(88 days)
Cryov Check™ Factor 2 Deficient Plasma is recommended for use as a substrate in clot-based factor II assays using the one stage prothrombin time (PT) assay.
Cryov Check™ Factor 2 Deficient Plasma is human plasma deficient in the Factor II coagulation protein while having all other coagulation factors within normal limits. It is recommended for use as a substrate in clot-based Factor II assays using the one stage prothrombin time (PT).
CryovCheck™ Factor 2 Deficient Plasma is frozen human plasma deficient in the Factor II coagulation protein. It is prepared from citrated pooled normal human plasma which has been depleted of Factor II by immunoadsorption. Activity levels of Factor II are assayed at less than 1% normal levels while all other coagulation factors are within normal levels.
Here's a summary of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Factor II activity level | Less than 1% normal levels |
| All other coagulation factors | Within normal limits |
| 24-hour open vial stability (PT and APTT assays) | No anomalous results detected |
| 24-hour open vial stability (Factor II recovery, Mean (% recovery), 2 SD, CV%) | Mean Factor II recovery: 83.07% (Reference Value = 85%). Max: 87%, Min: 80%. Acceptable values are: Mean (+/-) 5% of reference value (80.75% - 89.25%); and %C.V. < 5% (Actual CV = 2.25%). All within acceptable ranges. |
| Intra-lot reproducibility (Normal Sample, Factor II Deficient – Lot 1, CV%) | 1.4% |
| Intra-lot reproducibility (Normal Sample, Factor II Deficient – Lot 2, CV%) | 0.8% |
| Intra-lot reproducibility (Abnormal Sample, Factor II Deficient – Lot 1, CV%) | 2.0% |
| Intra-lot reproducibility (Abnormal Sample, Factor II Deficient – Lot 2, CV%) | 3.4% |
| Inter-lot reproducibility (Normal Sample, CV%) | 1.3% |
| Inter-lot reproducibility (Abnormal Sample, CV%) | 2.7% |
| Correlation with predicate device (R² value) | R² = 0.997 |
| Normal donor study (95% Confidence Interval for Factor II activity) | 92.7% - 133.5% (Based on a mean of 113.1% and SD of 10.195%). This establishes the normal reference range for the device. |
2. Sample Sizes Used for the Test Set and Data Provenance
- 24-Hour Open Vial Stability: 5 samples per time point (0, 8, 24 hours), totaling 15 unique measurements for the summary statistics.
- Intra-lot Reproducibility: 10 samples per lot for both normal and abnormal samples, for each of the two lots.
- Inter-lot Reproducibility: 20 samples per lot for both normal and abnormal samples.
- Correlation Study: 9 distinct sample types (normal, borderline, pathological, various factor deficiencies), with 2 results taken for each sample type for both the equivalent device and the predicate device, resulting in 18 measurements for each device.
- Normal Donor Study: 21 donors.
The data provenance is retrospective, as the studies were conducted to support the 510(k) submission for an already developed device. The country of origin for the device manufacturer is Canada (Nova Scotia). The origin of the plasma used for the device is human.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts to establish a "ground truth" in the way one might for diagnostic imaging or clinical decision support systems. This device is a lab reagent, and its performance is assessed against established laboratory methodologies and reference materials. The "ground truth" here is implied by the accuracy of the assays and the known characteristics of the samples (e.g., "known reference plasma," "samples with factor II levels in the normal, borderline, and pathological ranges," "healthy male and female donors"). The experts involved would likely be skilled laboratory professionals performing the assays and interpreting results against biochemical standards. Their specific qualifications are not detailed.
4. Adjudication Method for the Test Set
Not applicable. As a laboratory reagent, an adjudication method in the context of expert consensus or arbitration for results is not described. The results are quantitative measurements from lab instruments.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
Not applicable. This device is a laboratory reagent and not an AI-assisted diagnostic tool that would involve human readers or image interpretation. Therefore, an MRMC study is not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This device is a standalone reagent. Its performance is evaluated directly through its interaction with other laboratory reagents and samples in controlled assays (Prothrombin Time, Activated Partial Thromboplastin Time, Factor II assays). There is no "human-in-the-loop" performance in the sense of a diagnostic interpretation that needs human input for its direct output. The device itself performs its function as a substrate independently, with humans performing the assay.
7. The Type of Ground Truth Used
The ground truth is established through:
- Biochemical/Physiological Reference Standards: Known reference plasma for Factor II activity.
- Characterized Samples: Samples with known or defined levels of Factor II (normal, borderline, pathological) and other factor deficiencies.
- Clinically Defined Samples: Samples from healthy donors to establish a normal range.
