(260 days)
K031829 HemosIL Factor IX deficient plasma
No
The summary describes a standard chromogenic assay for measuring factor IX activity. There is no mention of AI, ML, or any related technologies in the device description, intended use, or performance studies. The analysis relies on comparing a chromogenic signal to a calibration curve, which is a traditional method.
No
This device is an in vitro diagnostic assay used to measure factor IX activity, which aids in identifying factor IX deficiency or monitoring patients on replacement therapy. It does not provide any direct therapeutic benefit to the patient.
Yes.
The device is intended for the "quantitative determination of factor IX activity" and is "indicated for use on patients when identifying factor IX deficiency or measuring factor IX activity from patients on replacement therapy," which are diagnostic purposes.
No
The device is described as an automated assay using a chromogenic method to determine factor IX activity in plasma. This involves reagents and likely hardware (the ACL TOP Family and ACL TOP Family 50 Series instruments) to perform the photometric measurements and analysis. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "photometric, quantitative determination of factor IX activity in 3.2% citrated plasma" and is "indicated for use on patients when identifying factor IX deficiency or measuring factor IX activity from patients on replacement therapy." This clearly describes a test performed on a biological sample (plasma) to provide information about a patient's health status (factor IX deficiency or activity).
- Device Description: The description details a method for analyzing a biological sample (plasma) using a chemical reaction and photometric measurement to determine a specific analyte (factor IX activity). This is characteristic of an in vitro diagnostic test.
- Care Setting: The test is performed in a "laboratory setting by a healthcare professional," which is the typical environment for IVD testing.
- Sample Type: The test uses "3.2% citrated plasma," a biological sample.
The information provided aligns perfectly with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic, monitoring, or compatibility purposes.
N/A
Intended Use / Indications for Use
HemosIL Chromogenic Factor IX is an automated assay for the photometric, quantitative determination of factor IX activity in 3.2% citrated plasma on the ACL TOP® Family and ACL TOP Family 50 Series in the laboratory setting by a healthcare professional. HemosIL Chromogenic Factor IX is indicated for use on patients when identifying factor IX deficiency or measuring factor IX activity from patients on replacement therapy. For adult population only. For prescription use only.
Product codes
GGP
Device Description
Factor IX activity in a patient's plasma is determined using a chromogenic method, in which human factor IX is activated by human factor XIa, and, when formed, factor IXa activates human factor X in the presence of human factor VIII, calcium and phospholipid. The amount of factor Xa generated is proportionate to the factor IX activity and is determined from the hydrolysis of a chromogenic factor Xa substrate. Results are determined by comparing a chromogenic signal to a calibration curve.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Adult population only.
Intended User / Care Setting
Healthcare professional in the laboratory setting.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Precision:
Within-run (repeatability) and total (within-device) precision were assessed in accordance with EP05-A3 for 20 days, with two runs per day and two replicates per run for each sample level (n=80) for three reagent lots on representative members of the ACL TOP Family. Three patient sample pools were tested, as well as two control levels.
Within-run (repeatability) and total (within-device) precision were assessed in accordance with EP05-A3 for 20 days, with two runs per day and two replicates per run for each sample level (n=80) for one reagent lot on representative members of the ACL TOP Family 50 Series. Three patient sample pools were tested, as well as two control levels.
Reproducibility:
Reproducibility studies were conducted in accordance with EP05-A3 at two external site using different operators (one operator per site) on three different ACL TOP Family 30 Series members (one instrument per site), using three reagent lots of HemosIL Chromogenic Factor IX. The same five patient pools and chree sites, as well as three patient sample pools spilled with a factor IX concentate. Each material was tested in triplicate, twice a day for five atotal of 30 replicates per level.
Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ):
Studies were performed in accordance with CLSI EP17-A2, using three reagent lots of HemosIL Chromogenic Factor IX on representative members of the ACL TOP Family and ACL TOP Family 50 Series.
Linearity:
Studies were performed in accordance with CLSI EP06, 2nd Edition, using three reagent lots of HemosIL Chromogenic Factor IX on a representative member of the ACL TOP Family and one reagent lot on a representative member of the ACL TOP Family 50 Series.
