(106 days)
The IRF parameter of the R-Series analyzers is intended for in-vit-vouse in --clinical laboratories. Its clinical use is to monitor bone marrow suppression and recovery in terms of erythropoiesis in situations of previous cancer chemotherapeutic bone marrow suppression and bone marrow transplantation. Qualified laboratory personnel are responsible for review of all abnormal results.
The R-1000, R-3000 and RAM-1 are table-top analyzer systems for automated reticulocyte counting. These instruments are dedicated flow cytometers which dilute and stain whole blood with a fluorescent dye (Auromine-O), then count and measure fluorescence and scatter of stained blood cells. The fluorescence intensity is measured, and the analyzer identifies the reticulocytes based on fluorescence and scatter. The fluorescent intensity of the reticulocytes is displayed on the analyzer as a scattergram, and this display is separated into three regions: Low Fluorescence Intensity (LFR), Middle Fluorescence Intensity (MFR), and High Fluorescence Intensity (HFR). These regions are reported as a ratio or percentage(sum = 100%), in addition to the analyzer's reporting total reticulocyte count and RBC count. The IRF parameter is determined by the sum of the MFR (Middle Fluorescence Ratio) and HFR (High Fluorescence Ratio) {MFR+HFR=IRF}.
Here's an analysis of the provided 510(k) summary regarding the Sysmex™ IRF parameter, focusing on acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes the intended use and performance of the Sysmex™ IRF parameter by comparing it to predicate methodologies. However, it does not explicitly state specific numerical acceptance criteria (e.g., sensitivity, specificity, accuracy thresholds) for the IRF parameter itself. Instead, it makes a general claim of similarity or superiority to existing methods.
| Acceptance Criteria (Not explicitly stated numerically in the document) | Reported Device Performance |
|---|---|
| Predictive indicator of bone marrow suppression and recovery for erythropoiesis in patients undergoing chemotherapy or bone marrow transplantation, similar or superior to predicate methods (WBC, ANC, reticulocyte count). | "The Immature Reticulocyte Fraction is similar to WBC and ANC, and similar or better than reticulocyte count as a monitor for bone marrow production." "Clinical studies have been performed which support this claim for patients receiving myeloablative chemotherapy." "In addition, several clinical studies have been published which support this claim for patients having undergone bone marrow transplantation." |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document does not specify the exact sample size for the test set used in the reported clinical studies. It vaguely mentions "clinical studies."
- Data Provenance: The document does not explicitly state the country of origin for the data or whether the studies were retrospective or prospective. It only refers to "clinical studies" and "published clinical studies."
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not provide information on the number of experts used or their qualifications to establish ground truth for the test set. Given the nature of the parameter (monitoring bone marrow activity), the "ground truth" would likely be derived from established clinical markers and patient outcomes rather than expert image interpretation.
4. Adjudication Method for the Test Set
The document does not specify any adjudication method (e.g., 2+1, 3+1, none) for the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was an MRMC study done? No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. The device (IRF parameter) is an automated laboratory test, not an imaging device requiring human reader interpretation. Therefore, a study to assess human reader improvement with AI assistance is not applicable.
- Effect size of human readers improving with AI vs. without AI assistance: Not applicable.
6. Standalone (Algorithm Only) Performance Study
- Was a standalone study done? Yes, the reported performance is inherently a standalone (algorithm only) performance. The Sysmex R-Series analyzers automatically calculate the IRF parameter. The clinical studies mentioned evaluate the predictive value of this automated parameter in monitoring bone marrow activity. The device is not designed as an AI assistant for human interpretation but rather as a direct measurement tool.
7. Type of Ground Truth Used
The ground truth for evaluating the IRF parameter's effectiveness appears to be:
- Clinical Outcomes/Established Clinical Markers: The ground truth is implied to be actual bone marrow suppression and recovery, as measured by established clinical indicators like WBC, ANC, and reticulocyte counts, and ultimately, patient outcomes in terms of erythropoiesis in the context of chemotherapy and bone marrow transplantation.
8. Sample Size for the Training Set
The document does not provide information on the sample size used for any training set. As this is an older 510(k) (1997) for a parameter derived from established flow cytometry principles (measuring fluorescence intensity), it's highly probable that traditional algorithms were used, not machine learning or AI models in the modern sense requiring extensive training sets with labeled ground truth in the same way. The device's underlying technology relies on physical measurements and thresholds.
