HemosIL FII & FV DNA Control is intended for in vitro diagnostic use as a heterozygous quality control to monitor analytical performance of the extraction, amplification and detection steps of the Xpert™ HemosIL FII & FV genotyping assay on the GeneXpert® Dx System used in the detection of both the Factor II 20210G>A and Factor V 1691G>A (Leiden) mutations.

Device Description

HemosIL FII & FV DNA Control is synthetic Factor V DNA suspended in a non-infectious blood-like matrix. Each vial includes normal and mutated Factor II and Factor V DNA sequences and is configured as a heterozygous control for both Factor II 20210G>A and Factor V 1691G>A (Leiden) mutations.

The quality control material is validated for use with Xpert™ HemosIL® FII & FV genotyping assay on the GeneXpert® Dx System and is processed exactly as whole blood samples during the extraction, amplification and detection steps.

AI/ML Overview

The HemosIL® FII & FV DNA Control is a quality control material intended to monitor the analytical performance of the Xpert™ HemosIL FII & FV genotyping assay on the GeneXpert® Dx System.

Here's an analysis of its acceptance criteria and the study that proves it meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this quality control device appear to be the consistent and correct genotyping of the FII and FV mutations. The performance data below supports this. While explicit percentage cutoffs for "acceptance" are not stated, 100% correct genotyping across all tests strongly indicates that the device met these criteria.

Acceptance Criteria	Reported Device Performance (Summary)
Correct Genotyping of FII Heterozygous/FV Heterozygous	Across 8 sites and 201 tests, 100% correct genotyping (201 correct, 0 incorrect, 1 indeterminate due to operator error).

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set: A total of 201 tests were performed with the HemosIL FII & FV DNA Control.
Data Provenance: The testing was conducted both internally at the control manufacturer and externally at multiple sites.
- External Sites: Seven external sites participated, including two clinical laboratory sites in Europe, one site at the instrument/assay manufacturer (Cepheid), one site at Instrumentation Laboratory Co., and three clinical laboratory sites in the United States. This indicates a mix of clinical and manufacturing settings.
- Retrospective or Prospective: The study design described (testing manufactured lots, using a specific assay) suggests a prospective study, specifically designed to evaluate the performance of the control.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

This information is not provided in the summary. For a quality control material, the "ground truth" for the test set is inherent in the design and manufacturing of the control itself. The control is engineered to have specific normal and mutated Factor II and Factor V DNA sequences. The method used to validate the presence of these mutations in the control during its manufacturing is stated as "Bi-directional sequencing," which is a highly accurate method for determining DNA sequences.

4. Adjudication Method for the Test Set

This information is not explicitly stated. However, for a quality control material designed to yield a specific and known genotype, the assessment of "correct genotype" is typically a direct comparison to the expected result. Discrepancies would likely be investigated, as was the case for the single indeterminate result attributed to "operator error."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is typically used for diagnostic or screening devices where human readers interpret results, and the AI's effect on human performance is being evaluated. The HemosIL FII & FV DNA Control is a quality control material, not a direct diagnostic device that requires human interpretation in the same way.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was done

This study primarily evaluates the standalone performance of the quality control material when processed by the Xpert HemosIL FII & FV Assay on the GeneXpert Dx System. The "algorithm" here is the assay system itself identifying the genotype of the control. The studies demonstrate the assay's consistent ability to correctly identify the known genotype of the control, thus, evaluating the performance of the control in conjunction with the automated assay. There is no external "human-in-the-loop" interpretation step being evaluated here for the control's performance.

7. The Type of Ground Truth Used

The ground truth for the HemosIL FII & FV DNA Control is based on the engineered composition of the control material itself, which contains specific, known normal and mutated Factor II and Factor V DNA sequences. This composition was validated using bi-directional sequencing during the control's manufacturing.

8. The Sample Size for the Training Set

This information is not applicable/not provided. The HemosIL FII & FV DNA Control is a quality control material, not an AI/algorithm that requires a "training set" in the conventional machine learning sense. The Xpert HemosIL FII & FV genotyping assay, which uses this control, would have its own development and validation data, but that is separate from the control product itself.

9. How the Ground Truth for the Training Set Was Established

This information is not applicable/not provided as the device is a quality control material and not an AI/algorithm requiring a training set.