Interferences and Limitations:
Interference studies were performed in accordance with CLSI EP07, 3dd Edition (where applicable), using a minimum of one reagent lot of HemosIL Chromogenic Factor IX on a representative member of the ACL TOP Family or ACL TOP Family 50 Series model.
Normal Reference Interval:
A normal reference interval study was performed in accordance with CLSI EP28-A3c on one reagent lot of HemosIL Chromogenic Factor IX with a representative ACL TOP Family instrument. A population of 120 plasma samples from apparently healthy individuals were tested. The nonparametric 95% reference interval with two-sided 90% confidence intervals was calculated as 71.1 to 134.1% (0.7-1.3 IU/mL).
Recovery of Factor IX Replacement Therapies:
A recovery study was performed using one reagent lot of HemosIL Chromogenic Factor IX on a representative member of the ACL TOP Family. Immunodepleted FIX deficient plasma was spiked with four factor IX replacement therapies at seven to fourteen concentrations, ranging from 0.5 to 200% and percent recovery was determined.
In-Use Stability and Shelf-life:
Studies were performed in accordance with CLSI EP25-A, using three reagent lots of HemosIL Chromogenic Factor IX on a representative ACL TOP Family model.
Sample Stability:
A sample stability study was performed using one reagent lot of HemosIL Chromogenic Factor IX on a representative ACL TOP Family model or ACL TOP Family 50 Series model.
Multicenter Method Comparison:
A multicenter method comparison study was conducted at four sites (three external and one internal) in accordance with CLSI EP09c to compare the accuracy of the HemosIL Chromogenic Factor IX assay relative to the predicate device, HemosIL Factor deficient plasma, on representative members of the ACL TOP Family and ACL TOP Family 50 Series, using samples from patients with von Willebrand disease, patients with hemophilia A and B and patients on factor IX replacement therapy.
Overall results for Multicenter Method Comparison: N=344, r=0.972, Slope=1.015 (95% CI: 0.994-1.037), Intercept=-0.920 (95% CI: -2.064 - -0.185).
Internal Method Comparison:
An internal method comparison study was performed comparing the performance of the ACL TOP Family 50 Series to the ACL TOP Family using representative systems from both families.
ACL TOP Family 50 Series vs ACL TOP Family: N=126, Slope=0.980, Intercept=1.731, r=0.998.
Key Metrics
Multicenter Method Comparison Bias:
Factor IX 1%: Predicted Bias -0.90, Lower CI -2.03, Upper CI -0.19
Factor IX 5%: Predicted Bias -0.84, Lower CI -1.89, Upper CI -0.17
Factor IX 50%: Predicted Bias -0.3%, Lower CI -2.5%, Upper CI 0.8%
Factor IX 100%: Predicted Bias 0.6%, Lower CI -1.4%, Upper CI 2.2%
Limit of Blank (LoB): 0.1%
Limit of Detection (LoD): 0.3%
Limit of Quantitation (LoQ): 0.6%
Linear range: 1.0 to 150%.
Predicate Device(s)
K031829 HemosIL Factor IX deficient plasma
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 864.7290 Factor deficiency test.
(a)
Identification. A factor deficiency test is a device used to diagnose specific coagulation defects, to monitor certain types of therapy, to detect coagulation inhibitors, and to detect a carrier state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene).(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name, "U.S. Food & Drug Administration," written out next to it.
