(163 days)
Not Found
No
The summary describes a traditional in vitro diagnostic assay based on chemical reactions and clotting time measurements. There is no mention of AI, ML, image processing, or any data analysis techniques that would suggest the use of such technologies. The performance studies focus on standard analytical metrics like precision, linearity, and method comparison.
No
The device is described as being for "in vitro diagnostic quantitative determination of Factor VIII activity," indicating it is used for diagnosis and not for direct therapeutic treatment.
Yes
This device is clearly stated as "intended for the in vitro diagnostic quantitative determination of Factor VIII activity in citrated plasma". The entire description details its use in diagnostic assays to measure Factor VIII activity, which is a diagnostic purpose.
No
The device is an in vitro diagnostic reagent (human plasma) used in conjunction with specific hardware (ACL TOP Family analyzers) to perform a quantitative determination. It is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states the device is "intended for the in vitro diagnostic quantitative determination of Factor VIII activity in citrated plasma". The phrase "in vitro diagnostic" is a direct indicator.
- Device Description: The description details how the assay works by measuring clotting time in the presence of various reagents, which is a typical in vitro process.
- Intended User/Care Setting: It states "For in-vitro diagnostic use only." and "For prescription use," further confirming its IVD nature.
The entire document describes a product used to test biological samples (plasma) outside of the body to diagnose or monitor a medical condition (Factor VIII deficiency), which is the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
HemosIL Factor VIII deficient plasma is human plasma, depleted of Factor VIII, which is intended for the in vitro diagnostic quantitative determination of Factor VIII activity in citrated plasma, based on the activated partial thromboplastin time (APTT) assay, on the ACL TOP® Family analyzers. HemosIL Factor VIII deficient plasma is indicated for use on patients who are suspected of congenital or acquired deficiency based on the activated partial thromboplastin time (APTT) assay results.
Product codes (comma separated list FDA assigned to the subject device)
GJT
Device Description
The assay determines the functional activity of Factor VIII by measuring the degree of prolongation of activated partial thromboplastin time in the presence of a contact activator, thromboplastin, phospholipids and calcium ions. Factor VIII activity is correlated with the prolongation of the clotting time of the Factor VIII deficient plasma to which diluted patient sample has been added.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Precision/Reproducibility: Precision was assessed utilizing 3 lots of plasma on representative members of the ACL TOP Family (ACL TOP base, ACL TOP 700 and ACL TOP 500 CTS). Precision was evaluated in accordance with CLSI EP05-A2, for 20 days, with 2 runs per day and 2 replicates per run for each sample level (n=80/ instrument/ lot), using a specific lot of APTT reagent (APTT-SP and SynthASil) and both normal and abnormal samples.
- Linearity: The Factor VIII activities of a high sample (level 1) and an intermediate sample (level 2) were determined from the respective means of 8 replicates, using the Factor VIII deficient plasma predicate. These two samples, together with HemosIL® Factor VIII deficient plasma (PN 00020012800), were used to setup samples with Factor VIII activities ranging from 150%. All Factor VIII samples were run in 4 replicates, using Factor VIII deficient plasma (PN0020012800) as a substrate, on the ACL TOP with the two reagent lots. The results demonstrated that the Factor VIII assay is linear, with the HemosIL® Factor VIII deficient plasma (PN0020012800) as a substrate, up to 150% activity on the ACL TOP Family.
- Interference Study: Factor VIII results on the ACL TOP Family are not affected by hemoglobin up to 530 mg/dL, triglycerides up to 2000 mg/dL, bilirubin up to 150 mg/dL, and Factor VIII inhibitors up to 0.1BU. Results are not affected by the presence of Lupus anticoagulant antibodies.
- Method comparison with predicate device (In-House Study): An in-house method comparison study was performed to compare the performance of the new Factor VIII deficient plasma with its predicate. The Deming regression analysis for the ACL TOP shows that the slope and correlation coefficient (r) are 1.064 and 0.9885 respectively, with the SynthASil reagent, and 0.893 and 0.9884 respectively, with the APTT-SP reagent. The Deming regression analysis for the ACL TOP 500 CTS shows that the slope and correlation coefficient (r) are 1.112 and 0.9923 respectively, with the SynthASil reagent, and 0.913 and 0.9926 respectively, with the APTT-SP reagent.
