(360 days)
No
The device description and performance studies focus on standard immunoturbidimetric assay principles and statistical analysis (spline-fitting, regression, agreement calculations). There is no mention of AI, ML, or related concepts.
No.
The device is an in-vitro diagnostic test intended to aid in the diagnosis of multiple myeloma by quantifying Kappa and Lambda Free Light Chains in serum, not to provide therapy.
Yes
The intended use section explicitly states that the device "aids in the diagnosis of multiple myeloma".
No
The device is an in-vitro diagnostic assay system consisting of reagents, calibrators, and controls, intended for use on a clinical chemistry analyzer (Hitachi 917). While the analyzer uses software, the core medical device being submitted is the assay kit itself, which is a collection of physical components.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states "For in-vitro diagnostic use only" for all components of the system (the assays, calibrator, and control).
- Nature of the Test: The device is designed to measure the concentration of specific substances (Kappa and Lambda Free Light Chains) in a biological sample (serum) outside of the human body. This is the fundamental definition of an in vitro diagnostic test.
- Purpose of the Measurement: The measurement of these substances is intended to "aid in the diagnosis of multiple myeloma in conjunction with other laboratory findings." This indicates a diagnostic purpose.
- Device Description: The description details reagents, calibrators, and controls used to perform a test on a clinical chemistry analyzer, which is typical for IVD devices.
- Performance Studies: The document includes performance studies (Precision, Linearity, Method Comparison, Detection limit, Interference, Hook Effect) that are standard for evaluating the performance of IVD devices.
- Predicate Devices: The mention of predicate devices with K numbers (FDA clearance numbers) further confirms its classification as a medical device, specifically an IVD.
N/A
Intended Use / Indications for Use
The Diazyme Human Kappa Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Kappa Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Kappa FLC in conjunction with Lambda FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only.
Diazyme Human Kappa/Lambda FLC Calibrator (DZ169A-CAL) is intended for use in establishing the calibration curve for the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only.
Diazyme Human Kappa/Lambda FLC Control (DZ169A-CON) is intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only.
The Diazyme Human Lambda Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Lambda Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Lambda FLC in conjunction with Kappa FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only.
Product codes
DFH, DEH
Device Description
Normal immunoglobulins are composed of smaller units called heavy chains and light chains. There are five types of heavy chains (alpha, delta, epsilon, gamma, and mu), and two types of light chains (kappa and lambda). The heavy and light chains are produced separately within plasma cells and are assembled to form a whole ("intact") immunoglobulin. When the light chains are attached to the heavy chains they are called bound, and when they are not attached they are called free. Kappa Free Light Chain (FLC) is a 22kD protein while Lambda FLC is usually a dimer of 44kD as presented in the serum. Elevated levels of Kappa or Lambda FLC are associated with plasma cell disorders such as multiple myeloma, lymphocytic neoplasms, Waldenström's macroglobulinemia. AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus.
Human Kappa (K) Free Light Chain Assay is based on a latex enhanced immunoturbidimetric assay. Kappa FLC in the sample binds to specific anti-Kappa FLC antibody, which is coated on latex particles, and causes agglutination. The degree of the turbidity caused by agglutination can be measured optically and is proportional to the amount of Kappa FLC in the sample. The instrument calculates the Kappa FLC concentration by interpolation of obtained signal of a 6point calibration curve prepared from calibrators of known concentrations.
The Diazyme Human Lambda (λ) Free Light Chain Assay is based on a latex enhanced immunoturbidimetric assay. Lambda FLC in the sample binds to specific anti-Lambda FLC antibody, which is coated on latex particles, and causes agglutination. The degree of the turbidity caused by agglutination can be measured optically and is proportional to the amount of Lambda FLC in the sample. The instrument calculates the Kappa FLC concentration by interpolation of obtained signal of a 6-point calibration curve prepared from calibrators of known concentrations.
Diazyme Human Kappa (k) /Lambda (2) Free Light Chain Assay System consists of the following items:
- Diazyme Human Kappa (k) Free Light Chain Assay: containing reagent R1 and Reagent R2. Reagent 1 contains 100 mmol/L tris buffer, and 0.09% sodium azide Reagent 2 containing anti-human Kappa Free Light Chain Ig fraction coated on polystyrene beads and 0.09% sodium azide.
- Diazyme Human Lambda (λ) Free Light Chain Assay: containing reagent R1 and Reagent R2. Reagent 1 contains 100 mmol/L tris buffer, and 0.09% sodium azide Reagent 2 containing anti-human Lambda Free Light Chain Ig fraction coated on polystyrene beads and 0.09% sodium azide.
- Diazyme Kappa and Lambda FLC Calibrator Set: 5 levels, serum based, liquid stable format, intended for use in establishing the calibration curve for the Diazyme Human Kappa (k) and Lambda (λ) Free Light Chain Assay.
- Diazyme Kappa and Lambda FLC Control Set: 2 levels, serum based, liquid stable format, intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa (K) and Lambda (λ) Free Light Chain Assay.
Diazyme Human Kappa (k) /Lambda (2.) Free Light Chain Assays are run on clinical chemistry analyzers such as Roche Hitachi 917 analyzer (K023009). They never come into direct contact with patients. The patient's venous blood sample is first collected by a phlebotomist and then submitted for determination of Kappa and Lambda FLC concentration using Diazyme Human Kappa (k) and Lambda (λ) FLC Assay by trained professionals.
The Control Unit of the Roche Hitachi 917 analyzer uses a graphical interface to control all instrument functions. The computer, keyboard, and touchscreen monitor allows users to navigate through the software, enter assay, calibrator, and control information, and make test selections. The Diazyme Kappa and Lambda FLC Hitachi 917 application parameters provided are programmed into the Hitachi 917 analyzer. The reagents, calibrators and controls are loaded into the analyzer. The Roche Hitachi 917 stores Diazyme Human Kappa (k) /Lambda (λ) Free Light Chain Assay reagents in a refrigerated compartment. Reagent and sample pipettes automatically aspirate and dispense specified amounts of reagent or calibrators, controls, and sample into reaction cells. The change in absorbance is measured at specified wavelengths.