December 13, 2023
Instrumentation Laboratory Company Carol Marble Senior Director of Regulatory Affairs 180 Hartwell Road Bedford, Massachusetts 01730
Re: K230852
Trade/Device Name: HemosIL Chromogenic Factor IX Regulation Number: 21 CFR 864.7290 Regulation Name: Factor deficiency test Regulatory Class: Class II Product Code: GGP Dated: March 27, 2023 Received: March 28, 2023
Dear Carol Marble:
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
1
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Min Wu-S
Min Wu, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
2
Indications for Use
510(k) Number (if known) K230852
Device Name HemosIL Chromogenic Factor IX
Indications for Use (Describe)
HemosIL Chromogenic Factor IX is an automated assay for the photometric, quantitative determination of factor IX activity in 3.2% citrated plasma on the ACL TOP® Family and ACL TOP Family 50 Series in the laboratory setting by a healthcare professional. HemosIL Chromogenic Factor IX is indicated for use on patients when identifying factor IX deficiency or measuring factor IX activity from patients on replacement therapy. For adult population only. For prescription 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) |
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3
werfen
510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
| Submitter's Information | Instrumentation Laboratory (IL) Company
180 Hartwell Road
Bedford, MA 01730, USA |
|---------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person | Carol Marble, Senior Director of Regulatory Affairs
Phone: 781-861-4467
Fax: 781-861-4207
Email: cmarble@werfen.com |
| Preparation Date | December 12, 2023 |
| Device Trade Name | HemosIL Chromogenic Factor IX |
| Regulatory Information | Regulation No. 21 CFR 864.7290
Regulation Description Factor deficiency test
Classification Class II
Product Code GGP
Classification Panel Hematology (81) |
| Predicate Device | K031829 HemosIL Factor IX deficient plasma |
| Device Description | Factor IX activity in a patient's plasma is determined using a chromogenic method, in
which human factor IX is activated by human factor XIa, and, when formed, factor
IXa activates human factor X in the presence of human factor VIII, calcium and
phospholipid. The amount of factor Xa generated is proportionate to the factor IX
activity and is determined from the hydrolysis of a chromogenic factor Xa substrate.
Results are determined by comparing a chromogenic signal to a calibration curve. |
| Intended Use /
Indications for Use | HemosIL Chromogenic Factor IX is an automated assay for the photometric,
quantitative determination of factor IX activity in 3.2% citrated plasma on the ACL
TOP Family and ACL TOP Family 50 Series in the laboratory setting by a healthcare
professional. HemosIL Chromogenic Factor IX is indicated for use on patients when
identifying factor IX deficiency or measuring factor IX activity from patients on
replacement therapy. For adult population only. For prescription use only. |
4
| Comparison to Predicate Device | ||
|---|---|---|
| Item | Predicate Device (K031829) | Subject Device |
| Proprietary and | ||
| Established Name | HemosIL Factor IX deficient plasma | HemosIL Chromogenic Factor IX |
| Legal Manufacturer | Instrumentation Laboratory Co. | Same |
| Similarities | ||
| Measurand | Factor IX activity | Same |
| Measurement | Quantitative | Same |
| Regulation No. | 21 CFR 864.7290 | Same |
| Regulation | ||
| Description | Factor deficiency test | Same |
| Classification | Class II | Same |
| Product Code | Classification Product Code: | |
| GJT | ||
| Subsequent Product Code: | ||
| GGP | GGP | |
| Review Panel | Hematology (81) | Same |
| Intended Use / | ||
| Indications for Use | HemosIL Factor IX deficient plasma is | |
| human plasma immunodepleted of factor | ||
| IX for the quantitative determination of | ||
| factor IX activity in citrated plasma, based | ||
| on activated partial thromboplastin time | ||
| (APTT) assay, on IL Coagulation Systems. | HemosIL Chromogenic Factor IX is an | |
| automated assay for the photometric, | ||
| quantitative determination of factor IX | ||
| activity in 3.2% citrated plasma on the ACL | ||
| TOP Family and ACL TOP Family 50 | ||
| Series in the laboratory setting by a | ||
| healthcare professional. HemosIL | ||
| Chromogenic Factor IX is indicated for use | ||
| on patients when identifying factor IX | ||
| deficiency or measuring factor IX activity | ||
| from patients on replacement therapy. For | ||