- Method comparison with predicate device (Field Site Study): A field site study was conducted at 2 US sites and one OUS site, comparing the new Factor VIII depleted plasma with its predicate. Both normal and abnormal samples were tested on an ACL TOP analyzer. The results showed a correlation (R) >0.9829 and a slope of 0.871-1.138 indicating that the performance of the two tests is statistically similar.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Precision:
- ACL TOP 500 CTS with SynthASil: Normal Control (Mean FVIII 80.3%, Within Run CV% 3.8, Total CV% 3.9), STC Level 2 (Mean FVIII 23.8%, Within Run CV% 4.0, Total CV% 5.5), Low Control I (Mean FVIII 12.1%, Within Run CV% 3.7, Total CV% 5.2), Low Control II (Mean FVIII 6.8%, Within Run CV% 4.1, Total CV% 6.4).
- Linearity:
- ACL TOP with SynthASil: Slope 0.971, Intercept 0.528, R2 0.995
- ACL TOP with APTT SP: Slope 1.045, Intercept 2.261, R2 0.997
- ACL TOP 500 CTS with SynthASil: Slope 1.040, Intercept -0.526, R2 0.998
- ACL TOP 500 CTS with APTT SP: Slope 0.964, Intercept -1.621, R2 0.996
- In-House Method Comparison:
- SynthASil, ACL TOP 500 CTS (N=90): Slope 1.112, Intercept -3.57, R 0.9923
- APTT SP, ACL TOP 500 CTS (N=90): Slope 0.913, Intercept 0.56, R 0.9926
- Field Site Study Method Comparison:
- OUS (n=109): Slope 1.074, Intercept -4.83, Correlation coefficient (R) 0.9829
- US #1 (n=125): Slope 0.871, Intercept -0.25, Correlation coefficient (R) 0.9935
- US #2 (n=102): Slope 1.138, Intercept -9.31, Correlation coefficient (R) 0.9842
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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
510K SUMMARY
ASSAY ONLY TEMPLATE
KI10237
| A. | 510(k) Number | TBD |
|---|---|---|
| B. | Purpose for Submission | Reagent formulation change |
| C. | Measurand | Factor VIII Activity |
| D. | Type of Test | Factor VIII Activity Test, based on activated |
| partial thromboplastin time (APTT) | ||
| E. | Applicant | Instrumentation Laboratory Co. |
| F. | Proprietary & Established Names | HemosIL Factor VIII deficient plasma |
| G. | Regulatory Information | |
| 1. | Regulation section: | 21CFR §864.7290 |
| 2. | Classification: | Class II |
| 3. | Product code: | GJT |
| 4. | Device classification name: | Plasma, Coagulation Factor Deficient |
H. Intended Use
1. Intended use(s):
HemosIL Factor VIII deficient plasma is human plasma, depleted of Factor VIII, which is intended for the in vitro diagnostic quantitative determination of Factor VIII activity in citrated plasma, based on the activated partial thromboplastin time (APTT) assay, on the ACL TOP® Family analyzers. HemosIL Factor VIII deficient plasma is indicated for use on patients who are suspected of congenital or acquired deficiency based on the activated partial thromboplastin time (APTT) assay results.
-
Indication(s) for use: 2.
Same as intended use. -
- Special conditions for use statement(s): For in-vitro diagnostic use only. For prescription use.
-
Special instrument requirements: 4. ACL TOP® Family analyzers
I. Device Description
The assay determines the functional activity of Factor VIII by measuring the degree of prolongation of activated partial thromboplastin time in the presence of a contact activator, thromboplastin, phospholipids and calcium ions. Factor VIII activity is correlated with the prolongation of the clotting time of the Factor VIII deficient plasma to which diluted patient sample has been added.
J. Substantial Equivalence Information:
- Predicate device name(s): 1. HemosIL Factor VIII deficient plasma (same name)
-
- Predicate 510(k) number(s):
·
1
3. Comparison with predicate: Similarities
The applicant, HemosIL Factor VIII deficient plasma (PN 00020012800) is substantially equivalent to its predicate, the HemosIL Factor VIII deficient plasma (K034007).
