The Prealbumin SPIA™ is a quantitative turbidimetric assay intended for the detection of prealbumin levels in human serum and plasma. Measurement of prealbumin levels may aid in the assessment of an individual's nutritional status.

Device Description

Raichem's Prealbumin SPIA ™ is a quantitative turbidimetric assay for the detection and measurement of prealbumin in human serum and plasma. The assay has been standardized to a CAP Reference Preparation. The assay reagents consist of a polymer diluent, a polyclonal antibody to human prealbumin, calibrators, and controls. In this assay, a complex forms between the prealbumin, and anti-prealbumin antibodies causing turbidity. The change in optical density is proportional to the amount of prealbumin present. A quantitative determination of the amount of prealbumin present in a serum/plasma sample is made by comparison to a standard curve.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The device, Prealbumin SPIA™, is a quantitative turbidimetric assay for detecting and measuring prealbumin in human serum and plasma. Its intended use is to aid in assessing an individual's nutritional status. The primary "acceptance criteria" for this 510(k) submission are related to demonstrating substantial equivalence to an existing predicate device. This is primarily shown through performance data that confirms the proposed device's analytical precision, correlation with the predicate, and suitability for its intended use.

Here's a table summarizing the performance data presented, which serves as the fulfillment of acceptance criteria for substantial equivalence:

Acceptance Criteria Category	Specific Metric/Study	Predicate/Comparator	Performance Goal/Expectation (Implicit)	Reported Device Performance
Precision	Inter-assay reproducibility	(Not applicable Directly)	Low Coefficient of Variation (%CV)	Inter-assay: %CV between 4.7% and 6.7% for various samples.
	Intra-assay reproducibility	(Not applicable Directly)	Low Coefficient of Variation (%CV)	Intra-assay: %CV between 2.5% and 5.7% for various samples.
Standardization	Calibrator standardization	CAP Reference Preparation	Standardization within dynamic range (0-55 mg/dL)	Standardized within dynamic range (0-55 mg/dL) using CAP Reference Preparation.
Assay Sensitivity	Detection Limit	(Not explicitly defined reference)	Low detection limit for clinical relevance	0.9 mg/dL
Method Comparison	Linear Correlation with Predicate Device	Incstar Antibody Reagent Set II for Prealbumin	High degree of linear correlation (e.g., r² close to 1, slope close to 1, intercept close to 0)	YPROPOSED = 1.06 XPREDICATE - 1.15 "Results indicated a high degree of linear correlation." (r² not explicitly stated here, but implied as strong)
Method Equivalency	Manual vs. Automated Method (COBAS-MIRA) Comparison	Manual method using Prealbumin SPIA™	High degree of linear correlation (e.g., r² close to 1, slope close to 1, intercept close to 0)	VAUTOMATED = 1.10 XMANUAL + 1.07, r² = 0.959 "Results indicated a high degree of linear correlation."
Interference	Tolerable concentrations of interfering substances	(No specific limits stated, but generally minimal interference)	Minimal effect (< 20% variation)	Hemoglobin: ≤ 500 mg/dL (no significant effect)Bilirubin: ≤ 20 mg/dL (no significant effect)Lipid: > 200 mg/dL (significant decreases)
Specimen Compatibility	Serum vs. Plasma (EDTA)	(No specific limits stated)	Accurate estimates in both human serum and EDTA-plasma	"Can provide accurate estimates of prealbumin levels in both human serum and EDTA-plasma."

Study Details for Acceptance Criteria

2. Sample Size Used for the Test Set and Data Provenance

Inter-assay reproducibility: 8 different serum samples, assayed 10 times over 6 different days.
Intra-assay reproducibility: 8 serum samples, assayed 20 consecutive times in a single run.
Method Comparison (Predicate): 134 serum specimens.
Method Comparison (Manual vs. Automated): 30 serum samples.
Assay Performance with Serum and Plasma: 25 matched serum and EDTA-plasma samples.

Data Provenance: The document does not explicitly state the country of origin for the samples or if they were retrospective or prospective. Given the context of a 510(k) submission in the US, it is reasonable to assume the studies were conducted in the US, likely with a mix of patient and healthy donor samples. The phrase "serum specimens from individuals being screened for prealbumin levels and apparently healthy blood donors" suggests a mix, likely from a clinical lab setting.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

Not applicable in the traditional sense for this type of device. This device is an in-vitro diagnostic (IVD) for measuring a biomarker. The "ground truth" for the test set is established by the analytical measurement itself, cross-referenced against established methods or reference materials.
For the standardization of calibrators, the College of American Pathologists (CAP) Reference Preparation for Proteins in Human Serum (Catalog Number RM002) served as the reference standard. This means an established, certified reference material sets the "ground truth" for the calibrators, not individual experts.

