(123 days)
Mission Glucose Reagent is intended for in vitro diagnostic use for the quantitative determination of glucose in serum, plasma, cerebrospinal fluid (CSF) and urine on Beckman Synchron CX® & CX® Delta Systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and pancreatic islet cell carcinoma.
Glucose concentration is determined by an oxygen rate method employing a Beckman Oxygen Electrode. Electronic circuits determine the rate of oxygen consumption, which is directly proportional to the concentration of glucose in the sample. Mission manufactures reagents intended to serve as direct replacements to like named products manufactured by Original Equipment Manufactures (OEM). All CX® & CX® Delta Systems that measure glucose utilize the same measurement method and reagent. The reagent is intended for use on equivalent OEM Instruments. Mission uses a similar composition, description and packaging as that used by the OEM in its products.
Here's an analysis of the provided text, outlining the acceptance criteria and the study used to demonstrate the device meets these criteria.
Acceptance Criteria and Device Performance for Mission Diagnostic Glucose Reagent
This medical device is an in-vitro diagnostic reagent intended for the quantitative determination of glucose in various biological samples (serum, plasma, CSF, and urine) on Beckman Synchron CX® & CX® Delta Systems. The goal of the 510(k) submission is to demonstrate substantial equivalence to an existing predicate device (Beckman PN 443355 Glucose Reagent). Therefore, the acceptance criteria are implicitly tied to demonstrating comparable performance to the predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
Given that this is a 510(k) for a glucose reagent intended to be substantially equivalent to an existing one, the "acceptance criteria" are not explicitly stated as strict pass/fail thresholds in the provided document. Instead, the study aims to show that the Mission Glucose Reagent performs similarly to the predicate Beckman reagent. The reported performance metrics are designed to demonstrate this similarity across various aspects.
| Performance Metric | Implied Acceptance Criterion (relative to predicate) | Mission Glucose Reagent Performance | Supporting Study/Data |
|---|---|---|---|
| Precision (Within-Run & Total %CV) | Should be comparable to or better than predicate, and clinically acceptable for glucose measurement. | CSF Control 1: Swr %CV 1.3%, ST %CV 6.3%CSF Control 2: Swr %CV 5.0%, ST %CV 10.1%Serum Control 1: Swr %CV 2.3%, ST %CV 6.7%Serum Control 2: Swr %CV 0.1%, ST %CV 7.0%Urine Control 1: Swr %CV 2.3%, ST %CV 5.1%Urine Control 2: Swr %CV 0.8%, ST %CV 5.0% | NCCLS Guideline EP5-A Precision Study |
| Method Comparison (Correlation with Predicate) | Strong linear correlation, slope near 1, intercept near 0, high R-squared value, and acceptable standard error of the estimate. | Serum: Mission = 1.038 x Beckman - 2.31; r² = 0.998; Range = 0 to 900 mg/dL; S(vx) = 9.00 mg/dL (n=50)Urine: Mission = 1.022 x Beckman + 1.067; r² = 0.998; Range = 1 to 293 mg/dL; S(vx) = 2.85 mg/dL (n=57)CSF: Mission = 1.014 x Beckman - 0.920; r² = 0.997; Range = 8 to 118 mg/dL; S(vx) = 1.68 mg/dL (n=36) | NCCLS Guideline EP9-A2 Method Comparison Study |
| Recovery to Expected Values | Percentage recovery of spiked/diluted samples should be similar for Mission and Beckman reagents across various concentrations. | Serum: Mission 83.3-115.4% (mean 103%), Beckman 83.3-117.5% (mean 103%)Urine: Mission 88-120% (mean 101%), Beckman 87-110% (mean 97%)CSF: Mission 88-98% (mean 94%), Beckman 88-100% (mean 95%) | Recovery to Expected Values Evaluation |
| Functional Sensitivity (Lower Limit of Detection) | Performance at low concentrations, particularly %CV less than 20% at clinically relevant low levels. | Lowest level with %CV < 20%:10 mg/dL (Mission), 8 mg/dL (Beckman) | Functional Sensitivity Study |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study:
- Sample Size: 80 measurements for each of the 6 control levels (CSF Control 1 & 2, Serum Control 1 & 2, Urine Control 1 & 2). This involved 20 days, 2 runs per day, 2 observations per run (20 * 2 * 2 = 80).
- Data Provenance: Not explicitly stated, but typically these samples are laboratory-prepared control materials. The study was conducted on an "instrument operated according to the manufacturers instructions," implying in a controlled lab environment. This would be considered prospective data collection.
