The RESOLVE® Systems Hemoglobin kit is designed to separate whole blood, cord blood or dried blood spot specimen for detection of normal and variant hemoglobins by isoelectric focusing. The kit is designed to be run on a flat-bed electrofocusing unit. This assay is intended for use as an aid in the diagnosis of neonatal and adult hemoglobinopathies.

Device Description

The preparation and separation of hemoglobin is accomplished through the application of a hemoglobin sample onto a precast agarose gel containing RESOLVE Ampholytes pH 6-8. RESOLVE Ampholytes are composed of low molecular weight amphoteric molecules with varying isoelectric points. When an electrical current is applied to the gel, these molecules migrate through the gel to their isoelectric points (pl's) along the gel, forming a stable pH gradient. The hemoglobin variants also migrate through the gel until they reach the area where their individual pl's equal the corresponding pH on the gel. At this point, the charges on the variants are zero and migration ceases. The electric field counteracts diffusion and the hemoglobin variant forms a discrete thin band. Hemoglobin bands are visualized by using the JB-2 Staining System containing o-dianisidine. o-dianisidine, the active component of the Gel Stain Concentrate, is oxidized in the presence of hydrogen peroxide at the site of hemoglobin. This reaction produces an insoluble, colored precipitate proportional to the amount of hemoglobin.

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided document for the RESOLVE® Hemoglobin kit:

Acceptance Criteria and Device Performance

The document describes a method comparison study to demonstrate substantial equivalence to predicate devices rather than pre-defined acceptance criteria with specific thresholds for sensitivity, specificity, or predictive values. The main performance metric used to establish equivalence is agreement percentage with the predicate devices. Precision is also evaluated.

Acceptance Criteria Category	Specific Metric (as presented in the document)	Reported Device Performance (RESOLVE® Hb kit)
Method Comparison	Agreement with Predicate Device 1 (BioRad VARIANT Sickle Cell Short Program)	Study 1: 99.8% (95% lower CL: 99.2%)Study 3: 99.1% (95% lower CL: 98.4%)
	Agreement with Predicate Device 2 (BioRad VARIANT nbs Sickle Cell Program)	Study 2: 97.7% (95% lower CL: 96.7%)
Precision	Within-gel precision (CV%) for Hb A1c vs. Hb C distance	2.2%
	Between-gel precision (CV%) for Hb A1c vs. Hb C distance	1.8%
	Total precision within laboratory (CV%) for Hb A1c vs. Hb C	2.8%
	Within-gel precision (CV%) for Hb A vs. Hb F distance	3.3%
	Between-gel precision (CV%) for Hb A vs. Hb F distance	2.9%
	Total precision within laboratory (CV%) for Hb A vs. Hb F	4.4%

Note: The document does not explicitly state pre-defined acceptance thresholds for these metrics, but rather presents the results as evidence of equivalence to the predicate devices, which are assumed to have acceptable performance. The FDA's 510(k) clearance confirms that these results were considered sufficient to demonstrate substantial equivalence.

Study Details

Sample Sizes and Data Provenance:
- Test Set (Method Comparison):
  - Study 1: 850 specimens
  - Study 2: 837 specimens
  - Study 3: 1031 specimens
  - Total: 2718 specimens
- Data Provenance: The samples were a mix of "routine DBS samples or retrospective samples." The document does not specify the country of origin, but the submitting company is based in Finland, and the predicate device manufacturers are likely US-based, suggesting a possibility of data from different regions or a multi-site study. It's explicitly stated that the study was conducted at three sites.
Number of Experts and Qualifications for Ground Truth of Test Set:
- The ground truth for the method comparison study was established by the predicate devices (BioRad's HPLC methods). The document does not mention the involvement of human experts to establish ground truth for the test set samples themselves, but rather the comparison is against the results generated by the established predicate devices. Therefore, the "experts" in this context are the predicate devices and their underlying methodologies.
Adjudication Method for the Test Set:
- There is no mention of an adjudication method in the traditional sense of human review. The comparison is directly between the RESOLVE® Hb kit's results and the predicate device's results. Any discrepancies would likely be investigated through further testing or expert review, but this process is not detailed.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) kit for laboratory use, not typically a "reader" type AI device that assists human interpretation in a clinical setting where MRMC studies are common. The comparison is between the new kit and existing laboratory methods.
Standalone Performance (Algorithm Only without Human-in-the-Loop Performance):
- Yes, the performance presented is standalone (algorithm/kit only without human-in-the-loop performance contribution). The RESOLVE® Hb kit is designed for laboratory separation of hemoglobins. While visual interpretation is part of the process (and an optional "Iso Scan imaging system" is mentioned), the "agreement" and "precision" metrics are based on the kit's ability to correctly categorize/separate hemoglobins compared to the predicate devices. The "interpretation" for the RESOLVE® Hb kit is described as "Visual interpretation of hemoglobin bands compared to position marker."
Type of Ground Truth Used:
- The ground truth for the method comparison was established by the results from the predicate devices (BioRad's HPLC methods: VARIANT Sickle Cell Short Program and VARIANT nbs Sickle Cell Program). These methods are considered established and cleared for their intended use, making their results a de facto "ground truth" for comparison.
Sample Size for the Training Set:
- The document does not provide information on a training set. This is expected because the RESOLVE® Hemoglobin kit operates on an isoelectric focusing principle, which is a biochemical separation technique, not an Artificial Intelligence (AI) or machine learning algorithm that typically requires a training set.
How the Ground Truth for the Training Set Was Established:
- As there is no mention of a "training set" for an AI/ML algorithm within the description of this device, this question is not applicable.

