(30 days)
The Bio-Rad VARIANT™nbs Sickle Cell Program is intended as a qualitative screen for the presence of hemoglobins F, A, S, D, C, and E in eluates of neonatal blood collected on filter paper by high-performance liquid chromatography (HPLC).
The Bio-Rad VARIANT™nbs Sickle Cell Program is intended for Professional Use Only. For In Vitro Diagnostic Use.
The Bio-Rad VARIANT™nbs Sickle Cell Program is for use only with the Bio-Rad VARIANT™nbs Newborn Screening System.
The presence of hemoglobin S (HbS) in a patient blood sample is indicative of sickle cell disease or sickle cell trait. Diagnosis of sickle cell disease prior to the age of four months allows for the administration of a prophylactic treatment with penicillin. Prophylactic treatment with penicillin has shown to decrease morbidity and mortality.
The VARIANTnbs Newborn Screening System uses the principles of high-performance liquid chromatography (HPLC). The VARIANTnbs Sickle Cell Program is based on the chromatographic separation of hemoglobins F, A, S, D, C, and E on a cation exchange cartridge.
The new feature in this submission is the upgrade of the Genetic Data Management (GDM) software. The current software (GDM 2.01) requires Microsoft Windows NT. This product is nearing the end of its lifecycle. GDM 3.0 software is needed to transfer the GDM software to the Microsoft Windows XP Operating System.
Acceptance Criteria and Study Details for Bio-Rad VARIANT™nbs Sickle Cell Program with GDM 3.0
This document outlines the acceptance criteria and the study conducted to demonstrate that the Bio-Rad VARIANT™nbs Sickle Cell Program run on the VARIANT™nbs Newborn Screening System using Genetic Data Management (GDM) 3.0 Software meets these criteria.
1. Table of Acceptance Criteria and Reported Device Performance
The primary acceptance criteria for the new GDM 3.0 software update was to maintain 100% agreement with the predicate device (GDM 2.01) in identifying the presence of specific hemoglobins.
| Acceptance Criteria | Reported Device Performance (GDM 3.0 vs. GDM 2.01) |
|---|---|
| 100% agreement for Hemoglobin | 100% agreement |
| Type FA | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type FAS | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type FAC | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type FAD | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type H | Not explicitly listed as "H" in the provided table, but |
| 100% agreement for all other | the overall "Total" agreement is 100%. |
| specific hemoglobin types | |
| (implied by overall "Total") |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The provided document does not explicitly state the total number of patient samples used in the correlation study. It lists categories of hemoglobin types (FA, FAS, FAC, FAD, and an unspecified "H" type) and indicates 100% agreement for each. While a total count of samples is not given, the implicit message is that all samples tested within these categories showed agreement.
- Data Provenance: The study was conducted "at an external site". The country of origin is not specified but is presumably the United States, given the FDA submission. The study compared results from the predicate device and the new device ran on the same samples on the same day, suggesting it was a prospective comparison of the new software's performance on existing samples, rather than entirely retrospective data analysis.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document describes a "method correlation study" where samples run on the predicate device (GDM 2.01) were repeated on the GDM 3.0 platform. The "ground truth" in this context is established by the results obtained from the predicate device (GDM 2.01). There is no mention of external human experts establishing a separate ground truth for this correlation study, as the comparison is specifically between the two software versions and their agreement.
4. Adjudication Method for the Test Set
No explicit adjudication method is described. The study directly compares the results of the two software versions. Since the goal was to demonstrate 100% agreement, any discrepancy would inherently require investigation. However, with 100% agreement reported, no further adjudication process for conflicting results was needed or mentioned.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic system for qualitative screening of hemoglobins using HPLC and software for data management, not an AI-assisted diagnostic imaging or interpretation tool for human readers. The change is an upgrade to the operating system and features of the data management software.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The study described is a standalone performance comparison between the GDM 3.0 software and the predicate GDM 2.01 software. It assesses the algorithm's (software's) ability to produce the same qualitative results as the older version when processing the same samples. While human operators are involved in running the HPLC system, the software's output is the focus of the comparison, making it a standalone assessment of the software's correlation with its predecessor.
7. The Type of Ground Truth Used
The ground truth used for this study was the results generated by the predicate device (VARIANT™nbs Sickle Cell Program with GDM 2.01). The objective was to demonstrate that the new GDM 3.0 software produced identical qualitative results to the previously cleared and established predicate device.
8. The Sample Size for the Training Set
The provided summary does not mention a training set in the typical sense for machine learning or AI models. The GDM 3.0 is a software upgrade to an existing HPLC system, primarily focusing on operating system compatibility and usability enhancements, not a new algorithm requiring a training phase from scratch. Therefore, the concept of a "training set" for the algorithm itself is not directly applicable in this context. The development process would have involved internal testing and validation, but this information is not part of the public summary provided.