After a 6-point calibration, spline-fitting is used to smoothly fit polynomial functions through mean values of the response for calibrators of known concentrations. The Roche Hitachi 917 calculates the kappa and lambda FLC concentration of a patient sample by interpolation of the obtained signal to a stored 6-point calibration curve.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
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Intended User / Care Setting
Trained professionals in a laboratory/clinical setting.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Method comparison for Diazyme Human Kappa (k) FLC Assay: A total of 126 serum samples ranging from 4.63-2975.80 mg/L were tested. Among the 126 samples, 39 were Multiple Myeloma (MM), 12 were Monoclonal Gammopathy of Undetermined Significance (MGUS), 34 were Abnormal (due to other disease states) and 41 were Normal (no disease). Data source: Clinical patient samples.
Method comparison for Diazyme Human Lambda (λ) FLC Assay: A total of 126 serum samples ranging from 6.19-3917.80 mg/L were tested. Among the 106 samples, in which 39 were Multiple Myeloma (MM), 12 were Monoclonal Gammopathy of Undetermined Significance (MGUS), 34 were Abnormal (due to other disease states) and 41 were Normal (no disease). Data source: Clinical patient samples.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision for Diazyme Human Kappa (к) FLC Assay:
Study type: CLSI EP5-A guideline.
Sample size: Eight levels of serum specimens containing kappa FLC spanning AMR and two levels of serum based kappa FLC controls. Tested with 2 runs per day with duplicates over 20 working days using multiple lots of the reagents on multiple analyzers.
Key results:
- One lot of the reagent on three analyzers, Mean (mg/L) and CV% are summarized:
- S1: Mean=9.38, Total CV=11.0%
- S2: Mean=35.30, Total CV=3.5%
- S3: Mean=122.37, Total CV=3.2%
- S4: Mean=5.95, Total CV=11.7%
- S5: Mean=15.76, Total CV=3.9%
- S6: Mean=25.92, Total CV=2.2%
- S7: Mean=139.23, Total CV=2.5%
- S8: Mean=2588.59, Total CV=3.3%
- Con1: Mean=16.70, Total CV=4.9%
- Con2: Mean=29.10, Total CV=6.7%
- Three lots of the reagents on one analyzer, Mean (mg/L) and CV% are summarized:
- S1: Mean=9.49, Total CV=11.6%
- S2: Mean=35.14, Total CV=3.5%
- S3: Mean=121.53, Total CV=3.8%
- S4: Mean=5.81, Total CV=7.4%
- S5: Mean=15.40, Total CV=3.5%
- S6: Mean=25.66, Total CV=1.7%
- S7: Mean=138.28, Total CV=1.8%
- S8: Mean=2588.45, Total CV=3.3%
- Con1: Mean=16.64, Total CV=5.6%
- Con2: Mean=27.82, Total CV=4.6%
Precision for Diazyme Human Lambda (λ) FLC Assay:
Study type: CLSI EP5-A guideline.
Sample size: Eight levels of serum specimens containing low, medium, and high lambda FLC respectively and two levels of serum based lambda FLC controls. Tested with 2 runs per day with duplicates over 20 working days using multiple lots of the reagents on multiple analyzers.
Key results:
- One lot of the reagent on three analyzers, Mean (mg/L) and CV% are summarized:
- S1: Mean=11.89, Total CV=9.9%
- S2: Mean=48.65, Total CV=2.7%
- S3: Mean=144.55, Total CV=2.4%
- S4: Mean=8.31, Total CV=7.3%
- S5: Mean=22.27, Total CV=4.3%
- S6: Mean=35.09, Total CV=2.9%
- S7: Mean=181.13, Total CV=2.0%
- S8: Mean=3472.59, Total CV=4.2%
- Con1: Mean=27.62, Total CV=4.0%
- Con2: Mean=62.58, Total CV=3.2%
- Three lots of the reagents on one analyzer, Mean (mg/L) and CV% are summarized:
- S1: Mean=11.78, Total CV=11.4%
- S2: Mean=48.95, Total CV=2.2%
- S3: Mean=142.63, Total CV=1.6%
- S4: Mean=8.16, Total CV=7.4%
- S5: Mean=21.90, Total CV=3.2%
- S6: Mean=34.79, Total CV=2.1%
- S7: Mean=183.02, Total CV=1.1%
- S8: Mean=3442.60, Total CV=3.8%
- Con1: Mean=28.13, Total CV=5.9%
- Con2: Mean=65.31, Total CV=2.3%
Linearity for Diazyme Human Lambda (λ) FLC Assay:
Study type: CLSI EP6-A guideline.
Key results: limit of quantitation (LOQ) = 6.10 mg/L; Analytical Measuring Range (AMR) is 6.1-200 mg/L in standard mode. AMR is 6.1-4000 mg/L including extended mode.
Method Comparison for Diazyme Human Kappa (k) FLC Assay:
Study type: CLSI EP9-A2 protocol.
Sample size: 126 serum samples.
Key results:
- Linear Regression: Slope = 0.958, Intercept = -2.536, Corr Coeff (R2) = 0.977. Sample range 4.63-2975.80.
- Deming Regression: Slope = 0.969, Intercept = -4.813, Corr Coeff (R2) = 0.977. Sample range 4.63-2975.80.
- The concordance between the subject and predicate Kappa FLC is 98%.
Method Comparison for Diazyme Human Lambda (λ) FLC Assay:
Study type: CLSI EP9-A2 protocol.
Sample size: 126 serum samples.
Key results:
- Linear Regression: Slope = 1.054, Intercept = 0.636, Corr Coeff (R2) = 0.972. Sample range 6.19-3917.80.
- Deming Regression: Slope = 1.070, Intercept = -3.160, Corr Coeff (R2) = 0.972. Sample range 6.19-3917.80.
- The concordance between the subject and predicate Lambda FLC was 95%.
Detection limit for Diazyme Human Kappa (K) FLC Assay:
Study type: CLSI EP17-A2.
Key results: LOB was 1.2 mg/L; LOD was 2.0 mg/L; LOQ was 4.5 mg/L.
Detection limit for Diazyme Human Lambda (^) FLC Assay:
Study type: CLSI EP17-A2.
Key results: LOB was 1.7 mg/L; LOD was 2.9 mg/L; LOQ was 6.1 mg/L.
Interference:
Key results: The following substances normally present in the blood produced less than 10% deviation when tested at levels equal to the concentrations listed below, according to CLSI EP7-A2.
