susceptibility testing.
BD BBL Sensi-Disc Lefamulin
Disc 20 µg (LMU-20) can be
used to determine susceptibility
to Lefamulin against the
following bacteria, as described
in the FDA-approved package
insert for this antimicrobial
agent.
Active in vitro and in Clinical
Infections Against:
Gram-positive Bacteria
Streptococcus pneumoniae
Staphylococcus aureus
(methicillin-susceptible
isolates)
Gram-negative Bacteria
Haemophilus influenzae | HardyDisk AST Disks are used
for semi-quantitative in vitro
susceptibility testing by the agar
diffusion test procedure (Kirby-
Bauer) of rapidly growing and
certain fastidious bacterial
pathogens. Standardized methods
for agar diffusion testing have
been described for
Enterobacteriaceae,
Staphylococcus spp.,
Pseudomonas spp.,
Acinetobacter spp., Listeria
monocytogenes, Enterococcus
spp., and by modified
procedures, Haemophilus spp.,
Neisseria gonorrhoeae, N.
meningitidis and Streptococcus
spp., including Streptococcus
pneumoniae.
Use of HardyDisk AST
Lefamulin 20µg (LMU20) for in
vitro agar diffusion susceptibility
testing is indicated when there is
the need to determine the
susceptibility of bacteria to
Lefamulin.
HardyDisk AST Lefamulin at
concentration 20µg can be used
to determine the zone diameter
(mm) of Lefamulin against the
following bacteria for which
Lefamulin has been shown to be
active both clinically and in
vitro:
Streptococcus pneumoniae
Staphylococcus aureus
(methicillin-susceptible isolates)
Haemophilus influenzae |
| Antimicrobial
Agent | Lefamulin | Same |
| Antimicrobial | | |
| Agent | 20 µg | Same |
| Concentration | | |
| Device &
Predicate Device: | Device:
K230651 | Predicate:
K192326 |
| Interpretation | The user will interpret the zone
diameter according to the
established interpretive criteria
for the drug. | Same |
| Methodology | Kirby-Bauer Disk Diffusion
Susceptibility Test Protocol
requires the user to determine
categorical interpretations
(S/I/R) using the measured zone
diameters. | Same |
| Result
Interpretation
Method | Measurement of zone size. | Same |
| General Device Characteristic Differences | | |
| Manufacturing
Specifications | BD's specifications | Hardy Diagnostics'
specifications |
6
7
VI Standards/Guidance Documents Referenced:
- CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 33rd ed. CLSI ● supplement M100. Clinical and Laboratory Institute; 2023.
- CLSI. Performance Standards for Antimicrobial Disk Susceptibility Tests. 13th ed. CLSI ● standard M02. Clinical and Laboratory Standards Institute; 2018.
- . CLSI. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria. 9th ed. CLSI standard M11. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
VII Performance Characteristics (if/when applicable):
Analytical Performance: A
1. Precision/Reproducibility:
Reproducibility was conducted at one external site using 15 organisms, tested in triplicate with two disc lots on three separate days using one lot of appropriate media (Mueller Hinton agar (MHA) for Staphylococcus aureus, Haemophilus Test Medium for Haemophilus influenzae, and MHA with 5% Sheep Blood for Streptococcus pneumoniae). Each test was visually read by three independent readers with results masked, resulting in 270 data points for evaluation (15 organisms x 2 disc lots x 1 media lot x 3 days x 3 independent readers = 270 data points).
The reproducibility study included 5 Haemophilus influenzae, 5 Staphylococcus aureus, and 5 Streptococcus pneumoniae. Reproducibility was calculated as the percent of results which were within ±3 mm difference in zone diameter comparing test results with the modal or median, if no mode is present, zone diameter value. Summary results between disk lots and across readers are shown in Table 1 below.
8
| Between Disc Lots | Across Readers | |||||
|---|---|---|---|---|---|---|
| Lot #1 | Lot #2 | All Lots | Reader #1 | Reader #2 | Reader #3 | All Readers |
| 100.00% | 100.00% | 100.00% | 96.67% | 100.00% | 100.00% | 98.89% |
| (135/135) | (135/135) | (270/270) | (87/90) | (90/90) | (90/90) | (267/270) |
Table 1: Reproducibility Summary
The reproducibility performance between disc lots and across readers is >95% and meets the acceptance criteria.
