The Atellica™ IM Ferritin (Fer) assay is for in vitro diagnostic use in the quantitative determination of ferritin in human serum and plasma (EDTA and lithium heparin) using the Atellica™ IM Analyzer. This assay can be used as an aid in the diagnosis of iron deficiency anemia and iron overload.

Device Description

The Atellica Ferritin Assay kit includes the following components: Lite Reagent: 5.0 mL/reagent pack. Contains Goat polyclonal anti-ferritin antibody (~0.64 µg/mL) labeled with acridinium ester in HEPES buffer; protein stabilizers; sodium azide (< 0.1%); preservatives Solid Phase Reagent: 22.5 mL/reagent pack. Contains Mouse monoclonal anti-ferritin antibody (~32.2 µg/mL) covalently coupled to paramagnetic particles in sodium barbital buffer; protein stabilizers; sodium azide (< 0.1%); preservatives

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Atellica IM Ferritin Assay, based on the provided document:

Acceptance Criteria and Reported Device Performance

Criteria	Acceptance Criteria	Reported Device Performance
Precision	CLSI EP05-A3 guidelines (Evaluation of Precision Performance of Quantitative Measurement Methods)	Repeatability (Within-run): CV ranges from 1.2% to 3.5% for samples (4.2 ng/mL to 1453.6 ng/mL) and 1.2% to 1.6% for controls (51.8 ng/mL to 374.0 ng/mL). Within-Lab (Total Imprecision): CV ranges from 4.0% to 7.2% for samples and 4.5% to 5.5% for controls.
Linearity/Assay Reportable Range	CLSI EP06-A (linearity of Quantitative Measurement Procedures). Implied: Acceptable percentage difference between observed and predicted values.	The linearity data supports an analytical measuring range of 0.9 - 1650 ng/mL. Predicted % Difference (Y-Ŷ)/Ŷ*100: values ranged from -8.88% to 9.47% (excluding the lowest observed value of 0.20 ng/mL which was < LoO).
Detection Limit (LoB, LoD, LoQ)	CLSI EP17-A (Protocols for Determination of Limits of Detection and Limits of Quantitation).	LoB: 0.3 ng/mL LoD: 0.7 ng/mL LoQ: 0.9 ng/mL (analyte concentration corresponding to 20% within lab CV).
Interference (Endogenous & Exogenous)	CLSI EP7-A2 guidelines. Implied: No significant interference (< ± 10% bias from control) up to tested concentrations.	Endogenous: No significant interference (< ± 10% bias) from Hemoglobin (900 mg/dL), Triglyceride (2000 mg/dL), Conjugated Bilirubin (60 mg/dL), and Un-conjugated Bilirubin (60 mg/dL). Exogenous: No significant interference (< ± 10% bias) from all listed substances (e.g., Heparin, N-acetylcysteine, Acetylsalicylic Acid, Ibuprofen, Prednisone, Ferrous Sulphate, Ascorbic Acid) at tested concentrations.
Specificity (Cross-reactivity)	Not explicitly stated as a numerical acceptance criterion, but implied to be acceptable based on comparison with substances.	Liver Ferritin: Cross-Reactivity ranged from 94% to 115% at various ferritin levels (when 285 ng/mL of liver ferritin was added). Spleen Ferritin: Cross-Reactivity ranged from 91% to 103% at various ferritin levels (when 225 ng/mL of spleen ferritin was added).
Dilution Recovery	Implied: Acceptable recovery range (likely around 90-110%).	Recoveries ranged from 89%-100% with a mean of 94% for samples diluted 1:2, 1:4, 1:8, and 1:16.
Spiking Recovery	Implied: Acceptable recovery range (likely around 90-110%).	Recoveries ranged from 90%-116% with a mean of 104% for samples spiked with varying amounts of ferritin.
High-Dose Hook Effect	Implied: No hook effect within the intended assay range or a specified high concentration.	The assay did not demonstrate a Hook Effect up to 80,000 ng/mL ferritin.
Traceability	Traceable to an international standard.	Traceable to World Health Organization 2nd International Standard (WHO 80/578).
Stability (Reagents)	Shelf-life, on-board stability, and calibration frequency must meet sponsor pre-defined acceptance criteria.	Shelf-life: 8 months at 2-8°C (unopened). On-board/Open-vial: Reagents stable for 28 days once placed on the system. Calibration frequency: 28 days. Sponsor pre-defined acceptance criteria were met.
Method Comparison (vs. Predicate)	Demonstrates substantial equivalence to the predicate device (ADVIA Centaur Ferritin Assay). Expected good correlation (high r-value) and close to 1 slope with minimal intercept.	r = 0.99 (Linear regression) Weighted Deming regression: y = 1.03x - 0.5 ng/mL Sample range: 3.4-1641.4 ng/mL
Matrix Comparison (Sample Types)	Demonstrates equivalence across different sample matrices (serum, K2 EDTA plasma, Lithium Heparin plasma). Expected good correlation (high r-value) and close to 1 slope with minimal intercept.	EDTA plasma vs. Serum: y = 0.96x + 1.6 ng/mL, r = 0.997. Lithium heparin vs. Serum: y = 0.95x + 0.1 ng/mL, r = 0.998. Sample range for both: 2.5-1440.7 ng/mL.
Expected Values/Reference Range	Established using appropriate methodology.	Established using the Atellica IM Analyzer in accordance with CLSI Document EP28-A3c. Normal Males (N=179): Median 58.9 ng/mL, 95th Percentile Range 10.5-307.3 ng/mL. Normal Females (N=275): Median 46.4 ng/mL, 95th Percentile Range 7.3-270.7 ng/mL.