- Method Comparison Study:
- Serum: n = 50 serum samples.
- Urine: n = 57 urine samples.
- CSF: n = 36 CSF samples.
- Data Provenance: Samples were "spiked or diluted." This suggests a combination of patient samples and artificially prepared samples. The origin (country/institution) is not specified. It is likely prospective data collection, as samples were "run in triplicate and tested with each reagent."
- Recovery to Expected Values Study:
- Sample Size: Numbers for specific dilutions/spikes are not provided, but generally involved "pooled serum," "urine control 1 & 2," and "CSF control 1 & 2" with various dilutions.
- Data Provenance: Laboratory-prepared spiked and diluted control materials and pooled samples. This is prospective data.
- Functional Sensitivity Study:
- Sample Size: 20 measurements (4 samples per run over 5 calibrated runs) for each of the 5 dilution levels (43, 14, 9, 2, 0 mg/dL expected values).
- Data Provenance: Laboratory-prepared dilutions of serum samples. This is prospective data.
3. Number of Experts Used to Establish Ground Truth and Qualifications of Experts
This type of device (glucose reagent for in-vitro diagnostics) does not typically involve human experts for establishing ground truth as understood in imaging or clinical decision support AI. The "ground truth" here is the actual concentration of glucose in a sample, determined by highly accurate reference methods or by the predicate device itself.
-
Ground Truth Establishment:
- For Method Comparison, the "ground truth" for comparison is the result obtained from the predicate Beckman Glucose Reagent.
- For Recovery to Expected Values, the "ground truth" is the gravimetrically determined or calculated expected concentration of glucose in the spiked/diluted samples.
- For Functional Sensitivity, the "ground truth" is the calculated expected value of the diluted serum samples.
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Number and Qualifications of Experts: Not applicable in the context of this device and study. The accuracy relies on the performance of the analytical instrument and comparison to a well-established predicate or gravimetric preparation.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used in studies where human expert interpretations are subject to disagreement. This is not relevant for an in-vitro diagnostic reagent study where quantitative measurements are compared.
- Adjudication Method: Not applicable. Measurements are quantitative, and differences are analyzed statistically.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was a MRMC study done? No. This type of study is for evaluating human reader performance, often with or without AI assistance, especially in imaging. It is not relevant for an in-vitro diagnostic reagent.
- Effect size of human readers improve with AI vs without AI assistance: Not applicable.
6. Standalone (Algorithm Only) Performance Study
- Was a standalone study done? Yes, in a sense. The studies described (Precision, Method Comparison, Recovery, Functional Sensitivity) evaluate the performance of the Mission Glucose Reagent (the "algorithm" or device under test) independently of human interpretation bias. Its performance is measured directly against the predicate or expected values. The instrument (Beckman Synchron CX® & CX® Delta Systems) executes the reagent's chemistry, and the results are read directly.
7. Type of Ground Truth Used
- Method Comparison: The predicate device's measurement (Beckman Glucose Reagent) was used as the comparative "ground truth."
- Recovery to Expected Values: Gravimetrically determined or calculated expected concentrations in spiked/diluted samples.
- Functional Sensitivity: Calculated expected values based on dilutions of known concentration.
- Precision: No external ground truth is used; it assesses the reproducibility of the device's own measurements.
8. Sample Size for the Training Set
The concept of a "training set" is usually associated with machine learning or AI models. This device is a chemical reagent, not an AI algorithm. Therefore, there is no "training set" in the conventional sense. The development of the reagent would involve formulation and optimization experiments, but these are distinct from a machine learning training set.
- Sample Size for Training Set: Not applicable.
9. How the Ground Truth for the Training Set Was Established
As there is no training set for this chemical reagent, this question is not applicable.
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510(k) Summary for Mission Diagnostic Glucose Reagent for Beckman Synchron CX® & CX® Delta Systems
| Mission Diagnostics331 Fiske StHolliston MA 01746FAX: 508-429-0452 | Linda StundtnQA/RA Manag508-429-0450 | |
|---|---|---|
| -------------------------------------------------------------------------------- | -- | ---------------------------------------------- |
| Establishment Registration Number: | 3003656721 |
|---|---|
| Date of Preparation: | Jan 16, 2004 |
- Identification of the Device:
| Proprietary/Trade name: | Glucose Reagent for Beckman SynchronCX® & CX® Delta Systems |
|---|---|
| Common or usual name | Glucose Reagent |
| Classification name: | Glucose test system |
| Device Classification | II |
Mission manufactures reagents intended to serve as direct replacements to like named products . manufactured by Original Equipment Manufactures (OEM)
21 CFR § 862.1345
Chemistry (75)
3. Predicate Device:
Panel:
Regulation Number:
Product Code:
- Mission claims substantial equivalence to the OEM Reagent listed below: .
