CRYO CHECK FACTOR 2 DEFICIENT PLASMA, MODELS FDPO2-10, FDP02-15

K990814 · Precision Biologic · GJT · Jun 7, 1999 · Hematology

Device Facts

• Record ID: K990814
• Device Name: CRYO CHECK FACTOR 2 DEFICIENT PLASMA, MODELS FDPO2-10, FDP02-15
• Applicant: Precision Biologic
• Product Code: GJT · Hematology
• Decision Date: Jun 7, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7290
• Device Class: Class 2

Intended Use

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.

Device Story

CryoCheck™ Factor 2 Deficient Plasma is a frozen human plasma product used as a substrate in clinical laboratory coagulation testing. It is prepared from citrated pooled normal human plasma depleted of Factor II via immunoadsorption. The device is used by laboratory technicians in clinical settings to perform one-stage prothrombin time (PT) assays. By providing a plasma base with <1% Factor II activity but normal levels of other coagulation factors, it allows for the quantification of Factor II in patient samples. The healthcare provider uses the resulting clotting time to determine Factor II levels, aiding in the diagnosis of coagulation disorders. The product offers a stable, standardized reagent for in vitro diagnostic assessment of hemostasis.

Clinical Evidence

Bench testing only. Studies included 24-hour open vial stability (PT/APTT assays), inter- and intra-lot reproducibility (CV <4%), and a correlation study against the predicate device (R2=0.997). A normal donor study (n=21) established a reference range of 92.7%–133.5%. Factor II activity was confirmed at <1%.

Technological Characteristics

Frozen human plasma; Factor II depleted via immunoadsorption. Factor II activity <1%; other coagulation factors within normal limits. Used as a reagent substrate for one-stage PT assays. No electronic components, software, or connectivity.

Indications for Use

Indicated for use as a substrate in one-stage prothrombin time (PT) assays to diagnose Factor II (prothrombin) deficiency in patients with suspected congenital or acquired coagulation factor deficiencies.

Predicate Devices

• Factor II Deficient Plasma (K900906)

Submission Summary (Full Text)

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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: [phone] [phone] Fax: E-mail: [e-mail]

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)

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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.<br>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 | % Activity<br>Equivalent Device<br>Factor II Def. | | | % Activity<br>Predicate Device<br>Factor 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<br>(95% Conf. Limits) | 92.7-133.5 |

-

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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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone], 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