Table of similarities:
| Item | Predicate Device | Applicant |
|---|---|---|
| K# | K034007 | TBD |
| Device Name | HemosIL Factor VIII deficient plasma | Same |
| Manufacturer | Instrumentation Laboratory Co. (self) | Same |
| Indications for | ||
| Use | HemosIL Factor VIII deficient plasma is human plasma | |
| depleted of Factor VIII and intended for the in vitro | ||
| diagnostic quantitative determination of Factor VIII | ||
| activity in citrated plasma, based on the activated | ||
| partial thromboplastin time (APTT) assay, on the ACL | ||
| TOP® Family analyzers. | Same | |
| Sample Type | Citrated plasma | Same |
| Test Principle | Functional clotting assay | Same |
| Methodology | Abnormalities of the intrinsic pathway factors are | |
| determined by performing a modified activated | ||
| partial thromboplastin time (APTT) test. Patient | ||
| plasma is diluted and added to plasma that is | ||
| deficient in Factor VIII. Correction of the clotting time | ||
| of the deficient plasma is proportional to the | ||
| concentration (% activity) of the Factor VIII in the | ||
| patient plasma, interpolated from a calibration curve. | Same | |
| Calibration | HemosIL Calibration plasma values are assigned for | |
| Factor VIII Activity and used to calibrate the standard | ||
| curve. | Same | |
| Kit Composition | Lyophilized human plasma deficient in Factor VIII. | Same |
Differences
The difference between the 2 products; the applicant HemosIL Factor VIII deficient plasma and its predicate, is that the applicant contains normal levels of von Willebrand factor, whereas the predicate is deficient not only in Factor VIII but also in von Willebrand Factor. The test results demonstrate that this change does not adversely affect the product's performance.
K. Standard/Guidance Document Referenced (if applicable):
No performance standard or FDA guidance has been established for FVIII deficient plasma.
L. Test Principle
Correction of the clotting time of the deficient plasma is proportional to the concentration (% activity) of the factor VIII in the patient plasma, interpolated from a calibration curve.
2
M. Performance Characteristics
1. Analytical performance:
Precision/Reproducibility a.
Precision was assessed utilizing 3 lots of plasma on representative members of the ACL TOP Family (ACL TOP base, ACL TOP 700 and ACL TOP 500 CTS). Precision was evaluated in accordance with CLSI EP05-A2, for 20 days, with 2 runs per day and 2 replicates per run for each sample level (n=80/ instrument/ lot), using a specific lot of APTT reagent (APTT-SP and SynthASil) and both normal and abnormal samples. Test data from a representative instrument, APTT reagent and plasma lot is included below:
| Instrument | Control Level | N | Mean
FVIII (%) | Within Run
CV% | Total
CV% |
|-------------------------|----------------|----|-------------------|-------------------|--------------|
| Controls with SynthASil | | | | | |
| ACL TOP 500
CTS | Normal Control | 80 | 80.3 | 3.8 | 3.9 |
| ACL TOP 500
CTS | STC Level 2 | 80 | 23.8 | 4.0 | 5.5 |
| ACL TOP 500
CTS | Low Control I | 80 | 12.1 | 3.7 | 5.2 |
| ACL TOP 500
CTS | Low Control II | 80 | 6.8 | 4.1 | 6.4 |
- Linearity/assay reportable range: b.
Linearity:
The Factor VIII activities of a high sample (level 1) and an intermediate sample (level 2) were determined from the respective means of 8 replicates, using the Factor VIII deficient plasma predicate. These two samples, together with HemosIL® Factor VIII deficient plasma (PN 00020012800), were used to setup samples with Factor VIII activities ranging from 150%.
All Factor VIII samples were run in 4 replicates, using Factor VIII deficient plasma (PN0020012800) as a substrate, on the ACL TOP with the two reagent lots, and the average activities for all the samples were plotted against their assigned values. The results demonstrated that the Factor VIII assay is linear, with the HemosIL® Factor VIII deficient plasma (PN0020012800) as a substrate, up to 150% activity on the ACL TOP Family.
| Instrument | FVIIIDP | Reagent | Slope | Intercept | R2 |
|---|---|---|---|---|---|
| ACL TOP | Lot 1 | SynthASil | 0.971 | 0.528 | 0.995 |
| ACL TOP | APTT SP | 1.045 | 2.261 | 0.997 | |
| ACL TOP 500 CTS | Lot 2 | SynthASil | 1.040 | -0.526 | 0.998 |
| ACL TOP 500 CTS | APTT SP | 0.964 | -1.621 | 0.996 |
Analytical Range:
System
| ACL TOP Family with SynthASil | 0.1 - 150% |
|---|---|
| ACL TOP Family with APTT-SP | 0.5 - 150% |
C. Traceability, Stability, Expected values (controls, calibrators, or methods): Based on the accelerated stability study, which projects 3 years of shelf life, a shelf life of 12 months is claimed for the product when stored at 2-8°C. Real-time stability testing is ongoing, and will be used to update the shelf life as more data becomes available.
3
d. Interference Study:
Factor VIII results on the ACL TOP Family are not affected by hemoglobin up to 530 mg/dL, triglycerides up to 2000 mg/dL, bilirubin up to 150 mg/dL, and Factor VIII inhibitors up to 0.1BU. Results are not affected by the presence of Lupus anticoagulant antibodies.