- Triglyceride: 1000 mg/dL for both Kappa and Lambda FLC
- Ascorbic Acid: 10 mM for both Kappa and Lambda FLC
- Bilirubin: 40 mg/dL for both Kappa and Lambda FLC
- Bilirubin Conjugated: 40 mg/dL for both Kappa and Lambda FLC
- Hemoglobin: 1000 mg/dL for both Kappa and Lambda FLC
- Rheumatoid Factor: 100 IU/mL for both Kappa and Lambda FLC
Hook Effect:
Key results: No high dose hook effect for Diazyme Human Kappa (k) FLC Assay was observed up to 100,000 mg/L. No high dose hook effect for Diazyme Human Lambda (λ) FLC Assay was observed up to 100,000 mg/L.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Kappa FLC:
Agreement% (using CLSI EP12-A2):
- PPA: 96.67% (95% CI: 90.65 to 98.86%)
- NPA: 100% (95% CI: 90.36 to 100%)
- TPA: 97.62% (95% CI: 93.23 to 99.19%)
Lambda FLC:
Agreement% (using CLSI EP12-A2):
- PPA: 95.65% (95% CI: 87.98 to 98.51%)
- NPA: 94.74% (95% CI: 85.63 to 98.19%)
- TPA: 95.24% (95% CI: 90.00 to 98.19%)
Predicate Device(s)
Freelite® Human Kappa Free Kit for use on the Hitachi 911/912/917/Modular P, Freelite® Human Lambda Free Kit for use on the Hitachi 911/912/917/Modular P
Reference Device(s)
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.5550 Immunoglobulin (light chain specific) immunological test system.
(a)
Identification. An immunoglobulin (light chain specific) immunological test system is a device that consists of the reagents used to measure by immunochemical techniques both kappa and lambda types of light chain portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an excess of light chains are produced by the antibody-forming cells. These free light chains, unassociated with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measurement of the various amounts of the different types of light chains aids in the diagnosis of multiple myeloma (cancer of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus.(b)
Classification. Class II (performance standards).
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines representing hair or clothing.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
November 18, 2016
DIAZYME LABORATORIES ABHIJIT DATTA DIRECTOR OF TECHNICAL OPERATIONS 12889 GREGG COURT POWAY CA 92064
Re: K153394
Trade/Device Name: Diazyme Human Kappa Free Light Chain Assay, Diazyme Human Lambda Free Light Chain Assay, Diazyme Human Kappa/lamda Free Light Chain Calibrator, Diazyme Human Kappa/lamda Free Light Chain Calibrator Regulation Number: 21 CFR 866.5550
Regulation Name: Immunoglobulin (light chain specific) immunological test system Regulatory Class: II Product Code: DFH, DEH Dated: October 28, 2016 Received: November 1, 2016
Dear Dr. Datta:
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 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
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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
Leonthena Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
| DEPARTMENT OF HEALTH AND HUMAN SERVICES | |
|---|---|
| Food and Drug Administration | |
| Indications for Use |
| Form Approved: OMB No. 0910-0120 | |
|---|---|
| Expiration Date: January 31, 2017 | |
| See PRA Statement below. |
| 510(k) Number (if known) | 153394 |
|---|---|
| Device Name | The Diazyme Human Kappa Free Light Chain Assay, Diazyme Human Kappa/Lambda FLC Calibrator Set, Diazyme Human Kappa/Lambda FLC Control Set. |
| Indications for Use (Describe) | The Diazyme Human Kappa Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Kappa Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Kappa FLC in conjunction with Lambda FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only. Diazyme Human Kappa/Lambda FLC Calibrator (DZ169A-CAL) is intended for use in establishing the calibration curve for the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only. Diazyme Human Kappa/Lambda FLC Control (DZ169A-CON) is intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only. |
| 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) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the
time to review instructions, search existing data sources, gather and maintain the data needed and complete
and review the collection of information. Send comments regarding this burden estimate or any other aspect
of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB number."
| FORM FDA 3881 (8/14) | Page 1 of 1 |
|---|---|
| ---------------------- | ------------- |
PSC Publishing Services (301) 443-6740
EF
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| Form Approved: OMB No. 0910-0120 |
|---|
| Expiration Date: January 31, 2017 |
| See PRA Statement below. |
| 510(k) Number (if known) | 153394 |
|---|---|
| Device Name | The Diazyme Human Lambda Free Light Chain Assay, Diazyme Human Kappa/Lambda FLC Calibrator Set, Diazyme Human Kappa/Lambda FLC Control Set. |
| Indications for Use (Describe) | The Diazyme Human Lambda Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Lambda Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Lambda FLC in conjunction with Kappa FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only. |
| Diazyme Human Kappa/Lambda FLC Calibrator (DZ169A-CAL) is intended for use in establishing the calibration curve for the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only. | |
| Diazyme Human Kappa/Lambda FLC Control (DZ169A-CON) is intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only. |
| 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) |
|---|---|
| ------------------------------------------------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
FORM FDA 3881 (8/14)
Page 1 of 1
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510(k) Summary
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.
