(57 days)
IVD DEVICE CALIBRATION IS MOST COMMONLY PERFORMED USING CALIBRATORS (REFERENCE MATERIALS) SPECIFICALLY INTENDED TO BE USED AS A STANDARD CURVE OR CUT-OFF POINT FOR AN ASSAY.
A CALIBRATOR HAS AN ASSIGNED VALUE THAT IS ESTABLISHED BY THE MANUFACTURER BY A REFERENCE METHOD. CALIBRATORS EXIST IN A VARIETY OF MATRICES SUCH AS SIMULATED AQUEOUS, SERUM. PLASMA OR OTHER TYPES OF SPECIMENS.
PRIMARY REFERENCE CALIBRATORS ARE HIGHLY PURIFIED CHEMICALS THAT CAN BE DIRECTLY WEIGHED OR MEASURED TO PRODUCE A SOLUTION OF KNOWN CONCENTRATION. ALTERNATIVELY, THEY MAY BE MORE COMPLEX BIOLOGICAL MATERIALS HAVING RECEIVED A VALUE ASSIGNMENT USING REFERENCE (STANDARD) METHODOLOGY. THEY ARE SUPPLIED WITH A CERTIFICATE OF ANALYSIS FOR EACH LOT (FOR EXAMPLE, STANDARD REFERENCE MATERIALS (SRMS) FROM THE U.S. NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY (NIST)).
THE PRIMARY CALIBRATOR "CALIBRATION SOLUTION FOR OSMOMAT 010 / 030 / auto" IS USED TO CALIBRATE THE OSMOMETERS "OSMOMAT 030" AND "OSMOMAT AUTO", WHICH BOTH ARE FREEZING-POINT OSMOMETERS FOR USE IN CLINICAL CHEMISTRY. THE OSMOLALITY OF THE CALIBRATOR IS EQUAL TO THE OSMOLALITY OF BODY-FLUIDS (ISOTONIC SOLUTION), PROVIDING THAT THE OSMOMETER WILL BE CALIBRATED CORRECTLY FOR THE FLUIDS TO BE MEASURED FOR MEDICAL PURPOSES.
A FREEZING-POINT OR CRYOSCOPIC OSMOMETER IS A DEVICE TO MEASURE THE NUMBER OF MOLECULES OR IONS DISSOLVED IN A FLUID, IN THIS CASE, WATER. THE PHYSICAL EFFECT THE MEASUREMENT IS BASED ON IS THAT DISSOLVED SUBSTANCES IN WATER DEPRESS THE FREEZING POINT OF THE SOLUTION. THIS DEPRESSION IN THE FREEZING TEMPERATURE ITSELF, MEASURED EXACTLY, GIVES AN EXACT MEASURE FOR HOW MANY MOLECULES OR IONS ARE DISSOLVED IN THE AQUEQUS CALIBRATOR OR SPECIMEN. THIS EFFECT IS PHYSICAL, WHICH MEANS THAT THE CHEMICAL PROPERTIES OF THE CALIBRATOR OR SPECIMEN REMAIN UNCHANGED. AS ANY DISSOLVABLE SUBSTANCE CAUSES THIS EFFECT, THE RESULT OF THE MEASUREMENT GIVES NO INFORMATION ABOUT THE IDENTITY AND/OR COMPOSITION OF THE SUBSTANCES DISSOLVED, IF THERE SHOULD BE SEVERAL. THE MEASURED VALUE EXPRESSES IF THE RANGE OF OSMOLALITY OF THE SPECIMEN IS TO BE EXPECTED AS BEING NORMAL FOR A SPECIMEN FROM A HEALTHY HUMAN BEING. OR THE OSMOLALITY SHOWS THAT SOMETHING IS WRONG WITH THE PATIENT. FURTHER MEDICAL EXAMINATIONS WOULD FOLLOW. IN THE CALIBRATOR THE ONLY SUBSTANCE DISSOLVED IS SODIUM CHLORIDE. SO THE VALUE OF THE OSMOLALITY ALSO REPRESENTS THE CONCENTRATION OF SODIUM CHLORIDE.
TO MEASURE THE FREEZING-POINT-DEPRESSION. THE SAMPLE IS FROZEN CAREFULLY. THE EXACT TEMPERATURE OF THE FLUID IS MEASURED AT ANY TIME WHILE THE SAMPLE IS COOLED DOWN. THE TEMPERATURE AT WHICH THE FLUID FREEZES TO ICE IS DETERMINED EXACTLY AND THE INTERNAL CALCULATOR OF THE OSMOMETER CALCULATES AND DISPLAYS THE EQUIVALENT OSMOLALITY OF THE LIQUID. IN MATRICES LIKE URINE THE MEASUREMENT SHOWS IF THE KIDNEYS WORK PROPERLY ASSUMABLY.
Here's an analysis of the provided 510(k) summary regarding the calibration solution, structured to address your specific questions.
Based on the provided text, it's crucial to understand that this submission is for a calibration solution, not a diagnostic device that performs measurements or generates diagnostic outputs in the way an AI algorithm would. Therefore, many of your questions, particularly those related to clinical studies, human reader performance, ground truth establishment for AI, and sample sizes for training/test sets, are not applicable to this type of device and are not addressed in the provided 510(k) summary.
