K Number
K982062
Date Cleared
1999-01-13

(212 days)

Product Code
Regulation Number
864.7925
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

Cryo✓Check™ PNP Platelet Lysate is intended for use in the Platelet Neutralization Procedure (PNP) which is useful in detecting the presence of lupus anticoagulants (LA) in human plasma.

Device Description

Cryo Check™ PNP Platelet Lysate is prepared from human platelets obtained from normal healthy donors. The platelets are collected, washed, and resuspended in buffer and then frozen and thawed to yield a suspension of ruptured platelet membranes. This suspension is aliquoted into cryovials and stored frozen.

AI/ML Overview

The provided text describes the performance of the Cryo✓Check™ PNP Platelet Lysate, but it does not explicitly state acceptance criteria in a formal, quantifiable manner. Instead, the conclusions of the non-clinical performance data serve as the de facto acceptance criteria, implying that the device's performance should be "comparable," "consistent," and "stable" to that of the predicate device or under various conditions.

Here's an attempt to structure the information based on the provided text, interpreting the conclusions as the performance goals the device met:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred from Conclusions)Reported Device Performance
Criterion 1: Comparable Specificity to Predicate Device for Normal and Lupus Anticoagulant Positive Patient Samples (Implicit: Results for normal samples should show minimal correction, and results for lupus samples should show significant, comparable correction to the predicate device.)Compared to BIO/DATA Platelet Extract Reagent (Predicate Device): Normal Plasmas (n=5): Cryo✓Check™ PNP Platelet Lysate Mean Correction: 0.34 sec BIO/DATA Platelet Extract Mean Correction: -0.6 sec Correlation Coefficient: -0.510 (attributed to short correction times, not defect) Lupus Plasmas (n=10): Cryo✓Check™ PNP Platelet Lysate Mean Correction: 15.72 sec BIO/DATA Platelet Extract Mean Correction: 14.56 sec Correlation Coefficient: 0.987 Conclusion: "Cryo✓Check™ PNP Platelet Lysate demonstrated comparable specificity to the predicate device when tested against normal plasma and lupus anticoagulant positive patient plasmas when used in a platelet neutralization procedure."
Criterion 2: Consistent Vial-to-Vial Reactivity Over 8-hour Period (Implicit: Low variability in correction times for both normal and lupus plasmas across multiple vials over 8 hours.)8 Hour Open Vial Stability Study (MLA 900 C Analyzer): Normal Plasma (5 vials): Mean Correction (Time=0 hrs): 4.7 sec (SD 0.292) Mean Correction (Time=8 hrs): 3.84 sec (SD 0.358) Lupus Plasma (5 vials): Mean Correction (Time=0 hrs): 12.6 sec (SD 1.39) Mean Correction (Time=8 hrs): 11.0 sec (SD 0.358) Conclusion: "PNP procedures using Cryo✓Check™ PNP Platelet Lysate exhibited consistent vial to vial reactivity over an 8-hour period."
Criterion 3: Stability on Automated Coagulation Analyzer for Greater Than 8 Hours (Implicit: Neutralization results should remain consistent over at least 8 hours when run on an automated analyzer.)14 Hour On-Board Stability Study (MDA 180 Analyzer): Normal Control (CCN-10): Neutralization (0 min): -4.6 sec Neutralization (8 hr): -4.4 sec Neutralization (14 hr): -3.9 sec Mean Neutralization (0-14 hr): -4.14 sec (Std. Dev. 0.291) Lupus Positive Control (CCLP-10): Neutralization (0 min): 17.3 sec Neutralization (8 hr): 17.5 sec Neutralization (14 hr): 18.9 sec Mean Neutralization (0-14 hr): 17.2 sec (Std. Dev. 0.819) "in-house" positive control (HRF): Neutralization (0 min): 28.3 sec Neutralization (8 hr): 29.9 sec Neutralization (14 hr): 31.2 sec Mean Neutralization (0-14 hr): 29.8 sec (Std. Dev. 1.055) Conclusion: "Cryo✓Check™ PNP Platelet Lysate is stable for greater than 8 hours on an MDA 180 automated coagulation analyzer."
Criterion 4: Consistent Results Across Different Automated Coagulation Systems (Implicit: Neutralization results for normal patient samples should be comparable, even if absolute values differ, between different types of coagulation analyzers.)Comparison of Reactivity on 2 Automated Coagulation Analyzers (25 Normal Patient Samples): MDA 180 (Photo-Optical Clot Detection): Mean neutralization: -2.084 sec (Std dev 1.051) Stago ST4 (Mechanical Clot Detection): Mean neutralization: -3.664 sec (Std dev 1.151) Conclusion: "Cryo✓Check™ PNP Platelet Lysate yielded consistent results when used on 2 different automated coagulation systems." (Note: While mean values differ, the 'consistency' likely refers to the overall behavior and relative neutrality shown for normal samples on both systems.)