-
- 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 (QC) Testing:
The CLSI-recommended quality control (QC) isolates, Haemophilus influenzae (ATCC 49247), Staphylococcus aureus (ATCC 25923), and Streptococcus pneumoniae (ATCC 49619), were tested a sufficient number of times (i.e., a minimum of 20 replicates per lot per reader). One Comparator disk lot and two BD disc lots were used. Each test was visually read by three independent readers, resulting in 129 data points (69 and 60 data points for Lot A and B, respectively) and 69 Comparator disk data points. The performance is shown in Table 2 below.
| QC Organism | Zone Diameter
(mm) | BD Lot 11
(N) | BD Lot 21
(N) | Comparator
disk2
(N) |
|-------------------------------------------------------------------------|-----------------------|------------------|------------------|----------------------------|
| Haemophilus influenzae
ATCC 49247
Expected Range:
22-28 mm | 19 | | | |
| | 20 | | | |
| | 21 | | | |
| | 22 | | | 6 |
| | 23 | | | 14 |
| | 24 | 1 | | 21 |
| | 25 | 9 | 4 | 24 |
| | 26 | 33 | 30 | 4 |
| | 27 | 25 | 25 | |
| | 28 | 1 | 1 | |
| | 29 | | | |
| | 30 | | | |
| | 31 | | | |
9
| QC Organism | Zone Diameter
(mm) | BD Lot 1¹
(N) | BD Lot 2¹
(N) | Comparator
disk²
(N) |
|----------------------------|-----------------------|------------------|------------------|----------------------------|
| | 23 | | | |
| | 24 | | | |
| | 25 | | | 1 |
| | 26 | | | 3 |
| | 27 | 11 | 6 | 15 |
| Staphylococcus aureus ATCC | 28 | 17 | 16 | 31 |
| 25923 | 29 | 30 | 31 | 21 |
| Expected Range: | 30 | 13 | 7 | |
| 26-32 mm | 31 | | | |
| | 32 | | | |
| | 33 | | | |
| | 34 | | | |
| | 35 | | | |
| | 16 | | | |
| | 17 | | | |
| | 18 | | | |
| | 19 | | | |
| | 20 | | | |
| Streptococcus pneumoniae | 21 | | | 1 |
| ATCC 49619 | 22 | | | 7 |
| | 23 | 3 | | 26 |
| Expected Range: | 24 | 21 | 16 | 24 |
| 19-27 mm | 25 | 33 | 28 | 8 |
| | 26 | 10 | 16 | 3 |
| | 27 | 2 | | |
| | 28 | | | |
| | 29 | | | |
| | 30 | | | |
ATCC = American Type Culture Collection
'Two BD disc lots were tested (Lot A and Lot B).
Two BD disc lots were tested (Lot A and Lot B).
2One Comparator disk lot was tested.
The BD disc QC performance is > 95% and is acceptable.
Inoculum Density Check:
Colony counts were conducted for all QC and reproducibility isolates, as well as 14.0% of clinical isolates. All were within the expected range.
-
- Detection Limit:
Not applicable.
- Detection Limit:
-
- Assay Cut-Off:
10
Not applicable.
B Comparison Studies:
1. Method Comparison with Predicate Device:
The BD BBL Sensi-Disc Lefamulin 20 ug (LMU-20) was compared with an FDA cleared disk of the same antimicrobial, mass/concentration, and content. The study was conducted at one testing site. Three independent operators participated in reading of test results with isolates evenly distributed to mimic testing at multiple sites. Testing was performed with one lot of discs from each test manufacturer (BD and comparator FDA-cleared disk), utilizing appropriate media following the method outlined in CLSI M02 and M100. An equivalent procedure to CLSI M11 was utilized for conducting colony counts.
Clinical:
Clinical testing was performed at one U.S. site with both the BD BBL Sensi-Disc Lefamulin disc and the comparator FDA cleared disk using a total of 270 clinical isolates including 90 Haemophilus influenzae, 90 Staphylococcus aureus (methicillin-susceptible isolates), and 90 Streptococcus pneumoniae.
Challenge:
Challenge testing was performed at one U.S site. A total of 66 challenge isolates were tested which included 22 Haemophilus influenzae, 22 Staphylococcus aureus (methicillinsusceptible isolates), and 22 Streptococcus pneumoniae.
Performance results for the total 336 clinical and challenge isolates are shown in Table 3. Performance of 39 MRSA isolates is not included in this table due to the lack of FDArecognized breakpoints for Lefamulin when testing MRSA.
| Total | CA# | CA% | S (#) | NS (#) | VMJ* | MAJ | ||
|---|---|---|---|---|---|---|---|---|
| Haemophilus influenzae | ||||||||
| Clinical | 90 | 89 | 98.9 | 90 | 0 | 0 | 1 | |
| Challenge | 22 | 19 | 86.4 | 13 | 9 | 3 | 0 | |
| Combined | 112 | 108 | 96.4 | 103 | 9 | 3 | 1 | |
| Staphylococcus aureus (methicillin-susceptible isolates) | ||||||||
| Clinical | 90 | 90 | 100.0 | 90 | 0 | 0 | 0 | |
| Challenge | 22 | 22 | 100.0 | 10 | 12 | 0 | 0 | |
| Combined | 112 | 112 | 100.0 | 100 | 12 | 0 | 0 | |
| Streptococcus pneumoniae | ||||||||
| Clinical | 90 | 89 | 98.9 | 89 | 1 | 1 | 0 | |
| Challenge | 22 | 22 | 100.0 | 19 | 3 | 0 | 0 | |
| Combined | 112 | 111 | 99.1 | 108 | 4 | 1 | 0 | |
| Overall | ||||||||
| Clinical | 270 | 268 | 99.3 | 269 | 1 | 1 | 1 | |
| Challenge | 66 | 63 | 95.5 | 42 | 24 | 3 | 0 | |
| Combined | 336 | 331 | 98.5 | 311 | 25 | 4 | 1 |
Table 3: Overall Performance of the BD BBL Sensi-Disc Lefamulin Disc vs. Comparator disk
- Due to the lack of an interpretive category other than susceptible and considering that a 3 mm disk zone diameter is equivalent to one MIC doubling dilution, because all potential VMJ errors had disk zone diameter measurement differences
11
| Total | CA# | CA% | S (#) | NS (#) | VMJ* | MAJ | |
|---|---|---|---|---|---|---|---|
| ≤3 mm compared to the FDA-cleared comparator disk and were ≤ an MIC doubling dilution-equivalent compared to the |
historical MIC result, the adjusted potential VMJ error rate is 0%.