| Submitter's name: | Diazyme Laboratories |
|---|---|
| Submitter's address: | 12889 Gregg Court |
| Poway, CA 92064 | |
| USA | |
| Name of Contact Person: | Dr. Abhijit Datta |
| Diazyme Laboratories | |
| 12889 Gregg Court | |
| Poway, CA 92064 | |
| Phone: 858-455-4762 | |
| Fax: 858-455-2120 | |
| Date the Summary was Prepared: | October 28, 2016 |
| Name of the Device | Diazyme Human Kappa (κ) Free Light Chain Assay |
| Diazyme Human Lambda (λ) Free Light Chain Assay | |
| Diazyme Human Kappa and Lambda FLC Calibrator | |
| Set | |
| Diazyme Human Kappa and Lambda FLC Control Set | |
| Trade Name: | Diazyme Human Kappa (κ) Free Light Chain Assay |
| Diazyme Human Lambda (λ) Free Light Chain Assay | |
| Diazyme Human Kappa and Lambda FLC Calibrator | |
| Set | |
| Diazyme Human Kappa and Lambda FLC Control Set | |
| Common/Usual Name | Diazyme Human Kappa (κ) Free Light Chain Assay |
| Diazyme Human Lambda (λ) Free Light Chain Assay | |
| Device Classification Name | Kappa, antigen, antiserum, control |
| Lambda, antigen, antiserum, control | |
| Product code: | DFH, Kappa, antigen, antiserum, control |
| DEH, Lambda, antigen, antiserum, control | |
| Panel: | Immunology (82) |
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| Submission Type | Traditional 510k |
|---|---|
| Regulation Number | 21CFR 866.5550 Immunoglobulin (light chain specific) |
| immunological test system | |
| Device Class | Class II |
| Predicate Device: | Freelite® Human Kappa Free Kit for use on the Hitachi |
| 911/912/917/Modular P | |
| Freelite® Human Lambda Free Kit for use on the | |
| Hitachi 911/912/917/Modular P | |
| Manufacturing Address | Diazyme Laboratories |
| 12889 Gregg Court | |
| Poway, CA 92064 | |
| USA | |
| Establishment Registration | 2032900 |
DESCRIPTION OF THE DEVICE
Clinical Significance
Normal immunoglobulins are composed of smaller units called heavy chains and light chains. There are five types of heavy chains (alpha, delta, epsilon, gamma, and mu), and two types of light chains (kappa and lambda). The heavy and light chains are produced separately within plasma cells and are assembled to form a whole ("intact") immunoglobulin. When the light chains are attached to the heavy chains they are called bound, and when they are not attached they are called free. Kappa Free Light Chain (FLC) is a 22kD protein while Lambda FLC is usually a dimer of 44kD as presented in the serum. Elevated levels of Kappa or Lambda FLC are associated with plasma cell disorders such as multiple myeloma, lymphocytic neoplasms, Waldenström's macroglobulinemia. AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus.
Assay Principle
Human Kappa (K) Free Light Chain Assay is based on a latex enhanced immunoturbidimetric assay. Kappa FLC in the sample binds to specific anti-Kappa FLC antibody, which is coated on latex particles, and causes agglutination. The degree of the turbidity caused by agglutination can be measured optically and is proportional to the amount of Kappa FLC in the sample. The instrument calculates the Kappa FLC concentration by interpolation of obtained signal of a 6point calibration curve prepared from calibrators of known concentrations.
The Diazyme Human Lambda (λ) Free Light Chain Assay is based on a latex enhanced immunoturbidimetric assay. Lambda FLC in the sample binds to specific anti-Lambda FLC antibody, which is coated on latex particles, and causes agglutination. The degree of the turbidity caused by agglutination can be measured optically and is proportional to the amount of Lambda FLC in the sample. The instrument calculates the Kappa FLC concentration by interpolation of obtained signal of a 6-point calibration curve prepared from calibrators of known concentrations.
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Detailed Device Description
Diazyme Human Kappa (K) /Lambda (2) Free Light Chain Assay System consists of the following items:
-
- Diazyme Human Kappa (k) Free Light Chain Assay: containing reagent R1 and Reagent R2. Reagent 1 contains 100 mmol/L tris buffer, and 0.09% sodium azide Reagent 2 containing anti-human Kappa Free Light Chain Ig fraction coated on polystyrene beads and 0.09% sodium azide.
-
- Diazyme Human Lambda (λ) Free Light Chain Assay: containing reagent R1 and Reagent R2. Reagent 1 contains 100 mmol/L tris buffer, and 0.09% sodium azide Reagent 2 containing anti-human Lambda Free Light Chain Ig fraction coated on polystyrene beads and 0.09% sodium azide.
-
- Diazyme Kappa and Lambda FLC Calibrator Set: 5 levels, serum based, liquid stable format, intended for use in establishing the calibration curve for the Diazyme Human Kappa (k) and Lambda (λ) Free Light Chain Assay.
-
- Diazyme Kappa and Lambda FLC Control Set: 2 levels, serum based, liquid stable format, intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa (K) and Lambda (λ) Free Light Chain Assay.
Diazyme Human Kappa (k) /Lambda (2.) Free Light Chain Assays are run on clinical chemistry analyzers such as Roche Hitachi 917 analyzer (K023009). They never come into direct contact with patients. The patient's venous blood sample is first collected by a phlebotomist and then submitted for determination of Kappa and Lambda FLC concentration using Diazyme Human Kappa (k) and Lambda (λ) FLC Assay by trained professionals.
The Control Unit of the Roche Hitachi 917 analyzer uses a graphical interface to control all instrument functions. The computer, keyboard, and touchscreen monitor allows users to navigate through the software, enter assay, calibrator, and control information, and make test selections. The Diazyme Kappa and Lambda FLC Hitachi 917 application parameters provided are programmed into the Hitachi 917 analyzer. The reagents, calibrators and controls are loaded into the analyzer. The Roche Hitachi 917 stores Diazyme Human Kappa (k) /Lambda (λ) Free Light Chain Assay reagents in a refrigerated compartment. Reagent and sample pipettes automatically aspirate and dispense specified amounts of reagent or calibrators, controls, and sample into reaction cells. The change in absorbance is measured at specified wavelengths.
See Reaction Scheme.
Image /page/6/Figure/9 description: The image shows two diagrams, one for Kappa FLC and one for Lambda FLC. The Kappa FLC diagram shows the following steps: R1 at 150 uL and a sample at 4.0 uL are added at time 0, then the mixture is heated to 37 degrees Celsius, R2 at 50 uL is added at 4.8 minutes, and the absorbance is measured at 570 nm after 10 minutes. The Lambda FLC diagram shows similar steps, but with different volumes and times.
Image /page/6/Figure/10 description: This image shows a timeline of a chemical reaction. At time zero, 120 microliters of R1 and 20 microliters of sample are added. The reaction is then incubated at 37 degrees Celsius, and at 4.8 minutes, 40 microliters of R2 are added. At 6 minutes, A1 is measured at 570nm, and at 10 minutes, A2 is measured at 570nm.
7
After a 6-point calibration, spline-fitting is used to smoothly fit polynomial functions through mean values of the response for calibrators of known concentrations. The Roche Hitachi 917 calculates the kappa and lambda FLC concentration of a patient sample by interpolation of the obtained signal to a stored 6-point calibration curve.
Indications for Use:
The Diazyme Human Kappa (K) Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Kappa Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Kappa FLC in conjunction with Lambda FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only.
The Diazyme Human Lambda (2) Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Lambda Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Lambda FLC in conjunction with Kappa FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only.
Diazyme Human Kappa/Lambda FLC Calibrator (DZ169A-CAL) is intended for use in establishing the calibration curve for the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only.