Study Details

Sample sizes used for the test set and the data provenance:
- Precision: 6 serum-based samples, plus calibrators and controls. 80 replicates per sample (20 days, 2 runs/day, duplicate).
- Linearity/Assay Reportable Range: 11 samples. Tested in triplicates.
- Detection Limit (LoB, LoD, LoQ):
  - LoB: 6 blank samples, 2 reagent lots, 2 replicates/day over 10 days (System 1) and 9 days (System 2).
  - LoD: 7 low-level human serum samples, 2 reagent lots, 10 days (System 1) and 9 days (System 2).
  - LoQ: 6 low human serum samples (System 1) and 5 low human serum samples (System 2), 2 reagent lots, 8 replicates/day over 5 days.
- Interference:
  - Endogenous: 2 human serum pools (~20 ng/mL and ~200 ng/mL) spiked with interferent. Tested in replicates of 3.
  - Exogenous: 2 human serum pools (~20 ng/mL and ~200 ng/mL) spiked with interferent. Tested in replicates of 3.
- Specificity (Cross-reactivity): 4 specimens with different endogenous ferritin levels. Replicates of 3.
- Dilution Recovery: 3 human serum samples.
- Spiking Recovery: 5 samples.
- High-dose hook effect: 11 serial dilution samples from a high-concentration sample.
- Method Comparison: 126 serum samples (107 included in final calculations).
- Matrix Comparison: 56 paired sample sets (serum, K2 EDTA plasma, Lithium Heparin plasma).
- Expected Values/Reference Range: 179 normal males, 275 normal females.
Data Provenance: The document explicitly states "human serum" and "human serum-based samples". The reference ranges were established using "apparently healthy male and female subjects." The document does not specify the country of origin for the samples and does not explicitly state whether the data was retrospective or prospective, though the nature of laboratory performance studies usually implies prospective collection for the specific tests, but potentially using residual samples for some evaluations.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in vitro diagnostic assay for quantitative determination of ferritin. The "ground truth" here is the actual concentration of Ferritin in the samples, measured by a reference method or known by spiking/dilution. It is not typically established by human experts in the same way imaging or pathology devices are. The accuracy of the analytical measurements themselves are the ground truth for these types of studies.
- For the "Expected Values/Reference Range" study, subjects selected had "normal liver function enzyme tests, bilirubin, and serum iron tests," which would imply medical expert evaluation of their health status, though no specific number or qualification of experts is mentioned for this selection.
Adjudication method for the test set:
- Not applicable in the context of an in vitro diagnostic assay for quantitative measurement. The results are numerical values from the assay, and "adjudication" in the sense of expert consensus on a diagnosis is not relevant for establishing the assay's analytical performance.
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:
- Not applicable. This is an in vitro diagnostic assay, not an AI-powered diagnostic imaging or pathology system that assists human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this entire submission describes the standalone performance of the Atellica IM Ferritin Assay (an in vitro diagnostic device). The performance characteristics are measured directly from the assay without human interpretation being part of the primary performance evaluation, beyond operating the instrument and interpreting the numerical output.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for the analytical performance studies (precision, linearity, detection limit, interference, recovery) is either:
  - Known concentrations: Achieved through spiking or dilution with known amounts of ferritin.
  - Reference method comparison: For the method comparison study, the predicate device (ADVIA Centaur Ferritin Assay) serves as the comparative "truth" or reference.
  - Traceability to an international standard: The assay is traceable to the WHO 2nd International Standard (WHO 80/578).
The sample size for the training set:
- For in vitro diagnostic assays of this type, a "training set" in the machine learning sense is not typically used for establishing the analytical performance characteristics. The assay is based on chemical reactions and optical detection, not a machine learning algorithm that learns from data.
- However, if you consider the development process, there would have been internal R&D studies using various samples to optimize reagents and calibration, but these are not disclosed as formal "training sets" in the 510(k) submission.
How the ground truth for the training set was established:
- As explained above, the concept of a "training set" and its associated ground truth in the context of machine learning does not directly apply to the analytical performance studies of this immunoassay. The validity comes from the known chemical properties of the reagents and the calibration against internationally recognized standards.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 31, 2017

