K Number
K213510
Device Name
IMMULITE/IMMULITE 1000 OM-MA, IMMULITE 2000 OM-MA
Date Cleared
2023-09-08

(675 days)

Product Code
Regulation Number
866.6010
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
For in vitro diagnostic use with the IMMULITE® 1000 Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second look procedures. For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures.
Device Description
The IMMULITE®/IMMULITE 1000 OM-MA Assay is comprised of OM-MA Test Units (beads coated with murine monoclonal anti-CA125 antibody), OM-MA Cycle 1 Reagent Wedge (alkaline phosphatase conjugated to rabbit polyclonal anti-CA125 antibody in buffer), OM-MA Cycle 2 Reagent Wedge (buffer), and OM-MA Adjustors (Low and High, CA125 in a nonhuman protein/buffer matrix). The IMMULITE® 2000 OM-MA Assay is a newer generation instrument that dispenses an individual bead from a pack into a separate reaction tube. It is comprised of OM-MA Bead Pack (beads coated with murine monoclonal anti-CA125 antibody), OM-MA Reagent Wedge (Well 1: alkaline phosphatase conjugated to rabbit polyclonal anti-CA125 antibody in buffer; Well 2: buffer), and OM-MA Adjustors (Low and High, CA125 in a nonhuman protein/buffer matrix). Both assays are solid-phase, two-site chemiluminescent immunometric assays that measure CA125 antigen quantitatively in serum.
More Information

Not Found

No
The summary describes a standard in vitro diagnostic immunoassay based on chemical reactions and quantitative measurement, with no mention of AI or ML in the device description, intended use, or performance studies.

No
Explanation: This device is an in vitro diagnostic assay used to measure CA125 antigen in serum. It aids in monitoring response to therapy and detecting residual cancer, but it does not directly provide therapy.

Yes

The "Intended Use / Indications for Use" section explicitly states "For in vitro diagnostic use" and describes its purpose as "an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer." This signifies its role in providing information for medical diagnosis and management.

No

The device description clearly outlines physical components like "beads coated with murine monoclonal anti-CA125 antibody," "Reagent Wedge," and "Adjustors," indicating it is an in vitro diagnostic assay kit with tangible reagents, not solely software.

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "For in vitro diagnostic use with the IMMULITE® 1000 Analyzers..." and "For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers...".

Furthermore, the device description details an assay that measures an analyte (CA125 antigen) in a biological sample (serum) to provide information for medical purposes (monitoring response to therapy and detecting residual cancer). This aligns with the definition of an in vitro diagnostic device.

N/A

Intended Use / Indications for Use

For in vitro diagnostic use with the IMMULITE® 1000 Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second look procedures.

For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures.

Product codes (comma separated list FDA assigned to the subject device)

LTK

Device Description

The IMMULITE®/IMMULITE 1000 OM-MA Assay is comprised of the following components:
Component: OM-MA Test Units (LOP1), Volume: 1 bead / test unit, Ingredients: murine monoclonal anti-CA125 antibody
Component: OM-MA Cycle 1 Reagent Wedge (LOPA), Volume: 7.5 mL, Ingredients: alkaline phosphatase (bovine calf intestine) conjugated to rabbit polyclonal anti-CA125 antibody in buffer, with preservative
Component: OM-MA Cycle 2 Reagent Wedge (LOPB), Volume: 5 mL, Ingredients: buffer, with preservative
Component: OM-MA Adjustors (Low and High, LOPL, LOPH), Volume: 3 mL each, Ingredients: CA125 in a nonhuman protein/buffer matrix, with preservative.

The IMMULITE® 2000 OM-MA Assay is a newer generation of the instrument. Rather than conducting the reactions in pre-packaged individual test units, this instrument dispenses an individual bead from a pack into a separate reaction tube. The IMMULITE® 2000 OM-MA Assay is comprised of the following components:
Component: OM-MA Bead Pack (L2KOP), Volume: 200 beads, Ingredients: murine monoclonal anti-CA125 antibody
Component: OM-MA Reagent Wedge (L2OPA2), Volume: Well 1 - 11.5 mL, Ingredients: alkaline phosphatase (bovine calf intestine) conjugated to rabbit polyclonal anti-CA125 antibody in buffer, with preservative
Component: OM-MA Reagent Wedge (L2OPA2), Volume: Well 2 – 6.5 mL, Ingredients: buffer, with preservative
Component: OM-MA Adjustors (Low and High, LOPL, LOPH), Volume: 3 mL each, Ingredients: CA125 in a nonhuman protein/buffer matrix, with preservative.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Substantial equivalence of the modified IMMULITE®/IMMULITE 1000 OM-MA Assay and IMMULITE® 2000 OM-MA Assay were demonstrated by testing performance characteristics including detection capability, linearity, method comparison, precision, spike recovery, hook effect and interference.

