(305 days)
Not Found
No
The summary describes a qualitative test kit based on chemical reagents and standard laboratory procedures, with no mention of AI or ML.
No.
This device is an in vitro diagnostic (IVD) test kit used to detect lupus anticoagulants in plasma, which is for diagnostic purposes, not for treating a disease or condition.
Yes
This device is an in vitro diagnostic test kit intended to aid in the detection of lupus anticoagulants, which is a diagnostic purpose.
No
The device description clearly states it is comprised of three reagents supplied in a frozen format, which are physical components, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in the "Intended Use / Indications for Use" section: "For in vitro diagnostic use." This is the primary indicator that the device is intended for use in diagnosing conditions outside of the body, which is the definition of an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
CRYOcheck Hex LA is for clinical laboratory use as a qualitative test kit intended to aid in the detection of lupus anticoagulants (LA) in 3.2% citrated human plasma by the application of hexagonal phase phospholipids. CRYOcheck Hex LA should be used as an integrated test for lupus anticoagulant detection. For in vitro diagnostic use. The performance of this device has not been established in neonate and pediatric patient populations.
Product codes
GFO
Device Description
CRYOcheck Hex LA is comprised of three reagents supplied in a frozen format as follows:
LA Start: Pooled normal plasma with buffer and a heparin neutralizer.
LA Correct: Pooled normal plasma with buffer, a heparin neutralizer, and inverted hexagonal phase phospholipid.
LA APTT: Silica-based lupus sensitive APTT reagent with stabilizer.
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
The performance of this device has not been established in neonate and pediatric patient populations.
Intended User / Care Setting
Clinical laboratory use.
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
Normal Range and Assay Cut-off:
A normal range study was performed in-house using on two analyzers using normal samples (Analyzer A, n = 137; Analyzer B, n = 126) according to CLSI EP28: A3c. Each sample was tested using three lots of CRYOcheck Hex LA. A pooled mean ±2 SD range was determined for delta correction results.
Method Comparison Studies:
A method comparison study was conducted to assess the efficacy of CRYOcheck Hex LA in the qualitative detection of LA relative to a comparator assay, Staclot® LA. A total of 446 samples were included in the study: 124 known (previously characterized) LA positive samples, 75 normal (presumed LA negative) samples from individuals with other medical conditions including autoimmune disorders and 220 LA target screening population samples. The study was conducted at one internal and three external sites. Each site performed the investigational device assay on their assigned portion of the samples using a single lot of CRYOcheck Hex LA. One external site, acting as the central laboratory, performed the comparator device testing on all 446 samples using the Staclot LA assay on a STA-R Evolution.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision:
An internal precision study was performed using three different lots of CRYOcheck Hex LA on a STA-R Evolution instrument in accordance with CLSI EP05-A3. Three lot numbers of CRYOcheck Hex LA were used to test three control plasmas and five plasmas with varying LA positivity, in duplicate, twice a day for 20 days. The results demonstrated a pooled precision of 10,000 platelets/μL) showed interference when compared with platelet poor or platelet free plasma samples.
Abnormally low factor II activities (below 50%) may interfere, potentially resulting in false negative results for weakly LA positive plasmas.
Factor VII and factor IX deficiencies do not interfere.
Abnormally low factor X activities (below 50%) do not interfere with interpretation but may increase delta correction for LA positive samples.
Method Comparison Studies:
A method comparison study was conducted to assess the efficacy of CRYOcheck Hex LA in the qualitative detection of LA relative to a comparator assay, Staclot® LA. A total of 446 samples were included in the study: 124 known (previously characterized) LA positive samples, 75 normal (presumed LA negative) samples from individuals with other medical conditions including autoimmune disorders and 220 LA target screening population samples. The study was conducted at one internal and three external sites. The data demonstrated positive percent agreement of 95.6% (95% Cl, 91-98%), negative percent agreement of 95.2% (95% Cl, 92%-97%), and overall agreement of 95.3% (95% Cl, 93%-97%).
Sample Integrity:
A sample integrity study was conducted to assess sample stability of fresh samples at room temperature, when stored at ≤ -70 ℃ and after up to two freeze-thaw cycles. Sixty-four samples were measured with a single lot of CRYOcheck Hex LA. Results were compared using regression analysis and support a fresh sample stability claim of 4 hours at room temperature and a frozen storage claim of 2 months at ≤ -70 ℃, including one freeze-thaw cycle.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement: 95.6% (95% Confidence Interval, 91% - 98%)
Negative Percent Agreement: 95.2% (95% Confidence Interval, 92% - 97%)
Overall Agreement: 95.3% (95% Confidence Interval, 93% - 97%)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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).