SIEMENS HEALTHCARE DIAGNOSTICS INC. KIRA GORDON, PHD SR. REGULATORY AFFAIRS SPECIALIST 511 BENEDICT AVE. TARRYTOWN NY 10591

Re: K171642

Trade/Device Name: Atellica IM Ferritin Assay Regulation Number: 21 CFR 866.5340 Regulation Name: Ferritin immunological test system Regulatory Class: II Product Code: DBF Dated: May 31, 2017 Received: June 2, 2017

Dear Dr. Gordon:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Kelly Oliner -S

For. Lea Carrington, M.S., MBA, MT Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K171642

Device Name Atellica IM Ferritin Assay

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary of Safety and Effectiveness for the Atellica IM Ferritin Assay

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

1. 510(k) Number:

2. Applicant:

Contact:	Kira Gordon, PhDSr. Regulatory Affairs Specialist
Address:	Siemens Healthcare Diagnostics Inc511 Benedict Ave,Tarrytown, NY 10591
Phone:	(914) 524-2996
FAX:	(914) 524-3579
Email:	kira.gordon@siemens-healthineers.com

August 24, 2017 3. Date:

4. Proprietary and Established Names: Atellica™ IM Ferritin (Fer) Assay

1. Measureand
  Ferritin

6. Regulatory Information:

Atellica™ Ferritin Assay Classification Names: Ferritin immunological test system. Regulation Number: 866.5340 Classification: Class II Product Code: DBF Atellica IM Ferritin Assay Trade name: Immunology Classification Panel:

7. Predicate Devices:

Device Name: ADVIA Centaur Ferritin Assay 510(k) Number: K992157 Manufacturer: Siemens Healthcare Diagnostics, Inc.

8. Intended Use:

See Indications for Use (Section 6)

9. Indications for Use:

The Atellica™ IM Ferritin (Fer) assay is for in vitro diagnostic use in the quantitative determination of ferritin in human serum and plasma (EDTA and lithium heparin) using the

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Atellica™ IM Analyzer. This assay can be used as an aid in the diagnosis of iron deficiency anemia and iron overload.