Detection Limits:
IMMULITE 1000 (U/mL): Limit of Blank (LoB) = 0.14, Limit of Detection (LoD) = 0.38, Limit of Quantitation (LoQ) = 2
IMMULITE 2000 (U/mL): Limit of Blank (LoB) = 0.18, Limit of Detection (LoD) = 0.43, Limit of Quantitation (LoQ) = 3

Linearity/Measuring Interval:
IMMULITE 1000 OM-MA assay: Linearity confirmed across the assay range by acceptable bias of ≤20% at each individual level. Supports measuring interval of 2 U/mL to 500 U/mL.
IMMULITE 2000 OM-MA assay: Linearity confirmed across the assay range by acceptable bias of ≤15% at each individual level. Supports measuring interval of 3 U/mL to 500 U/mL.

Method Comparison:
IMMULITE 1000: Compared to predicate device. Sample size: 246-247 patient samples per lot.
Lot 1: y = 0.995x - 0.199, Sample Range (U/mL): 1.03 - 466
Lot 2: y = 0.999x - 0.047, Sample Range (U/mL): 1.68 - 455
Lot 3: y = 1.022x - 0.821, Sample Range (U/mL): 1.27 - 471

IMMULITE 2000: Compared to predicate device. Sample size: 246 patient samples per lot.
Lot 1: y = 1.032x + 0.086, Sample Range (U/mL): 2.47 - 511
Lot 2: y = 0.955x - 0.256, Sample Range (U/mL): 2.11 - 525
Lot 3: y = 0.976x - 0.142, Sample Range (U/mL): 2.29 - 489
Regression analysis using Passing-Bablok.

Precision:
IMMULITE: Five serum samples tested in duplicate over 20 days, two runs per day (40 runs, 80 replicates per sample).
Level 1 (Mean Dose: 9.17 U/mL): Repeatability S.D. 0.41, %CV 4.5; Within-Lab Imprecision S.D. 0.49, %CV 5.3
Level 5 (Mean Dose: 427.48 U/mL): Repeatability S.D. 12.40, %CV 2.9; Within-Lab Imprecision S.D. 12.86, %CV 3.0

IMMULITE 2000: Five serum samples tested in duplicate over 20 days, two runs per day (40 runs, 80 replicates per sample).
Level 1 (Mean Dose: 11.23 U/mL): Repeatability S.D. 0.59, %CV 5.2; Within-Lab Imprecision S.D. 0.68, %CV 6.0
Level 5 (Mean Dose: 451.54 U/mL): Repeatability S.D. 22.58, %CV 5.0; Within-Lab Imprecision S.D. 26.82, %CV 5.9

Reproducibility:
IMMULITE: Three reagent lots, 5 x 5 x 3 experimental design (five serum samples, five days, five replicates per sample).
Sample 1 (Mean Dose: 9.41 U/mL): Between-Lot SD 0.54, %CV 5.73; Total Reproducibility SD 0.78, %CV 8.33
Sample 5 (Mean Dose: 420.97 U/mL): Between-Lot SD 25.32, %CV 6.02; Total Reproducibility SD 37.57, %CV 8.93

IMMULITE 2000: Three reagent lots, 5 x 5 x 3 experimental design.
Sample 1 (Mean Dose: 11.26 U/mL): Lot-to-Lot SD 0.53, %CV 4.66; Total Reproducibility SD 0.81, %CV 7.15
Sample 5 (Mean Dose: 425.82 U/mL): Lot-to-Lot SD 18.49, %CV 4.34; Total Reproducibility SD 33.43%CV 7.85

Recovery:
Spike and recovery studies performed with spiked CA 125 solutions.
IMMULITE: Observed/Expected percentages for spiked samples range from 83% to 109%.
IMMULITE 2000: Observed/Expected percentages for spiked samples range from 75% to 100%.

Hook Effect:
IMMULITE: CA 125 concentrations up to 84,500 U/mL will report as >500 U/mL.
IMMULITE 2000: CA 125 concentrations up to 80,000 U/mL will report as >500 U/mL. Confirmed in Instructions for Use.

Specificity (Cross-reactivity):
IMMULITE: AFP (10,000 IU/mL) and CA19-9 (4000 U/mL) are not detectable. CA15-3 (1753 U/mL) shows 0.41% cross-reactivity. CEA (10,000 ng/mL) shows 0.05% cross-reactivity.
IMMULITE 2000: AFP (10,000 IU/mL) and CA19-9 (4000 U/mL) are not detectable. CA15-3 (1753 U/mL) shows 0.41% cross-reactivity. CEA (10,000 ng/mL) shows 0.05% cross-reactivity.

Interference:
Conjugated Bilirubin (200 mg/L), Unconjugated Bilirubin (200 mg/L), Haemoglobin (IMMULITE: 381 mg/dL, IMMULITE 2000: 192 mg/dL), Intralipid (Triglycerides) (3000 mg/dL), Biotin (3500 ng/mL) showed ≤10% bias.

Reference Range:
Verified existing healthy Reference Interval (Healthy Individuals ≤ 21 U/mL) using apparently healthy female samples.
IMMULITE: 93%-94% of tested samples were

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

September 8, 2023

Siemens Healthcare Diagnostics Products Ltd Stefani Vinkemeier Regulatory Affairs Professional Glyn Rhonwy, Llanberis Caernarfon Llanberis, Gwynedd LL55 4EL United Kingdom

Re: K213510

Trade/Device Name: IMMULITE/IMMULITE 1000 OM-MA IMMULITE 2000 OM-MA Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: LTK Dated: February 24, 2023 Received: February 27, 2023

Dear Stefani Vinkemeier:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

1

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4. Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Ying Mao -S

Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K213510

Device Name IMMULITE/IMMULITE 1000 OM-MA IMMULITE 2000 OM-MA

Indications for Use (Describe)

I

For in vitro diagnostic use with the IMMULITE® 1000 Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second look procedures.

For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures.

Type of Use (Select one or both, as applicable)
---------------------------------------------------

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

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

The assigned 510(k) number is: K213510____________________________________________________________________________________________________________________________

5.1 Submitter

Contact Person:Stefani Vinkemeier
Address:Siemens Healthcare Diagnostics Products Ltd
Glyn Rhonwy, Llanberis Caernarfon, Llanberis,
Gwynedd LL55 4EL GBR
E-mail:stefani.vinkemeier@siemens-healthineers.com
Phone:302-489-9232
Date of Preparation:May 11, 2023

5.2 Device

Regulatory Information

Trade Name:IMMULITE®/IMMULITE 1000 OM-MA,
IMMULITE® 2000 OM-MA
Common Name:Test, Epithelial Ovarian Tumor-associated Antigen (Ca125)
Classification Name:Tumor-associated antigen immunological test system
Regulation Number:21 CFR 866.6010
Classification:Class II
Product Code:LTK
Review Panel:Immunology (82)

Design and Use of the Device

QuestionYesNo
Is the device intended for prescription use (21 CFR 801 subpart D)?X
Is the device intended for over-the-counter use (21 CFR 801 subpart C)?X
Does the device contain components derived from a tissue or other biologic source?X
Is the device provided sterile?X
Is the device intended for single use?X
Is the device a reprocessed single use device?X
Does the device contain a drug?X
Does the device contain a biologic?X
Does the device use software?X
Does the submission include clinical information?X
Is the device implanted?X

5.3 Predicate Device

The predicate devices, IMMULITE 1000 OM-MA and IMMULITE 2000 OM-MA, manufactured by Siemens Healthcare Diagnostics Products Ltd, Glyn Rhonwy, Llanberis, Wales, United Kingdom, were cleared by the FDA under K981297 and K983391.

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5.4 Device Description

The IMMULITE®/IMMULITE 1000 OM-MA Assay is comprised of the following components:

ComponentVolumeIngredients
OM-MA Test Units (LOP1)1 bead / test unitmurine monoclonal anti-CA125
antibody
OM-MA Cycle 1 Reagent Wedge
(LOPA)7.5 mLalkaline phosphatase (bovine
calf intestine) conjugated to
rabbit polyclonal anti-CA125
antibody in buffer, with
preservative
OM-MA Cycle 2 Reagent Wedge
(LOPB)5 mLbuffer, with preservative
OM-MA Adjustors (Low and
High, LOPL, LOPH)3 mL eachCA125 in a nonhuman
protein/buffer matrix, with
preservative.

The IMMULITE® 2000 OM-MA Assay is a newer generation of the instrument. Rather than conducting the reactions in pre-packaged individual test units, this instrument dispenses an individual bead from a pack into a separate reaction tube. The IMMULITE® 2000 OM-MA Assay is comprised of the following components:

ComponentVolumeIngredients
OM-MA Bead Pack (L2KOP)200 beadsmurine monoclonal anti-CA125
antibody
OM-MA Reagent Wedge (L2OPA2)Well 1 - 11.5 mLalkaline phosphatase (bovine calf intestine) conjugated to rabbit polyclonal anti-CA125
antibody in buffer, with preservative
Well 2 – 6.5 mLbuffer, with preservative
OM-MA Adjustors (Low and High, LOPL, LOPH)3 mL eachCA125 in a nonhuman protein/buffer matrix, with
preservative.

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5.5 Test Principle

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 OM-MA are solid-phase, two-site chemiluminescent immunometric assays. There are two incubation cycles of 30 minutes each.

During the initial 30-minute cycle, the patient sample is incubated with biotinylated antibody coated bead and alkaline phosphatase antibody conjugate. This cycle creates a bead pair immunocomplex sandwich consisting of capture Ab-antiqen-detection Ab. During the second 30-minute cycle, buffer is added to remove unbound conjugate, which is then removed by centrifugal wash.

The amount of alkaline phosphate bound is directly proportional to the analyte in the patient sample. Following the two 30-minute incubation periods, IMMULITE chemiluminescent substrate (LSUBX or L2SUBM) is added for a further 10-minute incubation period to generate the luminogenic reaction.

The chemiluminescent substrate underqoes hydrolysis in the presence of the alkaline phosphatase to yield an unstable intermediate, which then emits photons. The sustained emissions are measured by the luminometer. The resulting relative light units (RLU) are proportional to the concentration of CA 125 in the sample, which is expressed as U/mL.

5.6 Intended Use / Indications for Use

IMMULITE/IMMULITE® 1000 OM-MA Assay

For in vitro diagnostic use with the IMMULITE® and IMMULITE® 1000 Analyzers — for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the resoonse to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second look procedures.

IMMULITE® 2000 OM-MA Assay

For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers — for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures.

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5.7 Comparison to Predicate Device

| Attribute | Candidate Device:
IMMULITE®/IMMULITE 1000 OM-MA
Assay, modified | Predicate Device:
IMMULITE®/IMMULITE 1000 OM-MA Assay, K981297 |
|---------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use /
Indications for Use | For in vitro diagnostic use with the
IMMULITE® and IMMULITE® 1000
Analyzers — for the
quantitative measurement of CA125
antigen in serum, as an aid in
monitoring the response to therapy
for patients with epithelial ovarian
cancer, and in detecting residual
ovarian cancer in patients who have
undergone first-line therapy and
would be considered for diagnostic
second look procedures. | Same |
| Analyte | Cancer Antigen 125 | Same |
| Automated | Automated assay | Same |
| Measurement | Quantitative | Same |
| Sample Type | Human serum | Same |
| Detection Limit | LoB: 0.14 U/mL
LoD: 0.38 U/mL
LoQ: 2 U/mL | Analytical Sensitivity: 1 U/mL |
| Assay Measuring
Interval | 2 - 500 U/mL | 1 - 500 U/mL |
| Operating Principle | Immunologic sandwich | Same |
| Technology | Direct chemiluminescent | Same |
| Instrument | IMMULITE® 1000 systems | Same |
| Sample Volume | 50 μL | Same |
| Calibrator
(Adjustors) | CA125 in a nonhuman protein/buffer
matrix, with
preservative. | Same |
| Controls | Commercially available, minimum of 2
levels | Same |
| Detection Antibody | alkaline phosphatase (bovine calf
intestine) conjugated to rabbit
polyclonal anti-CA125 antibody | Same |
| Capture Antibody | monoclonal mouse anti-CA125 | Same |
| Biotin interference | Specimens that contain biotin at a
concentration of 3500 ng/mL
demonstrate a less than or equal to
10% change in results. Biotin
concentrations greater than this may
lead to incorrect results for patient | Specimens that contain biotin at a
concentration of 2 ng/mL
demonstration less than of equal to
10% change in results. Biotin
concentrations greater than this
may lead to falsely elevated results. |

Comparison Table of Technological Characteristics for IMMULITE/IMMULITE 1000

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Candidate Device:Predicate Device:
IMMULITE® 2000 OM-MA Assay,
modifiedIMMULITE® 2000 OM-MA Assay,
K983391
Attribute
Intended Use /
Indications for UseFor in vitro diagnostic use with
the IMMULITE® 2000 Systems
Analyzers — for the quantitative
measurement of CA125 antigen
in serum, as an aid in monitoring
the response to therapy for
patients with epithelian ovarian
cancer, and in detecting residual
ovarian cancer in patients who
have undergone first-line
therapy and would be
considered for diagnostic
second-look procedures.Same
AnalyteCancer Antigen 125Same
AutomatedAutomated assaySame
MeasurementQuantitativeSame
Sample TypeHuman serumSame
Detection LimitLoB: 0.18 U/mL
LoD: 0.43 U/mL
LoQ: 3 U/mLAnalytical Sensitivity: 1 U/mL
Assay Measuring
Interval3 - 500 U/mL1 - 500 U/mL
Operating PrincipleImmunologic sandwichSame
TechnologyDirect chemiluminescentSame
InstrumentIMMULITE® 2000 and
IMMULITE® 2000 XPi systemsSame
Sample Volume50 μLSame
Calibrator
(Adjustors)CA125 in a nonhuman
protein/buffer matrix, with
preservative.Same
ControlsCommercially available,
minimum of 2 levelsSame
Detection Antibodyalkaline phosphatase (bovine calf
intestine) conjugated to rabbit
polyclonal anti-CA125 antibodySame
Capture Antibodymonoclonal mouse anti-CA125Same
Biotin interferenceSpecimens that contain biotin at
a concentration of 3500 ng/mL
demonstrate a less than or equal
to 10% change in results. Biotin
concentrations greater than this
may lead to incorrect results for
patient samples.Specimens that contain biotin at a
concentration of 2 ng/mL
demonstration less than of equal to
10% change in results. Biotin
concentrations greater than this may
lead to falsely elevated results.

Comparison Table of Technological Characteristics for IMMULITE 2000

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5.8 Summary of Performance Testing

Substantial equivalence of the modified IMMULITE®/IMMULITE 1000 OM-MA Assay and IMMULITE® 2000 OM-MA Assay were demonstrated by testing performance characteristics including detection capability, linearity, method comparison, precision, spike recovery, hook effect and interference.

The resulting performance data are provided in support of a substantial equivalence determination.

5.8.1 Detection Limits

LoB. LoD, and LoO were determined in accordance with Clinical and Laboratory Standards Institute (CLSI) EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures: Approved Guideline - Second Edition. The LoB/LoD/LoQ estimates are summarized below:

IMMULITE 1000 (U/mL)IMMULITE 2000 (U/mL)
Limit of Blank (LoB)0.140.18
Limit of Detection (LoD)0.380.43
Limit of Quantitation (LoQ)23

5.8.2 Measuring Interval / Linearity

Linearity was verified by testing samples spanning the assay range prepared by combining a high serum pool with a low serum sample to produce nine different levels.

For the IMMULITE 1000 OM-MA assay, linearity was confirmed across the assay range by acceptable bias of ≤20% at each individual level. Linear regression analysis of expected versus observed values confirm an overall recovery bias of ≤20% and supports the measuring interval of 2 U/mL to 500 U/mL.

For the IMMULITE 2000 OM-MA assay, linearity was confirmed across the assay range by acceptable bias of ≤15% at each individual level. Linear regression analysis of expected versus observed values confirm an overall recovery bias of ≤15% and supports the measuring interval of 3 U/mL to 500 U/mL.

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5.8.3 Method Comparison: Quantitative Assay

Method comparison studies were performed comparing the modified devices to the currently-marketed predicate devices (IMMULITE 1000 and IMMULITE 2000). A total of 253 patient samples covering the full range of the assay were analyzed on both methods.

A single replicate was processed for each sample. Passing-Bablok regression was used to compare the methods.

| Lot | Specimen
Type | Comparison
Assay (x) | N | Regression
Equation | Sample Range
(U/mL) |
|-----|------------------|-------------------------|-----|------------------------|------------------------|
| 1 | Serum | IMMULITE 1000 | 246 | $y = 0.995x - 0.199$ | 1.03 - 466 |
| 2 | Serum | IMMULITE 1000 | 246 | $y = 0.999x - 0.047$ | 1.68 - 455 |
| 3 | Serum | IMMULITE 1000 | 247 | $y = 1.022x - 0.821$ | 1.27 - 471 |

IMMULITE 1000

IMMULITE 2000

| Lot | Specimen
Type | Comparison
Assay (x) | N | Regression
Equation | Sample Range
(U/mL) |
|-----|------------------|-------------------------|-----|------------------------|------------------------|
| 1 | Serum | IMMULITE 2000 | 246 | $y = 1.032x + 0.086$ | 2.47 - 511 |
| 2 | Serum | IMMULITE 2000 | 246 | $y = 0.955x - 0.256$ | 2.11 - 525 |
| 3 | Serum | IMMULITE 2000 | 246 | $y = 0.976x - 0.142$ | 2.29 - 489 |

5.8.4 Verification of Assay Precision

Precision studies were conducted on one reagent lot per platform in accordance with CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures. For each assay, testing was performed on five serum samples spanning the range of the assays. Each sample was tested in duplicate over a period of 20 days, two runs per day, for a total of 40 runs and 80 replicates. The results are given in the following tables.

Results for Within Run and Total precision for IMMULITE

| | Mean Dose
(U/mL) | Repeatability | | Within-Lab
Imprecision | |
|---------|---------------------|---------------|-----|---------------------------|-----|
| | | S.D. | %CV | S.D. | %CV |
| Level 1 | 9.17 | 0.41 | 4.5 | 0.49 | 5.3 |
| Level 2 | 19.21 | 0.86 | 4.5 | 0.95 | 5.0 |
| Level 3 | 41.36 | 1.38 | 3.3 | 1.77 | 4.3 |
| Level 4 | 225.95 | 8.87 | 3.9 | 9.41 | 4.2 |
| Level 5 | 427.48 | 12.40 | 2.9 | 12.86 | 3.0 |

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| Precision
Sample | Mean
Dose
(U/mL) | Repeatability | | Within-Lab
Imprecision | |
|---------------------|------------------------|---------------|-----|---------------------------|-----|
| | | S.D. | %CV | S.D. | %CV |
| Level 1 | 11.23 | 0.59 | 5.2 | 0.68 | 6.0 |
| Level 2 | 23.69 | 1.45 | 6.1 | 1.82 | 7.7 |
| Level 3 | 42.59 | 1.86 | 4.4 | 2.19 | 5.1 |
| Level 4 | 226.17 | 10.57 | 4.7 | 11.66 | 5.2 |
| Level 5 | 451.54 | 22.58 | 5.0 | 26.82 | 5.9 |

Results for Within Run and Total precision for IMMULITE 2000

5.8.5 Verification of Assay Reproducibility

Reproducibility studies were conducted on three reagents lot per platform in accordance with CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures, using the 5 x 5 x 3 experimental design. For each assay, testing was performed on five serum samples spanning the range of the assays. Each sample was tested in over a period of five days, with five replicates per sample. The results are given in the following tables.

| Sample | Mean Dose
(U/mL) | Between-Lot | | Total
Reproducibility | |
|--------|---------------------|-------------|------|--------------------------|------|
| | | SD | %CV | SD | %CV |
| 1 | 9.41 | 0.54 | 5.73 | 0.78 | 8.33 |
| 2 | 18.72 | 1.21 | 6.45 | 1.75 | 9.37 |
| 3 | 39.68 | 2.53 | 6.38 | 3.64 | 9.18 |
| 4 | 215.20 | 11.30 | 5.25 | 16.24 | 7.55 |
| 5 | 420.97 | 25.32 | 6.02 | 37.57 | 8.93 |

