(181 days)
No
The device description and intended use describe a physical disc used in a standard laboratory test method (agar diffusion). There is no mention of software, algorithms, or data processing that would suggest the use of AI/ML. The performance studies focus on comparing the disc's performance to a predicate device using standard microbiological metrics.
No
The device is used for in vitro susceptibility testing of bacteria to Cefiderocol, which means it helps determine if bacteria are susceptible or resistant to an antibiotic. It does not directly treat or diagnose a disease in a patient.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "used in the semi-quantitative agar diffusion test method for in vitro susceptibility testing," and specifically "can be used to determine susceptibility to Cefiderocol." This indicates its role in identifying the susceptibility of bacteria to an antimicrobial agent, which is a diagnostic function.
No
The device is a physical disc impregnated with an antimicrobial agent, used in a laboratory test method. It is 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 BD BBL Sensi-Disc Antimicrobial Susceptibility Test (AST) Discs are used for "in vitro susceptibility testing." This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, treatment, or prevention of disease.
- Device Description: The description details a physical product (discs impregnated with a substance) designed to be used in a laboratory setting for testing purposes.
- Performance Studies: The document describes clinical and challenge testing performed on isolates, which is typical for evaluating the performance of an IVD.
- Key Metrics: The performance metrics (Category Agreement, minor errors, major errors, very major errors) are standard measures used to evaluate the accuracy and reliability of antimicrobial susceptibility testing devices, which are a type of IVD.
- Predicate Device: The mention of a "Predicate Device" with a K number (K193504) indicates that this device is being compared to another legally marketed device, which is a common pathway for regulatory clearance of IVDs.
All these elements strongly indicate that the BD BBL Sensi-Disc Antimicrobial Susceptibility Test (AST) Discs, specifically the Cefiderocol Disc 30 uq (FDC-30), are intended for in vitro diagnostic use.
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 Cefiderocol Disc 30 ug (FDC30) can be used to determine susceptibility to Cefiderocol against the following bacteria, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in Clinical Infections Against:
| Complicated Urinary Tract Infections, Including Pyelonephritis | Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) |
|---|---|
| Gram-negative Bacteria | Gram-negative Bacteria |
| Escherichia coli | Acinetobacter baumannii complex |
| Enterobacter cloacae complex | Escherichia coli |
| Klebsiella pneumoniae | Enterobacter cloacae complex |
| Proteus mirabilis | Klebsiella pneumoniae |
| Pseudomonas aeruginosa | Pseudomonas aeruginosa |
| Active in vitro Against: | Serratia marcescens |
| Citrobacter freundii complex | |
| Citrobacter koseri | |
| Klebsiella aerogenes | |
| Klebsiella oxytoca | |
| Morganella morganii | |
| Proteus vulgaris | |
| Providencia rettgeri |
Product codes
JTN
Device Description
The BD BBL™ Sensi-Disc™ Cefiderocol 30 µg (FDC30) device is a 6 mm disc prepared by impregnating high quality absorbent paper with accurately determined amounts of Cefiderocol. Discs are clearly marked on both sides with the code FDC30. The code designates the agent Cefiderocol (FDC) and the drug content (30 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 BBLTM Sensi-Disc ™ Antimicrobial Susceptibility Test Discs can be dispensed using a BD BBLTM Sensi-Disc TM 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
Not Found
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
Reproducibility was conducted at one external site using 15 organisms, tested in triplicate with two disk lots on three separate days using one lot of Mueller Hinton agar (MHA media). Each test was visually read by three independent readers with results masked, resulting in 270 data points for evaluation (15 organisms x 2 disk lots x 1 media lot x 3 days x 3 independent readers = 270 data points).
The reproducibility study included 11 Enterobacterales (1 Citrobacter koseri, 1 Enterobacter cloacae, 2 Escherichia coli, 1 Klebsiella aerogenes, 3 Klebsiella pneumoniae, 1 Morganella morganii, 1 Proteus mirabilis, 1 Proteus vulgaris, 1 Serratia marcescens), 2 Pseudomonas aeruginosa, and 1 Acinetobacter baumannii. Reproducibility was calculated as the percent of results which were within ±3 mm difference in zone diameter comparing test results with the modal zone diameter value.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Analytical Performance: Precision/Reproducibility
Sample Size: 270 data points (15 organisms x 2 disk lots x 1 media lot x 3 days x 3 independent readers)
Key Results: The reproducibility performance between disc lots and across readers is >95% and meets the acceptance criteria.