- Detection limit: e. Not Applicable
- f Analytical specificity: Not Applicable
- Assay cut-off: g. Not Applicable
-
- Comparison studies:
- Method comparison with predicate device: a.
In-House Study
An in-house method comparison study was performed to compare the performance of the new Factor VIII deficient plasma with its predicate.
The Deming regression analysis for the ACL TOP shows that the slope and correlation coefficient (r) are 1.064 and 0.9885 respectively, with the SynthASil reagent, and 0.893 and 0.9884 respectively, with the APTT-SP reagent.
The Deming regression analysis for the ACL TOP 500 CTS shows that the slope and correlation coefficient (r) are 1.112 and 0.9923 respectively, with the SynthASil reagent, and 0.913 and 0.9926 respectively, with the APTT-SP reagent.
The above results satisfy the product specifications for method comparison and demonstrate comparable performance is achieved for the 2 reagents.
| Reagent | Instrument | N | Slope | Intercept | R |
|---|---|---|---|---|---|
| SynthASil | ACL TOP 500 CTS | 90 | 1.112 | -3.57 | 0.9923 |
| APTT SP | ACL TOP 500 CTS | 90 | 0.913 | 0.56 | 0.9926 |
Field Site Study
A field site study was conducted at 2 US sites and one OUS site, comparing the new Factor VIII depleted plasma with its predicate. Both normal and abnormal samples were tested on an ACL TOP analyzer. The results showed a correlation (R) >0.9829 and a slope of 0.871-1.138 indicating that the performance of the two tests is statistically similar.
| Within Lin. Range (1st Replicate) | OUS | US #1 | US #2 |
|---|---|---|---|
| Slope | 1.074 | 0.871 | 1.138 |
| Intercept | -4.83 | -0.25 | -9.31 |
| Correlation coefficient (R) | 0.9829 | 0.9935 | 0.9842 |
| n | 109 | 125 | 102 |
- b. Matrix comparison: NA
4
-
- Clinical studies:
- Clinical Sensitivity: NA a.
- b. Clinical Specificity: NA
- Other clinical supportive data (when a. and b. are not applicable): NA C.
-
- Clinical cut-off: NA
- Expected values/Reference range*: 5.
Factor VIII: 50-150% (0.50-1.50 IU)
*Due to the many variables which may affect clotting times (including the population age), each laboratory should establish its own normal range.
N. Proposed Labeling
The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.
0. Conclusion
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
P. Administrative Information
Applicant Contact Information
| Name of applicant: | Instrumentation Laboratory Co. |
|---|---|
| Mailing address: | 180 Hartwell Road |
| Bedford, MA 01730, USA | |
| Phone #: | 781-861-4350 |
| Fax #: | 781-861-4207 |
| E-mail address: | jemery@ilww.com |
| Contact: | Jacqueline Emery, BSEE |
| Regulatory Affairs Manager | |
| Date Prepared | July 5, 2011 |
5
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center-WO66-G609 Silver Spring, MD 20993-0002
Instrumentation Laboratory Co. c/o Ms. Jacqueline Emery Regulatory Affairs Manager 180 Hartwell Rd. Bedford, MA 01730
JUL 0 8 2011
Re: K110237
Trade/Device Name: HemosIL® Factor VIII Deficient Plasma Regulation Number: 21 CFR 864.7290 Regulation Name: Factor deficiency test Regulatory Class: Class II Product Code: GJT Dated: June 27, 2011 Received: June 29, 2011
Dear Ms. Emery,
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 class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter
Image /page/5/Picture/11 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name arranged in a circular fashion around the perimeter. In the center is a stylized graphic of an abstract symbol, consisting of three angled lines that resemble a person with outstretched arms.
6
Page 2 - Ms. Jacqueline Emery
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 proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Reena Philip
Tota
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
7
Indications for Use Statement
510(k) Number (if known): K110237
Device Name: HemosIL* Factor VIII deficient plasma
Indications for Use:
HemosIL Factor VIII deficient plasma is human plasma, depleted of Factor VIII, which is intended for the in vitro diagnostic quantitative determination of Factor VIII activity in citrated plasma, based on the activated partial thromboplastin time (APTT) assay, on the ACL TOP® Family analyzers. HemosIL Factor VIII deficient plasma is indicated for use on patients who are suspected of congenital or acquired deficiency based on the activated partial thromboplastin time (APTT) assay results.
Prescription Use (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 IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off
Office of In Vitro Diagnestic Device Evaluation and Safety
510(k) K110237