| adult population only. For prescription use | ||
| only. | ||
| Sample Type | Citrated plasma | Same |
| Type of Test | Quantitative | Same |
| Reporting Units | % Activity, U/mL and/or sec | % Activity and/or IU/mL |
| Instruments | ACL Elite/Elite Pro | |
| ACL TOP Family | ||
| ACL TOP Family 50 Series | ACL TOP Family | |
| ACL TOP Family 50 Series | ||
| Controls | ||
| (Sold Separately) | HemosIL Normal Control Assayed | |
| HemosIL Special Test Control Level 2 | Same | |
| Calibrator | ||
| (Sold Separately) | HemosIL Calibration Plasma | Same |
| Linear Range | 1.0-150% | Same |
| Differences | ||
| Item | Predicate Device (K031829) | Subject Device |
| Test Principle | Factor IX activity in a patient's plasma is | |
| determined by performing a modified | ||
| activated partial thromboplastin time test | ||
| (APTT). Patient plasma is diluted and added | ||
| to a plasma deficient in factor IX. Correction | ||
| of the clotting time of the deficient plasma is | ||
| proportional to the concentration (% activity) | ||
| of that factor in the patient plasma, | ||
| interpolated from a calibration curve. | Factor IX activity in a patient's plasma is | |
| determined using a chromogenic method, in | ||
| which human factor IX is activated by human | ||
| factor XIa, and, when formed, factor IXa | ||
| activates human factor X in the presence of | ||
| human factor VIII, calcium and phospholipid. | ||
| The amount of factor Xa generated is | ||
| proportionate to the factor IX activity and is | ||
| determined from the hydrolysis of a | ||
| chromogenic factor Xa substrate. Results are | ||
| determined by comparing a chromogenic signal | ||
| to a calibration curve. | ||
| Methodology | Functional clotting assay | Chromogenic assay |
| Kit Components | Factor IX deficient plasma: Lyophilized | |
| human plasma that has been artificially | ||
| depleted of factor IX containing buffer and | ||
| stabilizers. The residual factor IX activity is | ||
| less than or equal to 1% whereas all other | ||
| coagulation factors have normal levels. | Reagent A: Lyophilized preparation containing human factor VIII, human factor | |
| X, bovine factor V, bovine serum albumin and a fibrin polymerization inhibitor. Reagent B: Lyophilized preparation containing human factor XIa, human factor | ||
| II, bovine serum albumin, calcium chloride and phospholipids. Substrate: Solution containing 2.5 mmol/L chromogenic factor Xa substrate (Z-D-Arg- | ||
| Gly-Arg-pNA), a thrombin inhibitor and preservative. Buffer: Stock solution of buffer containing a heparin antagonist, bovine serum albumin | ||
| and preservative. Diluted Buffer Barcode Labeled Vials: | ||
| Empty vials with linear barcode labels for Diluted Buffer (to be prepared). |
5
6
Performance Summary
Precision
Within-run (repeatability) and total (within-device) precision were assessed in accordance with EP05-A3 for 20 days, with two runs per day and two replicates per run for each sample level (n=80) for three reagent lots on representative members of the ACL TOP Family. To span the assay range, three patient sample pools were tested, as well as two control levels. The tables below show data for one representative reagent lot on one instrument and also aggregated data for the three reagent lots on one instrument.
| Representative Reagent Lot on ACL TOP Family Instrument | |||||
|---|---|---|---|---|---|
| Material | Mean | ||||
| (%) | Within-run | Total | |||
| SD | %CV | SD | %CV | ||
| Normal Control Assayed | 111.7 | 3.9 | 3.5 | 6.3 | 5.6 |
| Special Test Control Level 2 | 33.3 | 1.1 | 3.3 | 1.7 | 5.1 |
| Sample 1 (Pool) | 4.3 | 0.2 | 5.4 | 0.3 | 7.3 |
| Sample 2 (Pool) | 65.7 | 2.5 | 3.7 | 3.4 | 5.1 |
| Sample 3 (Pool) | 102.7 | 3.4 | 3.3 | 5.3 | 5.2 |
| Aggregated Data (Reagent Lots 1, 2 and 3) | |||||
| Material | Mean | ||||
| (%) | Total | ||||
| (Within-Laboratory) | |||||
| SD | %CV | ||||
| Normal Control Assayed | 110.6 | 6.4 | 5.8 | ||
| Special Test Control Level 2 | 33.0 | 1.8 | 5.3 | ||
| Sample 1 (Pool) | 4.2 | 0.4 | 8.4 | ||
| Sample 2 (Pool) | 65.3 | 3.5 | 5.4 | ||
| Sample 3 (Pool) | 101.8 | 5.9 | 5.8 |
7
Further, within-run (repeatability) and total (within-device) precision were assessed in accordance with EP05-A3 for 20 days, with two runs per day and two replicates per run for each sample level (n=80) for one reagent lot on representative members of the ACL TOP Family 50 Series. To span the assay range, three patient sample pools were tested, as well as two control levels. The table below shows data for one instrument.