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

  • Test 1 (PNP Comparison to Predicate Device):

    • Sample Size: 5 normal plasma samples, 10 lupus plasma samples.
    • Data Provenance: Not explicitly stated, but clinical samples are implied ("normal and known lupus anticoagulant positive patient samples"). Likely in vitro/laboratory-based.
  • Test 2 (8 Hour Open Vial Stability):

    • Sample Size: 5 vials of Cryo✓Check™ PNP Platelet Lysate paired with one "Normal Plasma: Cryo✓Check™ Normal (CCN)" and one "Lupus Plasma: Cryo✓Check™ Lupus (CCLP)".
    • Data Provenance: In vitro, using commercially available control plasmas.
  • Test 3 (14 Hour On-Board Stability):

    • Sample Size: One lot of Cryo✓Check™ PNP Platelet Lysate tested with three control plasmas (Normal, Lupus Positive, HRF "in-house" positive control) over 14 time points.
    • Data Provenance: In vitro, using commercially available and "in-house" control plasmas.
  • Test 4 (Coagulation Analyzer Comparison):

    • Sample Size: 25 normal patient samples.
    • Data Provenance: Not explicitly stated, but "Normal Patient Samples" implies retrospective or prospective collection from patients. Likely from Canada, given the submitter's location.

3. Number of Experts Used to Establish Ground Truth and Qualifications

Not applicable. This device is a diagnostic reagent, and the 'ground truth' in these studies is established by the clinical classification of the plasma samples (normal vs. lupus anticoagulant positive) and measurement against established laboratory methods (APTT, Platelet Neutralization Procedure). No human expert interpretation of images or other subjective data is involved. The ground truth for plasma samples (e.g., "Lupus Plasma") would have been established through prior diagnostic testing, but the details of those classifications are not provided.

4. Adjudication Method for the Test Set

Not applicable. As this involves laboratory measurements with quantitative outputs (seconds for APTT and correction), not subjective interpretation, an adjudication method for a test set is not relevant in the way it would be for, e.g., image analysis by multiple readers.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically used for diagnostic imaging devices where human readers interpret cases with or without AI assistance. The described studies are non-clinical performance evaluations of a laboratory reagent.

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

Yes, the studies described are standalone performance evaluations in the context of a laboratory reagent. The device (Cryo✓Check™ PNP Platelet Lysate) is evaluated on its own performance characteristics (specificity, stability, consistency) in conjunction with standard laboratory instruments and established protocols (PNP, APTT). There is no "human-in-the-loop" AI component.

7. The Type of Ground Truth Used

The ground truth used for these studies is clinical classification of patient plasma samples (normal vs. known lupus anticoagulant positive) and established laboratory methods (specifically, the Platelet Neutralization Procedure (PNP) and Activated Partial Thromboplastin Time (APTT) measurements). For the stability and analyzer comparison studies, commercially available control plasmas and patient samples classified as "normal" or "lupus positive" served as the reference.

8. The Sample Size for the Training Set

Not applicable. This device is a laboratory reagent; there is no mention of an algorithm or AI that would require a "training set." The studies performed are validation studies for the performance characteristics of the physical reagent.

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

Not applicable, as there is no training set for an algorithm.