Study Type: Quality Control (QC) Testing
Sample Size: 148 data points (74 data points per lot) and 74 FDA cleared disk data points.
Key Results: The BD disc QC performance is > 95% and is acceptable.
Study Type: Method Comparison with FDA Cleared Disk - Clinical
Sample Size: 296 clinical isolates including 207 Enterobacterales, 52 Pseudomonas aeruginosa, and 37 Acinetobacter baumannii complex.
Key Results: Overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for Enterobacterales group (Table 3) is acceptable with 100% CA for clinical isolates. For P. aeruginosa group, 98.1% CA. For Acinetobacter baumannii group, 94.6% CA.
Study Type: Method Comparison with FDA Cleared Disk - Challenge
Sample Size: 61 challenge isolates including 49 Enterobacterales, 5 Pseudomonas aeruginosa, and 7 Acinetobacter baumannii complex.
Key Results: Overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for Enterobacterales group (Table 3) is acceptable with 91.8% CA for challenge isolates. For P. aeruginosa group, 100.0% CA. For Acinetobacter baumannii group, 100.0% CA.
Study Type: Method Comparison with FDA Cleared Disk - Combined (Clinical and Challenge)
Sample Size: 357 clinical and challenge isolates
Key Results: The overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for Enterobacterales group (Table 3) is acceptable with 98.4% CA. There were 4 minor errors and no major or very major errors.
The overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for P. aeruginosa group (Table 3) is acceptable with 98.2% CA. There was 1 minor error and no major or very major errors.
The overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for Acinetobacter baumannii group (Table 3) is acceptable with 95.5% CA. There were 2 minor errors and no major or very major errors.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Reproducibility:
Between Disc Lots: 99.63% (100% for Lot #1, 99.26% for Lot #2)
Across Readers: 99.63% (100% for Reader #1, 100% for Reader #2, 99% for Reader #3)
QC performance: > 95%
Category Agreement (CA):
Enterobacterales Combined (Clinical): 100%
Enterobacterales Combined (Challenge): 91.8%
Enterobacterales Combined (Overall): 98.4%
Pseudomonas aeruginosa (Clinical): 98.1%
Pseudomonas aeruginosa (Challenge): 100.0%
Pseudomonas aeruginosa (Overall): 98.2%
Acinetobacter baumannii complex (Clinical): 94.6%
Acinetobacter baumannii complex (Challenge): 100.0%
Acinetobacter baumannii complex (Overall): 95.5%
Overall (Clinical): 99.0%
Overall (Challenge): 93.4%
Overall (Combined): 98.0%
Errors:
Enterobacterales Combined: 4 minor errors, 0 major errors, 0 very major errors
Pseudomonas aeruginosa: 1 minor error, 0 major errors, 0 very major errors
Acinetobacter baumannii complex: 2 minor errors, 0 major errors, 0 very major errors
Overall: 7 minor errors, 0 major errors, 0 very major errors
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the symbol of the Department of Health & Human Services on the left and the FDA acronym along with the full name of the agency on the right. The FDA part is in blue, with "U.S. FOOD & DRUG" on the top line and "ADMINISTRATION" on the bottom line.