4. Adjudication Method for the Test Set

Not applicable. Adjudication typically refers to expert review processes for subjective data (e.g., imaging, pathology slides). For quantitative IVD assays, the "truth" is determined by the analytical method and reference materials, not by expert consensus or review of conflicting interpretations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC study was not done. MRMC studies are typically used for diagnostic imaging or other subjective interpretation tasks where multiple human readers interpret cases, often with and without AI assistance, to assess the impact of AI on reader performance. This device is an automated, quantitative assay, not an assistive tool for human interpretation in that context.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this entire submission effectively describes standalone performance. The Prealbumin SPIA™ device is an automated or manual assay that directly produces quantitative results without requiring human interpretation for its primary function. The performance data (precision, sensitivity, correlation) are all measures of the algorithm/reagent system's intrinsic analytical capabilities. The "manual method" comparison is still about the assay's performance, not human interpretation.

7. The Type of Ground Truth Used

Analytical Reference Standards and Comparative Methods.
- For calibrator standardization, the ground truth was the College of American Pathologists (CAP) Reference Preparation for Proteins in Human Serum.
- For method comparison studies, the "ground truth" was established by the predicate device (Incstar Antibody Reagent Set II for Prealbumin) or the manual method of the proposed device, to which the automated method was compared for correlation. These are accepted analytical methods rather than clinical outcomes or pathology.
- For precision and sensitivity, the ground truth is statistical derivation from multiple measurements around known concentrations or the absence of the analyte.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" as would be typical for machine learning algorithms. This device is a reagent-based turbidimetric assay, not a machine learning model that undergoes a distinct training phase with a dedicated dataset. The development and optimization of the assay would involve internal testing and validation, but this is not usually referred to as a "training set" in the context of traditional IVD development.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As noted above, there's no mention of a distinct "training set" in the machine learning sense. The ground truth for developing and optimizing the assay would have been established through a combination of using purified prealbumin, established reference methods, and internal quality control materials to ensure the assay reagents and protocols accurately measure prealbumin concentrations.

Summary

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510(k) Summary

AUG 28 1997

Submitter's Name/Contact Person 1.

Joseph M. Califano Manager, Regulatory Affairs

Address

Hemagen Diagnostics, Inc. 34-40 Bear Hill Road Waltham, MA, 02154

(617) 890-3766 Phone: (617) 890-3748 Fax: icalifano@hemagen.com email:

Date Prepared

25 July 1997

Device Name 2.

Trade Name:	Prealbumin SPIATM
Common Name:	Prealbumin
Classification Name:	System, Test, immunological, prealbumin

Predicate Device 3.

Incstar Antibody Reagent Set II for Prealbumin {510 (k) Docket No. K 884297}

За. Methods

Described in Immunoturbidimetry of transthyretin (prealbumin) in Manual method: human sera. Clin. Chem: 33: 7, 1260 1987. Ledue T.B., Rifai N, Irish, G.R., Silverman, L.M.

COBAS-MIRA Analyzer. {510 (k) Docket No. K 851172} Automated System:

100000

510(k) Summary Page 1

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4. Description of Device

In this assay, a complex forms between the prealbumin, and anti-prealbumin antibodies causing turbidity. The change in optical density is proportional to the amount of prealbumin present. A quantitative determination of the amount of prealbumin present in a serum/plasma sample is made by comparison to a standard curve.

5. Intended Use of Device

Technological Characteristics 6.(A)

Proposed Device

Raichem's Prealbumin SPIA ™ is a quantitative turbidimetric assay. This assay is performed manually following clinically accepted methodologies. The assay is designed to enable users to readily adapt it for use with automated systems such as the Roche COBAS MIRA Analyzer.

Predicate Device

Incstar's Antibody Reagent Set II for Prealbumin is also a quantitative turbidimetric assav that utilizes immunoprecipitin analysis for the determination of prealbumin levels.

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Performance Data 6.(B)

Precision .

To evaluate precision, inter-assay and intra-assay studies were conducted with the Raichem's Prealbumin SPIA ™ on an automated system {COBAS-MIRA}

A. Inter-assay reproducibility

Eight different serum samples were assayed ten times over six different days.

