(90 days)
Etest® is a quantitative technique for determination of antimicrobial susceptibility of both non-fastive and Gram positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in ug/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.
This submission is for additional indications for the antimicrobial Etest® Ceftaroline at concentrations of 0.002 – 32 µg/ mL. Etest® Ceftaroline has been shown to be active in vitro against fastidious strains of the microorganisms listed below, according to the FDA label for this antimicrobial agent:
Streptococcus pneumoniae, Streptococcus agalactiae. Haemophilus influenzae.
The Etest gradient technology is based on a combination of the concepts of dilution and diffusion principles for susceptibility testing.
The Etest consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries the minimum inhibitory concentration (MIC) reading scale expressed in ug/mL. The other side of the strip contains a predefined continuous exponential gradient of antibiotic concentrations.
When the Etest strip is applied to an inoculated agar surface, an immediate and effective transfer of the preformed antibiotic gradient on the plastic carrier surface into the agar matrix occurs. Following incubation, a symmetrical inhibition ellipse centered along the strip is seen. The MIC value is read from the scale in term of ug/mL where the ellipse edge intersects the strip.
Here's a breakdown of the acceptance criteria and study information for the Etest® Ceftaroline device, based on the provided document:
Acceptance Criteria and Device Performance Study
The submission details the performance of the Etest® Ceftaroline for determining antimicrobial susceptibility against specific bacteria. The key metrics reported are Essential Agreement (EA) and Category Agreement (CA) when compared to a reference method.
1. Table of Acceptance Criteria and Reported Device Performance
The document states that the Etest® Ceftaroline demonstrated acceptable performance for overall Essential Agreement (EA) and for overall Category Agreement (CA) with the reference method. While explicit numerical acceptance criteria for EA and CA are not stated in the provided text as standalone thresholds, the reported percentages are presented as meeting the acceptable performance standard. However, based on typical FDA guidance for AST devices, an Essential Agreement of ≥ 90% and a Category Agreement of ≥ 90% (often nearing 95-100% for category) are generally expected. The device's performance aligns with these general expectations.
Below is a table summarizing the reported device performance:
FDA Breakpoints. Broth Microdilution Reading at 18 hr. Clinical and Challenge Combined
| Organism Group | Total Tested | # EA | % EA | # CA | % CA |
|---|---|---|---|---|---|
| S. pneumoniae | 283 | 269 | 95.1% | 283 | 100.00% |
| S. agalactiae | 276 | 259 | 93.8% | 276 | 100.00% |
| H. influenzae | 285 | 265 | 93.0% | 285 | 100.00% |
| All Organisms | 844 | 793 | 94.0% | 844 | 100.00% |
FDA Breakpoints. Broth Microdilution Reading at 23 hr. Clinical and Challenge Combined
| Organism Group | Total Tested | # EA | % EA | # CA | % CA |
|---|---|---|---|---|---|
| S. pneumoniae | 283 | 272 | 96.1% | 283 | 100.00% |
| S. agalactiae | 276 | 269 | 97.5% | 276 | 100.00% |
| H. influenzae | 285 | 270 | 94.7% | 285 | 100.00% |
| All Organisms | 844 | 811 | 96.1% | 844 | 100.00% |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The total number of isolates tested across all organisms was 844. This was broken down as:
- S. pneumoniae: 283 isolates
- S. agalactiae: 276 isolates
- H. influenzae: 285 isolates
- Data Provenance: The external evaluations were conducted using fresh and stock clinical isolates, as well as a set of challenge strains. The document does not specify the country of origin, but the use of "clinical isolates" suggests real-world samples, and "challenge strains" implies strains selected for their specific resistance profiles or difficulty of testing.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This information is not provided in the document. The ground truth method, CLSI broth microdilution, is a standardized laboratory procedure, not typically an expert consensus reading in the same way an image interpretation might be. Therefore, the concept of "experts" to establish its "ground truth" doesn't directly apply here in the way it would for, say, radiology reads. The accuracy of the reference method relies on adherence to the CLSI protocol.