December 21, 2022
Becton Dickinson, and Company Kamisha Gray Senior Regulatory Affairs Specialist 7 Loveton Circle Sparks, Maryland 21152-0999
Re: K221826
Trade/Device Name: BD BBL Sensi-Disc Cefiderocol 30ug (FDC-30) Regulation Number: 21 CFR 866.1620 Regulation Name: Antimicrobial Susceptibility Test Disc Regulatory Class: Class II Product Code: JTN Dated: June 20, 2022 Received: June 23, 2022
Dear Kamisha Gray:
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/ofdocs/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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
1
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 (QS) 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) Branch Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
BD BBL™ Sensi-Disc™ Cefiderocol 30μg (FDC-30)
Indications for Use (Describe) 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 Cefiderocol Disc 30 uq (FDC-30) can be used to determine susceptibility to Cefiderocol against the following bacteria, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in Clinical Infections Against:
| Complicated Urinary Tract Infections, | Hospital-acquired Bacterial Pneumonia and Ventilator-associated |
|---|---|
| Including Pyelonephritis | Bacterial Pneumonia (HABP/VABP) |
| Gram-negative Bacteria | Gram-negative Bacteria |
| Escherichia coli | Acinetobacter baumannii complex |
| Enterobacter cloacae complex | Escherichia coli |
| Klebsiella pneumoniae | Enterobacter cloacae complex |
| Proteus mirabilis | Klebsiella pneumoniae |
| Pseudomonas aeruginosa | Pseudomonas aeruginosa |
| Active in vitro Against: | Serratia marcescens |
| Citrobacter freundii complex | |
| Citrobacter koseri | |
| Klebsiella aerogenes | |
| Klebsiella oxytoca |
Morganella morganii Proteus vulgaris Providencia rettgeri
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: 6/22/2022
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™ Cefiderocol 30 µg (FDC30)
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 Cefiderocol Antimicrobial Susceptibility Test Disc.
B Measurand:
Cefiderocol Disc 30 µg (FDC30)
C Type of Test:
Antimicrobial Susceptibility Test Disc
III Intended Use/Indications for Use:
- A Intended Use:
4
See Indication for Use below.
B Indications 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 Cefiderocol Disc 30 ug (FDC30) can be used to determine susceptibility to Cefiderocol against the following bacteria, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in Clinical Infections Against:
| Complicated Urinary Tract Infections,
Including Pyelonephritis | Hospital-acquired Bacterial Pneumonia and
Ventilator-associated Bacterial Pneumonia
(HABP/VABP) |
|-------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------|
| Gram-negative Bacteria | Gram-negative Bacteria |
| Escherichia coli | Acinetobacter baumannii complex |
| Enterobacter cloacae complex | Escherichia coli |
| Klebsiella pneumoniae | Enterobacter cloacae complex |
| Proteus mirabilis | Klebsiella pneumoniae |
| Pseudomonas aeruginosa | Pseudomonas aeruginosa |
Active in vitro Against:
Citrobacter freundii complex Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca Morganella morganii Proteus vulgaris Providencia rettgeri
Serratia marcescens
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 ability of the BD BBL Sensi Disc to detect resistance with the following combination(s) is unknown because an insufficient number of resistant strains were encountered at the time of comparative testing: Cefiderocol (30ug) and Enterobacterales
5
group, P. aeruginosa and Acinetobacter baumannii. If such a strain is encountered, it should be submitted to a reference laboratory for further testing.
- . While the categorical agreement for BD BBL Sensi-Disc Cefiderocol compared to FDA cleared Disk analysis was >95% for Pseudomonas aeruginosa and Acinetobacter baumannii complex, categorical agreement for BD BBL Sensi-Disc Cefiderocol compared to historical BMD MIC values was below 90%, caused by the occurrence of false susceptible results and minor errors. Test results for Cefiderocol/P. aeruginosa which provide a disc zone of inhibition ≥ 22 mm, and test results for Cefiderocol/4. baumannii complex which provide a disc zone of inhibition ≥ 19 mm, should be interpreted in conjunction with other clinical and laboratory information.
- While the categorical agreement for BD BBL Sensi-Disc Cefiderocol compared to FDA cleared Disk analysis was > 95% for Enterobacterales group organisms, categorical agreement for BD BBL Sensi-Disc Cefiderocol compared to historical BMD MIC values resulted in false susceptible results. Citrobacter freundii complex, Citrobacter koseri, Klebsiella pneumoniae, Morganella morganii, and Proteus mirabilis isolates that provide a disc zone of inhibition ≥ 16 mm should be interpreted in conjunction with other clinical and laboratory information.
D Special Instrument Requirements:
Not applicable.