Diazyme Human Kappa/Lambda FLC Control (DZ169A-CON) is intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only.
| Predicate Kappa FLC Assay | Diazyme Human Kappa (κ) FLC Assay |
|---|---|
| Reagent 1: Supplementary Reagent | |
| containing 0.099% Azide as | |
| preservative. | Reagent 1 |
| 100 mM Tris, 0.09% azide as preservative, ready to | |
| use | |
| Reagent 2: Consisting of polyclonal | |
| monospecific antibody coated onto | |
| polystyrene latex. | Reagent 2 |
| Latex particles coated with polyclonal rabbit and goat | |
| anti-Kappa FLC antibodies | |
| Calibrator: | |
| Human sera that contain polyclonal | |
| kappa free light chain with | |
| preservatives. | Calibrators |
| Liquid stable calibrators prepared with serum, | |
| purified Kappa Free Light Chains with preservatives. | |
| Calibrator Set | Calibrator Set |
| 2 x 1.5 mL Single-Level Calibrator | |
| diluted on board to 5 level calibrator | 1 x 1.0 mL Calibrator 1 |
| 1 x 1.0 mL Calibrator 2 | |
| 1 x 1.0 mL Calibrator 3 |
Table 1 Summary of Assay Kit Components
8
| | 1 x 1.0 mL Calibrator 4
1 x 1.0 mL Calibrator 5 |
|---------------------------|----------------------------------------------------|
| Control Set (serum based) | Control Set (serum based) |
| 1 x 1.0mL Control 1 | 1 x 3.0mL Control 1 |
| 1 x 1.0mL Control 2 | 1 x 3.0mL Control 2 |
| Predicate Lambda FLC Assay | Diazyme Human Lamda (λ) FLC Assay |
|---|---|
| Reagent 1: Supplementary Reagent | |
| containing 0.099% Azide as | |
| preservative. | Reagent 1 |
| 100 mM Tris, 0.09% azide as preservative, ready to use | |
| Reagent 2: Consisting of polyclonal | |
| monospecific antibody coated onto | |
| polystyrene latex. | Reagent 2 |
| Latex particles coated with polyclonal rabbit anti- | |
| Lambda FLC antibodies | |
| Calibrator: | |
| Human sera that contain polyclonal | |
| kappa free light chain with | |
| preservatives. | Calibrators |
| Liquid stable calibrators prepared with serum, | |
| purified Kappa Free Light Chains with preservatives. | |
| Calibrator Set | Calibrator Set |
| 2 x 1.5 mL Single-Level Calibrator | |
| diluted on board to 5 level calibrator | 1 x 1.0 mL Calibrator 1 |
| 1 x 1.0 mL Calibrator 2 | |
| 1 x 1.0 mL Calibrator 3 | |
| 1 x 1.0 mL Calibrator 4 | |
| 1 x 1.0 mL Calibrator 5 | |
| Control Set (serum based) | Control Set (serum based) |
| 1 x 1.0mL Control 1 | |
| 1 x 1.0mL Control 2 | 1 x 3.0mL Control 1 |
| 1 x 3.0mL Control 2 |
Substantial Equivalence Comparison
Indications for Use
| Freelite® Human Kappa Free Kit for use
(K023009) Freelite® Human Lambda Free
Kit for use on the Hitachi 911/912/917/
Modular P (K023131), (K040009) | Diazyme Human Kappa (κ) and
Lambda (λ) Free Light Chain Assay. | Equivalency |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| Kappa: This kit is intended for the
quantitation of kappa free light chains
in serum and urine on the Roche
Hitachi 911 and Hitachi 912.
Measurement of the various amounts | The Diazyme Human Kappa (κ) Free
Light Chain Assay is intended as a latex
particle enhanced immunoturbidimetric
assay for the quantitative determination
of Kappa Free Light Chain (FLC) | Similar |
9
| of the different types of light chains
aids in the diagnosis and monitoring of
multiple myelomas, lymphocytic
neoplasms, Waldenstrom's
macroglobulinemia and connective
tissue diseases, such as systemic lupus | concentration in serum on Hitachi 917
analyzers. The measurement of Kappa
FLC in conjunction with Lambda FLC
aids in the diagnosis of multiple
myeloma in conjunction with other
laboratory findings. For in-vitro |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| erythematosus. | diagnostic use only. |
| Lambda: This kit is intended for the
quantitation of lambda free light chains
in serum and urine on the Roche
Hitachi 911 and Hitachi 912.
Measurement of the various amounts
of the different types of light chains
aids in the diagnosis and monitoring of
multiple myelomas, lymphocytic
neoplasms, Waldenstrom's | The Diazyme Human Lambda (λ) Free
Light Chain Assay is intended as a latex
particle enhanced immunoturbidimetric
assay for the quantitative determination
of Lambda Free Light Chain (FLC)
concentration in serum on Hitachi 917
analyzers. The measurement of Lambda
FLC in conjunction with Kappa FLC
aids in the diagnosis of multiple |
| macroglobulinemia and connective | myeloma in conjunction with other |
| tissue diseases, such as systemic lupus | laboratory findings. For in-vitro |
| erythematosus. | diagnostic use only |
Principle
| Principle | Equivalency | |
|---|---|---|
| Freelite® Human Kappa Free Kit for use | ||
| (K023009) Freelite® Human Lambda Free | ||
| Kit for use on the Hitachi 911/912/917/ | ||
| Modular P (K023131), (K040009) | Diazyme Human Kappa (κ) and Lambda (λ) Free Light Chain Assay. | |
| Evaluating the concentration of a | ||
| soluble antigen by turbidimetry | ||
| involves the addition of the test sample | ||
| to a solution containing the appropriate | ||
| antibody in a reaction vessel or cuvette. | ||
| A beam of light is passed through the | ||
| cuvette and as the antigen-antibody | ||
| reaction proceeds, the light passing | ||
| through the cuvette is scattered | ||
| increasingly as insoluble immune | ||
| complexes are formed. Light scatter is | ||
| monitored by measuring decrease in | ||
| intensity of the incident beam of light. | ||
| The antibody in the cuvette is in excess | ||
| so the amount of immune complex | ||
| formed is proportional to the antigen | ||
| concentration. A series of calibrators of | ||
| known antigen concentration are | ||
| assayed initially to produce a | ||
| calibration curve of measured light | Human Kappa (κ) and Lambda (λ) Free | |
| Light Chain Assay is based on a latex | ||
| enhanced immunoturbidimetric assay. | ||
| Kappa FLC in the sample binds to | ||
| specific anti-Kappa FLC antibody, which | ||
| is coated on latex particles, and causes | ||
| agglutination. The degree of the turbidity | ||
| caused by agglutination can be measured | ||
| optically and is proportional to the | ||
| amount of Kappa FLC in the sample. | Same |
10
| scatter versus antigen concentration.
