(58 days)
Pasco MIC and MIC/ID panels are used for quantitatively measuring (with the exception of the Breakpoint/ID panel which provides qualitative measurement of category results) the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of those organisms.
This 510(k) notification is for the addition of Levotloxacin to Pasco panels at concentrations of 0.25-8 mcg/ml for use in determining the susceptibility of S. pneumoniae and non-pneumococcal streptococci.
Varying concentrations of antimicrobial agents (usually in two-fold dilutions) are dispensed into the Pasco panels and the panels are then frozen. Panels are thawed prior to use, inoculated with the test organisms, incubated the traditional 16-24 hours and panels are then observed for visible growth or color changes as described in the package insert. The lowest concentration of each antimicrobial agent with no apparent visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC). Changes in pH and production of specific metabolites from growth in biochemical substrates are interpreted as described in the package insert for conventional tubed media.
Here's a breakdown of the acceptance criteria and the study details for the Pasco MIC and MIC/ID Panels, specifically for the inclusion of Levofloxacin:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document defines "acceptance criteria" through the lens of what is considered "acceptable" for Essential Agreement (EA), Category Agreement (CA), and error rates (Major, Very Major, Minor). The reported device performance demonstrates that these criteria were met or exceeded.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (S. pneumoniae) | Reported Device Performance (Non-pneumococcal streptococci) |
|---|---|---|---|
| Essential Agreement (EA) | Acceptable agreement (not explicitly quantified but demonstrated by 100%) | 100% EA on initial testing | 100% EA on initial testing |
| Major Errors (M) | No Major Errors permitted | No Major Errors observed | No Major Errors observed |
| Very Major Errors (VM) | No Very Major Errors permitted | No Very Major Errors observed | No Very Major Errors observed |
| Minor Errors | Acceptable (e.g., small number, within EA) | No Minor Errors observed | 1 random Minor Error noted (within EA) |
| Category Agreement (CA) | Acceptable agreement (not explicitly quantified but demonstrated by 100%) | 100% CA | 100% CA |
| Reproducibility | 100% within +/- 1 dilution | 100% within +/- 1 dilution (11/12 organisms on-scale) | 100% within +/- 1 dilution (11/12 organisms on-scale) |
| QC Endpoints | Within recommended NCCLS acceptable range | Within recommended NCCLS acceptable range (S. pneumoniae ATCC 49619) | Within recommended NCCLS acceptable range (S. pneumoniae ATCC 49619) |
2. Sample Size Used for the Test Set and Data Provenance
- S. pneumoniae strains: 101
- Non-pneumococcal streptococci strains: 130
- QC organism (S. pneumoniae ATCC 49619): Tested throughout.
- Reproducibility organisms: 12 organisms at each of two sites (totaling 24 instances of reproducibility testing).
- Data Provenance: The study was "comparative testing...performed at two sites using CDC challenge strains and clinical isolates." This suggests a mix of standardized and real-world samples, likely prospective for the specific testing conducted for this submission. The country of origin is not explicitly stated but implied to be the US given the FDA submission context.
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 or qualifications of experts used to establish the ground truth. Ground truth for antimicrobial susceptibility testing typically involves comparison to a recognized gold standard method (often broth microdilution or agar dilution) performed by trained microbiologists. The reference to "reference panel" and "CDC challenge strains" implies that the ground truth was established by highly controlled and standardized methods, likely overseen by qualified laboratory personnel.
4. Adjudication Method for the Test Set
The document does not specify an adjudication method (such as 2+1, 3+1, none). Given the nature of antimicrobial susceptibility testing, which typically yields a definitive MIC result, a formal adjudication process between multiple readers is often not explicitly needed for individual readings but rather for resolving discrepancies between the test device and the reference method if they occur. The "reference panel" serves as the comparative gold standard.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is more common for diagnostic imaging where human interpretation varies significantly. For antimicrobial susceptibility testing, the focus is on the device's ability to accurately determine the MIC compared to a highly standardized reference method. The "human-in-the-loop" aspect is primarily the reading of the results from both the test and reference panels, but the study is not designed to measure an improvement in human reading performance with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device described is an "Antimicrobial Susceptibility Test Microbiology Panel," which involves physical panels inoculated with organisms and then observed for growth or color changes. While the interpretation of the lowest concentration of antimicrobial agent with no apparent growth is a critical step, the "device" itself is the physical panel and its methodology. This is not a standalone algorithm in the modern sense (e.g., an AI software reading an image). The "reading" is done by a laboratory technician based on visible changes. Therefore, the concept of "standalone algorithm performance" as separate from "human-in-the-loop" is not directly applicable in the way it is for AI/imaging devices. The device's performance is intrinsically linked to the observation and interpretation, which is typically a human task.
7. The Type of Ground Truth Used
The ground truth was established by a "reference panel". This typically refers to a standardized, well-accepted method for determining antimicrobial susceptibility (e.g., broth microdilution or agar dilution) performed in parallel with the test device. This "reference panel" constitutes a gold standard for comparison. Additionally, the study used "CDC challenge strains" which are well-characterized, standardized bacterial isolates with known susceptibility profiles, contributing to the robustness of the ground truth.
8. The Sample Size for the Training Set
The document does not specify a training set sample size. This is typical for a device based on established chemical and biological reactions, rather than a machine learning or AI-driven device. The "training" in this context refers to the development and optimization of the panel manufacturing and assay conditions, which would involve internal R&D and quality control, not a distinct "training set" in the AI sense.