IV Device/System Characteristics:
Device Description: A
The BD BBL™ Sensi-Disc™ Cefiderocol 30 µg (FDC30) device is a 6 mm disc prepared by impregnating high quality absorbent paper with accurately determined amounts of Cefiderocol. Discs are clearly marked on both sides with the code FDC30. The code designates the agent Cefiderocol (FDC) and the drug content (30 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 BBLTM Sensi-Disc ™ Antimicrobial Susceptibility Test Discs can be dispensed using a BD BBLTM Sensi-Disc TM Dispenser.
Principle of Operation: B
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
6
recognized zone diameter ranges for the specific antimicrobial agent/organism combinations being tested.
V Substantial Equivalence Information:
A FDA Cleared Disk Name:
HardyDisk AST Cefiderocol 30μg (FDC30)
B FDA Cleared Disk 510(k) Number:
C Comparison with FDA Cleared Device:
| Device & FDA
Cleared Device
(Predicate): | Device:
K221826 | FDA Cleared Device
(Predicate):
K193504 |
|------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------|
| Device Trade Name | BD BBL™ Sensi-Disc™
Cefiderocol 30 µg (FDC30) | HardyDisk™ AST
Cefiderocol 30 µg (FDC30) |
| General Device Characteristic Similarities | | |
| Regulation | 866.1620 | Same |
| Product Code | JTN | Same |
| Intended Use/
Indications for Use | Semi-quantitative in vitro
susceptibility testing by
standardized agar diffusion
test procedures. | Same |
| Antimicrobial Agent | Cefiderocol | Same |
| Antimicrobial Agent
Concentration | 30 µg | Same |
| 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 |
VI Standards/Guidance Documents Referenced:
7
- Antibacterial Susceptibility Test Interpretive Criteria (FDA STIC) Cefiderocol Injection. ● Food and Drug Administration Web site. Content current as of 06 June 2022. https://www.fda.gov/drugs/development-resources/cefiderocol-imjection. Last accessed 22 June 2022.
- CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI supplement M100. Clinical and Laboratory Institute; 2021.
- . CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 32nd ed. CLSI supplement M100. Clinical and Laboratory Institute; 2022.
- 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):
A Analytical Performance:
-
- Precision/Reproducibility:
Reproducibility was conducted at one external site using 15 organisms, tested in triplicate with two disk lots on three separate days using one lot of Mueller Hinton agar (MHA media). Each test was visually read by three independent readers with results masked, resulting in 270 data points for evaluation (15 organisms x 2 disk lots x 1 media lot x 3 days x 3 independent readers = 270 data points).
- Precision/Reproducibility:
The reproducibility study included 11 Enterobacterales (1 Citrobacter koseri, 1 Enterobacter cloacae, 2 Escherichia coli, 1 Klebsiella aerogenes, 3 Klebsiella pneumoniae, 1 Morganella morganii, 1 Proteus mirabilis, 1 Proteus vulgaris, 1 Serratia marcescens), 2 Pseudomonas aeruginosa, and 1 Acinetobacter baumannii. Reproducibility was calculated as the percent of results which were within ±3 mm difference in zone diameter comparing test results with the modal zone diameter value. Summary results between disk lots and across readers are shown in Table 1 below.
| Between Disc Lots | Across Readers | |||||
|---|---|---|---|---|---|---|
| Lot #1 | Lot #2 | All Lots | Reader #1 | Reader #2 | Reader #3 | All Readers |
| 100% | 99.26% | 99.63% | 100% | 100% | 99% | 99.63% |
| (135/135) | (134/135) | (269/270)a | (90/90) | (90/90) | (89/90) | (269/270) |
Table 1: Reproducibility Summary
3 The combination of Lot #1 and Lot #2 yields the result shown because when these two lots were combined, a new mode was calculated, resulting in only one (1) result falling out of ± 3 mm.
The reproducibility performance between disc lots and across readers is >95% and meets the acceptance criteria.
-
- Linearity:
Not applicable.