Samples of unknown antigen
concentration can then be assayed and
the results read from the calibration
| curve. | ||
|---|---|---|
| ----------------------------------------------------------------------------------------------------------------------------------------------------------------- | -- | -- |
Test Objective
| Freelite® Human Kappa Free Kit for use
(K023009) Freelite® Human Lambda
Free Kit for use on the Hitachi
911/912/917/ Modular P(K023131),
(K040009) | Diazyme Human Kappa (κ) and
Lambda (λ) Free Light Chain Assay. | Equivalency |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------|-------------|
| The quantitative determination of
Kappa(κ) /Lambda(λ) Free Light Chain
concentration | For the quantitative determination of
Kappa and Lambda Free Light Chain
(FLC) concentration | Same |
Type of Test
| Freelite® Human Kappa Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023009) Freelite® Human Lambda Free
Kit for use on the Hitachi 911/912/917/
Modular P (K023131), (K040009) | Diazyme Human Kappa (κ) and
Lambda (λ) Free Light Chain Assay. | Equivalency |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------|-------------|
| Quantitative | Quantitative | Same |
Specimen Type
| Freelite® Human Kappa Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023009)
Freelite® Human Lambda Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023131), (K040009) | Diazyme Human Kappa (κ) and
Lambda (λ) Free Light Chain Assay. | Equivalency. |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------|--------------|
| Human serum. | Human serum. | Same |
| Human Urine | Human serum only | N/A |
Product Type
| Freelite® Human Kappa Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023009) | Diazyme Human Kappa ( $κ$ ) and
Lambda ( $λ$ ) Free Light Chain Assay. | Equivalency |
| --------------------------------------------------------------------------------------------- | --------------------------------------------------------------------------- | ------------- |
|---|
11
| Freelite® Human Lambda Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023131)
| (K040009) | ||
|---|---|---|
| Assay reagent kit, calibrator kit, quality | ||
| control kit. | Assay reagent kit, calibrator kit, quality | |
| control kit. | Same |
Performance
| Freelite® Human Kappa Free Kit for use
on the Hitachi 911/912/917/Modular P (K023009)
Freelite® Human Lambda Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023131),(K040009) | Diazyme Human Kappa (κ) and Lambda (λ)
Free Light Chain Assay. |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Linear Range:
Kappa: 6.0-180 mg/L
150-4,500 mg/L and 3,000–90,000 mg/L (extended)
Lambda: 8.0-270 mg/L
200-6750 mg/L and 4,000-135,000 mg/L (extended) | Linear Range:
Kappa FLC 4.5-150 mg/L
Lambda FLC 6.1-200 mg/L |
| Precision:
Kappa FLC Within-run
CV 3.1% to 4.84%; 13.56 mg/L to 51.06 mg/L
Kappa FLC Between-run
CV 6.27% to 8.38%; 12.02 mg/L to 54.66 mg/L
Lambda FLC Within-run
CV 5.2% to 8.4%; 15.12 mg/L to 71.84 mg/L
Lambda FLC Between-run
CV 4.72%-8.08%; 18.43 mg/L to 71.71 mg/L | Extended Linear Range:
Kappa FLC 90-3000 mg/L;
Lambda FLC 122-4000 mg/L;
Precision:
Kappa FLC Within-run
CV 1.4% to 7.6%; 6.0 mg/L to 2588.6 mg/L
Kappa FLC Between-run
CV 1.2% to 7.3%; 6.0 mg/L to 2588.6 mg/L
Lambda FLC Within-run
CV 0.8% to 6.5%; 8.3 mg/L to 3472.6 mg/L
Lambda FLC Between-run
CV 0.9%-6.4%; 8.3 mg/L to 3472.6 mg/L |
| Method comparison:
Kappa FLC
Linear regression analysis yielded y = 0.9818x +
4.5206 and the correlation coefficient (r) was
0.9956 ;
Lambda FLC
Linear regression yielded y = 0.9266x + 9.5556
and the correlation coefficient (r) was 0.9752 | Method comparison:
Kappa FLC
Slope = 0.958
Correlation Coefficient (R²) = 0.977
Lambda FLC
Slope = 1.054
Correlation Coefficient (R²) = 0.972 |
12
Calibrator Comparison
| Freelite® Human Kappa Free Kit for use
on the Hitachi 911/912/917/Modular P (K023009)
Freelite® Human Lambda Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023131), (K040009) | Diazyme Human Kappa (κ) and
Lambda (λ) Free Light Chain
Assay. | Equivalency |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------|-------------|
| Human sera based solution containing Kappa and
Lambda free light chain | Human sera based solution
containing Kappa and Lambda
free light chain | Same |
| Liquid Stable One level calibrator for on-board
automatic dilution | Liquid stable five level
calibrator set is provided ready
to use | Similar |
Control Comparison
| Freelite® Human Kappa Free Kit for use
on the Hitachi 911/912/917/Modular P (K023009)
Freelite® Human Lambda Free Kit for use
on the Hitachi 911/912/917/Modular P
(K023131), (K040009) | Diazyme Human Kappa (κ)
and Lambda (λ) Free Light