4. Adjudication Method for the Test Set
The concept of an adjudication method (like 2+1 or 3+1) is typically used when human readers are involved in interpreting results and their interpretations need to be reconciled for ground truth. Since the ground truth is established by a standardized laboratory reference method (CLSI broth microdilution), no adjudication method between human readers/interpreters is mentioned or likely applicable in this context.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done because this is an in vitro diagnostic device for antimicrobial susceptibility testing. It directly measures Minimum Inhibitory Concentration (MIC) and categorizes susceptibility (e.g., susceptible, intermediate, resistant). Its performance is compared to a reference lab method, not to human readers interpreting complex medical cases with and without AI assistance. Therefore, there is no effect size reported for human readers improving with AI.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)
Yes, a standalone performance study was done. The Etest® Ceftaroline device's results (MIC values and categorical interpretations) were directly compared to the CLSI broth microdilution reference method's results. This comparison assesses the device's accuracy independently, without a human "interpreter" making a diagnosis based on the device's output and then having that diagnosis compared to a human-made ground truth. The Etest strip itself provides the MIC reading, which is then interpreted by a trained laboratory professional in the context of breakpoints.
7. The Type of Ground Truth Used
The ground truth used was the CLSI (Clinical and Laboratory Standards Institute) M07-A9 January 2012 broth microdilution reference method. This is a laboratory reference standard widely accepted as the gold standard for determining antimicrobial susceptibility.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" sample size. In the context of antimicrobial susceptibility testing devices, the "training" (or development) often involves internal testing during the design phase to optimize the device's performance characteristics. The reported numbers (844 isolates) are for the "external evaluations" which serve as the primary performance validation against the reference method.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, a distinct "training set" with established ground truth is not explicitly detailed for this type of device. The development and validation of the Etest® Ceftaroline would have followed established microbiological practices and standards, likely comparing preliminary versions to the same CLSI broth microdilution reference method during its development. The "ground truth" would consistently be the CLSI reference method.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 October 7, 2015
BIOMERIEUX SA CLAIRE DUMAS REGULATORY AFFAIRS SENIOR SPECIALIST 5. RUE DES AQUEDUCS CRAPONNE 69290 FRANCE
Re: K151873
Trade/Device Name: Etest® Ceftaroline (0.002 - 32ug/ml) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: JWY Dated: June 30, 2015 Received: July 9, 2015
Dear Ms. Dumas:
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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Ribhi Shawar -S
For Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K151873
Device Name Etest® Ceftaroline (0.002-32 ug/mL)
Indications for Use (Describe)
Etest® is a quantitative technique for determination of antimicrobial susceptibility of both non-fastive and Gram positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in ug/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.
This submission is for additional indications for the antimicrobial Etest® Ceftaroline at concentrations of 0.002 – 32 µg/ mL. Etest® Ceftaroline has been shown to be active in vitro against fastidious strains of the microorganisms listed below, according to the FDA label for this antimicrobial agent:
Streptococcus pneumoniae, Streptococcus agalactiae. Haemophilus influenzae.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) SUMMARY
Etest® Ceftaroline
A. 510(k) Submission Information:
| Submitter's Name: | bioMérieux SA |
|---|---|
| Address: | 5 rue des Aqueducs69290 CRAPONNE, France |
| Contact Person: | Claire DumasSenior Regulatory Affairs Specialist |
| Phone Number: | +33 (0) 4 78 87 75 22 |
| Fax Number: | +33 (0) 4 78 87 76 65 |
| Date of Preparation: | June 30, 2015 |
B. Device Name:
| Formal/Trade Name: | Etest® Ceftaroline(0.002 – 32 µg/mL) |
|---|---|
| Classification Name: | 21 CFR 866.1640Antimicrobial Susceptibility Test (AST) PowderProduct Code - JWY |
| Common Name: | Manual Antimicrobial Susceptibility TestSystems |
| Predicate Device: | Etest® Ceftaroline (K121002) |
(0.002 – 32 µg/mL) - Product code: CPT
D. Device Description
C.
The Etest gradient technology is based on a combination of the concepts of dilution and diffusion principles for susceptibility testing.
The Etest consists of a thin, inert, nonporous plastic strip that is used to determine the antimicrobial susceptibility of bacteria. One side of the strip carries
BIOMÉRIEUX
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the minimum inhibitory concentration (MIC) reading scale expressed in ug/mL. The other side of the strip contains a predefined continuous exponential gradient of antibiotic concentrations.