- Comparison to Predicate Device: The predicate device serves as a benchmark for performance comparison.
8. The Sample Size for the Training Set
Not applicable. This is a laboratory reagent, not a machine learning model, so there is no "training set." The product is manufactured and then tested to ensure quality and performance.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this type of device.
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7 1999 JUN
510(k) Summary for Cryov Check™ Factor 2 Deficient Plasma
Submitter's Address and Contact Information 1.
- a) Address Precision BioLogic Incorporated 900 Windmill Rd. Unit # 100 Dartmouth, Nova Scotia Canada B3B 1P7
b) Contact …
Mr. Sandy Morrison Manager, Technical Operations Phone: (902) 468-6422 (902) 468-6421 Fax: E-mail: smorrison@precisionbiologic.com
Date Prepared: February 16, 1999 c)
2. Device Name
- Cryov Check™ Factor 2 Deficient Plasma Proprietary (trade) name: a)
Factor II (2) Deficient Plasma (human) b) Common name:
Classification name: Coagulation Factor Deficient Plasma c)
- Classification information : Regulatory Class II d) Hematology Panel Product Code - 81 GJT
3. Device Description:
CryovCheck™ Factor 2 Deficient Plasma is frozen human plasma deficient in the Factor II coagulation protein. It is prepared from citrated pooled normal human plasma which has been depleted of Factor II by immunoadsorption. Activity levels of Factor II are assayed at less than 1% normal levels while all other coagulation factors are within normal levels.
V - 1
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Intended Use 4.
CryovCheck™ Factor 2 Deficient Plasma is recommended for use as a substrate in clot-based factor II assays using the one stage prothrombin time (PT) assay.
Substantially Equivalent Device న.
- 510(k) number: K900906 a)
- Factor II Deficient Plasma b) Trade Name:
- Manufacturer: Sigma c)
- Substantial Equivalence Comparison d)
Cryo / Check™ Factor 2 Deficient Plasma is similar to the predicate device in that they both have the same "indications for use", target population, and are both made from human plasma.
Cryo Check™ Factor 2 Deficient Plasma differs from the predicate device in that it is a frozen liquid preparation and not a lyophillized product. Additionally, Cryo Check™ Factor 2 Deficient Plasma is prepared from normal human plasma from which Factor II has been immunoadsorbed, while the predicate device is derived from human donors with a congenital Factor II deficiency.
To our knowledge, these differences do not affect the intended use or performance of the device.
- Non-Clinical Performance Data 24 Hour Open Vial Stability : 6.
- a) Testing Performed:
- Prothrombin Time (PT) assays and Activated Partial Thromboplastin i) Time (APTT) assays were performed on vials of Cryo Check™ Factor 2 Deficient Plasma at 0 hours, 8 Hours and 24 hours. No anomalous results were detected.
- ii) Factor II assays were performed on a known reference plasma using vials of Cryor Check™ Factor 2 Deficient Plasma as a substrate. Recovered Factor II values were measured at 0 hours, 8 Hours and 24 hours. (see table S1 for results)
- iii) Inter- and intra-lot reproducibility testing on normal and abnormal samples using two lot numbers of factor II deficient plasma. (see tables S2 for results)
- a) Testing Performed:
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- Correlation study with a predicate device using samples with factor II iv) levels in the normal, borderline, and pathological ranges. (see table S3 for results)
- Normal donor study using healthy male and female donors. (see table S4 v) for results)
- Conclusions: b)
- Factor II level for Cryo Check™ Factor 2 Deficient Plasma is less i) than 1%
- ii) All other coagulation factors are within normal limits
- iii) No anomalous results for PT and APTT assays were observed during a 24 hour open vial stability study
- Factor II values were within expected levels following factor II iv) assays over a 24 hour open vial stability study
- Inter and intra-lot CV's of < 4 % were recovered v)
- Correlation studies showed an R2 value of 0.997 with the predicate vi) device
- Normal donor studies showed a normal range based on 95% vii) confidence interval of 92.7% - 133.5%
| Table S1 | ||||
|---|---|---|---|---|
| Open Vial Stability of Cryo✓Check™ | ||||
| Factor 2 Deficient Plasma | ||||
| Summary Statistics (% Recovery) | ||||
| 0 Hours | 8 Hours | 24 Hours | 24Hr.Average | |
| MEAN | 83.2 % | 82.8 % | 83.2 % | 83.07 % |
| MAXIMUM | 85 % | 85 % | 87 % | 87 % |
| MINIMUM | 82 % | 82 % | 80 % | 80 % |
| S.D. | 1.64 | 1.30 | 2.77 | 1.87 |
| 2 S.D. | 3.29 | 2.61 | 5.55 | 3.74 |
| SAMPLE SIZE | 5 | 5 | 5 | 15 |
| C.V.% | 1.97 | 1.57 | 3.34 | 2.25 |
Note: Reference Value = 85% Factor II
Acceptable values are: Mean (+/-) 5% of reference value; and %C.V. < 5%
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Table S2
Intra Lot Reproducibility of Cryo✓Check™ Factor 2 Deficient Plasma
Normal Sample
Factor II Deficient – Lot 1
| Number | 10 |
|---|---|
| Mean (sec) | 102.2 |
| Standard Deviation | 1.398 |
| C.V. (%) | 1.4 |
Normal Sample
| Number | 10 |
|---|---|
| Mean (sec) | 103.5 |
| Standard Deviation | 0.850 |
| C.V. (%) | 0.8 |
Abnormal Sample
| Factor II Deficient -- Lot 1 | |
|---|---|
| Number | 10 |
| Mean (sec) | 36.9 |
| Standard Deviation | 0.738 |
| C.V. (%) | 2.0 |
Abnormal Sample
. . . . . . . .