9. How the Ground Truth for the Training Set Was Established
As there is no explicitly defined "training set" in the AI sense, the establishment of ground truth for such a set is not applicable. The development of the Pasco panels and their performance characteristics would have been guided by traditional microbiological methods and NCCLS (now CLSI) guidelines for susceptibility testing.
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SEP 3 1999
510(k) SUMMARY (page 1 of 2)
199229
| DATE: | June 23, 1999 |
|---|---|
| CONTACT PERSON: | Linda K. DillonChuck Lakel |
| TRADE NAME OF DEVICE: | Pasco MIC and MIC/ID Panels |
| COMMON NAME: | Antimicrobial Susceptibility Test |
| CLASSIFICATION NAME: | Class II Antimicrobial Susceptibility Test Microbiology Panel#83 |
SUBSTANTIAL EQUIVALENCE:
In review of previous 510(k) notifications for the Pasco MIC and MIC/ID panels (most recently: K982235, July 30, 1998 RE: Minocycline; K982156, July 29, 1998 RE: Cefdinir; K980955 May 18, 1998 RE: Trovafloxacin; K974362, February 12, 1998 RE: Cefepime; K973317, November 14, 1997 RE: Cefpodoxime; K973695, November 5, 1997 RE: Meropenem; K972567, August 20,1997 RE: Sparfloxacin; K971951, August 15, 1997 RE: Levofloxacin; and K946126, January 17, 1995 RE: Detection of resistant pneumococci), the FDA has determined the Pasco panels to be substantially equivalent to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments.
The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug, and Cosmetic Act, as amended and as applied under 21 CFR 807, Subpart E under which a device can be marketed without pre-market approval or reclassification. A determination of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or their application by the courts.
DESCRIPTION OF THE DEVICE:
Varying concentrations of antimicrobial agents (usually in two-fold dilutions) are dispensed into the Pasco panels and the panels are then frozen. Panels are thawed prior to use, inoculated with the test organisms, incubated the traditional 16-24 hours and panels are then observed for visible growth or color changes as described in the package insert.
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510(k) SUMMARY (page 2 of 2)
The lowest concentration of each antimicrobial agent with no apparent visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC). Changes in pH and production of specific metabolites from growth in biochemical substrates are interpreted as described in the package insert for conventional tubed media.
INTENDED USE FOR THE PASCO MIC AND MIC/ID PANELS:
PASCO MIC AND MIC/ID PANELS are used for quantitatively measuring (with the exception of the Breakpoint/ID panel which provides qualitative measurement or category results) the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of those organisms.
SUMMARY/CONCLUSION OF SUBSTANTIAL EQUIVALENCE TESTING:
Test panels containing Levofloxacin at concentrations ranging from 8-0.25 mcg/ml were prepared in-house at Pasco using routine manufacturing procedures. Comparative testing of the Pasco test panel to a reference panel was performed at two sites using CDC challenge strains and clinical isolates.
Test results of the 101 S. pneumoniae strains demonstrated acceptable Essential Agreement (EA) of 100% on initial testing. No major (M), very major (VM) or minor errors were observed. Category agreement (CA) was 100% with no random minor errors noted. Test results of the 130 nonpneumococcal streptococci strains demonstrated acceptable Essential Agreement (EA) of 100% on initial testing. No major (M), very major (VM) or minor errors were observed. Category Agreement (CA) was 100% with 1 random minor error noted (within EA).
QC endpoints for the QC organism S. pneumoniae ATCC 49619 from both the reference and Pasco panels throughout testing were within the recommended NCCLS acceptable range.
Reproducibility testing of 12 organisms at each site provided 11 organisms with on-scale endpoints. Overall reproducibility data demonstrated 100% within the acceptable plus or minus 1 dilution.
The results of the clinical testing, reproducibility testing and OC performance testing supports Substantial Equivalence as outlined in the FDA draft document "Review Criteria For Assessment Of Antimicrobial Susceptibility Devices" (May 1991).
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Image /page/2/Picture/1 description: The image is a seal for the Department of Health & Human Services (USA). The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the top half of the circle. In the center of the seal is an abstract image of an eagle's head.
SEP , 3 1999
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Linda K. Dillon Technical Manager Pasco Laboratories, Inc. 12750 West Forty-Second Avenue Wheat Ridge, Colorado 80033
K992297 Re:
Trade Name: PASCO MIC and MIC/ID Panels; Inclusion of Levofloxacin Regulatory Class: II Product Code: JTN Dated: June 23, 1999 Received: July 7, 1999
Dear Ms. Dillon:
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 (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). 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 Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS 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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Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
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 predicate device results in a classification 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 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Putman
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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ਹੈ
Device Name:
PASCO MIC and MIC/ID Panels; Inclusion of Levofloxacin
Indication For Use:
Pasco MIC and MIC/ID panels are used for quantitatively measuring (with the exception of the Breakpoint/ID panel which provides qualitative measurement of category results) the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of those organisms.
This 510(k) notification is for the addition of Levotloxacin to Pasco panels at concentrations of 0.25-8 mcg/ml for use in determining the susceptibility of S. pneumoniae and non-pneumococcal streptococci.
Woody Dubois
(Division Sign Off) Division of Clinical Laboratory Devices 510(k) Number .
§ 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).