(95 days)
For the IN VITRO diagnostic use as calibrators for the DCL CRP-ADVANCE Assay for the quantitation of C-reactive protein in serum.
The CRP-ADVANCE Multi-Calibrator Set, Cat. No. SE-250 are C-reactive protein standards containing known quantities of human c-reactive protein. These calibrators are to be use with the DCL CRP-ADVANCF Assay.
The provided document is a 510(k) premarket notification letter from the FDA regarding a CRP-ADVANCE Multi-Calibrator Set. This device is a calibrator used for in vitro diagnostic assays to quantify C-reactive protein in serum.
Given the nature of this device (a calibrator, not an AI/ML-driven diagnostic device or imaging device), the requested information about acceptance criteria, study design, expert involvement, and ground truth establishment, as typically applied to AI/ML or imaging diagnostics, is largely not applicable or would be addressed through different types of validation studies (e.g., analytical validation studies for calibrators).
Nevertheless, I will interpret the request based on the information that can be inferred or is typically required for such a device.
Here's an attempt to answer the questions, highlighting when information is not present in the provided document or is not applicable to this type of device:
1. A table of acceptance criteria and the reported device performance
The provided document (an FDA 510(k) clearance letter) does not contain detailed acceptance criteria or detailed performance data from a specific study. Instead, it states that the device is "substantially equivalent" to a legally marketed predicate device. For a calibrator, acceptance criteria would typically revolve around its ability to:
- Accurately assign values (e.g., target concentrations of C-reactive protein).
- Demonstrate stability over its shelf life.
- Show lot-to-lot consistency.
- Be compatible with the intended assay (DCL CRP-ADVANCE Assay).
The "reported device performance" is essentially the FDA's determination of substantial equivalence, meaning it performs as intended and is as safe and effective as the predicate device. Specific numerical performance metrics are not provided in this regulatory letter but would have been part of the 510(k) submission.
| Acceptance Criteria (Inferred for a Calibrator) | Reported Device Performance (Inferred/Stated) |
|---|---|
| Accurate assignment of C-reactive protein values across the calibration range. | Not explicitly detailed in this letter. The FDA's substantial equivalence determination implies acceptable performance in this regard, consistent with the predicate device. |
| Stability (e.g., maintaining assigned values over specified temperature/time). | Not explicitly detailed in this letter. Assumed to meet required stability metrics as part of the 510(k) submission. |
| Lot-to-lot consistency in performance. | Not explicitly detailed in this letter. Assumed to meet required consistency metrics. |
| Compatibility with the DCL CRP-ADVANCE Assay (e.g., proper calibration curve generation). | Stated indication for use: "For the IN VITRO diagnostic use as calibrators for the DCL CRP-ADVANCE Assay for the quantitation of C-reactive protein in serum." This implies successful studies demonstrating compatibility and functionality with the specified assay were submitted. |
| Substantial equivalence to a predicate device. | The FDA determined the device is "substantially equivalent" to legally marketed predicate devices, meaning it meets the necessary standards for safety and effectiveness. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
This information is not present in the FDA 510(k) clearance letter. For a calibrator, a "test set" wouldn't typically involve patient data in the way an AI diagnostic would. Instead, it would involve:
- A set of calibrator lots (for lot-to-lot variability studies).
- Reference materials or samples with known C-reactive protein concentrations (to verify assigned values).
- Samples tested on the DCL CRP-ADVANCE Assay using the calibrators.
The provenance (country, retrospective/prospective) is also not specified.
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 is not applicable in the context of this device. Calibrators do not have "ground truth" in the sense of expert human interpretation of images or clinical data. The "ground truth" for a calibrator would be its assigned concentration of C-reactive protein, which is established through rigorous analytical methods, often traceable to international reference standards or highly precise laboratory measurements, not subjective expert consensus.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This is not applicable for a calibrator. Adjudication methods like 2+1 or 3+1 are used for resolving disagreements among multiple human readers/experts when establishing ground truth for diagnostic decisions, typically in imaging or clinical scenarios.
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
This is not applicable to a calibrator. MRMC studies are used for evaluating diagnostic devices, especially those involving human interpretation, often in the context of AI assistance. A calibrator is a foundational component of an assay; it doesn't involve human 'readers' or 'cases' in this manner, nor does it involve AI.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is not applicable to a calibrator. A calibrator is a physical reagent set, not an algorithm, and does not have a "standalone performance" in the context of AI. Its performance is demonstrated through its ability to accurately calibrate an assay.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
For a calibrator, the "ground truth" for its values (C-reactive protein concentrations) would be established by:
- Traceability to a primary reference material or standard: Often established through highly accurate analytical techniques, possibly gravimetric or spectroscopic methods, benchmarked against international standards.
- Value assignment studies: Using precise analytical methods within a well-controlled laboratory environment to determine the concentration of the analyte in each calibrator level.
This is a measured, analytically derived ground truth, not based on expert consensus, pathology, or outcomes data.
8. The sample size for the training set
This is not applicable to a calibrator in the way it applies to AI/ML devices. Calibrators are not "trained" on data. Their formulation and characteristics are developed through chemical and biological engineering, and their values are assigned through analytical validation.
9. How the ground truth for the training set was established
This is not applicable as there is no "training set" for a calibrator. The "ground truth" of the calibrator's assigned values is established through the analytical methods described in point 7.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three talons, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is written around the perimeter of the circle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Penny White Regulatory Affairs Coordinator External, Diagnostic Division Diagnostic Chemicals Limited 16 McCarville Street Charlottetown, PE C1E 2A6
APR 2 4 2006
Re: K060140 Trade/Device Name: CRP-ADVANCE Multi-Calibrator Set Regulation Number: 21 CFR§862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIT Dated: March 14, 2006 Received: March 17, 2006
Dear Ms. White:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours.
Alberto Gutt
Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
100140 510(k) Number (if known):_____________________________________________________________________________________________________________________________________________________
Device Name: CRP-ADVANCE Multi-Calibrator Set
Indications For Use:
For the IN VITRO diagnostic use as calibrators for the DCL CRP-ADVANCE Assay for the quantitation of C-reactive protein in serum.
Identification.
The CRP-ADVANCE Multi-Calibrator Set, Cat. No. SE-250 are C-reactive protein standards containing known quantities of human c-reactive protein. These calibrators are to be use with the DCL CRP-ADVANCF Assay.
Prescription Use X (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 CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Carol Benem
Revision Sign-Off
Page 1 of
Ciffice of In Vitro Diagnostic Device Evaluation and Safety
K0600140
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.