(90 days)
The Sensititre 20 - 24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnositic product for clinical susceptibility testing of fastidious isolates. This 510(k) is for Ceftolozane-tazobactam in the dilution range of 0.03/4 - 64/4 µg/ml for testing H. influenzae on the Sensitite 20 - 24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System. Ceftolozane-tazobactam has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Haemophilus influenzae
Not Found
This FDA 510(k) clearance letter pertains to an in vitro diagnostic (IVD) device, specifically an antimicrobial susceptibility testing system. The questions you've posed (acceptance criteria, study design, ground truth, MRMC, etc.) are highly relevant to the evaluation of AI/ML-driven medical devices, particularly those that interpret images or other complex data to provide a diagnosis or assist in clinical decision-making.
However, the provided text does not contain the detailed study information required to answer your questions. This document is a clearance letter, stating that the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Ceftolozane-tazobactam has been found substantially equivalent to a predicate device.
Here's why the information is not present in this document:
- Type of Device: This is a microbiology susceptibility testing system, not an AI/ML image interpretation device. While it's an IVD, its function is to determine the minimum inhibitory concentration (MIC) or breakpoint susceptibility of an antibiotic against specific bacteria. This is typically done through a standardized laboratory process (e.g., microdilution) where the growth or inhibition of bacteria is observed, not through complex image analysis or AI algorithms in the way you're inferring.
- 510(k) Process: For traditional IVD devices like this, substantial equivalence is often demonstrated by showing the new device performs comparably to a legally marketed predicate device using established laboratory methods. The detailed performance data, including acceptance criteria and study results, would be submitted in the 510(k) application itself, but not typically summarized in the public clearance letter.
- Lack of AI/ML Component: There is no mention of AI or machine learning in the device description. Therefore, concepts like "human readers," "AI assistance," "effect size," "standalone algorithm," "training set," or "adjudication methods" for image interpretation are not applicable to the Sensititre system as described here.
To answer your questions accurately, one would need access to the actual 510(k) submission (K232310) which is often not publicly available in its entirety, or more specifically, the performance data section of that submission.
For illustrative purposes, if this were an AI/ML imaging device, a typical response addressing your questions would look like this (but again, the provided text does not support this):
Hypothetical Example (if this were an AI/ML imaging device and the information was available):
(Disclaimer: The following is entirely hypothetical and fabricated to demonstrate how your questions would be answered if the provided document were about an AI/ML medical device and contained the necessary study details. This information is NOT present in the provided FDA 510(k) clearance letter.)
The device is an AI-powered system designed to assist radiologists in detecting subtle findings on chest X-rays.
1. Table of Acceptance Criteria and Reported Device Performance
| Metric | Acceptance Criteria | Reported Device Performance (%) (95% CI) |
|---|---|---|
| Sensitivity (Standalone) | ≥ 90% for detecting actionable findings | 92.5% (91.1-93.8) |
| Specificity (Standalone) | ≥ 80% for non-actionable findings | 83.2% (82.0-84.3) |
| F-score (Standalone) | ≥ 0.85 | 0.88 |
| Reader Sensitivity (AI-assisted) | ≥ 5% improvement over unaided reading | 7.2% improvement (Statistically significant) |
| Reader False Positives (AI-assisted) | No significant increase over unaided reading | -1.5% change (Not statistically significant) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 5,000 anonymized chest X-ray images (DICOM format).
- Data Provenance: Retrospective study. Data collected from 10 different hospitals across the United States (70%), Canada (15%), and the UK (15%). Images covered a range of scanner types and patient demographics.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Number of Experts: 3 independent expert radiologists.
- Qualifications: All were board-certified radiologists with subspecialty training in thoracic imaging and a minimum of 10 years of post-fellowship clinical experience reading chest X-rays.
4. Adjudication Method for the Test Set
- Adjudication Method: 2+1. Two independent expert radiologists initially reviewed each case. If their initial assessments disagreed, a third, senior expert radiologist reviewed the case to reach a consensus for the final ground truth label.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Readers Improving with AI vs. Without AI Assistance
- MRMC Study: Yes, an MRMC study was conducted.
- Effect Size:
- Sensitivity: Human readers demonstrated a statistically significant increase in sensitivity of 7.2 percentage points (e.g., from 78.0% unaided to 85.2% with AI assistance) for detecting actionable findings.
- Specificity: No statistically significant change in specificity was observed, indicating the AI assistance did not lead to a significant increase in false positives.
- Reading Time: Average reading time per case decreased by 15% with AI assistance.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Standalone Performance: Yes, standalone performance was evaluated against the ground truth.
- Sensitivity: 92.5%
- Specificity: 83.2%
- AUC: 0.94 (Receiver Operating Characteristic Area Under the Curve)
7. The Type of Ground Truth Used
- Ground Truth Type: Expert consensus of 3 board-certified thoracic radiologists, further supported by correlation with available clinical outcomes data (e.g., follow-up imaging, pathology reports, surgical findings) where applicable and available in the retrospective dataset.
8. The Sample Size for the Training Set
- Training Set Sample Size: 50,000 anonymized chest X-ray images.
9. How the Ground Truth for the Training Set Was Established
- Ground Truth for Training:
- Initial labeling was performed by a team of trained clinical annotators.
- A subset of 10% of the training data was reviewed and verified by a single board-certified radiologist to ensure labeling consistency and accuracy.
- For particularly challenging or ambiguous cases during annotation, an internal consensus review by two radiologists was performed.
- A semi-supervised learning approach was employed where initial labels were used for training, and the model's performance on a validation set guided further expert review and refinement of labels for challenging cases.
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October 31, 2023
Thermo Fisher Scientific Dylan Staats Research Scientist III R&D Technical Lead, Global Clinical Trials Team Microbiology Division One Thermo Fisher Way Oakwood Village, Ohio 44126
Re: K232310
Trade/Device Name: Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Ceftolozane-tazobactam in the dilution range of 0.03/4 - 64/4ug/ml Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: JWY, LRG, LTT Dated: July 31, 2023 Received: August 2, 2023
Dear Dylan Staats:
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a
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change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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
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Indications for Use
510(k) Number (if known) K232310
Device Name
Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MC or Breakpoint Susceptibility System with Ceftolozanetazobactam in the dilution range of 0.03/4 - 64/4ug/ml
Indications for Use (Describe)
The Sensititre 20 - 24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnositic product for clinical susceptibility testing of fastidious isolates.
This 510(k) is for Ceftolozane-tazobactam in the dilution range of 0.03/4 - 64/4 µg/ml for testing H. influenzae on the Sensitite 20 - 24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System.
Ceftolozane-tazobactam has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: 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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§ 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).