(77 days)
The Sensititre® 18 - 24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates. This 510(k) is for the removal of the limitation for the ability to detect resistance for Meropenem (0.004 - 8μg/mL) and Enterobacteriaceae and for the addition of the newly approved breakpoints (S≤1, |=2, R≥4) on the Sensititre® 18 - 24 hour MIC panel for testing Gram negative isolates. The approved primary, "Indications for Use" and clinical significance for Enterobacteriaceae is for the following species: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis. In vitro data, without clinical correlation is provided for: Aeromonas hydrophila, Citrobacter koseri (formerly diversus), Citrobacter freundii, Enterobacter cloacae, Hafnia alvei, Klebsiella oxytoca, Morganella morganii, Proteus vulgaris, Serratia marcescens.
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This document is an FDA 510(k) clearance letter for a medical device called the "Sensititre 18-24 hour MIC Susceptibility System." As such, it does not contain the detailed study information generally associated with acceptance criteria and device performance studies (e.g., sample sizes, expert qualifications, ground truth methodology) for a typical AI/ML-based medical device.
Instead, this document focuses on the regulatory clearance process for an in vitro diagnostic product (antimicrobial susceptibility test). The "acceptance criteria" here refer to the performance standards for antimicrobial susceptibility testing (AST), which are typically defined by regulatory bodies (like FDA) and standardized by organizations (like CLSI - Clinical and Laboratory Standards Institute).
The key performance metrics for AST devices focus on how accurately they categorize bacterial isolates as susceptible, intermediate, or resistant to an antibiotic.
However, based on the provided text, I can extract and infer some information, particularly regarding the Indications for Use and the context of the device clearance.
Here's a breakdown of what can be extracted/inferred:
1. A table of acceptance criteria and the reported device performance:
The document doesn't provide a typical table of statistical acceptance criteria (e.g., sensitivity, specificity thresholds) and corresponding reported performance values like a clinical study report would. Instead, it states the purpose of the 510(k) is:
- "for the removal of the limitation for the ability to detect resistance for Meropenem (0.004 - 8μg/mL) and Enterobacteriaceae"
- "for the addition of the newly approved breakpoints (S≤1, I=2, R≥4) on the Sensititre® 18 - 24 hour MIC panel for testing Gram negative isolates."
This implies that the "acceptance criteria" were met by demonstrating that the device:
- Can reliably detect resistance to Meropenem for Enterobacteriaceae within the specified MIC range.
- Accurately applies the updated breakpoints for Meropenem in Gram-negative isolates.
To meet these, the device's performance would have been compared against a reference method (likely broth microdilution or agar dilution as per CLSI standards) and statistical agreement measured. The FDA would have assessed Essential Agreement (EA) and Categorical Agreement (CA), and typically very major, major, and minor error rates. While the specific numerical acceptance criteria (e.g., >90% EA, >90% CA) commonly used for ASTs are not explicitly stated in this letter, they would have been part of the underlying submission.
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- Sample Size: Not specified in the provided document. For AST devices, sample sizes are typically determined by the number of unique clinical isolates tested, often across multiple strains and resistance mechanisms, as per CLSI guidelines, to ensure adequate statistical power for assessing agreement.
- Data Provenance: Not specified in the provided document. Such studies are generally conducted in CLSI-compliant laboratories, often in the US, but the specific country of origin is not mentioned. They would be prospective in the sense that the device is being tested on newly identified bacterial strains, though the strains themselves might be from a collection (retrospective repository) but cultured and tested prospectively.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
- This type of device (antimicrobial susceptibility test) does not typically involve human "experts" establishing a "ground truth" in the way an imaging AI device would.
- Ground Truth Establishment: The ground truth for antimicrobial susceptibility testing is established by a reference method, most commonly a standardized broth microdilution or agar dilution method, as defined by organizations like CLSI. The interpretation of these reference method results (e.g., determining S, I, or R based on MIC values) follows established guidelines, not individual expert opinion. The "experts" involved would be trained microbiologists performing the reference method in a GLP-compliant laboratory environment.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Adjudication Method: Not applicable for this type of device. Adjudication methods (like 2+1 or 3+1) are used to resolve disagreements between human readers in image interpretation. Here, the ground truth is an objective laboratory reading, and the device's result is compared directly to it.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- MRMC Study: Not applicable. This is an automated in vitro diagnostic device, not an AI-assisted diagnostic tool designed to improve human reader performance. The device provides a result directly.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Standalone Performance: Yes, this device's performance is inherently "standalone." It is an automated system that determines antimicrobial susceptibility without human interpretation of raw data points to categorize. Human involvement is in setting up the test and interpreting the final device output.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Ground Truth: The ground truth for this device is established by a standardized reference method, typically broth microdilution or agar dilution, interpreted according to established clinical breakpoints (e.g., CLSI guidelines).
8. The sample size for the training set:
- Training Set: Not applicable in the context of traditional machine learning training sets for AI devices. This device is likely based on chemical reactions and optical readings rather than a deep learning algorithm trained on a large dataset of results. Its "development" phase would involve optimizing the reagents, reading algorithms, and interpretive logic.
9. How the ground truth for the training set was established:
- Training Set Ground Truth: Not applicable, as explained above. The underlying principles are established microbiological methods and their correlation to clinical outcomes over decades of research, rather than a machine learning training process with a specific ground truth dataset.
In summary, the provided document is a regulatory clearance for a traditional in vitro diagnostic device, not an AI/ML-based device. Therefore, many of the requested details about study design (e.g., expert-driven ground truth, MRMC studies, AI training sets) are not relevant or present in this type of document. The acceptance criteria would have been met by demonstrating sufficient agreement (essential and categorical) with a recognized reference method for antimicrobial susceptibility testing.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
THERMO FISHER SCIENTIFIC C/O CYNTHIA KNAPP DIRECTOR OF CLINICAL OPERATIONS I THERMO FISHER WAY OAKWOOD VILLAGE OH 44146
. February 27, 2014
Re: K133773
Trade/Device Name: Sensititre 18-24 hour MIC Susceptibility System Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: JWY, LRG, LTT Dated: December 12, 2013 Received: December 13, 2013
Dear Ms. Knapp:
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 (QS) 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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Page 2-Ms. Knapp
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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 Small Manufacturers, International and Consumer Assistance 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" (21CFR 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 Small Manufacturers, International and Consumer Assistance 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.
Uwe Scherf -S for
Sally A. Hojvat, 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): K133773
Device Name: The Sensititire® 18 - 24 hour MIC Susceptibility System Test Panel with Meropenem (0.004 - 8μg/mL)
Indications for Use:
The Sensititre® 18 - 24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates.
This 510(k) is for the removal of the limitation for the ability to detect resistance for Meropenem (0.004 - 8μg/mL) and Enterobacteriaceae and for the addition of the newly approved breakpoints (S≤1, |=2, R≥4) on the Sensititre® 18 - 24 hour MIC panel for testing Gram negative isolates.
The approved primary, "Indications for Use" and clinical significance for Enterobacteriaceae is for the following species:
Escherichia coll Klebsiella pneumoniae Proteus mirabilis
In vitro data, without clinical correlation is provided for:
Aeromonas hydrophila Citrobacter koseri (formerly diversus) Citrobacter freundii Enterobacter cloacae Hafnia alvei Klebsiella oxytoca Morganella morganii Proteus vulgaris Serratia marcescens
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of Center for Devices and Radiological Health (CDRH)
Ribhi Shawar 2014.02.26 17:
§ 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).