Special Conditions for Use Statement(s): For prescription use only

10. Device Description:

Solid Phase Reagent: 22.5 mL/reagent pack. Contains Mouse monoclonal anti-ferritin antibody (~32.2 µg/mL) covalently coupled to paramagnetic particles in sodium barbital buffer; protein stabilizers; sodium azide (< 0.1%); preservatives

11. Test Principle

Sandwich immunoassay using direct chemiluminometric technology

12. Substantial Equivalence Information:

Device Name: ADVIA Centaur Ferritin Assay 510(k) Number: K992157/K041133

Comparison with Predicate:

Item	New Device:	Predicate Device:
Intended Use	The Atellica™ IM Ferritin (Fer)assay is for in vitro diagnostic usein the quantitative determinationof ferritin in human serum andplasma (EDTA and lithiumheparin) using the Atellica™ IMAnalyzer.This assay can be used as an aid inthe diagnosis of iron deficiencyanemia and iron overload.	For in vitro diagnostic use in thequantitative determination offerritin in serum or plasma usingthe ADVIA Centaur®, ADVIACentaur XP, and ADVIA CentaurXPT systems to aid in the diagnosisof iron deficiency anemia and ironoverload.
Instrument	Atellica IM	ADVIA Centaur
Measurement	Quantitative	Same
Technology	Chemiluminescence	Same
Assay Protocol	2-site sandwich immunoassay	Same
Reagents	Lite Reagent - goat polyclonalanti-ferritin antibody labeled withacridinium ester.Solid Phase Reagent - mousemonoclonal anti-ferritin antibodycovalently coupled toparamagnetic particles.	Same
Sample type	Serum, Heparinized Plasma,EDTA Plasma	Same
Assay Range	0.9-1650 ng/mL	0.5-1650 ng/mL
Calibrators	2-point calibration	Same

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13. Standard/Guidance Document Reference

The following recognized standard and guidance documents were used:

Format for Traditional and Abbreviated 510(k)s Guidance for Industry and FDA Staff -
-In Vitro Diagnostic Devices: Guidance for the Preparation of 510(k) Submissions
Guidance for Industry and FDA Staff Assayed and Unassaved Quality Control Material -
EP05-A3 (7-251) Evaluation of Precision Performance of Quantitative Measurement -Methods: Approved Guideline
-EP06-A (7-193) Evaluation of the Linearity Of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
EP07-A2 (7-127) Interference Testing in Clinical Chemistry; Approved Guideline; Approved -Guideline
-EP09-A3 (7-245) Measurement Procedure Comparison And Bias Estimation Using Patient Samples: Approved Guideline
-EP17-A2 (7-233) Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures: Approved Guideline
EP25-A (7-235) Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline -
-EP28-A3c (7-224) Defining, Establishing, And Verifying Reference Intervals In The Clinical Laboratory; Approved Guideline

14. Performance Characteristics

Substantial equivalence was demonstrated by testing performance characteristics, listed below, including method comparison, precision, interfering and cross-reactive substances.

1. Analytical Performance

a. Precision

Precision estimates were computed according to CLSI document EP05-A3, Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline. Within run (repeatibility) and total imprecision were evaluated by testing 6 serum based samples. calibrators and controls. The elevated levels were spiked with ferritin (liver source) to achieve appropriate concentrations. The samples were assayed in duplicate over the course of 20 days, two runs per day, for a total of 40 runs and 80 replicates.

			Repeatability		Within-Lab
		Mean	SD		SD
Sample	Reps	(ng/mL)	(ng/mL)	CV (%)	(ng/mL)	CV (%)
Serum A	80	4.2	0.15	3.5	0.31	7.2
Serum B	80	8.2	0.14	1.8	0.44	5.4
Serum C	80	41.9	0.57	1.4	1.78	4.2
Serum D	80	65.4	0.82	1.3	2.89	4.4
Serum E	80	118.3	1.44	1.2	4.79	4.0
Serum F	80	487.1	8.00	1.6	20.39	4.2
Serum G	80	779.9	20.69	2.7	44.48	5.7
Serum H	80	1453.6	49.51	3.4	91.40	6.3
Control 1	80	51.8	0.84	1.6	2.49	4.8
Control 2	80	132.7	1.61	1.2	6.01	4.5
Control 3	80	374.0	4.97	1.3	20.69	5.5

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b. Linearity/assav reportable range:

Linearity studies were conducted according to CLSI EP06-A: Evaluation of the Linearity of Ouantitative Measurement Procedures. Eleven samples with ferritin concentrations distributed throughout the assay range were prepared using high and low human serum pools (low <0.5, ng/mL; high pool >1650 ng/mL concentration of ferritin). Samples were tested in triplicates.