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JAN 1 3 1999

Image /page/0/Picture/1 description: The image is a black and white photograph. The image is mostly white, with a few black spots scattered throughout. The black spots are small and irregular in shape. The spots are concentrated in the lower half of the image, with a few scattered in the upper half.

K982062

510(k) Summary for Cryo✓Check™ PNP Platelet Lysate

    1. Submitter's Address and Contact Information
    • a) Company 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 Fax: (902) 468-6421 E-mail: smorrison@precisionbiologic.com

  • c) Date Prepared:
    June 5, 1998

    1. Device Name
    • Proprietary (trade) name: Cryov Check™ PNP Platelet Lysate a)
    • b) Common name: Platelet Extract (human)
    • Classification name: Partial Thromboplastin Time, Reagents, Controls c)
    • d) Classification information : Regulatory Class II Hematology Panel Product Code - 81 GIT

Device Description 3.

  • a)
    Cryo Check™ PNP Platelet Lysate is prepared from human platelets obtained from normal healthy donors. The platelets are collected, washed,

V - 1

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and resuspended in buffer and then frozen and thawed to yield a suspension of ruptured platelet membranes. This suspension is aliquoted into cryovials and stored frozen.

Intended Use 4.

Cryo Check™ PNP Platelet Lysate is intended for use in the Platelet Neutralization Procedure (PNP). The PNP is useful in detecting the presence of lupus anticoagulants in human plasma.

    1. Substantially Equivalent Device
    • 510(k) number: K873382 a)
    • Trade Name: Platelet Extract Reagent b)
    • Manufacturer: BIO/DATA Corporation c)
    • d) Substantial Equivalence Comparison

Cryo Check™ PNP Platelet Lysate is similar to the equivalent device in that they are both intended for use in the PNP for detecting the presence of lupus anticoagulants; have the same target population; and are both made from human platelets.

Cryo Check™ PNP Platelet Lysate differs from the equivalent device in that it is a frozen liquid preparation and not a lyophilized product.

To our knowledge, this difference does not affect the intended use or performance of the device.

    1. Non Clinical Performance Data
    • Tests Performed a)
      • i) PNP's of normal and known lupus anticoagulant positive patient samples comparing the performance of Cryo Check™ PNP Platelet Lysate to the predicate device (see Table V-1)
      • ii) 8 hour open vial stability study to demonstrate consistent vial to vial PNP results with normal plasma and lupus anticoagulant positive plasma (see Table V-2)
      • iii) 14 hour open vial stability on an MDA-180 automated coagulation analyzer (see Table V-3)

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  • iv) Comparison of PNP's of LA negative patient samples using Cryov Check™ PNP Platelet Lysate on two different automated coagulation analyzer systems: 1. MDA-180 using a photo-optical clot detection system: 2. Stago ST4 using a mechanical clot detection system (see Table V-3)

b) Conclusions

  • CryovCheck™ PNP Platelet Lysate demonstrated comparable i) specificity to the predicate device when tested against normal plasma and lupus anticoagulant positive patient plasmas when used in a platelet neutralization procedure.
  • PNP procedures using Cryo Check™ PNP Platelet Lysate exhibited ii) consistent vial to vial reactivity over an 8-hour period.
  • Cryov Check™ PNP Platelet Lysate is stable for greater than 8 iii) hours on an MDA 180 automated coagulation analyzer.
  • Cryov Check™ PNP Platelet Lysate yielded consistent results iv) when used on 2 different automated coagulation systems.

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Table V-1

Comparison of Cryo Check PNP Platelet Lysate to BIO/DATA Platelet Extract Reagent

Procedure: Platelet Neutralization Procedure Instrument: Diagnostica Stago ST4 Organon Teknika Automated APTT Lot# 161152 Reagent:

SalineCryo
DilutionBIO/DATACheck
Baseline50:50PNPPNP
APTTAPTTcorrectioncorrection
Sample(sec.)(sec.)(sec.)(sec.)
Normal 131.435.8-2.00.6
Normal 228.730.40.4-0.9
Normal 332.632.3-0.50.1
Normal 430.535.4-0.40.9
Normal 531.934.7-0.41.0
Lupus 175.663.122.722.1
Lupus 255.843.67.16.1
Lupus 351.740.97.64.5
Lupus 4103.889.640.644.5
Lupus 562.549.46.57.3
Lupus 653.7475.76.6
Lupus 747.141.24.53.4
Lupus 880.57023.828.9
Lupus 964.757.715.319.5
Lupus 1073.359.211.814.3
summary -
PNP's of normal plasmasPNP's of Lupus plasmas
CryoCheckPNPPlateletLysateBIO/DATAPlateletExtractCryoCheckPNPPlateletLysateBIO/DATAPlateletExtract
mean 0.34-0.6mean 15.7214.56
correlation coefficient* -0.510correlation coefficient 0.987

*The low correlation coefficient with the normal samples is attributed to the short correction time values and does not indicate that either product is defective.

V - 4

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Table V-2

8 Hour Open Vial Stability Study

System Information:

    1. Analyzer: MLA 900 C
2. APTT Reagent: Dade Actin FSLLot#: FSL164AExpiry: Feb., 1999
3. Normal Plasma: Cryo ✓ Check™ Normal (CCN)Lot #: 1600Expiry: April, 2000
4. Lupus Plasma: Cryo ✓ Check™ Lupus (CCLP)Lot#: 6100Expiry: Sept., 2000
5. Platelets: Cryo ✓ Check™ PNP Platelet Lysate (PNP)Lot#: PL01Expiry: April, 2000

Test Method:

    1. Baseline APTT's determined for normal plasma and lupus anticoagulant positive plasma
    1. APTT's determined for 1:1 mixture of above plasmas diluted with saline
    1. APTT's determined for 1:1 mixture of above plasmas with PNP Platelet Lysate
    1. Corrections calculated by subtracting the time in seconds of the plasma : platelet lysate mixture from the time in seconds of the plasma : saline mixture

Test Results:

Time = 0 hrsTime = 8 hrs
Normal PlasmaLupus PlasmaNormal PlasmaLupus Plasma
APTT(seconds)Correction(seconds)APTT(seconds)Correction(seconds)APTT(seconds)Correction(seconds)APTT(seconds)Correction(seconds)
Baseline28.3N/A59.8N/A27.6N/A58.3N/A
Saline42.3N/A54.2N/A40.3N/A53.4N/A
PNP Vial 137.25.139.314.936.43.942.910.5
PNP Vial 237.54.843.011.237.03.342.710.7
PNP Vial 338.04.341.412.836.53.842.111.3
PNP Vial 437.64.741.912.336.43.942.111.3
PNP Vial 537.74.642.212.036.04.342.411.0
Mean4.7Mean12.6Mean3.84Mean11.0
SD0.292SD1.39SD0.358SD0.358