The 510(k) summary focuses on demonstrating that the calibration solution is substantially equivalent to a legally marketed predicate device, primarily through its intended use and performance as a calibrator.
Acceptance Criteria and Device Performance for Calibration Solution
Given the nature of the device (a primary calibrator), the "acceptance criteria" relate to its ability to accurately provide a known osmolality for the osmometer to be calibrated against, and its similarity to the predicate device. The performance is assessed against the established value of the calibrator itself.
1. A table of acceptance criteria and the reported device performance
| Acceptance Criteria Category | Acceptance Criteria (Implied from the document) | Reported Device Performance |
|---|---|---|
| Intended Use | To be used as a primary calibrator for freezing-point osmometers (specifically OSMOMAT 010 / 030 / auto) in clinical chemistry. | The device is explicitly described as "THE PRIMARY CALIBRATOR 'CALIBRATION SOLUTION FOR OSMOMAT 010 / 030 / auto' IS USED TO CALIBRATE THE OSMOMETERS 'OSMOMAT 030' AND 'OSMOMAT AUTO', WHICH BOTH ARE FREEZING-POINT OSMOMETERS FOR USE IN CLINICAL CHEMISTRY." This directly matches the intended use. |
| Composition/Nature of Calibrator | Consist of highly purified chemicals (e.g., sodium chloride) that can produce a solution of known concentration/osmolality. | "IN THE CALIBRATOR THE ONLY SUBSTANCE DISSOLVED IS SODIUM CHLORIDE." "THE MEASURED VALUE EXPRESSES IF THE RANGE OF OSMOLALITY OF THE SPECIMEN IS TO BE EXPECTED AS BEING NORMAL FOR A SPECIMEN FROM A HEALTHY HUMAN BEING." "THE CALIBRATOR HAS AN ASSIGNED VALUE THAT IS ESTABLISHED BY THE MANUFACTURER BY A REFERENCE METHOD." This confirms it's a primary calibrator with a known composition and assigned value. |
| Osmolality Value | Provide an osmolality value suitable for calibrating osmometers for body fluids (isotonic solution). | "THE OSMOLALITY OF THE CALIBRATOR IS EQUAL TO THE OSMOLALITY OF BODY-FLUIDS (ISOTONIC SOLUTION), PROVIDING THAT THE OSMOMETER WILL BE CALIBRATED CORRECTLY FOR THE FLUIDS TO BE MEASURED FOR MEDICAL PURPOSES." This indicates the calibrator's value aligns with physiological relevance. |
| Substantial Equivalence to Predicate | Performance and characteristics must be substantially equivalent to the predicate device (K931834: King Diagnostics, Sodium/Potassium standard modified). | The FDA's 510(k) clearance letter explicitly states, "We have reviewed your Section 510(k) premarket notification... and have determined the device is substantially equivalent... to legally marketed predicate devices." This is the overarching finding of the 510(k) process, indicating that the device meets the criteria for substantial equivalence to the specified predicate. No specific performance data (e.g., precision, stability) for the new calibrator is provided in this summary, but its substantial equivalence implies that its performance is comparable to the predicate. |
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 applicable and not provided in the 510(k) summary because the device is a calibrator, not a diagnostic test. There isn't a "test set" of patient data in the context of clinical studies for an AI-powered device. The "test" for a calibrator involves verifying its stated value and stability, which would be done internally by the manufacturer using laboratory methods.
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 and not provided. The "ground truth" for a calibrator is its assigned osmolality value, which is established by the manufacturer through rigorous analytical methods (e.g., gravimetric preparation, reference measurement systems), not by clinical expert consensus.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This is not applicable and not provided. Adjudication methods are relevant for resolving discrepancies in expert interpretations of clinical data, which is not relevant for a calibration solution.
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 and not provided. MRMC studies are for evaluating the performance of diagnostic systems (often AI-assisted) and their impact on human reader performance. This device is a calibrator, not a diagnostic system.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
This is not applicable and not provided. This question pertains to the performance of an AI algorithm in isolation. The device is a physical calibration solution, not an algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" for this device is its assigned osmolality value, which is established by the manufacturer using reference analytical methodologies (e.g., gravimetric methods, comparison to NIST traceable standards if available, or other validated laboratory methods) for highly purified chemicals like sodium chloride. The document states: "A CALIBRATOR HAS AN ASSIGNED VALUE THAT IS ESTABLISHED BY THE MANUFACTURER BY A REFERENCE METHOD." and "PRIMARY REFERENCE CALIBRATORS ARE HIGHLY PURIFIED CHEMICALS THAT CAN BE DIRECTLY WEIGHED OR MEASURED TO PRODUCE A SOLUTION OF KNOWN CONCENTRATION."
8. The sample size for the training set
This is not applicable and not provided. There is no "training set" for a calibration solution. This concept applies to machine learning algorithms.
9. How the ground truth for the training set was established
This is not applicable and not provided. As there is no training set, there's no ground truth to establish for it in this context.
§ 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.