Summary

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MAR 8 2006 kin Elmer Life and Analytical Sciences 20101 Turku Finland

http://www.perkinelmer.com

510(k) SUMMARY

(as required by 21 CFR 807.92)

The assigned 510(k) number is: K050709

Submitted by: Raija Koskivaara Registration Manager Wallac Oy Mustionkatu 6, 20750 Turku P.O. Box 10, 20101 Turku Finland
RESOLVE® Hemoglobin kit Device Name:

Isoelectric focusing of hemoglobins Common Name:

Abnormal hemoglobin assay Classification: Class II per 21 CFR § 862.7415

Product Code: GKA
BioRad VARIANT Sickle Cell Short Program K924813 Predicate Device: BioRad VARIANT nbs Sickle Cell Program K051072

Device Description:

The hemoglobin variants also migrate through the gel until they reach the area where their individual pl's equal the corresponding pH on the gel.

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At this point, the charges on the variants are zero and migration ceases. The electric field counteracts diffusion and the hemoglobin variant forms a discrete thin band.

Hemoglobin bands are visualized by using the JB-2 Staining System containing o-dianisidine. o-dianisidine, the active component of the Gel Stain Concentrate, is oxidized in the presence of hydrogen peroxide at the site of hemoglobin. This reaction produces an insoluble, colored precipitate proportional to the amount of hemoglobin.

Indications for Use:

Comparison with Predicate Devices:

Features	DeviceRESOLVE® Hb kit	Predicate DeviceBio-Rad VARIANTSickle Cell ShortProgram (K924813)	Predicate DeviceBio-Rad VARIANTnbs Sickle CellProgram (K051072)
A. Similarities
Intended Use	The RESOLVE®Systems Hemoglobinkit is designed toseparate wholeblood, cord blood ordried blood spotspecimen fordetection of normaland varianthemoglobins byisoelectric focusing.This assay isintended for use asan aid in thediagnosis of neonataland adulthemoglobinopathies.	The VARIANT SickleCell Short Program isdesigned as aqualitative screen forthe presence ofhemoglobinsF,A,S,D,C and E ineluates of neonatalblood collected onfilter paper by highperformance liquidchromatography(HPLC).	The VARIANT nbsSickle Cell Programis designed as aqualitative screen forthe presence ofhemoglobinsF,A,S,D,C and E ineluates of neonatalblood collected onfilter paper by highperformance liquidchromatography(HPLC).
Human Factors	For in vitro diagnosticuse. For professionaluse only.	For in vitro diagnosticuse. For professionaluse only.	For in vitro diagnosticuse. For professionaluse only.

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Design- analytesidentified	Hemoglobins F, A, E,D, S, C. In addition Gand α- and β-thalassemia (e.g. HbBart's and HbH) canbe identified.	Six retention timewindows forhemoglobins F, A, E,D, S and C areshown.	Six retention timewindows forhemoglobins F, A, E,D, S and C areshown.
Design- sampletype	Neonatal dried bloodspots on filter paperand in addition wholeblood and cord bloodspecimen.	Neonatal dried bloodspots on filter papercollection cards.	Neonatal dried bloodspots on filter papercollection cards.
Design- targetpopulation	Neonates and alsoadults	Neonates	Neonates
Performance-precision	Total precision withinlaboratory:Hb A1C vs C: 2.82%Hb A vs F: 4.36%	Peak retention timeprecision is < 1% forall hemoglobinpeaks.	Peak retention timeprecision is < 1% forall hemoglobinpeaks.
		B. Differences
Design- assayprinciple	Hemoglobins areseparated based ontheir specificisoelectric point (pl)on the IsoElectricFocusing (IEF) gels.	Hemoglobins areseparated in cationexchange HPLCcolumn generating apre-determined ionicstrength gradient.	Hemoglobins areseparated in cationexchange HPLCcolumn generating apre-determined ionicstrength gradient.
Design-interpretation	Visual interpretationof hemoglobin bandscompared to positionmarker (Iso Scanimaging systemoptional).	Pre-determinedretention timewindows for specifichemoglobin variantsbased on theretention timemarkers.	Pre-determinedretention timewindows for specifichemoglobin variantsbased on theretention timemarkers.