Chain Assay. | Equivalency |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------|-------------|
| Human sera based solution containing Kappa and
Lambda free light chain | Human sera based solution
containing Kappa and Lambda
free light chain | Same |
| Separately packaged quality control kit designed
for specific assay. | Separately packaged quality
control kit designed for
specific assay. | Same |
PERFORMANCE TESTING SUMMARIES
Precision
Precision for Diazyme Human Kappa (к) FLC Assay
The precision of the Assay was evaluated according to CLSI EP5-A guideline. In the study, eight levels of serum specimens containing kappa FLC spanning AMR and two levels of serum based kappa FLC controls were tested with 2 runs per day with duplicates over 20 working days using multiple lots of the reagents on multiple analyzers. The precision data was analyzed according to three-way nested ANOVA and the results of mean (mg/L) and CV% are summarized below: One lot of the reagent on three analyzers
| ID | Mean
n=240 | Within-Run | Between
Run | Between
day | Between
Instr | Total |
|----|---------------|------------|----------------|----------------|------------------|-------|
| S1 | 9.38 | 7.6% | 4.9% | 3.5% | 5.1% | 11.0% |
| S2 | 35.30 | 2.1% | 1.5% | 1.3% | 2.0% | 3.5% |
| S3 | 122.37 | 2.4% | 0.9% | 1.8% | 0.8% | 3.2% |
| S4 | 5.95 | 7.5% | 3.0% | 8.5% | N/A | 11.7% |
| S5 | 15.76 | 2.9% | 1.6% | 2.1% | 0.2% | 3.9% |
13
| S6 | 25.92 | 1.7% | 1.3% | 0.5% | 0.4% | 2.2% |
|---|---|---|---|---|---|---|
| S7 | 139.23 | 1.5% | 1.5% | 0.7% | 1.1% | 2.5% |
| S8 | 2588.59 | 1.4% | 0.6% | 2.6% | 1.5% | 3.3% |
| Con1 | 16.70 | 3.2% | 2.6% | 2.4% | 0.9% | 4.9% |
| Con2 | 29.10 | 2.1% | 1.2% | 2.1% | 5.9% | 6.7% |
Three lots of the reagents on one analyzer
| ID | Mean
n=240 | Within-Run | Between
Run | Between
day | Between
lot | Total |
|------|---------------|------------|----------------|----------------|----------------|-------|
| S1 | 9.49 | 7.9% | 5.7% | 5.7% | 2.6% | 11.6% |
| S2 | 35.14 | 2.9% | 0.8% | 1.5% | 0.8% | 3.5% |
| S3 | 121.53 | 2.6% | 1.5% | 2.3% | N/A | 3.8% |
| S4 | 5.81 | 6.3% | 2.6% | 2.7% | 0.7% | 7.4% |
| S5 | 15.40 | 2.4% | 0.9% | 0.6% | 2.2% | 3.5% |
| S6 | 25.66 | 1.1% | 0.3% | 0.6% | 1.0% | 1.7% |
| S7 | 138.28 | 1.1% | N/A | 1.0% | 1.0% | 1.8% |
| S8 | 2588.45 | 1.3% | 1.0% | 2.5% | 1.5% | 3.3% |
| Con1 | 16.64 | 4.2% | 1.4% | 3.0% | 1.6% | 5.6% |
| Con2 | 27.82 | 3.2% | N/A | 2.7% | 1.8% | 4.6% |
Precision for Diazyme Human Lambda (λ) FLC Assay
The precision of the Assay was evaluated according to CLSI EP5-A guideline. In the study, eight levels of serum specimens containing low, medium, and high lambda FLC respectively and two levels of serum based lambda FLC controls were tested with 2 runs per day with duplicates over 20 working days using multiple lots of the reagents on multiple analyzers. The precision data was analyzed according to three-way nested ANOVA and the results of mean (mg/L) and CV% are summarized below:
| ID | Mean
n=240 | Within-Run | Between Run | Between day | Between Instr | Total |
|------|---------------|------------|-------------|-------------|---------------|-------|
| S1 | 11.89 | 6.3% | 4.5% | 6.1% | N/A | 9.9% |
| S2 | 48.65 | 2.1% | 0.7% | 1.3% | 0.8% | 2.7% |
| S3 | 144.55 | 1.6% | 1.0% | 1.3% | 0.6% | 2.4% |
| S4 | 8.31 | 6.5% | 0.4% | 3.1% | 0.8% | 7.3% |
| S5 | 22.27 | 3.0% | 1.4% | 2.6% | 1.1% | 4.3% |
| S6 | 35.09 | 2.1% | 1.2% | 1.4% | 1.0% | 2.9% |
| S7 | 181.13 | 0.8% | 0.7% | 1.3% | 1.1% | 2.0% |
| S8 | 3472.59 | 3.6% | N/A | 2.1% | 0.6% | 4.2% |
| Con1 | 27.62 | 3.9% | N/A | 0.9% | 0.1% | 4.0% |
| Con2 | 62.58 | 1.3% | 0.7% | N/A | 2.9% | 3.2% |
One lot of the reagent on three analyzers
14
| ID | Mean
n=240 | Within-Run | Between
Run | Between
day | Between
lot | Total |
|------|---------------|------------|----------------|----------------|----------------|-------|
| S1 | 11.78 | 5.9% | 4.0% | 7.4% | 4.9% | 11.4% |
| S2 | 48.95 | 1.3% | N/A | 1.7% | 0.3% | 2.2% |
| S3 | 142.63 | 1.1% | 0.8% | 0.5% | 0.8% | 1.6% |
| S4 | 8.16 | 6.3% | 2.3% | N/A | 3.1% | 7.4% |
| S5 | 21.90 | 2.9% | 1.3% | N/A | 0.6% | 3.2% |
| S6 | 34.79 | 2.0% | 0.4% | 0.3% | N/A | 2.1% |
| S7 | 183.02 | 0.6% | 0.3% | 0.8% | 0.3% | 1.1% |
| S8 | 3442.60 | 3.2% | N/A | 2.0% | N/A | 3.8% |
| Con1 | 28.13 | 4.5% | N/A | 0.2% | 3.8% | 5.9% |
| Con2 | 65.31 | 1.9% | 0.6% | N/A | 1.2% | 2.3% |
Three lots of the reagents on one analyzer
Linearity for Diazyme Human Lambda (λ) FLC Assay
The linearity of the Assay was evaluated according to CLSI EP6-A guideline. Based on the linearity data, limit of quantitation (LOQ=6.10 mg/L), the Analytical Measuring Range (AMR) is claimed to be 6.1-200 mg/L in standard mode. AMR is 6.1-4000 mg/L including extended mode.