CA - Category Agreement S - Susceptible isolates
NS - Nonsusceptible isolates
MAJ - major errors VMJ - very major errors
Category Agreement (CA) is when the BD result interpretation agrees exactly with the FDA cleared comparator result interpretation. The overall performance of the BD BBL Sensi-Disc Lefamulin disc as compared to the Comparator disk for Haemophilus influenzae group (Table 3) was acceptable with 96.4% (108/112) CA. There were 3 very major errors and 1 major error.
The overall performance of the BD BBL Sensi-Disc Lefamulin disc as compared to the Comparator disk for Staphylococcus aureus (methicillin-susceptible isolates) group (Table 3) was acceptable with 100.0% (112/112) CA. There were no very major or major errors.
The overall performance of the BD BBL Sensi-Disc Lefamulin disc as compared to the Comparator disk for Streptococcus pneumoniae group (Table 3) was acceptable with 99.1% (111/112) CA. There was 1 very major error and no major errors.
As required under 511A(b)(2)(C)(ii)(1) of the Federal Food, Drug and Cosmetic Act, the following statement is included in the 'Warnings and Precautions' section in the device labeling to address testing of non-indicated species:
"Per the FDA-Recognized Susceptibility Test Interpretive Criteria website, the safety and efficacy of antimicrobial drugs, for which antimicrobial susceptibility is tested by this AST device, may or may not have been established in adequate and well-controlled clinical trials for treating clinical infections due to microorganisms outside of those found in the indications and usage in the drug label. The clinical significance of susceptibility information in those instances is unknown. The approved labeling for specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved."
Resistant Isolates:
A total of 336 clinical and challenge isolates were tested when the BD BBL Sensi-Disc Lefamulin was compared to the FDA cleared comparator disk. However, an insufficient number of resistant isolates were available for testing. The following limitation was added in the device labeling:
"The current absence of resistant isolates precludes defining any results other than "Susceptible." Isolates yielding results other than "Susceptible" should be submitted to a reference laboratory for further testing."
-
- Matrix Comparison
Not applicable.
- Matrix Comparison
C Clinical Studies:
-
- Clinical Sensitivity:
12
Not applicable
-
- Clinical Specificity:
Not applicable
- Clinical Specificity:
-
- Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable
- Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
D Clinical Cut-Off:
Not applicable
E Expected Values/Reference Range:
The FDA-identified interpretive criteria for Lefamulin are listed in Table 4.
| Table 4: Interpretive Categories and Breakpoints for Lefamulin | ||
|---|---|---|
| | Minimum Inhibitory
Concentration (µg/mL) | | | Disk Diffusion
(zone diameter in mm) | | |
|---------------------------------------------------------------------|---------------------------------------------|---|---|------------------------------------------|---|---|
| Pathogen | S | I | R | S | I | R |
| Staphylococcus aureus (methicillin-
susceptible isolates) | $ \u22640.25 $ | - | - | $ \u226523 $ | - | - |
| Streptococcus pneumoniae | $ \u22640.5 $ | - | - | $ \u226519 $ | - | - |
| Haemophilus influenzae | $ \u22642 $ | - | - | $ \u226518 $ | - | - |
1 According to the FDA STIC Website, which recognizes CLSI M100-Ed33.
Note: The current absence of resistant isolates precludes defining any results other than "Susceptible". Isolates yielding MIC results other than "Susceptible" should be submitted to a reference laboratory for further testing.
S = Susceptible
I = Intermediate
R = Resistant
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.
To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission included a breakpoint change protocol that was reviewed and accepted by FDA. This protocol addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/drugs/developmentresources/antibacterial-susceptibility-test-interpretive-criteria). The protocol outlined the specific procedures and acceptance criteria that Becton, Dickinson, and Company (BD Diagnostic Systems) intends to use to evaluate the BD BBL Sensi-Disc Lefamulin 20µg (LMU-20) when revised breakpoints for Lefamulin are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, BD Diagnostic Systems will update the Lefamulin 20ug device label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation.