(28 days)
Lumipulse® G CA19-9-N is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative measurement of CA 19-9 in human serum or plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System.
The assay is to be used as an aid in the management of patients diagnosed with cancer of the exocrine pancreas who have detectable levels of CA 19-9 at some point in their disease process. Serial testing for patient CA 19-9 assay values should be used in conjunction with other clinical methods used for monitoring cancer of the exocrine pancreas.
The Lumipulse G CA19-9-N Immunoreaction Cartridges (cat. # 235126) consists of 3 x 14 tests. Each kit contains the following:
- Antibody-Coated Particle Solution (Liquid when used, 250 µL/Immunoreaction Cartridge) Contains 150 µq/mL anti-CA19-9 monoclonal antibody (mouse)-coated particles, protein stabilizers (bovine and mouse) and chemical stabilizers in 0.15 M sodium chloride/Tris buffer. This solution contains gelatin and turns into gel at 15 ℃ or lower. Preservative: sodium azide.
- Enzyme-Labeled Antibody Solution (Liquid, 350 µL/Immunoreaction Cartridge) Contains 0.5 µg/mL alkaline phosphatase (ALP: calf)-labeled anti-CA19-9 monoclonal antibody (mouse), protein stabilizers (bovine, calf, and mouse) and chemical stabilizers in 0.05 M sodium chloride/Bis-Tris buffer. Preservative: sodium azide.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Context: This document describes a Special 510(k) submission for the Lumipulse G CA19-9-N device, specifically addressing a change in the tested concentration of the therapeutic interferent Tamoxifen. The device is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative measurement of CA 19-9, used as an aid in the management of patients with cancer of the exocrine pancreas.
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Individual samples must have a percent difference of ± 10% difference from the control. | -2% to 1% (Met acceptance criteria) |
Study Details
-
Sample Size Used for the Test Set and Data Provenance:
- Sample Size: Not explicitly stated for the "Supplemental Therapeutic Interference Study." However, the tables comparing the cleared vs. modified device list "Samples (Mean Test Concentrations (U/mL) (n=3))" and "Samples (Mean Control Concentrations (U/mL) (n=3))" for three serum pools. This suggests that for each serum pool, there were likely 3 replicates tested (n=3).
- Data Provenance: Not specified, but given it's an in vitro diagnostic measuring a biomarker, the samples would be human serum/plasma. The document does not mention country of origin or whether the data was retrospective or prospective, though interference studies are typically laboratory-based and prospective using spiked samples or naturally interfering samples.
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Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications: Not applicable. This study is an interference study for an in vitro diagnostic device measuring a quantitative biomarker (CA 19-9). Ground truth is established by the known concentration of the substance being measured (CA 19-9) and the known concentration of the interferent (Tamoxifen). Expert consensus or pathologist review is not relevant for this type of test.
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Adjudication Method for the Test Set: Not applicable. This is an interference study for a quantitative assay, not a subjective diagnostic interpretation.
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If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done: No, an MRMC study was not done. This type of study is typically performed for image-based diagnostics where multiple readers interpret cases with and without AI assistance. This document pertains to an in vitro diagnostic assay.
-
If a Standalone Performance Study was done: Yes, a standalone performance study in the form of a "Supplemental Therapeutic Interference Study" was conducted. This study assessed the device's performance (specifically, its susceptibility to Tamoxifen interference) without human interpretation in the loop, by comparing results with and without the interferent to a control.
-
The Type of Ground Truth Used: The ground truth for this interference study is established by:
- The known, pre-established concentrations of CA 19-9 in the serum pools used.
- The known concentration of Tamoxifen added to the samples.
- The "control" measurements (samples without Tamoxifen) serve as the reference for determining the "percent difference."
-
The Sample Size for the Training Set: Not applicable. This is not a machine learning or AI-based device that requires a training set in the conventional sense. The "training" for such an assay is its analytical development and optimization.
-
How the Ground Truth for the Training Set was Established: Not applicable, as there is no training set for this type of in vitro diagnostic device in the context of machine learning. The assay is built on established chemical and immunological principles, with performance characteristics determined through analytical validation studies (like interference studies).
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Image /page/0/Picture/0 description: The image shows 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, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
May 14, 2020
Fujirebio Diagnostics, Inc. Kristin Maddaloni Regulatory Affairs Specialist 201 Great Valley Parkway Malvern, Pennsylvania 19355
Re: K200997
Trade/Device Name: Lumipulse G CA19-9-N Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: NIG Dated: April 15, 2020 Received: April 16, 2020
Dear Kristin Maddaloni:
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.
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
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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 (OS) 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 mediation-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,
Carolina Kagan Acting Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health 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) K200997
Device Name Lumipulse G CA19-9-N
Indications for Use (Describe)
WARNING: The concentration of CA19-9 in a given specimen, as determined by assays from different manufacturers, can vary due to differences in assay methods and reagent specificity. The results reported by the laboratory to the physician must include the identity of the assay for CA19-9 used. Values obtained with different assay methods cannot be used interchangeably. If, in the course of monitoring a patient, the assay method used for determining serial levels of CA 19-9 is changed, the laboratory must perform additional serial testing to confirm baseline values. Prior to changing assays, the laboratory MUST confirm baseline values for patients being serially monitored. Lumipulse & CA19-9-N should not be used for cancer screening or diagnosis.
WARNING: Patients known to be genotypically negative for the Lewis blood group antigen will be unable to produce the CA 19-9 antigen even in the presence of malignant tissue. Phenotyping for the presence of the Lewis antigen may be insufficient to detect true Lewis antigen negative individuals. Even patients who are genotypically positive for the Lewis antigen may produce varying levels of CA19-9 based on gene dosage effect.
Lumipulse & CA19-9-N is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative measurement of CA19-9 in human serum or plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System.
The assay is to be used as an aid in the management of patients diagnosed with cancer of the exocrine pancreas who have detectable levels of CA19-9 at some point in their disease process. Serial testing for patient CA19-9 assay values should be used in conjunction with other clinical methods used for monitoring cancer of the exocrine pancreas.
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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SPECIAL 510(k) SUMMARY
A. GENERAL INFORMATION
Submission Date: April 15, 2020
Submitter Information:
Submitted By:
Fujirebio Diagnostics, Inc. 201 Great Valley Parkway Malvern, PA 19355
Contact Person:
Kristin Maddaloni Regulatory Affairs Specialist Fujirebio Diagnostics, Inc. 201 Great Valley Pkwy Malvern, PA 19355 Office: 484-395-2126 maddalonik@fdi.com
B. PURPOSE FOR SUBMISSION
Special 510(k) for a test concentration change to therapeutic interferent Tamoxifen for Lumipulse G CA19-9-N.
C. MEASURAND
CA 19-9
D. TYPE OF TEST
Quantitative, Chemiluminescent Immunoassay
E. APPLICANT
Fujirebio Diagnostics, Inc.
F. PROPRIETARY AND ESTABLISHED NAMES
Lumipulse® G CA 19-9-N Lumipulse® G CA19-9-N Immunoreaction Cartridges
G. REGULATORY INFORMATION
| Trade Name: | Lumipulse G CA19-9-N |
|---|---|
| Classification: | Class II |
| Regulation: | 21 CFR 866.6010 |
| Regulation Name: | Tumor-Associated Antigen Immunological Test System |
| Product Code: | NIG – System, Test, Carbohydrate antigen (CA 19-9) for monitoring and management of pancreatic cancer |
| Panel: | 82, Immunology |
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Image /page/4/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo consists of a blue and white abstract symbol on the left, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font, and "Diagnostics, Inc." is in a smaller font below it.
H. INTENDED USE / INDICATIONS FOR USE
1. Warning Statements
The concentration of CA 19-9 in a given specimen, as determined by assays from different manufacturers, can vary due to differences in assay methods and reagent specificity. The results reported by the laboratory to the physician must include the identity of the assay for CA 19-9 used. Values obtained with different assay methods cannot be used interchangeably. If, in the course of monitoring a patient, the assay method used for determining serial levels of CA 19-9 is changed, the laboratory must perform additional serial testing to confirm baseline values. Prior to changing assays, the laboratory MUST confirm baseline values for patients being serially monitored. Lumipulse G CA19-9-N should not be used for cancer screening or diagnosis.
Patients known to be genotypically negative for Lewis blood group antigen are unable to produce the CA 19-9 antigen even in the presence of malignant tissue. Phenotyping for the presence of the Lewis blood group antigen may be insufficient to detect true Lewis antigen negative individuals. Even patients who are genotype positive for the Lewis antigen may produce varying levels of CA 19-9 as the result of gene dosage effect. pancreas.
-
- Intended Use / Indications for use
Lumipulse® G CA19-9-N is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative measurement of CA 19-9 in human serum or plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System.
- Intended Use / Indications for use
The assay is to be used as an aid in the management of patients diagnosed with cancer of the exocrine pancreas who have detectable levels of CA 19-9 at some point in their disease process. Serial testing for patient CA 19-9 assay values should be used in conjunction with other clinical methods used for monitoring cancer of the exocrine pancreas.
-
- Special instrument requirements:
Lumipulse G System
- Special instrument requirements:
DEVICE DESCRIPTION .
Reagents
The Lumipulse G CA19-9-N Immunoreaction Cartridges (cat. # 235126) consists of 3 x 14 tests. Each kit contains the following:
-
- Antibody-Coated Particle Solution (Liquid when used, 250 µL/Immunoreaction Cartridge) Contains 150 µq/mL anti-CA19-9 monoclonal antibody (mouse)-coated particles, protein stabilizers (bovine and mouse) and chemical stabilizers in 0.15 M sodium chloride/Tris
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Image /page/5/Picture/1 description: The image shows the logo for FUJIREBIO Diagnostics, Inc. The logo features a stylized, abstract shape in blue and green on the left, followed by the company name in blue, bold letters. Below the company name, the words "Diagnostics, Inc." are written in a smaller, black font.
buffer. This solution contains gelatin and turns into gel at 15 ℃ or lower. Preservative: sodium azide.
-
- Enzyme-Labeled Antibody Solution (Liquid, 350 µL/Immunoreaction Cartridge) Contains 0.5 µg/mL alkaline phosphatase (ALP: calf)-labeled anti-CA19-9 monoclonal antibody (mouse), protein stabilizers (bovine, calf, and mouse) and chemical stabilizers in 0.05 M sodium chloride/Bis-Tris buffer. Preservative: sodium azide.
J. DESCRIPTION OF MODIFIED DEVICE
-
- Modified device: Tamoxifen was tested at 6.0 mg/dL. Tamoxifen test concentration was originally tested at 0.228 mg/dL in the cleared device under K191973, but now it has been tested at 6.0 mg/dL for the modified device.
| Lumipulse® G CA19-9-N Clearedunder K191973 | Lumipulse® G CA19-9-N ModifiedDevice | |
|---|---|---|
| SIMILARITIES | ||
| Assay Intended Use | Lumipulse® G CA19-9-N is aChemiluminescent EnzymeImmunoassay (CLEIA) for thequantitative measurement of CA19-9 in human serum or plasma(sodium heparin, lithium heparin,or dipotassium EDTA) on theLUMIPULSE G System.The assay is to be used as an aidin the management of patientsdiagnosed with cancer of theexocrine pancreas who havedetectable levels of CA 19-9 atsome point in their diseaseprocess. Serial testing for patientCA19-9 assay values should beused in conjunction with otherclinical methods used formonitoring cancer of the exocrinepancreas. | Same |
| Product Code | NIG | Same |
| Regulation | 21 CFR 866.6010 | Same |
| Antibody Type and Source | monoclonal antibody (mouse) | Same |
| Sample Type | human serum and plasma | Same |
| Reagent Storage | Store at 2-10°C | Same |
| Sample Size | 100 µL | Same |
| Calibration Frequency | Every 30 days | Same |
| Instrument | Lumipulse G System | Same |
| Methodology | CLEIA | Same |
| Measuring Range | 0.7-500 U/mL | Same |
2. Modified Device Comparison to the Cleared Device:
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Image /page/6/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left, featuring blue and white shapes, followed by the company name in blue, bold letters. Below the company name, the words "Diagnostics, Inc." are written in a smaller, lighter font.
| Lumipulse® G CA19-9-N Clearedunder K191973 | Lumipulse® G CA19-9-N ModifiedDevice | |
|---|---|---|
| Capture | Monoclonal anti-CA19-9 antibody(mouse)-coated particles | Same |
| Conjugate Antibody | ALP (calf)-labeled anti-CA19-9monoclonal mouse antibody | Same |
| Calibrators | 2 level set (1 vial/level):• Cal 1: 0 U/mL• Cal 2: 500 U/mL | Same |
| Calibration Range | 0-500 U/mL | Same |
| Controls | 2 levels every 24 hours | Same |
| DIFFERENCES | ||
| Tamoxifen Test Concentration | Tamoxifen test concentration wasoriginally tested at 0.228 mg/dLaccording to the study protocol;(however in the 510(k), atypographical error occurred, and itwas listed as 6.0 mg/dL.) | Tamoxifen test concentration is testedat 6.0 mg/dL per a new protocol andstudy report. |
| Samples(Mean Test Concentrations(U/mL) (n=3)) | Serum Pool 1 = 30.1Serum Pool 2 = 189.5Serum Pool 3 = 330.1 | Serum Pool 1 = 31.2Serum Pool 2 = 184.4Serum Pool 3 = 327.8 |
| Samples(Mean Control Concentrations(U/mL) (n=3)) | Serum Pool 1 = 30.1Serum Pool 2 = 187.5Serum Pool 3 = 322.4 | Serum Pool 1 = 31.3Serum Pool 2 = 187.9Serum Pool 3 = 324.0 |
| Test Concentration | 0.228 mg/dL | 6.0 mg/dL |
| % Difference Results | 0% to 2% | -2% to 1% |
K. STANDARDS/GUIDANCE DOCUMENTS REFERENCED
- . CLSI EP07 - Interference Testing in Clinical Chemistry; Approved Guideline - Third Edition. 2018
- CLSI EP37 Supplemental Tables for Interference Testing in Clinical Chemistry; . Approved Guideline - First Edition. 2018
L. TEST PRINICIPLE
Lumipulse® G CA19-9-N is an assay system, including a set of immunoassay reagents, for the quantitative measurement of CA 19-9 in human serum and plasma (sodium heparin, lithium heparin, or dipotassium EDTA) based on CLEIA technology by a two-step immunoassay method on the LUMIPULSE G1200 System. CA 19-9 in specimens specifically binds to anti-CA19-9 monoclonal antibody (mouse) on the particles, and antigenantibody immunocomplexes are formed. The particles are washed and rinsed to remove unbound materials. Alkaline phosphatase (ALP: calf)-labeled anti-CA19-9 monoclonal antibody (mouse) specifically binds to CA 19-9 of the immunocomplexes on the particles, and additional immunocomplexes are formed. The particles are washed and rinsed to
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remove unbound materials. Substrate Solution is added and mixed with the particles. AMPPD contained in the Substrate Solution is dephosphorylated by the catalysis of ALP indirectly coniugated to particles. Luminescence (at a maximum wavelength of 477 nm) is generate by the cleavage reaction of dephosphorylated AMPPD. The luminescent signal reflects the amount of CA 19-9.
Indicated for the serial measurement of CA 19-9 to aid in the management of patients diagnosed with cancers of the pancreas. Serial testing with Lumipulse® G CA19-9-N for CA 19-9 patient values is used in conjunction with other clinical methods in the management of pancreatic cancer patients.
M. SUMMARY OF DESIGN CONTROL ACTIVITIES
Design Control Activities Summary for Test Concentration Change for Therapeutic InterferentTamoxifen
| DeviceChange | Risks | Verification/Validation Method(s) | AcceptanceCriteria | Summary ofResults |
|---|---|---|---|---|
| Tamoxifen istested atconcentrationof 6.0 mg/dL | There is no risk tothis devicechange. The testconcentration totamoxifen isbeing updated toensure theconcentrationlisted in our PI isappropriate forthe intended usepopulation. | Supplemental TherapeuticInterference Study performed fortamoxifen. (protocol andacceptance criteria were the sameas found in K191973 019_Section18_Lumipulse G CA19-9-N_Bench, without any deviations)The Supplemental TherapeuticInterference Study was run tomitigate any risk because it wasperformed with a higherconcentration of Tamoxifen thanwas originally reported in the510(k) labeling. | Individualsamples musthave a percentdifference of ±10% differencefrom thecontrol. | -2% to 1%(Met acceptance of±10% difference foreach individualsample between thetest and controlsamples.) |
N. ADDITIONAL UPDATE
In the original 510(k) Summary and labeling for K191973, there was a typo for Streptozotocin. It was listed as 3.96 mg/dL but should have been 28 mg/dL. This update has been made to the 510(k) Summary and labeling and is included in this submission.
O. DECLARATION OF CONFORMITY (DOC)
Please see K191973, 010_Section 9_Lumipulse G CA19-9-N 510k_Decl of Conformity for the declaration of conformity.
§ 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.