9. How the Ground Truth for the Training Set Was Established
As explained above, a dedicated "training set" for an AI algorithm is not applicable to this software upgrade. The "ground truth" for ensuring the functionality of the GDM 3.0 software during its development would have been established through rigorous software testing against known sample profiles and expected outputs, confirming its accuracy in processing the chromatographic data according to the established scientific principles of HPLC for hemoglobin separation. This typically involves using reference materials and clinically characterized samples.
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Summary of Safety and Effectiveness
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.
The assigned 510(k) number is: K 0809 /
: Submitter:
Bio-Rad Laboratories, Inc., Clinical Systems Division, 4000 Alfred Nobel Drive, Hercules, California 94547
Phone: (510) 741-6114, Fax: (510) 741-6471
Contact Person:
Jolene Bartilson, Regulatory Affairs Representative
Device Name:
VARIANT™nbs Sickle Cell Program run on the VARIANT™nbs Newborn Screening System using Genetic Data Management (GDM) 3.0 Software
Classification Name:
Assay, Abnormal Hemoglobin, GKA
Predicate Device(s):
VARIANTTMnbs Sickle Cell Program, Bio-Rad Laboratories, Inc., K051072
Intended Use:
The Bio-Rad VARIANT™nbs Sickle Cell Program is intended as a qualitative screen for the presence of hemoglobins F, A, S, D, C, and E in eluates of neonatal blood collected on filter paper by high-performance liquid chromatography (HPLC).
The Bio-Rad VARIANTnbs Sickle Cell Program is intended for Professional Use Only. For In Vitro Diagnostic Use.
The Bio-Rad VARIANTnbs Sickle Cell Program is for use only with the Bio-Rad VARIANTnbs Newborn Screening System.
Indications for Use;
The presence of hemoglobin S (HbS) in a patient blood sample is indicative of sickle cell disease or sickle cell trait. Diagnosis of sickle cell disease prior to the age of four months
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treatment with penicillin has shown to decrease morbidity and mortality. 1
- Gaston, M.H.; Verter, J.I.; Woods, G .; Pegelow, C .; Kelleher, J .; Presbury, G .; Zarkowsky, H.; Vichinsky, E.; Lyer, R.; Lobel, J.S.; Diamond, S.; Holbrook, C.T.; Gill, F.M .; Ritchey, K .; Falleta, J.M. Prophylaxis With Oral Penicillin in Children With Sickle Cell Anemia: A Randomized Trial. N. Engl. J. Med. 1986, 314 (25), 1593-1599.
Description of the Device:
The VARIANTnbs Newborn Screening System uses the principles of high-performance liquid chromatography (HPLC). The VARIANTnbs Sickle Cell Program is based on the chromatographic separation of hemoglobins F, A, S, D, C, and E on a cation exchange cartridge.
The new feature in this submission is the upgrade of the Genetic Data Management (GDM) software. The current software (GDM 2.01) requires Microsoft Windows NT. This product is nearing the end of its lifecycle. GDM 3.0 software is needed to transfer the GDM software to the Microsoft Windows XP Operating System.
Technical Characteristics Compare to the Predicate:
The VARIANTnbs Sickle Cell Program runs on the VARIANTnbs Newborn Screening System with GDM 3.0 and has the same basic technical characteristics as the predicate VARIANTnbs Sickle Cell Program, K051072. The technical characteristics between the two submissions are summarized in the following table:
| Characteristic | New Device: VARIANTnbs Sickle Cell Programrun on the VARIANTnbs Newborn ScreeningSystem with GDM 3.0 | Predicate Device: VARIANTnbs Sickle CellProgram run on the VARIANTnbs NewbornScreening System with GDM 2.01 (K051072) |
|---|---|---|
| IntendedUse | The Bio-Rad VARIANT™nbsSickle Cell Program is intended as aqualitative screen for the presenceof hemoglobins F, A, S, D, C, and Ein eluates of neonatal bloodcollected on filter paper by high-performance liquid chromatography(HPLC). The Bio-RadVARIANTnbs Sickle Cell Programis intended for Professional UseOnly. For In Vitro Diagnostic Use.The Bio-Rad VARIANTnbs SickleCell Program is for use only withthe Bio-Rad VARIANTnbsNewborn Screening System. | The Bio-Rad VARIANT™nbsSickle Cell Program is intended as aqualitative screen for the presenceof hemoglobins F, A, S, D, C, and Ein eluates of neonatal bloodcollected on filter paper by high-performance liquid chromatography(HPLC). The Bio-RadVARIANTnbs Sickle Cell Programis intended for Professional UseOnly. For In Vitro Diagnostic Use.The Bio-Rad VARIANTnbs SickleCell Program is for use only withthe Bio-Rad VARIANTnbsNewborn Screening System. |
| Indications | The presence of hemoglobin S | The presence of hemoglobin S |
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| for Use | (HbS) in a patient blood sample isindicative of sickle cell disease orsickle cell trait. Diagnosis of sicklecell disease prior to the age of fourmonths allows for theadministration of a prophylactictreatment with penicillin.Prophylactic treatment withpenicillin has shown to decreasemorbidity and mortality.1 | (HbS) in a patient blood sample isindicative of sickle cell disease orsickle cell trait. Diagnosis of sicklecell disease prior to the age of fourmonths allows for theadministration of a prophylactictreatment with penicillin.Prophylactic treatment withpenicillin has shown to decreasemorbidity and mortality.1 |