CGA
Substantial Equivalence Table of Product PN & Trade Names
| Mission Product | OEM Equivalent | ||
|---|---|---|---|
| BK-443355D | Glucose Reagent | 443355 | Glucose Reagent |
- The predicate reagent, Beckman PN 443355, is encompassed in the 510(k)'s K942676 & ● K864236 cleared 11/02/1994 & 12/31/1986 respectively.
4. Device Description:
- Glucose concentration is determined by an oxygen rate method employing a Beckman Oxygen . Electrode Electronic circuits determine the rate of oxygen consumption, which is directly proportional to the concentration of glucose in the sample45
Intended Use:
- Mission Glucose Reagent is intended for the quantitative determination of glucose in serum, . plasma, cerebrospinal fluid (CSF) and urine on Beckman Synchron CX® & CX® Delta Systems.
- Glucose measurements are used in the diagnosis and treatment of carbohydrate . metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and pancreatic islet cell carcinoma.
133055
Contact Person:
Linda Stundtner anager 0450
JAN S 0 2004
Submitter's Name & Address
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- All CX® & CX® Delta Systems that measure glucose utilize the same measurement method . and reagent.
- The original equipment manufacturer (OEM) of the instruments and the predicate reagents . are necessary for the continued operation and use of the instruments.
- The reagent is intended for use on equivalent OEM Instruments. .
- Mission uses a similar composition, description and packaging as that used by the OEM in its . products, as shown in the packaging section of this submission.
5. Performance Characteristics:
Precision and correlation data are collected per:
- SOP23-01-02 Performance Study Protocol for 510(k) Submission .
Precison and Correlation are summarized below:
Precision data was collected following the guidelines of NCCLS Guideline EP5-A
- Samples were run for 20 days, 2 runs per day, 2 observations per run on an instrument . operated according to the manufacturers instructions. The following data was obtained:
| N | TestMeanmg/dL | Swrwithinrun sd | % CV | STTotalsd | %CV | |
|---|---|---|---|---|---|---|
| CSF Control 1 | 80 | 59 | 0.8 | 1.3 | 3.8 | 6.3 |
| CSF Control 2 | 80 | 30 | 1.5 | 5.0 | 3.0 | 10.1 |
| Serum Control 1 | 80 | 89 | 2.1 | 2.3 | 6.0 | 6.7 |
| Serum Control 2 | 80 | 308 | 2.2 | 0.1 | 21.7 | 7.0 |
| Urine Control 1 | 80 | 45 | 1.0 | 2.3 | 2.3 | 5.1 |
| Urine Control 2 | 80 | 287 | 2.4 | 0.8 | 14.4 | 5.0 |
Method Comparison of Mission Glucose Reagent to Beckman Reagent following the guidelines of NCCLS Guideline EP9-A2 was conducted.
Serum samples were spiked or diluted and run in triplicate and tested with each reagent, Mission Glucose Reagent and Beckman Glucose Reagent in separate calibrated runs. Recoveries of individual observations were compared by least squares regression. The following statistics were obtained:
Mission = 1.038 x Beckman - 2.31 Range = 0 to 900 mg/dL; r2 = 0.998; df = 49; n = 50; S(vx) = 9.00 mg/dL
Urine controls were spiked or diluted and run in triplicate and tested with each reagent, Mission Glucose Reagent and Beckman Glucose Reagent in separate calibrated runs. Recoveries were compared by least squares regression. The following statistics were obtained:
Mission = 1.022 x Beckman + 1.067 Range = 1 to 293 mg/dL; r2 = 0.998; df = 56; n = 57; Sq(x) = 2.85 mg/dL
CSF controls were spiked or diluted and run in triplicate and tested with each reagent, Mission Glucose Reagent and Beckman Glucose Reagent in separate calibrated runs. Recoveries of individual observations were compared by least squares regression. The following statistics were obtained:
Mission = 1.014 x Beckman =0.920 Range = 8 to 118 mg/dL; r2 = 0.997; df = 35; n = 36; S((x) = 1.68 mg/dL
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Recovery to Expected Values was evaluated for each matrix; serum, urine and CSF. Dilutions of the respective matrices were made and measured with Mission and Beckman reagent.