Summary

{0}------------------------------------------------

KC093737

510(k) Summary

MAY - 4 2010

Applicant Contact Information:

Applicant:	Instrumentation Laboratory Co.
Address:	180 Hartwell RoadBedford, MA 01730
Contact Person:	Carol Marble, Regulatory Affairs Director
Phone Number:	781-861-4467
Fax Number:	781-861-4207
Preparation Date:	December 3, 2009

Device Trade Name:

HemosIL® FII & FV DNA Control

Device Regulatory Information:

Regulation No.:	21 CFR 866.5910
Regulation Name:	Quality Control, Genetics, DNA
Regulatory Class:	Class II
Product Code:	NZB
Panel:	Immunology (82)

Predicate Device:

K083171	INTROLTM CF Panel I Control
---------	-----------------------------

Device Description:

Device Intended Use:

HemosIL FII & FV DNA Control is intended for the quality control of the Xpert HemosIL FII & FV genotyping assay on the GeneXpert Dx System.

{1}------------------------------------------------

510(k) Summary (Cont.)

Substantial Equivalence:

Differences andSimilarities	Predicate Device (K083171):INTROL CF Panel I Control	New Device:HemosIL FII & FV DNA Control
Physical Composition	Synthetic (recombinant) DNAwith non-human carrier DNA,preservatives, dye and stabilizers	Same
Physical Format	Ready-to-use liquid	Same
Gene Segment	CFTR (38 mutations; 4 variants)	Factor II (20210G>A)Factor V (1691G>A Leidenmutation)
Assay StepsMonitored	Extraction, Amplification andDetection	Same
RecommendedStorage	2-8°C	Same
Method to ValidatePresence Mutations	Bi-directional sequencing	Same
Directions for Use	Handle control in the samemanner as the patient sample	Same

Summary Performance Data:

All Test Results

For the stability and performance studies, three lots of HemosIL FII & FV DNA Control were manufactured and tested using the Xpert HemosIL FII & FV Assay on the GeneXpert Dx system. Testing was conducted both internally at the control manufacturer and externally at multiple sites as detailed in the table on the next page.

In all cases, genotypes were called correctly.

Numberof Sites	Number ofTests	Correct Genotype:FII Heterozygous/FV Heterozygous)	Incorrect Result	IndeterminateResult	PercentCorrect
8	201	201	0	1*	100%

Operator error; one test was repeated

{2}------------------------------------------------

510(k) Summary (Cont.)

Summary Performance Data (Cont.):

External Site Testing

HemosIL FII & FV DNA Control was tested at seven external sites using the Xpert HemosIL . FII & FV Assay on the GeneXpert Dx System:
- Site Nos. 1 and 2: Two clinical laboratory sites in Europe tested one lot of control daily in . duplicate for six days (n=12 per site) with a different operator at each site.
- Site No. 3: One site at the instrument/assay manufacturer (Cepheid) tested three lots of . control in duplicate (n=6) with a single operator.
- Site No. 4: One site at Instrumentation Laboratory Co. tested one lot of control in . singlicate for thirty days (n=30) with a single operator and a second lot of control in singlicate for 6 days (n=6).
- Site Nos. 5-7: Three clinical laboratory sites in the United States tested one lot of control . in singlicate for ten days (n= 10 per site) with a different operator at each site.

Site	Numberof Tests	Correct Genotype:FII Heterozygous/FV Heterozygous)	IndeterminateResult	PercentCorrect
Site No. 1	12	12	1*	100%
Site No. 2	12	12	0	100%
Site No. 3	6	6	0	100%
Site No. 4	36	36	0	100%
Site No. 5	10	10	0	100%
Site No. 6	10	10	0	100%
Site No. 7	10	10	0	100%

In all cases, genotypes were called correctly.

Operator error; one test was repeated

{3}------------------------------------------------

0(k) Summary (Con

Summary Performance Data (Cor

eproducibili

ough HemosIL FII & FV DNA Control is a qualitative control (genotype present or absent), the GeneXpert Dr. provides mudi NOTE
-Run Testing: With-in run reproducibility was demonstrated with one operator by tesing two lots of HemolL FII & FV DN
cates of five using a single lot of Xpert HemosiL Factor

genotypes were called correctly. Within-run reproducibility was excellent, with Ct SD

Control Lot #	No. ofTests	AssayLot #	Correct Results(FII Heterozygous/FV Heterozygous)	FII G NormalMean Ct	FII G NormalSD	FII A MutantMean Ct	FII A MutantSD	FV G NormalMean Ct	FV G NormalSD	FV A MutantMean Ct	FV A MutantSD
A21FEB08	5	201	5	27.3	0.4	26.4	0.5	27.3	0.6	27.4	0.7
B26FEB08	5	201	5	27.0	0.5	25.9	0.4	26.8	0.4	27.0	0.3
A21FEB08	5	301	5	25.9	0.3	25.4	0.3	26.1	0.4	26.2	0.4

Lot Testing: Lot-lot reproducibility was demonstrated by testing three lots of Hemos!L FII & FV DNA Control using a sin
emosIL Factor II & Factor V Assay on the GeneXpert Dx
ases, genotypes were called correctly. No significant differences were seen between control lots, with Ct SD < 1.0 and %C