SAMPLE	Mean mg/dL	Std. Dev	% CV	Mean Delta	Std. Dev	% CV
1	36.3	1.9	5.2	0.272	0.007	2.7
2	17.1	1.1	6.6	0.188	0.007	3.5
3	7.7	0.4	5.6	0.115	0.004	3.3
4	14.1	0.9	6.4	0.168	0.006	3.7
5	22.3	1.1	4.8	0.217	0.004	1.9
6	26.3	1.2	4.7	0.237	0.004	1.9
7	36.7	2.5	6.7	0.273	0.008	2.9
8	50.4	2.5	4.9	0.305	0.007	2.2

B. Intra-assay reproducibility

The eight serum samples were also assayed 20 consecutive times in a single run.

SAMPLE	Mean mg/dL	Std. Dev	% CV	Mean Delta	Std. Dev	% CV
1	34.3	1.6	4.8	0.280	0.006	2.2
2	17.4	0.7	4.1	0.195	0.003	1.7
3	8.0	0.2	2.6	0.114	0.002	1.8
4	13.7	0.8	5.7	0.159	0.006	3.7
5	22.7	0.6	2.5	0.214	0.003	1.4
6	28.6	1.0	3.6	0.240	0.004	1.7
7	34.7	1.4	4.0	0.263	0.005	1.8
8	50.7	2.7	5.3	0.304	0.006	1.8

Standardization of the Calibrators 11.

The set of 5 calibrators supplied with the assay have been standardized within the dynamic range { 0 to 55 mg/dL} using the College of American Pathologists Reference Preparation for Proteins in Human Serum, Catalog Number RM002.

111. Assay Sensitivity

The detection limit of the assay was determined by running multiple replicates the 0 mg/dL Calibrator and computing the mean and standard deviation. The resultant detection limit was found to be 0.9 mg/dL. {Mean + 2SD}

510(k) Summary Page 3

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Comparison Studies IV.

The Prealbumin SPIA ™ and the Incstar Antibody Reagent Set II for Prealbumin a. were used to assay serum specimens from individuals being screened for prealbumin levels and apparently healthy blood donors. The specimens were assayed concurrently with both the proposed and predicate devices, using an automated method {COBAS-MIRA}
A total of 134 samples were evaluated. The results indicated a high degree of linear correlation between the proposed and predicate device. The resultant linear regression relationship is:

YPROPOSED = 1.06 XPREDICATE = 1.15,

Comparison of a manual method and an automated method{COBAS-MIRA} b.

The Raichem Prealbumin SPIA ™ was used to assay serum specimens concurrently by a manual method and an automated method {COBAS-MIRA}

A total of 30 samples were evaluated. The results indicated a high degree of linear correlation between the manual and automated methods. The resultant linear regression relationship is:

VAUTOMATED = 1.10 XMANUAL + 1.07, r2 = 0.959

V Assay performance with Serum and Plasma

Twenty five (25) matched serum and EDTA-plasma samples were compared. Half of the volume of each sample was converted to serum by recalcification using a standard Ca2"/thrombin methodology. Each of the plasma and converted serum samples were evaluated with the proposed device on an automated system {COBAS-MIRA}. The results of the evaluation with the proposed device indicate that it can provide accurate estimates of prealbumin levels in both human serum and EDTA-plasma.

VI. Interfering Substances

Lipemic, hemolytic, and icteric samples were evaluated with the assay. The results indicate that there is no significant effect (< 20 % variation) on the assay for samples with:

Hemoglobin concentration:	≤ 500 mg/dL
Bilirubin concentration:	≤ 20 mg/dL

Lipid concentrations of > 200 mg/dL showed significant decreases in prealbumin values.

7. Conclusion

The results of the comparative studies support the claim that the Prealbumin SPIA ™ is substantially equivalent to the predicate device.

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__, and the list goes on.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 28 1997

Mr. Joseph M. Califano Manager, Regulatory Affairs Hemagen Diagnostics, Inc. 34-40 Bear Hill Road ... ...... Waltham, Massachusetts 02154

Re : K972812 Trade Name: Prealbumin SPIA™ Requlatory Class: I Product Code: DDS Dated: July 25, 1997 Received: July 28, 1997

Dear Mr. Califano:

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, 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 requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (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 miqht 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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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) Additionally, for questions on the promotion and 594-4588. advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the requlation 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 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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Device Name:

Prealbumin SPIA ™

Indication(s) For Use

The use of these reagents is indicated for the measurement of prealbumin levels in human serum or plasma.

(PLEASE DO NOT WRITE BELOW THIS LINE)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter-Use_

Peter S. Makim

(Division Sign-Off) Division of Clinical Laboratory Devices 610(k) Number ___

Regulation Number and Section

§ 866.5060 Prealbumin immunological test system.

(a)
Identification. A prealbumin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the prealbumin (a plasma protein) in serum and other body fluids. Measurement of prealbumin levels in serum may aid in the assessment of the patient's nutritional status.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.