(50 days)
The Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Susceptibility plate is an in vitro diagnostic device for the quantitative determination of susceptibility of Streptococcus pneumoniae and Haemophilus influenzae. This 510(k) is for the addition of Linezolid in the dilution range of 0.25 - 32 µgml to the Sensititre Haemophilus/Streptococcus pneumoniae MIC panel for testing Streptococcus pneumoniae isolates. The approved primary "Indications for Use" for the Sensititre Haemophilus/Streptococcus pneumoniae MIC panel for testing Streptococcus pneumoniae and Haemophilus influenzae isolates remains unchanged. Clinical correlation is provided for: Streptococcus pneumoniae (penicillin-susceptible strains) and Streptococcus pneumoniae (penicillin-resistant strains).
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This is a 510(k) premarket notification for the addition of Linezolid to the Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Susceptibility Plates. The document describes the device, its indications for use, and a summary of the performance data to support substantial equivalence.
Here's an analysis of the provided information, focusing on the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for antimicrobial susceptibility testing (AST) devices, particularly for broth microdilution methods like the Sensititre plates, are typically based on agreement with a reference method (e.g., NCCLS (now CLSI) broth microdilution). The key metrics are:
- Essential Agreement (EA): The MIC value obtained with the device is within +/- 1 twofold dilution of the reference method.
- Categorical Agreement (CA): The interpretation of susceptible, intermediate, or resistant (SIR call) from the device matches the reference method.
- Major Discrepancies (MD): The device calls susceptible, but the reference calls resistant. (Considered a serious error).
- Very Major Discrepancies (VMD): The device calls resistant, but the reference calls susceptible. (Considered a very serious error).
The document states, for "Linezolid vs. Streptococcus pneumoniae" and "Linezolid vs. Haemophilus influenzae" that the "overall Essential Agreement (EA) values were >90%" and "Categorical Agreement (CA) values were >90%". It also provides specific rates for VMD and MD.
Here's the table of acceptance criteria and reported device performance based on the executive summary:
| Metric | Acceptance Criteria (Typically) | Reported Device Performance (Linezolid vs. S. pneumoniae) | Reported Device Performance (Linezolid vs. H. influenzae) |
|---|---|---|---|
| Essential Agreement (EA) | ≥ 90% | 98.4% | 99.1% |
| Categorical Agreement (CA) | ≥ 90% | 98.3% | 99.1% |
| Very Major Discrepancy (VMD) | ≤ 1.5% | 0.0% | 0.0% |
| Major Discrepancy (MD) | ≤ 3.0% | 1.7% | 0.9% |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Streptococcus pneumoniae: 298 isolates (including 116 challenge isolates)
- Haemophilus influenzae: 200 isolates (including 50 challenge isolates)
- Data Provenance: The document does not explicitly state the country of origin. However, the study involved both "reference organisms" and "clinical isolates." The clinical isolates are typically collected from diverse patient populations within the context of clinical microbiology laboratories, but a specific country is not mentioned. The study is retrospective, as it used pre-existing isolates (clinical and challenge) to test the new drug-device combination.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts or their qualifications for establishing the ground truth. However, the ground truth for AST is typically established by performing the NCCLS (now CLSI) reference broth microdilution method. This method is standardized and performed by trained microbiologists following strict protocols. The "expert" in this context is the consensus interpretation of the reference method's results.
4. Adjudication Method for the Test Set
The document does not describe an "adjudication method" in the sense of multiple human experts reviewing conflicting interpretations. For AST studies, discrepancies (Major or Very Major) are typically investigated to determine the root cause, which might involve retesting or further analysis using other methods if the reference method itself is believed to be inaccurate. The primary adjudication is essentially the comparison to the established NCCLS reference method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is more common for diagnostic imaging or subjective interpretation tasks where human readers' performance is directly measured and compared with and without AI assistance. For AST devices, the primary goal is typically to show accurate and reproducible results compared to a standardized reference method, not to evaluate human reader improvement.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance study was done. The Sensititre system, in this context, is an automated or semi-automated system that reads and interprets the MIC values. The performance statistics (EA, CA, VMD, MD) directly reflect the device's ability to accurately determine MICs and SIR calls without human intervention in the interpretative step (beyond setting up the test and potentially validating the results). The "device performance" reported is the algorithm's performance compared to the reference method.