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... .. .. . Table Ữ - 3

ﮨﮯ

ON BOARD STABILITY STUDY CryoCheck PNP Platelet Lysate

Instrument: MDA 180Reagent: Platelin-LLot #: 161132
Precision Biologicals Normal Control: CCN-10 lot# 1580; expires Mar.'00
saline/1580PNP/1580Neutralization
test timesecondssecondsseconds
0 min22.727.3-4.6
30 min22.627.2-4.6
45 min22.727-4.3
1 hr22.827.2-4.4
2 hr23.226.9-3.7
3 hr23.027.2-4.2
4 hr23.326.9-3.6
5 hr23.027.2-4.2
6 hr23.227-3.8
7 hr23.127.3-4.2
8 hr23.127.5-4.4
9 hr23.627.5-3.9
10 hr23.627.9-4.3
11 hr23.827.8-4
12 hr23.627.7-4.1
13 hr23.928-4.1
14 hr23.927.8-3.9
mean23.227.4-4.14
Std. Dev.0.4270.3560.291
Precision Biologicals Lupus Positive Control:CCLP-10 lot# 6100; expires Sept.'00
saline/6100PNP/6100Neutralization
test timesecondssecondsseconds
0 min54.837.517.3
30 min54.137.216.9
45 min54.637.217.4
1 hr54.737.717
2 hr54.537.417.1
3 hr55.537.418.1
4 hr5537.117.9
5 hr53.337.615.7
6 hr55.437.717.7
7 hr56.538.318.2
8 hr55.638.117.5
9 hr55.137.917.2
10 hr55.238.716.5
11 hr54.938.516.4
12 hr5538.816.2
13 hr54.838.416.4
14 hr57.438.518.9
mean55.137.917.2
Std. Dev.0.9020.5630.819
HRF "in-house" positive control
test timesaline/HRFsecondsPNP/HRFsecondsNeutralizationseconds
0 min69.641.328.3
30 min7041.828.2
45 min70.441.528.9
1 hr70.141.129
2 hr72.142.229.9
3 hr72.242.729.5
4 hr72.242.929.3
5 hr70.542.128.4
6 hr71.542.429.1
7 hr74.343.830.5
8 hr74.644.729.9
9 hr75.245.130.1
10 hr76.145.530.6
11 hr76.845.831
12 hr75.945.730.2
13 hr77.946.131.8
14 hr77.946.731.2
mean73.443.629.8
std. Dev.2.8891.9101.055

V - 6

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Table V -4

Cryo Check PNP Platelet Lysate Comparison of Reactivity on 2 Automated Coagulation Analyzers With Normal Patient Samples

Instrument: MDA 180 Type: Photo-Optical Clot Detection Instrument: ST4 Type: Mechanical Clot Detection

Sample #50:5050:50
Sal./SampleAPTT (sec.)PL/SampleAPTT (sec.)neutraliz.(sec.)Sal./SampleAPTT (sec.)PL/SampleAPTT (sec.)neutraliz.(sec.)
123.125.6-2.523.025.7-2.7
218.819.7-0.929.232.7-3.5
325.226.3-1.131.233.6-2.4
424.427.6-3.230.134.7-4.6
525.127.2-2.128.433.7-5.3
622.023.8-1.827.431.1-3.7
732.434.9-2.537.842.4-4.6
823.726.1-2.428.933.8-4.9
921.223.7-2.527.531.9-4.4
1024.124.7-0.630.133.0-2.9
1121.223.1-1.926.330.6-4.3
1226.325.90.427.732.7-5
1324.728.1-3.434.034.7-0.7
1422.725.8-3.131.835.9-4.1
1524.727.6-2.932.537.1-4.6
1619.221.9-2.724.827.8-3
1730.933.2-2.337.742.2-4.5
1820.624.2-3.627.231.1-3.9
1923.925.1-1.228.831.7-2.9
2018.320.7-2.424.127-2.9
2124.726.9-2.229.133.1-4
2224.625.5-0.931.032.4-1.4
2323.724.0-0.328.931.4-2.5
2419.922.4-2.525.129.7-4.6
2522.926.4-3.529.733.9-4.2
mean-2.084mean-3.664
std dev1.051std dev1.151

{7}------------------------------------------------

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 1 3 1999

Mr. Sandy Morrison Manager, Technical Operations Precision BioLogic Incorporated 900 Windmill Road Unit # 100 Dartmouth, Nova Scotia CANADA B3B 1P7

Re: K982062

Trade Name: Cryo Check™ PNP Platelet Lysate Regulatory Class: II Product Code: GGW Dated: June 5, 1998 Received: June 15, 1998

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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K982062 510(k) Number: ___

Device Name: CryovCheck™ PNP Platelet Lysate

Indications for Use

Cryo✓Check™ PNP Platelet Lysate is intended for use in the Platelet Neutralization Procedure (PNP) which is useful in detecting the presence of lupus anticoagulants (LA) in human plasma.

Peter E. Mapes

oratory Devices | (GB 2062

Prescription
Use

§ 864.7925 Partial thromboplastin time tests.

(a)
Identification. A partial thromboplastin time test is a device used for primary screening for coagulation abnormalities, for evaluation of the effect of therapy on procoagulant disorders, and as an assay for coagulation factor deficiencies of the intrinsic coagulation pathway.(b)
Classification. Class II (performance standards).