Control Lot #	No. of Tests	Correct Results(FII Heterozygous/FV Heterozygous)	FII G Normal			FII A Mutant			FV G Normal			FV A Mutant
			MeanCt	SD	%CV	MeanCt	SD	%CV	MeanCt	SD	%CV	MeanCt	SD	%CV
A21FEB08	22	22	26.4	0.7	2.5%	25.9	0.6	2.5%	26.8	0.8	2.8%	27.0	0.8	2.9%
B26FEB08	17	17	26.4	0.6	2.4%	25.9	0.6	2.4%	26.7	0.7	2.5%	27.0	0.7	2.7%
A28FEB08	15	15	26.6	0.7	2.5%	26.0	0.7	2.7%	26.9	0.8	2.8%	27.0	0.8	3.0%
All	54	54	26.4	0.7	2.5%	25.9	0.6	2.5%	26.8	0.7	2.7%	27.0	0.8	2.8%

Section

mosIL FII & FV DNA Control

Page 4 of

{4}------------------------------------------------

0(k) Summary (Cont

mmary Performance Data (Con

roducibility (Cont

atability Testings Repeats) into Ins was demonstrated by tosting II IFF & FV DNA Control usin
ent lols of Xpert Hemostl Factor V Assy on he GeneXpert Dr multiple

Lot #	No. ofTests	Correct Results(FII Heterozygous/FV Heterozygous)	FII G Normal			FII A Mutant			FV G Normal			FV A Mutant
			Mean Ct	SD	%CV	Mean Ct	SD	%CV	Mean Ct	SD	%CV	Mean Ct	SD	%CV
EB08	45	45	26.5	0.9	3.3%	25.9	0.8	3.0%	26.8	0.9	3.3%	27.0	0.9	3.2%
EB08	122	122	26.1	0.7	2.7%	25.3	0.7	2.6%	26.2	0.8	2.9%	26.2	0.8	2.9%
EB08	34	34	26.8	0.6	2.2%	26.0	0.6	2.3%	26.9	0.7	2.4%	26.9	0.7	2.6%
EB08	201	201	26.3	0.8	2.9%	25.6	0.7	2.8%	26.5	0.8	3.0%	26.6	0.8	3.1%

tor Testing (Single vs. Multiple): Control results of one compared to the contol results of seven other operator.
genotypes were called correctly. There was no significant

No. ofOperators	No. ofTests	Correct Results(FII Heterozygous/FV Heterozygous)	FII G Normal			FII A Mutant			FV G Normal			FV A Mutant
			Mean Ct	SD	%CV	Mean Ct	SD	%CV	Mean Ct	SD	%CV	Mean Ct	SD	%CV
1 Operator	51	51	26.6	0.7	2.6%	25.9	0.6	2.4%	26.9	0.7	2.6%	27.0	0.8	2.8%
7 OtherOperators	55	55	26.5	0.8	2.8%	25.7	0.8	3.1%	26.7	0.9	3.3%	26.8	0.9	3.3%
All Operators	106	106	26.6	0.7	2.7%	25.8	0.7	2.8%	26.8	0.8	3.0%	26.9	0.8	3.1%

{5}------------------------------------------------

Image /page/5/Picture/0 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" around the perimeter. Inside the circle is a stylized symbol that resembles three abstract shapes stacked on top of each other, creating a sense of movement or flow.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Instrumentation Laboratory Co. c/o Ms. Carol Marble Regulatory Affairs Director 180 Hartwell Road Bedford. MA 01730

MAY 0 4 2010

Re: K093737

Trade/Device Name: HemosIL FII & FV DNA Control Regulation Number: 21 CFR $866.5910 Regulation Name: Quality control material for cystic fibrosis nucleic acid assays Regulatory Class: Class II Product Code: NZB Dated: March 31, 2010 Received: April 1, 2010

Dear Ms. 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 (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

{6}------------------------------------------------

Page 2 - Carol Marble

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 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,

108

Reena Philip

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):

K 093737

HemosIL® FII & FV DNA Control Device Name:

Indications for Use:

V Prescription Use _ (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 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)

Reena Philip
Division Sign-Off

Office of In Vitro Diagnos Device Evaluation and S

510K K093737

Regulation Number and Section

§ 866.5910 Quality control material for cystic fibrosis nucleic acid assays.

(a)
Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for cystic fibrosis nucleic acid assays is a device intended to help monitor reliability of a test system by detecting analytical deviations such as those that may arise from reagent or instrument variation in genetic testing. This type of device includes recombinant, synthetic, and cell line-based DNA controls.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays.” See § 866.1(e) for the availability of this guidance document.