When the Etest strip is applied to an inoculated agar surface, an immediate and effective transfer of the preformed antibiotic gradient on the plastic carrier surface into the agar matrix occurs. Following incubation, a symmetrical inhibition ellipse centered along the strip is seen. The MIC value is read from the scale in term of ug/mL where the ellipse edge intersects the strip.
E. Intended Use
Etest® is a quantitative technique for determination of antimicrobial susceptibility of both non-fastidious Gram negative and Gram positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in ug/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.
This submission is for additional indications for the antimicrobial Etest® Ceftaroline at concentrations of 0.002 – 32 µg/mL. Etest® Ceftaroline has been shown to be active in vitro against fastidious strains of the microorganisms listed below, according to the FDA label for this antimicrobial agent:
Streptococcus pneumoniae, Streptococcus agalactiae, Haemophilus influenzae.
Note: Etest® Ceftaroline (0.002 - 32 ug/mL) is already cleared for in vitro activity against Staphylococcus aureus (including methicillin-susceptible and - resistant isolates) (510(k) K121002 - Oct 2012).
F. Comparison of the technological characteristics of the device compared to the predicate device
This submission is for additional indications for the antimicrobial Etest Ceftaroline at concentrations of 0.002 – 32 µg/mL. Etest® Ceftaroline has been shown to be active in vitro against Streptococcus pneumoniae, Streptococcus agalactiae, Haemophilus influenzae in addition to Staphylococcus aureus
BIOMERIEUT
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(including methicillin-susceptible and - resistant isolates) which claim has already been 510(k) cleared (K121002 - Oct 2012).
The technological characteristics between the two devices are exactly the same (same design, same development, same antimicrobial with same concentrations, same features, storage, handling, intended users and environment of use).
G. Performance data
Etest Ceftaroline demonstrated substantially equivalent performance when compared with the CLSI M07-A9 January 2012 broth microdilution reference method, following rules as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA. Issued on August 28, 2009 and following specifications as defined in CLSI M100-S24 January 2014.
This Premarket Notification (510[k]) presents data in support of Etest® Ceftaroline Streptococcus pneumoniae, Streptococcus agalactiae, Haemophilus for influenzae. External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The external evaluations were designed to establish the performance of Etest® Ceftaroline by comparing with the CLSI broth microdilution reference method read at 18 hrs (following recommendation of Antimicrobial agent package insert) and at 23h (following CLSI recommendation of 20-24h).
Etest® Ceftaroline demonstrated acceptable performance for overall Essential Agreement (EA) and for overall Category Agreement (CA) with the reference method read at 18h and 23h for each strain. Reproducibility and Quality Control demonstrated acceptable results. Details can be found in the submission.
| FDA Breakpoints. Broth Microdilution Reading at 18 hr. Clinical and Challenge Combined | |||||
|---|---|---|---|---|---|
| OrganismGroup | Total Tested | # EA | % EA | # CA | % CA |
| S. pneumoniae | 283 | 269 | 95.1% | 283 | 100.00% |
| S. agalactiae | 276 | 259 | 93.8% | 276 | 100.00% |
| H. influenzae | 285 | 265 | 93.0% | 285 | 100.00% |
| All Organisms | 844 | 793 | 94.0% | 844 | 100.00% |
Performance details:
FDA Breakpoints. Broth Microdilution Reading at 23 hr. Clinical and Challenge Combined
BIOMERIEUX
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| OrganismGroup | Total Tested | # EA | % EA | # CA | % CA |
|---|---|---|---|---|---|
| S. pneumoniae | 283 | 272 | 96.1% | 283 | 100.00% |
| S. agalactiae | 276 | 269 | 97.5% | 276 | 100.00% |
| H. influenzae | 285 | 270 | 94.7% | 285 | 100.00% |
| All Organisms | 844 | 811 | 96.1% | 844 | 100.00% |
H. Conclusion
The performance data presented in this submission support a substantial equivalence decision. The Etest® Ceftaroline is substantially equivalent to the Etest® Ceftaroline (K121002).
BIOMÉRIEUX
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).