|---|---|---|
| AssayPrinciple | Cation exchange high-performanceliquid chromatography | Cation exchange high-performanceliquid chromatography |
| OperatingSystem | Microsoft Windows XP | Microsoft Windows NT |
| ObjectStore | ObjectStore Version 6.2 | ObjectStore Version 4.0 |
| BarcodeReader | Active | Inactive |
| WorklistSetup | Improved to provide flexibility inthe setup and a simplified dailyworkflow | Feature not available |
| XtraGridControl | XtraGrid Control OTS Software(version 2.1.1) added to managedata represented in the WorklistSetup tables | Not included, Worklist Setupfeature not available |
| ArchiveViewer | Standalone software applicationthat allows the user to view adatabase from an earlier GDMsoftware version | Feature not available |
! Testing to Establish Substantial Equivalence: Correlation:
A method correlation study between the VARIANTnbs Sickle Cell Program with GDM 3.0 and the VARIANTnbs Sickle Cell Program with GDM 2.01 was conducted at an external site to demonstrate equivalence. Samples run on the predicate device were repeated on the GDM 3.0 platform on the same day. Below is a representation of the results from this study.
| Vnbs Sickle Cell Program with GDM 3.0 vs. Vnbs Sickle Cell Program with GDM 2.0 | |
|---|---|
| --------------------------------------------------------------------------------- | -- |
| Patient Sample | GDM 2.01 | GDM 3.0 (New | Agreement |
|---|---|---|---|
| Type | (Predicate) | Device) | 0/0 |
| E A | tSept. However, House, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, Market, | t2000 | 100% |
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| FAS | 100% | |
|---|---|---|
| FAC | 100% | |
| FAD | 100% | |
| Amind Transformer of It is in theHS | 100% | |
| Total | «««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««««»»»»»»»»»»»»»»»» ««««««««««««««««««««««««««««»»»»»»»»»»»»»»» «««««««««««««« | 11 Specificant F. REVEREAL ARTIN' (REPORTER P |
Conclusion:
I The modifications to the VARIANTnbs Sickle Cell Program run on the
VARIANTubs Newborn Screening System with GDM 3.0 do not affect the intended use or indications for use of the device as described in the labeling, raise any new issues of safety or effectiveness, nor do they alter the fundamental scientific technology of the device. Therefore, we trust that the information provided in this Special 510(k) submission will support a decision of substantial equivalence of the VARIANTnbs Sickle Cell Program run on the VARIANTnbs Newborn Screening System with GDM 3.0 to its predicate.
0
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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, symbolizing protection and care. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle. The logo is in black and white.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAY - 2 2008
Bio-Rad Laboratories, Inc. Clinical Systems Division C/O J.B. Bartilson 4000 Alfred Nobel Drive Hercules, California 94547
Re: K080911
Trade/Device Name: Variant NBS Sickle Cell Program Reagent Kit, Variant NBS Newborn Screening Regulation Number: 21 CFR 864.7415 Regulation Name: Abnormal Hemoglobin Assay Regulatory Class: Class II Product Code: GKA Dated: April 1, 2008 Received: April 2, 2008
Dear J.B. Bartilson:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean 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); and good manufacturing practice
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Page 2 - Bio-Rad Laboratories, Inc.
requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to procced to the market.
If vou desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Robert M. Roskel
Robert L. Becker, Jr., M.D./Ph.D. Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K0809 / /
Device Name: VARIANT™nbs Sickle Cell Program run on the VARIANT™abs Newborn Screening System using Genetic Data Management (GDM) 3.0 Software
Indications for Use:
The Bio-Rad VARIANTTMnbs Sickle Cell Program is intended as a qualitative screen for the presence of hemoglobins F, A, S, D, C, and E in eluates of neonatal blood collected on filter paper by high-performance liquid chromatography (HPLC).
The Bio-Rad VARIANT™nbs Sickle Cell Program is intended for Professional Use Only. For In Vitro Diagnostic Use.
The Bio-Rad VARIANT™nbs Sickle Cell Program is for use only with the Bio-Rad VARIANT™nbs Newborn Screening System.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K080911
§ 864.7415 Abnormal hemoglobin assay.
(a)
Identification. An abnormal hemoglobin assay is a device consisting of the reagents, apparatus, instrumentation, and controls necessary to isolate and identify abnormal genetically determined hemoglobin types.(b)
Classification. Class II (special controls). A control intended for use with an abnormal hemoglobin assay is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.