	Observedng/mL (Y)	Expectedng/mL	Predictedng/mL(Ŷ)	Predicted %Difference(Y-Ŷ)/Ŷ*100
A	0.20	0.2	-0.71	n/a
B	6.05	7.06	5.57	8.65%
C	11.28	13.93	11.84	-4.69%
D	22.22	27.65	24.39	-8.88%
E	46.04	55.11	49.49	-6.96%
F	98.38	110.03	99.68	-1.30%
G	200.39	219.86	200.07	0.16%
H	401.92	439.53	400.84	0.27%
I	810.18	878.86	802.39	0.97%
J	1267.43	1318.2	1203.94	5.27%
K	1757.53	1757.53	1605.50	9.47%
	Weighted linear fit:	Y=0.914*X-0.888

The linearity data supports analytical measuring range of the Atellica Ferritin Assay of 0.9 - 1650 ng/mL. Values below the LoO are reported as < 0.9 ng/mL.

c. Detection Limit

Limit of Blank (LoB). Limit of Detection (LoD). and Limit of Quantification (LoO) of the Atellica Ferritin Assay were determined according to CLSI EP17- A: Protocols for Determination of Limits of Detection and Limits of Quantitation: Approved Guideline. LoB was determined by testing a total of 6 blank samples (human serum based sample pools with no detectable amounts of ferritin) using two reagent lots in 2 replicates, twice a day over a period of 10 days on one system and over a period of 9 days on a second system. LoB was established as the ferritin value corresponding to the 95th rank position. The LoB was determined to be 0.3 ng/mL.

A total of seven low level human serum-based samples were evaluated using two reagent lots for ten days on one instrument and nine days on a second instrument. The LoD, according to the guideline, is the median or mean of the lowest level material in which the 500 percentile equals or exceeds the Limit of Blank. The LoD was determined to be 0.7 ng/mL. To calculate LoQ (six low human serum samples were tested using two 2 reagent lots in 8

replicates once a day over a period of 5 days on one system and five low human serum samples were tested using two 2 reagent lots in 8 replicates once a day over a period of 5 days on a second system. LoQ for each reagent lot was determined as the analyte concentration corresponding to 20% within lab CV. The LoO was determined to be 0.9 ng/mL.

d. Interference

Endogenous Interference

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Following guidelines recommended by CLSI EP7-A2, two human serum pools (~20 ng/mL and ~200 ng/mL) were spiked with interferent stock solution (hemoglobin up to 900 mg/dL, triglyceride up to 2000 mg/dL or conjugated and un-conjugated bilirubin up to 60 mg/dL normal) or the same amount diluent (control). Testing was complete on one Atellica system testing all samples in replicates of 3. The interferents showed no significant interference (< ± 10% bias from control) up to the concentrations tested.

Hemoglobin (900 mg/dL)

Triglyceride (2000 mg/dL)

Conjugated Bilirubin (60 mg/dL)

Un-conjugated Bilirubin (60 mg/dL)

Exogenous Interference

Following guidelines recommended by CLSI EP7-A2, two human serum pools (~20 ng/mL and ~200 ng/mL) were spiked with interferent stock solution. Testing was complete on one Atellica system testing all samples in replicates of 3. The interferents showed no significant interference (< ± 10% bias from control) up to the concentrations tested.

Heparin 3000 IU/L
N-acetylcysteine 17.6 mM
Acetysalicylic Acid 2.78 mM
Ampicillin 152 uM
Dobesilate 33.3 ug/mL
Ibuprofen 2425 uM
Levodopa 1.3 mM
Metronidazole 701 uM
Rifampicin 78.1 uM
Theophylline 222 uM
Phenylbutazone 650 uM
Valproic Acid 3.5 mM
Methotrexate 2.0 mM
Prednisone 0.5 mM
Ferrous Sulphate 1.0 mM
Ascorbic Acid 176mg/dL

Specificity (Cross-reactivity )

The cross reactivity of human liver Ferritin and human spleen Ferritin was determined by adding stock solution of liver ferritin and spleen ferritin to four specimens with four different endogenous ferritin levels of approximately 50, 120, 430 and 740 ng/mL). All samples were tested replicates of 3. The results are shown in the following table:

Substance	Substance TestConcentration(ng/mL)	AnalyteConcentration(ng/mL)	MeasuredFerritinConcentration(ng/mL)	Cross-Reactivity(%)
Liver Ferritin	285	52.1	380.3	115%
Liver Ferritin	285	120.5	401.8	99%
Liver Ferritin	285	433.8	704.1	95%
Liver Ferritin	285	741.2	1010.3	94%

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225	51.5	282.5	103%
225	121.0	342.4	98%
225	421.4	633.3	94%
225	739.2	944.9	91%

e. Dilution Recovery Study:

Three human serum samples in the range of 1713.9-1750.6 ng/mL of ferritin were diluted 1:2, 1:4, 1:8, and 1:16 with equine-based diluent and assayed for recovery. The recoveries ranged from 89%-100% with a mean of 94%.

f. Spiking Recovery Study:

Varying amounts of ferritin were added to 5 samples with endogenous ferritin levels of 34.0-321.5 ng/mL. The recoveries ranged from 90%-116% with a mean of 104%.

g. High-dose hook effect:

To test for High Dose "Hook Effect" associated with the Ferritin assay, 11 serial dilution samples were prepared from a sample with 100,000 ng/mL ferritin and tested on Atellica system. The assay did not demonstrate a Hook Effect up to 80,000 ng/mL ferritin

h. Traceability and Stability

Traceability

The Atellica IM Ferritin assay is traceable to World Health Organization 2nd International Standard (WHO 80/578). Assigned values for calibrators are traceable to this standardization. Stability:

Shelf-life studies:

The shelf-life of the Atellica Ferritin reagents is 8 months at 2-8°C. For unopened product, see the expiration date on the reagent carton.

On-board and open-vial studies:

Reagent On-board reagent stability: for opened products, once placed on the system reagents are stable for 28 days.

Reagent Calibration frequency is assigned at 28 days

Sponsor pre-defined acceptance criteria were met in each of these studies.

2. Comparison Studies

a. Method Comparison with predicate device

A total of 126 serum samples with ferritin concentrations across assay measuring interval were tested using the Atellica IM Ferritin assay and the predicate device. Results were analyzed by both linear and Deming Regression. Final calculations were performed with 107 samples (samples outside the range of either assay were not included in final calculations)

Atellica IM Fer (y) vs Centaur FER (x) (Weighted Deming regression): y = 1.03x - 0.5 ng/mL, r=0.99, sample range 3.4-1641.4 ng/mL Note - corr. coefficient calculated using linear regression

b. Matrix Comparison

To evaluate anticoagulant effects, paired serum, K2 EDTA plasma, Lithium Heparin plasma samples were tested on the Atellica IM Ferritin Assay. A total of 56 paired sample sets were tested. To ensure that the concentrations of ferritin were distributed across the measuring

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interval of the assay, five high levels samples spiked with stock solution of ferritin and two diluted samples were included.

Results were analyzed by both linear and Deming Regression. EDTA plasma (v) vs Serum (x) (Deming regression): y = 0.96x + 1.6 ng/mL, r=0.997. sample range 2.5-1440.7 ng/mL Lithium heparin (y) vs Serum(x) (Deming regression): y = 0.95x + 0.1 ng/mL. r=0.998. sample range 2.5-1440.7 ng/mL Note - corr. coefficient calculated using linear regression

3. Expected Values/Reference Range

The following values for apparently healthy male (age range 15-95 years old) and female (age range 16-94 years old) subjects with normal liver function enzyme tests, bilirubin, and serum iron tests, were established using the Atellica IM Analyzer in accordance with CLSI Document EP28-A3c

Category	N	Median (ng/mL)	95th Percentile Range (ng/mL)
Normal Males	179	58.9	10.5-307.3
Normal Females	275	46.4	7.3-270.7

As with all in vitro diagnostic assays, each laboratory should determine its own reference interval for the diagnostic evaluation of patient results.

15. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

16. Conclusions

Comparative testing of the Atellica® Ferritin Assay is substantially equivalent in principle and performance to the predicate device - ADVIA Centaur Ferritin assay.

Regulation Number and Section

§ 866.5340 Ferritin immunological test system.

(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).