- Linearity:
8
-
- 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, Escherichia coli (ATCC® 25922), and Pseudomonas aeruginosa (ATCC® 27853), were tested a sufficient number of times (i.e., a minimum of 20 replicates per lot per reader). One FDA cleared disk lot and two BD disc lots were used. Each test was visually read by three independent readers, resulting in 148 data point (74 data points per lot) and 74 FDA cleared disk data points. The performance is shown in Table 2 below.
| QC Organism | Zone
Diameter
(mm) Range | BD Lot 11
(N) | BD Lot 21
(N) | Comparator
Disc2
(N) |
|-----------------------------------------------------------------------|--------------------------------|------------------|------------------|----------------------------|
| Escherichia coli ATCC® 25922
Expected Range:
25-31 mm | 22 | | | |
| | 23 | | | |
| | 24 | | 2 | 2 |
| | 25 | 7 | 11 | 11 |
| | 26 | 18 | 12 | 16 |
| | 27 | 15 | 13 | 14 |
| | 28 | 21 | 21 | 20 |
| | 29 | 11 | 14 | 10 |
| | 30 | 1 | | |
| | 31 | | | |
| | 32 | | | |
| | 33 | | | |
| | 34 | | | |
| | 19 | | | |
| | 20 | | | |
| | 21 | | | |
| Pseudomonas aeruginosa ATCC® 27853
Expected Range:
22-31 mm | 22 | | | 1 |
| | 23 | 2 | 3 | 4 |
| | 24 | 10 | 7 | 14 |
| | 25 | 23 | 17 | 28 |
| | 26 | 32 | 38 | 23 |
| | 27 | 6 | 8 | 4 |
| | 28 | 1 | 1 | |
| | 29 | | | |
| | 30 | | | |
| | 31 | | | |
| | 32 | | | |
| | 33 | | | |
| | 34 | | | |
ATCC = American Type Culture Collection
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1Two BD disc lots were tested (Lot A and Lot B). 2One comparator disc lot was tested.
The BD disc QC performance is > 95% and is acceptable.
Inoculum Density Check:
Colony counts were conducted for OC, reproducibility isolates, and 9.7% of clinical isolates. All were within the expected range.
-
- Detection Limit:
Not applicable.
- Detection Limit:
-
- Assay Cut-Off:
Not applicable.
- Assay Cut-Off:
B Comparison Studies:
1.Method Comparison with FDA Cleared Disk:
The BD BBL™ Sensi-Disc™ Cefiderocol 30 µg (FDC30) 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 disk of each test manufacturer (BD and comparator FDA-cleared disc), utilizing MHA media following the method outlined in CLSI M02, M11, and M100.
Clinical:
Clinical testing was performed at one U.S. site with both the BD Cefiderocol disc and the comparator FDA cleared disk using a total of 296 clinical isolates including 207 Enterobacterales (10 Citrobacter freundii, 2 Citrobacter koseri, 10 isolates of Enterobacter cloacae. 30 isolates of Escherichia coli. 3 isolates of Klebsiella aerogenes. 18 isolates of Klebsiella oxytoca, 62 isolates of Klebsiella pneumoniae, 17 isolates of Morganella morganii, 30 isolates of Proteus mirabilis, 2 isolates of Proteus vulgaris, 8 isolates of Providencia rettgeri, 15 isolates of Serratia marcescens), 52 Pseudomonas aeruginosa, and 37 Acinetobacter baumannii complex.
Challenge:
Challenge testing was performed at one U.S site. A total of 61 challenge isolates were tested which included 49 Enterobacterales (1 Citrobacter braakii, 3 Citrobacter freundii, 2 Citrobacter koseri, 1 Enterobacter asburiae , 3 Enterobacter cloacae, 6 Escherichia, 3 Klebsiella aerogenes, 2 Klebsiella oxytoca, 9 Klebsiella pneumoniae, 3 Morganella morganii, 2 Proteus mirabilis, 5 Proteus vulgaris, 4 Providencia rettgeri, 1 Providencia stuartii, 4 Serratia marcescens), 5 Pseudomonas aeruginosa, and 7 Acinetobacter baumannii complex.
Performance results for the total 357 clinical and challenge isolates are shown in Table 3.