Reproducibility Results for IMMULITE

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| Reproducibility
Sample | Mean Dose
(U/mL) | Lot-to-Lot | | Total
Reproducibility | |
|---------------------------|---------------------|------------|------|--------------------------|------|
| | | SD | %CV | SD | %CV |
| 1 | 11.26 | 0.53 | 4.66 | 0.81 | 7.15 |
| 2 | 22.94 | 1.13 | 4.94 | 1.76 | 7.66 |
| 3 | 40.49 | 1.34 | 3.30 | 2.64 | 6.52 |
| 4 | 213.03 | 4.02 | 1.89 | 13.18 | 6.19 |
| 5 | 425.82 | 18.49 | 4.34 | 33.43 | 7.85 |

Reproducibility Results for IMMULITE 2000

5.8.6 Recovery

Spike and recovery studies were performed by spiking samples 1 to 19 with three CA 125 solutions of differing concentrations.

SolutionObservedExpected%O/E
1-2.7--
A323397%
B556387%
C10612585%
2-4.3--
A3734109%
B636597%
C128127101%
3-2.9--
A323397%
B536483%
C10812586%
4-8.7--
A3838100%
B666996%
C12613196%

IMMULITE – Spiking solutions 602, 1218 and 2450 U/mL

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SolutionObservedExpected%O/E
1-16--
A566290%
B8810485%
C15120175%
2-28--
A637386%
B8611575%
C16521278%
3-63--
A107107100%
B13514991%
C22224690%
4-95--
A11913787%
B16917994%
C24727689%

IMMULITE 2000 - Spiking solutions 933, 1776 and 3716 U/mL

5.8.7 Hook Effect

CA 125 concentrations as high as 84,500 U/mL for the IMMULITE and 80,000 U/mL for the IMMULITE 2000 will report as >500 U/mL. The high-dose hook effect information provided in the Instructions for Use for the modified IMMULITE OM-MA and IMMULITE 2000 OM-MA was confirmed and remain as presented in K981297 and K983391, respectively.

5.8.8 Specificity (Cross-reactivity)

Specificity (cross-reactivity) of the modified OM-MA assays to compounds with structural similarities to the CA 125 tumor marker were evaluated. Cross-reactant solutions were prepared by dissolving each potential cross-reactant into an appropriate solvent. The resulting solutions were spiked into patient sample pools to produce final concentrations approximately equal to the concentrations listed in the labeling. The samples were compared to the appropriate level patient sample pool that was mixed with an equal volume of solvent to determine a percent cross-reactivity. The specificity information provided in the Instructions for Use for the modified IMMULITE OM-MA and IMMULITE 2000 OM-MA was confirmed and remains as presented in K981297 and K983391, respectively.

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IMMULITE Specificity

CompoundAmount AddedApparent U/mL% Cross- reactivity
AFP10,000 IU/mLNDND
CA15-31753 U/mL7.10.41%
CA19-94000 U/mLNDND
CEA10,000 ng/mL4.80.05%

ND: not detectable

IMMULITE 2000 Specificity

CompoundAmount AddedApparent U/mL% Cross- reactivity
AFP10,000 IU/mLNDND
CA15-31753 U/mL7.10.41%
CA19-94000 U/mLNDND
CEA10,000 ng/mL4.80.05%

ND: not detectable

5.8.9 Interference

Verification of the assay interference was conducted in accordance with CLSI EP07-ED3, Interference Testing in Clinical Chemistry. The tested substances were determined to have no substantial interference.

IMMULITE Interfering Substances

Interfering SubstanceAmount Added% Bias
Conjugated Bilirubin200 mg/L≤10%
Unconjugated Bilirubin200 mg/L≤10%
Haemoglobin381 mg/dL≤10%
Intralipid (Triglycerides)3000 mg/dL≤10%
Biotin3500 mg/mL≤10%

IMMULITE 2000 Interfering Substances

Interfering SubstanceAmount Added% Bias
Conjugated Bilirubin200 mg/L≤10%
Unconjugated Bilirubin200 mg/L≤10%
Haemoglobin192 mg/dL≤10%
Intralipid (Triglycerides)3000 mg/dL≤10%
Biotin3500 ng/mL≤10%

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5.8.10 Reference Range

The reference range was verified by assaying apparently healthy female samples according to CLSI EP28-A3, Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory, to verify the existing healthy Reference Interval (Healthy Individuals ≤ 21 U/mL).

IMMULITE Reference Range Results

Lot 1Lot 2Lot 3
n505045
n