Summary of the performance data to establish Equivalence:

Method comparison

The method comparison of the RESOLVE® Hb kit to predicate device was performed at three sites. Two of these used the BioRad's HPLC method VARIANT Sickle Cell Short Program (1) as a comparative method and one site used the VARIANT nbs Sickle Cell Program (2). The studied samples were either routine DBS samples or retrospective samples. More than half of the samples were normal samples (FA). The rest of the samples had hemoglobin combinations with Hb S or hemoglobin combinations with other Hb variants such as Hb C, Hb D, Hb E. Hb G-Philadelphia, a-thalassemia and ß-thalassemia.

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The results are presented in the following table:

	Number ofspecimens	HPLCmethod	Agreement -%	95% lower CL
Study 1	850	1	99.8	99.2
Study 2	837	2	97.7	96.7
Study 3	1031	1	99.1	98.4

Precision

The precision study was based on the results obtained from the comparison studies with the predicate devices. The variation was estimated by measuring the distance of certain Hb bands of FASC controls used in the studies. The analysis of variance approach was used to calculate the following variations:

	Number ofspecimens	Averagedistance(mm)	Within-gelprecision(CV%)	Between-gelprecision(CV%)	Total precisionwithin laboratory(CV%)
Hb A1c vs. Hb C	216	17.8	2.2	1.8	2.8
Hb A vs. Hb F	223	2.1	3.3	2.9	4.4

Substantial Equivalence:

The RESOLVE® Hb kit has the same Intended Use and Indications for Use as the Predicate Devices BioRad's HPLC method VARIANT Sickle Cell Short Program (K924813) and the VARIANT nbs Sickle Cell Program (K051072).

Based on the method comparison data and the precision results one may conclude that the RESOLVE® Hb kit is substantially equivalent to the cleared and currently marketed predicate devices BioRad's HPLC method VARIANT Sickle Cell Short Program and the VARIANT nbs Sickle Cell Program.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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2006 MAR 8

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Raija Koskivaara Registration Manager Wallac Oy, PerkinElmer LAS Mustionkatu 6, 20750 Turku P.O. Box 10, 20101 Turku Finland

K050709 Re:

Trade/Device Name: RESOLVE® Hemoglobin Kit Regulation Number: 21 CFR § 864.7415 Regulation Name: Abnormal hemoglobin assay Regulatory Class: II Product Code: GKA Dated: January 18, 2006 Received: January 20, 2006

Dear Mr. Koskivaara:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your became of 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, de neces may been roch require approval of a premarket approval application (PMA). alla Cosmetic rear (110) that be nevice, subject to the general controls provisions of the Act. The I ou may, dicroro, mains of the Act include requirements for annual registration, listing of general controll provision 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 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 r lease be deviced that I bromination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must or any 1 vith 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 CI IC Fart 607), laceming (21 the quality systems (QS) regulation (21 CFR Part 820). This letter requirements as bet form marketing your device as described in your Section 510(k) premarket wntification. The FDA finding of substantial equivalence of your device to a legally marketed nredicate device results in a classification for your device and thus, permits your device to proceed to the market.

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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 or quotions on the proce Evaluation and Safety at (240) 276-0484. Also, please note the vitro Daglioine De Misbranding by reference to premarket notification" (21 CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I ou may obtain other generers, 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 yours,

lobatz Beckerh

Robert L. Becker, Jr., MD, PH.D Director Division of Immunology and Hematology 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): K050709

Device Name:

RESOLVE® Hemoglobin kit

Indications For Use:

The RESOLVE® Systems Hemoglobin kit is designed to separate whole blood or cord blood samples for detection of normal and variant hemoglobins by isoelectronic focusing. The kit is designed to be run on a flat-bed electrofocusing unit.

This assay is intended for use as an aid in the diagnosis of neonatal and adult hemoglobinopathies.

Prescription Use __ > (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _ (21 CFR 801 Subpart C)

(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	K050709

Regulation Number and Section

§ 864.7415 Abnormal hemoglobin assay.

(a)
Identification. An abnormal hemoglobin assay is a device consisting of the reagents, apparatus, instrumentation, and controls necessary to isolate and identify abnormal genetically determined hemoglobin types.(b)
Classification. Class II (special controls). A control intended for use with an abnormal hemoglobin assay is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.