| Representative Reagent Lot on ACL TOP Family 50 Series Instrument | |||||
|---|---|---|---|---|---|
| Material | Mean | ||||
| (%) | Within-run | Total | |||
| SD | %CV | SD | %CV | ||
| Normal Control Assayed | 111.9 | 3.0 | 2.7 | 5.0 | 4.5 |
| Special Test Control Level 2 | 33.5 | 0.8 | 2.5 | 1.3 | 3.9 |
| Sample 1 (Pool) | 4.1 | 0.1 | 3.3 | 0.2 | 5.3 |
| Sample 2 (Pool) | 66.4 | 2.1 | 3.1 | 2.5 | 3.8 |
| Sample 3 (Pool) | 103.5 | 3.5 | 3.4 | 4.6 | 4.5 |
8
Reproducibility
Reproducibility studies were conducted in accordance with EP05-A3 at two external site using different operators (one operator per site) on three different ACL TOP Family 30 Series members (one instrument per site), using three reagent lots of Hemostl. Chromogenic Pactor IX with each site total a with each site total a different reagent lot. The same five patient pools and chree sites, as well as three patient sample pools spilled with a factor IX concentate. Each material was tested in triplicate, twice a day for five atotal of 30 replicates per level. The table belows the pooled three-site data for all reagent lots.
| Pooled Three-Site Data | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Level | Mean (%) | N | Repeatability (Within-Run) | Between-Run | Between-Day | Between-Site | Reproducibility (Total) | |||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| Normal Control Assayed | 108.9 | 90 | 5.5 | 5.0 | 4.4 | 4.0 | 3.7 | 3.4 | 4.3 | 3.9 | 9.0 | 8.3 |
| Special Test Control Level 2 | 30.7 | 90 | 1.2 | 3.9 | 0.5 | 1.6 | 1.0 | 3.3 | 0.5 | 1.5 | 1.7 | 5.6 |
| Sample 1 (Pool) | 1.3 | 90 | 0.2 | 15.2 | 0.0 | 0.0 | 0.2 | 12.7 | 0.1 | 7.1 | 0.3 | 21.1 |
| Sample 2 (Pool) | 4.0 | 90 | 0.2 | 5.3 | 0.0 | 0.0 | 0.1 | 3.3 | 0.1 | 3.3 | 0.3 | 7.1 |
| Sample 3 (Pool) | 33.6 | 90 | 1.2 | 3.6 | 0.9 | 2.7 | 0.7 | 2.1 | 0.4 | 1.2 | 1.7 | 5.1 |
| Sample 4 (Pool) | 73.9 | 90 | 3.0 | 4.1 | 1.4 | 1.9 | 3.1 | 4.2 | 0.0 | 0.0 | 4.5 | 6.1 |
| Sample 5 (Pool) | 109.7 | 90 | 4.9 | 4.5 | 1.7 | 1.5 | 5.4 | 4.9 | 0.0 | 0.0 | 7.5 | 6.8 |
| Concentrate Sample 1 (Pool) | 3.7 | 90 | 0.2 | 6.2 | 0.0 | 0.0 | 0.1 | 1.7 | 0.1 | 3.4 | 0.3 | 7.3 |
| Concentrate Sample 2 (Pool) | 30.1 | 90 | 1.1 | 3.6 | 0.1 | 0.3 | 0.9 | 3.1 | 0.4 | 1.3 | 1.5 | 4.9 |
| Concentrate Sample 3 (Pool) | 98.8 | 90 | 3.8 | 3.8 | 1.5 | 1.5 | 4.1 | 4.1 | 0.3 | 0.3 | 5.8 | 5.8 |
9
Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ)
LoB, LoD and LoQ studies were performed in accordance with CLSI EP17-A2, using three reagent lots of HemosIL Chromogenic Factor IX on representative members of the ACL TOP Family and ACL TOP Family 50 Series.