... .. ..
... ... ......................................................................................................................................................................
... ... ..... .
... -.....
Factor II Deficient -Lot 2
| Number | 10 |
|---|---|
| Mean (sec) | 36.7 |
| Standard Deviation | 1.252 |
| C.V. (%) | 3.4 |
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Table S2
Inter Lot Reproducibility of Cryo✓Check™ Factor 2 Deficient Plasma
Normal Sample
| Number | 20 |
|---|---|
| Mean (sec) | 102.9 |
| Standard Deviation | 1.309 |
| C.V. (%) | 1.3 |
Abnormal Sample
| Number | 20 |
|---|---|
| Mean (sec) | 36.8 |
| Standard Deviation | 1.005 |
| C.V. (%) | 2.7 |
Table S3
Correlation Study of Cryo✓Check™ Factor 2 Deficient Plasma
| Sample Type | % ActivityEquivalent DeviceFactor II Def. | % ActivityPredicate DeviceFactor II Def. | ||||
|---|---|---|---|---|---|---|
| Result 1 | Result 2 | Mean | Result 1 | Result 2 | Mean | |
| Normal Range | 106 | 106 | 106 | 98 | 98 | 98 |
| Normal Range | 103 | 105 | 104 | 98 | 98 | 98 |
| Borderline Range | 36 | 37 | 37 | 38 | 37 | 38 |
| Borderline Range | 40 | 38 | 39 | 38 | 32 | 35 |
| Pathological Range | 8 | 8 | 8 | 8 | 9 | 9 |
| Factor VIII Deficient | 84 | 85 | 85 | 87 | 85 | 86 |
| Factor X Deficient | 92 | 92 | 92 | 85 | 83 | 84 |
| Factor XII Deficient | 108 | 111 | 110 | 103 | 106 | 105 |
| Factor II Deficient | 0 | 0 | 0 | 1 | 0 | 1 |
| Factor II Deficient | 0 | 0 | 0 | 1 | 1 | 1 |
Regression analysis gave an R2 = 0.997
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Table S4
Normal Donor Study with Cryo✓Check™ Factor 2 Deficient Plasma
| Number | 21 |
|---|---|
| Mean | 113.1 |
| Standard Deviation | 10.195 |
| Reference Range(95% Conf. Limits) | 92.7-133.5 |
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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with three human profiles incorporated into its design. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.
7 1999 JUN
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Sandy Morrison Manager, Technical Operations Precision BioLogic Inc. 900 Windmill Road, Suite 100 Dartmouth, Nova Scotia Canada B3B 1P7
Re: K990814
Trade Name: Cryov Check™ Factor 2 Deficient Plasma Regulatory Class: II Product Code: GJT Dated: May 6, 1999 Received: May 13, 1999
Dear Mr. Morrison:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 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 Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D, M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number: K 990814
Device Name: Cryo Check™ Factor 2 Deficient Plasma
Indications for Use
Deficiencies in coagulation factors may have congenital or acquired etiologies and can compromise in vivo hemostasis. Factor II (also known as prothrombin) is a serine protease located in the "common coagulation pathway" and is essential to normal hemostasis. Factor II deficiency is commonly diagnosed in vitro through the use of a modified prothrombin time (PT) assay.
Cryov Check™ Factor 2 Deficient Plasma is human plasma deficient in the Factor II coagulation protein while having all other coagulation factors within normal limits. It is recommended for use as a substrate in clot-based Factor II assays using the one stage prothrombin time (PT).
Peter E. Mafem
Prescription
§ 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).