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| Total | CA# | CA% | S(#) | I(#) | R(#) | VMJ | MAJ | MIN | |
|---|---|---|---|---|---|---|---|---|---|
| Enterobacterales Combined | |||||||||
| Clinical | 207 | 207 | 100% | 207 | 0 | 0 | 0 | 0 | 0 |
| Challenge | 49 | 45 | 91.8% | 37 | 10 | 2 | 0 | 0 | 4 |
| Combined | 256 | 252 | 98.4% | 244 | 10 | 2 | 0 | 0 | 4 |
| Pseudomonas aeruginosa | |||||||||
| Clinical | 52 | 51 | 98.1 | 51 | 1 | 0 | 0 | 0 | 1 |
| Challenge | 5 | 5 | 100.0 | 2 | 2 | 1 | 0 | 0 | 0 |
| Combined | 57 | 56 | 98.2 | 53 | 3 | 1 | 0 | 0 | 1 |
| Acinetobacter baumannii complex | |||||||||
| Clinical | 37 | 35 | 94.6 | 28 | 5 | 4 | 0 | 0 | 2 |
| Challenge | 7 | 7 | 100.0 | 2 | 2 | 3 | 0 | 0 | 0 |
| Combined | 44 | 42 | 95.5 | 30 | 7 | 7 | 0 | 0 | 2 |
| Overall | |||||||||
| Clinical | 296 | 293 | 99.0 | 286 | 6 | 4 | 0 | 0 | 3 |
| Challenge | 61 | 57 | 93.4 | 41 | 14 | 6 | 0 | 0 | 4 |
| Combined | 357 | 350 | 98.0 | 327 | 20 | 10 | 0 | 0 | 7 |
CA - Category Agreement
MIN – minor errors
S - Susceptible isolates
MAJ - major errors VMJ - very major errors
I - Intermediate isolates R - Resistant isolates
Category Agreement (CA) is when the BD result interpretation agrees exactly with the comparator HardyDisk result interpretation.
The overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for Enterobacterales group (Table 3) is acceptable with 98.4% CA. There were 4 minor errors and no major or very major errors.
The overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for P. aeruginosa group (Table 3) is acceptable with 98.2% CA. There was 1 minor error and no major or very major errors.
The overall performance of the BD BBL™ Sensi-Disc™ Cefiderocol disc as compared to the FDA cleared disk for Acinetobacter baumannii group (Table 3) is acceptable with 95.5% CA. There were 2 minor errors and no major or very 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
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specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved. "
Resistant Isolates:
A total of 357 clinical and challenge isolates were tested when the BD BBL Sensi-Disc 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 ability of the BD BBL Sensi Disc to detect resistance with the following combination(s) is unknown because an insufficient number of resistant strains were encountered at the time of comparative testing: Cefiderocol (30µg) and Enterobacterales group, P. aeruginosa and Acinetobacter baumannii. If such a strain is encountered, it should be submitted to a reference laboratory for further testing".
-
- Matrix Comparison
Not applicable.
- Matrix Comparison
C Clinical Studies:
-
- Clinical Sensitivity:
Not applicable
- Clinical Sensitivity:
-
- Clinical Specificity:
Not applicable
- Clinical Specificity:
-
- Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable
D Clinical Cut-Off:
Not applicable
E Expected Values/Reference Range:
The FDA-identified interpretive criteria for Cefiderocol are listed in Table 4.
Table 4: Interpretive Categories and Breakpoints for Cefiderocol1
| | Minimum Inhibitory
Concentrations (µg/mL) | | | Disk Diffusion
(zone diameters in mm) | | |
|------------------------------------|----------------------------------------------|---|-----|------------------------------------------|-------|-----|
| Pathogen | S | I | R | S | I | R |
| Enterobacteriaceae2,3 | ≤4 | 8 | ≥16 | ≥16 | 9-15 | ≤8 |
| Pseudomonas aeruginosa | ≤1 | 2 | ≥4 | ≥22 | 13-21 | ≤12 |
| Acinetobacter baumannii
complex | ≤1 | 2 | ≥4 | ≥19 | 12-18 | ≤11 |
1 According to the FDA STIC Website.
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2 Clinical efficacy was shown for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae complex in patients with complicated urinary tract infections (cUTI).
3 Clinical efficacy was shown for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Serratia marcescens in patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).
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.