- Pooled Serum was spiked to an expected value of 950 mg/dL by adding glucose gravimetrically. . Dilutions were made using the spiked serum, serum, and/or Human serum albumin (HmSA).
- Urine recovery samples were made by mixing Urine Control 2 (expected value = 300 mg/dL), Urine . Control 1 (expected value = 50 mg/dL), and/or Normal saline.
- CSF recovery samples were made by mixing CSF Control 2 (expected value = 100 mg/dL), CSF . Control 1 (expected value = 50 mg/dL), and/or Human Serum Albumin.
% Recovery = (Measured/expected) x100 was calculated for both Mission and Beckman. Mission and Beckman exhibited similar recoveries across the range of values in all matrices. See table below:
| Matrix | Range of Conc.Expected, mg/dL | Reagent | Range of average %Recovery | Overall MeanRecovery |
|---|---|---|---|---|
| Serum | 835 - 30 mg/dL | Mission | 83.3 - 115.4 | 103 |
| Serum | 835 - 30 mg/dL | Beckman | 83.3 - 117.5 | 103 |
| Urine | 300 - 10 mg/dL | Mission | 88 - 120 | 101 |
| Urine | 300 - 10 mg/dL | Beckman | 87 - 110 | 97 |
| CSF | 100 - 25mg/dL | Mission | 88 - 98 | 94 |
| CSF | 100 - 25mg/dL | Beckman | 88 - 100 | 95 |
Functional sensitivity was evaluated on dilutions of serum samples made from a starting serum of an approximately concentration of 42.5 mg/dL; and dilutions of 1:3, 1:5.1:11 and a zero. Dilutions were tested as 4 samples per run over 5 calibrated runs.
- The lowest level where the % CV was less than 20% was with the dilution at an expected . value of 9 mg/dL Glucose which measured/recovered as:
- 10 mg/dL with Mission reagent .
- . 8 mg/dL with Beckman reagent.
The CX Delta reports Glucose values to the whole number.
| Dilution | Expected value mg/dL | Mission Reagent | Beckman Reagent | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean | sd | N | %CV | Mean | sd | N | %CV | ||
| 1 | 43 | 41.9 | 1.52 | 20 | 3.6 | 40.5 | 0.83 | 20 | 2.0 |
| 2 | 14 | 14.7 | 0.75 | 20 | 5.1 | 13.3 | 0.64 | 20 | 4.8 |
| 3 | 9 | 9.8 | 0.95 | 20 | 9.7 | 8.2 | 0.37 | 20 | 4.5 |
| 4 | 2 | 3.6 | 1.35 | 20 | 37.6 | 2.1 | 0.55 | 20 | 26.3 |
| 5 | 0 | 2.0 | 0.65 | 20 | 32.4 | 0.5 | 0.51 | 20 | 113.4 |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/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 stripes extending from its body, representing health and human services. The eagle is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA", which is arranged in a circular fashion around the logo.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN 5 0 2004
Ms. Linda M. Stundtner OA/RA Manager Diamond Diagnostics Mission Diagnostics Division 331 Fiske St. Holliston. MA 01746
K033055 Re:
Trade/Device Name: Mission Diagnostic Glucose Reagent for Beckman Synchron CX® & CX® Delta Systems
Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CGA Dated: December 22, 2003 Received: December 24, 2003
Dear Ms. Stundtner:
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 for use based in 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, de rices that have been require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, allere, mass 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 If your device 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 I least be devilsed that I Dr bration that your device complies with other requirements of the Act that I Dri has made a aoved regulations administered by other Federal agencies. You must or any I ederal banales and states and mot 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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Page 2
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 (301) 594-3084. 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/dsma/dsmamain.html.
Sincerely yours,
Jean M. Cooper, MS, DVM.
MC, MS DVM
Yean M. Cooper, MS. D.V.M. 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
510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________
Device Name: Mission Diagnostic Glucose Reagent for Beckman Synchron CX® & CX® Delta Systems
Indications For Use:
- Mission Glucose Reagent is intended for in vitro diagnostic use for the quantitative determination . Mission Glucose in serum, plasma, cerebrospinal fluid (CSF) and urine on Beckman Synchron CX® & CX® Delta Systems.
- Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism . Oldoose meader omromo are esellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.
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 CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Carol C. Benam for Jean Cooper. NM
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K033055
Page 1 of 1
§ 862.1345 Glucose test system.
(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.