The following maximum limits were determined:
| Limit of Blank (LoB) | Limit of Detection (LoD) | Limit of Quantitation (LoQ) |
|---|---|---|
| 0.1% | 0.3% | 0.6% |
Linearity
Linearity studies were performed in accordance with CLSI EP06, 2nd Edition, using three reagent lots of HemosIL Chromogenic Factor IX on a representative member of the ACL TOP Family and one reagent lot on a representative member of the ACL TOP Family 50 Series. The studies support a reportable linear range on the ACL TOP Family and ACL TOP Family 50 Series of 1.0 to 150%.
Interferences and Limitations
Interference studies were performed in accordance with CLSI EP07, 3dd Edition (where applicable), using a minimum of one reagent lot of HemosIL Chromogenic Factor IX on a representative member of the ACL TOP Family or ACL TOP Family 50 Series model. The studies support that results on the ACL TOP Family and ACL TOP Family 50 Series are not affected by the following interferents up to:
| Hemoglobin | 1000 mg/dL |
|---|---|
| Bilirubin (unconjugated) | 40 mg/dL |
| Bilirubin (conjugated) | 40 mg/dL |
| Triglycerides | 1500 mg/dL |
| Unfractionated heparin | 2.0 IU/mL |
| Low molecular weight heparin | 2.0 IU/mL |
| Dabigatran | 5.0 mg/L |
| Rivaroxaban | 0.05 mg/L |
| Fondaparinux | 1.02 mg/L |
| Lupus anticoagulant | dRVVT Screen/Confirm Ratio 1.8 |
Note: Warfarin inhibits vitamin K dependent coagulation factors and interferes with the quantification of factor IX activity.
Due to different methodologies used to assign potency for factor IX replacement therapies, differences between factor IX recovery may exist. For recommendations on monitoring factor IX replacement therapy, refer to current guidance and factor IX replacement therapy prescribing information.
To avoid discrepancies that have been reported, consider performing both a chromogenic and one stage factor IX clotting assay for the laboratory investigation of patients being assessed due to the clinical suspicion of hemophilia B. Results of this test should always be interpreted in conjunction with the patient's medical history, clinical presentation and other findings.
10
Normal Reference Interval
A normal reference interval study was performed in accordance with CLSI EP28-A3c on one reagent lot of HemosIL Chromogenic Factor IX with a representative ACL TOP Family instrument. A population of 120 plasma samples from apparently healthy individuals were tested. The nonparametric 95% reference interval with two-sided 90% confidence intervals was calculated as 71.1 to 134.1% (0.7-1.3 IU/mL).
Due to many variables which may affect the results (including the population age), each laboratory should determine its own normal range.
Recovery of Factor IX Replacement Therapies
A recovery study was performed using one reagent lot of HemosIL Chromogenic Factor IX on a representative member of the ACL TOP Family. Immunodepleted FIX deficient plasma was spiked with four factor IX replacement therapies at seven to fourteen concentrations, ranging from 0.5 to 200% and percent recovery was determined. HemosIL Chromogenic Factor IX accurately evaluated the potency of factor IX concentrates including AlphaNine SD, BeneFIX, and Rebinyn.
| Product | Mean Percent Recovery (%) |
|---|---|
| AlphaNine SD | 90 |
| BeneFIX | 93 |
| Rebinyn | 112 |
| Idelvion* | 159 |
- Per the manufacturer's recommendations, a one stage clotting assay is recommended for measurement of Idelvion and results may vary based on the APTT reagent in use.
In-Use Stability and Shelf-life
In-use stability and shelf-life studies were performed in accordance with CLSI EP25-A, using three reagent lots of HemosIL Chromogenic Factor IX on a representative ACL TOP Family model. The studies support the following labeled claims on the ACL TOP Family and ACL TOP Family 50 Series:
- . Reagent A: Stability after reconstitution: 72 hours at 2-8℃ in the closed original vial or 4 months at