7. The Type of Ground Truth Used
The type of ground truth used is the NCCLS (now CLSI) reference broth microdilution method. This is a well-established, standardized, and internationally accepted method for determining antimicrobial minimum inhibitory concentrations (MICs). It serves as the gold standard for comparing new AST devices.
8. The Sample Size for the Training Set
The document does not explicitly state a separate training set sample size. For an AST device like the Sensititre plates, the "training" (or development and calibration) of the system for a new antimicrobial like Linezolid often involves a different approach than typical machine learning models. The system's underlying methodology for reading MICs from growth patterns and applying interpretive breakpoints is generally pre-established. The introduction of a new drug primarily requires:
- Validation that the specific drug lot performs correctly on the plate.
- Verification that the established interpretive breakpoints (e.g., from NCCLS/CLSI) are correctly applied by the system.
- Confirmation of agreement with the reference method across a range of concentrations and diverse isolates.
While there might have been internal development data used to optimize the plate formulation or reading algorithms for Linezolid, it's not typically referred to as a "training set" in the context of this type of 510(k) submission, which focuses on validation data against a reference standard.
9. How the Ground Truth for the Training Set Was Established
Given that a distinct "training set" is not explicitly mentioned as per common AI/ML terminology in this context, the ground truth for any internal development or calibration would also have been established based on:
- NCCLS (CLSI) reference broth microdilution method: To ensure the system correctly measures MICs of Linezolid against relevant organisms.
- Known interpretive breakpoints: These are established by independent expert bodies (like CLSI) based on clinical outcomes, pharmacokinetic/pharmacodynamic data, and surveillance data.
In essence, the "ground truth" used throughout the entire development and validation process for AST devices revolves around agreement with the established reference method and adherence to recognized interpretive guidelines.
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Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features a stylized eagle with three lines representing its wings and body. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
AUG 2 9 2001
Ms. Cynthia C. Knapp Director Lab Services Trek Diagnostic Systems, Inc. 29299 Clemens Road, Suite 1-K Westlake, OH 44145
K012151 Re:
Trade/Device Name: Sensititre™ Haemophilus/Streptococcus pneumoniae (HP) MIC Susceptibility Plates Regulation Number: 21 CFR 866.1640 Regulatory Class: II
Product Code: JWY Dated: July 10, 2001 Received: July 10, 2001
Dear Ms. Knapp:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed notheation. The I Dri imalig of baction for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 1 If you desire specific darices jagnostic devices), please contact the Office of Compliance at additionally 607.10 for in This clegitestions on the promotion and advertising of your device, (301) 594-4560. Additionary, 10. quest at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Information on your responsibilities and er Assistance at its toll-free number (800) 638-2041 or Manufacturers International and Collisanter Fixsware da gov/cdrb/dsma/dsmamain.html".
(301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".
Sincerely yours,
Steven Butman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510 (k) Number (If known): Yolal Si
Device Name: Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Susceptibility Plates.
Indications For Use:
The Sensititre Haemophilus/Streptococcus pneumoniae (HP) MIC Susceptibility plate is an in The Sensiture Haemopinius/Sucptococcus phoundomio (Streptococcus pneumoniae and Haemophilus influenzae.
This 510(k) is for the addition of Linezolid in the dilution range of 0.25 - 32 µgml to the This 510(K) is for the adultion of Encezond in the and for testing Streptococcus
Sensititre Haemophilus/Streptococcus pneumoniae MIC panel for testing Streptococcus Sensititre Haemophilus Streptococcus picanoneae isolates. The approved primary "Indications for pneumoniae and Haemopilius innuctize isources. The scoccus pneumonide (penicillin-Ose" and cinneal significance of Enterprise of Entical correlation is provided for: Streptococcus pneumoniae (penicillin- resistant strains)
(PLEASE DO NOT WRITE BELOW THIS LINE- CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Freddie Warren Poole
Division Sign-Off) Division of Clinical Laboratory Devices
510(k) Number K012151
Prescription Use (Per 21 CFR 801.109
OR
Over-The-Counter Use_
§ 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).