9. How the Ground Truth for the Training Set Was Established
The document does not provide information on how ground truth was established for any training set. As mentioned, the technology likely predates modern AI training methodologies. The parameters (LFR, MFR, HFR, IRF) are based on the intrinsic fluorescent properties of reticulocytes at different maturation stages, and the "ground truth" for identifying these populations would have been established through extensive research into flow cytometry and reticulocyte biology. The "training" would have involved optimizing physical parameters and thresholds within the instrument's design based on known biological characteristics, rather than a data-driven machine learning approach.
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510(k) Summary of Safety and Effectiveness
Sysmex Corporation of America Gilmer Road 6699 RFD Long Grove, IL 60047-9596 (847)726-3662 Fax: (847)726-3505 Attention: Cathy Trester Date Prepared: May 5, 1997
AUG 26 1997
Sysmex™ IRF parameter (MFR+HFR) on R-1000, R-3000, RAM-1 analyzers, Trade name and Common name
The Sysmex™ IRF parameter is substantially equivalent to the reticulocyte count, and shows agreement to the WBC count as predictive indicators of bone marrow suppression and recovery.
The IRF parameter is obtained from the Sysmex R-1000(Premarket Notification K894539) R-3000 (Premarket Notification K912494) or SE/RAM-1(Premarket Notification K964375). The Sysmex™ R-3000, R-1000 and SE/RAM-1 are classified as Class II devices. The IRF parameter is classified as a Class III device.
Intended Use
The IRF is a clinical parameter obtained from the Sysmex™ R-Series automated reticulocyte analyzers. It is intended for in-vitro use in clinical laboratories. Its clinical use is to monitor bone marrow suppression and recovery in terms of erythropoiesis in situations of previous cancer chemotherapeutic bone marrow suppression and bone marrow transplantation. Qualified laboratory personnel are responsible for review of all abnormal results.
Device Description and Principles
The R-1000, R-3000 and RAM-1 are table-top analyzer systems for automated reticulocyte counting.
These instruments are dedicated flow cytometers which dilute and stain whole blood with a fluorescent dye (Auromine-O), then count and measure fluorescence and scatter of stained blood cells.
The fluorescence intensity is measured, and the analyzer identifies the reticulocytes based on fluorescence and scatter. The fluorescent intensity of the reticulocytes is displayed on the analyzer as a scattergram, and this display is separated into three regions: Low Fluorescence Intensity (LFR), Middle Fluorescence Intensity (MFR), and High Fluorescence Intensity (HFR). These regions are reported as a ratio or percentage(sum = 100%), in addition to the analyzer's reporting total reticulocyte count and RBC count. The IRF parameter is determined by the sum of the MFR (Middle Fluorescence Ratio) and HFR (High Fluorescence Ratio) {MFR+HFR=IRF}.
Comparison to Predicate Methodology and Clinical Data
In the area of assessment of bone marrow production, the predicate methodology is use of the white blood cell count (WBC), the absolute neutrophil count (ANC), or the reticulocyte count. The Immature Reticulocyte Fraction is similar to WBC and ANC, and similar or better than reticulocyte count as a monitor for bone marrow production. Clinical studies have been performed which support this claim for patients receiving myeloablative
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chemotherapy. In addition, several clinical studies have been published which support this claim for patients having undergone bone marrow transplantation.
Conclusion
The Sysmex™ Immature Reticulocyte Fraction (IRF) parameter provided by the R-Series reticulocyte analyzers has been shown to be a parameter of predictive value for bone marrow suppression and recovery.
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Image /page/2/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES" in a bold, sans-serif font. The text is arranged on a single line and is centered horizontally. The words are capitalized, and the overall appearance is clean and professional.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Catherine M. Trester, M.T. (ASCP) Clinical and Regulatory Affairs SYSMEX™ Corporation Gilmer Road, 6699 RFD AUG 26 1997 Long Grove, Illinois 60047-9596 ... ...
Re : K971736/S1 Trade Name: Sysmex™ Immature Reticulocyte Fraction (IRF) Parameter Requlatory Class: III Product Code: GKZ July 16, 1997 Dated: Received: July 18, 1997
Dear Ms. Trester:
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 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, Druq, 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 requirement, as set forth in the Quality System Requiation (QS) for Medical Devices: General requiation (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 requlatory 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 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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/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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Page_
510(k) Number (if known):
Device Name: Immature Reticulocyte Fraction on R-Series Analyzers
Indications For Use:
The IRF parameter of the R-Series analyzers is intended for in-vit-vouse in --clinical laboratories. Its clinical use is to monitor bone marrow suppression and recovery in terms of erythropoiesis in situations of previous cancer chemotherapeutic bone marrow suppression and bone marrow transplantation. Qualified laboratory personnel are responsible for review of all abnormal results.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number __
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use __
(Optional Format 1-2-96)
§ 864.5220 Automated differential cell counter.
(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”