Method Comparison
Method comparison for Diazyme Human Kappa (k) FLC Assay
The method comparison of the assay was evaluated following CLSI EP9-A2 protocol. A total of 126 serum samples ranging from 4.63-2975.80 mg/L were tested in comparison with predicate assay. Among the 126 samples, 39 were Multiple Myeloma (MM), 12 were Monoclonal Gammopathy of Undetermined Significance (MGUS), 34 were Abnormal (due to other disease states) and 41 were Normal (no disease), the concordance between the subject and predicate Kappa FLC is 98%. The results of regression analysis are summarized in the following table:
| Parameter | Linear Regression | Deming Regression |
|---|---|---|
| n | 126 | 126 |
| Slope | 0.958 | 0.969 |
| 95% CI | 0.932 to 0.985 | 0.943 to 0.996 |
| Intercept | -2.536 | -4.813 |
| 95% CI | -14.703 to 9.632 | -17.014 to 7.388 |
| Corr Coeff (R2) | 0.977 | 0.977 |
| Sample range | 4.63-2975.80 | 4.63-2975.80 |
Using CLSI EP12-A2: Evaluation of Qualitative Test Performance; Approved Guideline, Second Edition as guideline, the positive percent agreement (PPA), negative percent agreement (NPA) and overall percent agreement (TPA) for Kappa FLC comparisons to predicate and associated 95% confidence intervals were calculated. The results are listed in the table below:
| PPA | NPA | TPA | |
|---|---|---|---|
| -- | ----- | ----- | ----- |
15
| Agreement% | 96.67% | 100% | 97.62% |
|---|---|---|---|
| 95% CI | 90.65 to 98.86% | 90.36 to 100% | 93.23 to 99.19% |
Method comparison for Diazyme Human Lambda (λ) FLC Assay
The method comparison of the assay was evaluated following CLSI EP9-A2 protocol. A total of 126 serum samples ranging from 6.19-3917.80 mg/L were tested in comparison with predicate assay. Among the 106 samples, in which 39 were Multiple Myeloma (MM), 12 were Monoclonal Gammopathy of Undetermined Significance (MGUS), 34 were Abnormal (due to other disease states) and 41 were Normal (no disease), the concordance between the subject and predicate Lambda FLC was 95%. The results of regression analysis are summarized in the following table:
| Parameter | Linear Regression | Deming Regression |
|---|---|---|
| n | 126 | 126 |
| Slope | 1.054 | 1.070 |
| 95% CI | 1.021 to 1.086 | 1.038 to 1.102 |
| Intercept | 0.636 | -3.160 |
| 95% CI | -20.746 to 22.018 | -24.630 to 18.310 |
| Corr Coeff (R2) | 0.972 | 0.972 |
| Sample range | 6.19-3917.80 | 6.19-3917.80 |
Using CLSI EP12-A2: Evaluation of Qualitative Test Performance; Approved Guideline, Second Edition as guideline, the positive percent agreement (PPA), negative percent agreement (NPA) and overall percent agreement (TPA) for Lambda FLC comparisons to predicate and associated 95% confidence intervals were calculated. The results are listed in the table below:
| PPA | NPA | TPA | |
|---|---|---|---|
| Agreement% | 95.65% | 94.74% | 95.24% |
| 95% CI | 87.98 to 98.51% | 85.63 to 98.19% | 90.00 to 98.19% |
Detection limit
Detection limit for Diazyme Human Kappa (K) FLC Assay
The LOB, LOD, LOQ of the Assay was determined according to CLSI EP17-A2. The LOB was determined to be 1.2 mg/L; the LOD was determined to be 2.0 mg/L; the LOQ was determined to be 4.5 mg/L.
Detection limit for Diazyme Human Lambda (^) FLC Assay
The LOB, LOD, LOQ of the Assay was determined according to CLSI EP17-A2. The LOB was determined to be 1.7 mg/L; the LOD was determined to be 2.9 mg/L; the LOQ was determined to be 6.1 mg/L.
Interference
The following substances normally present in the blood produced less than 10% deviation when tested at levels equal to the concentrations listed below, according to CLSI EP7-A2.
| Interferent | Kappa FLC Concentration
Tolerance | Lambda FLC Concentration
Tolerance |
| ------------- | -------------------------------------- | --------------------------------------- |
|---|
16
| Interferent | Kappa FLC Concentration
Tolerance | Lambda FLC Concentration
Tolerance |
|----------------------|--------------------------------------|---------------------------------------|
| Triglyceride | 1000 mg/dL | 1000 mg/dL |
| Ascorbic Acid | 10 mM | 10 mM |
| Bilirubin | 40 mg/dL | 40 mg/dL |
| Bilirubin Conjugated | 40 mg/dL | 40 mg/dL |
| Hemoglobin | 1000 mg/dL | 1000 mg/dL |
| Rheumatoid Factor | 100 IU/mL | 100 IU/mL |
Hook Effect
No high dose hook effect for Diazyme Human Kappa (k) FLC Assay was observed up to 100,000 mg/L.
No high dose hook effect for Diazyme Human Lambda (λ) FLC Assay was observed up to 100,000 mg/L.
Rationale for Considering the Device Substantially Equivalent to Devices Approved for Inter-State Commerce
Freelite® Human Kappa Free Kit/ Freelite® Human Lambda Free Kit was selected for method comparison with Diazyme Human Kappa(x)/Lambda (2.) Free Light Chain Assay. The reagents used for the Diazyme Human Kappa (x) and Lambda (λ) Free Light Chain Assay are similar to the predicate and were used to develop the application for the Hitachi 917 analyzer. The similarities and differences between the predicate reagent and the Diazyme Human Kappa (x) and Lambda (λ) Free Light Chain Assay are given in the table above. Detailed performance characteristics and comparison analysis are given in the filing and demonstrate substantial equivalence to predicate device.
The performance characteristics of the Diazyme Human Kappa (K) and Lambda (λ) Free Light Chain Assay are substantially similar to that of the approved predicate test. Performance data and risk analysis indicates that differences should not affect the safety and effectiveness of the Diazyme Human Kappa (k) and Lambda (λ) Free Light Chain Assay and offers users an in vitro diagnostic device system to measure Human Kappa (k) and Lambda (λ) Free Light Chain in human serum.
Conclusion
Detailed method comparison analysis presented in this 510k submission, together with linearity, precision and interference studies, demonstrates that the Diazyme Human Kappa(k)/Lambda (λ.) Free Light Chain Assay performance is acceptable, safe and effective. There is no significant deviations between the results obtained by Diazyme Human Kappa (k) and Lambda (λ) Free Light Chain Assay and the legally marketed predicate device Freelite® Human Kappa Free Kit/ Freelite® Human Lambda Free Kit (K023009, K023131, K040009) when testing clinical patient samples and is thus substantially similar.