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name, "U.S. Food & Drug Administration," written out next to it.
October 23, 2020
Precision BioLogic Karen Black VP of Compliance and Product Development 140 Eileen Stubbs Avenue Dartmouth, Nova Scotia B3B 0A9 Canada
Re: K193556
Trade/Device Name: Cryocheck Hex LA Regulation Number: 21 CFR 864.7925 Regulation Name: Partial Thromboplastin Time Tests Regulatory Class: Class II Product Code: GFO Dated: December 20, 2019 Received: December 23, 2019
Dear Karen Black:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Takeesha Taylor-Bell Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K193556
Device Name Cryocheck Hex LA
Indications for Use (Describe)
Cryocheck Hex LA is for clinical laboratory use as a qualitative test kit intended to aid in the detection of lupus anticoagulants (LA) in 3.2% citrated human plasma by the application of hexagonal phase phospholipids. Cryocheck Hex LA should be used as an integrated test for lupus anticoagulant detection. For in vitro diagnostic use. The performance of this device has not been established in neonate and pediatric patient populations.
Type of Use (Select one or both, as applicable)
| ☒ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| -------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------- |
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3
� 510(k) Summary
510(k) Summary cryocheck™ Hex LA™
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is K193556
| Submitter's
Information | Precision BioLogic Inc.
140 Eileen Stubbs Ave.
Dartmouth, Nova Scotia B3B 0A9
Canada | | | Similarities | | |
|--------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|-----------------------------------------------------------|--------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person | Karen M. Black, VP of Compliance & Product Development
Phone: 902-468-6422 ext. 226, or 902-706-3125
E-mail: kblack@precisionbiologic.com | | | | Staclot LA | CRYOcheck Hex LA |
| Preparation Date | 14 October 2020 | | | Measurand | lupus anticoagulant | lupus anticoagulant |
| Device Trade Name | CRYOcheck ™ Hex LA | | | Product Code | GFO | GFO |
| Regulatory
Information | Regulation Number and
Description | | 21 CFR 864.7925
Partial thromboplastin time test | | Partial thromboplastin time tests | Partial thromboplastin time tests |
| | Classification | | Class II | Regulation Section | 21 CFR 864.7925 | 21 CFR 864.7925 |
| | Product Code | | GFO; Partial thromboplastin time test; 21
CFR 864.7290 | | Partial thromboplastin time tests | Partial thromboplastin time test |
| | Classification Panel | | Hematology | Classification | Class II | Class II |
| | | | | Panel | 81 (Haematology) | 81 (Haematology) |
| Predicate Device | Staclot LA (K923731) | | | Intended Use | The Staclot LA test kit is a reagent
system designed for the qualitative
detection of lupus anticoagulants
(LA) in plasma by the use of
hexagonal HII phase phospholipid
molecules. (In the USA this
procedure has been assigned to
the high complexity category per
CLIA 1988 - CDC Analyte Code
3728; CDC Test System Code
13285). | CRYOcheck Hex LA is for clinical
laboratory use as a qualitative
test kit intended to aid in the
detection of lupus anticoagulants
(LA) in 3.2% citrated human
plasma by the application of
hexagonal phase phospholipids.
CRYOcheck Hex LA should be
used as an integrated test for
lupus anticoagulant detection.
For in vitro diagnostic use. The
performance of this device has
not been established in neonate
and pediatric patient
populations. |
| Indication for Use/
Intended Use | CRYOcheck Hex LA is for clinical laboratory use as a qualitative test kit
intended to aid in the detection of lupus anticoagulants (LA) in 3.2%
citrated human plasma by the application of hexagonal phase
phospholipids. CRYOcheck Hex LA should be used as an integrated
test for lupus anticoagulant detection. For in vitro diagnostic use. The
performance of this device has not been established in neonate and
pediatric patient populations. | | | Assay Type | Qualitative; hexagonal phase
neutralization test | Qualitative; hexagonal phase
neutralization test |
| Device Description | CRYOcheck Hex LA is comprised of three reagents supplied in a frozen
format as follows:
LA Start: Pooled normal plasma with buffer and a heparin neutralizer.
LA Correct: Pooled normal plasma with buffer, a heparin neutralizer,
and inverted hexagonal phase phospholipid.
LA APTT: Silica-based lupus sensitive APTT reagent with stabilizer. | | | Methodology | The Staclot LA test procedure is
based on the following principle:
the test plasma that is suspected to
contain LA is first allowed to
incubate at 37°C with (Tube 2) and
without (Tube 1) hexagonal phase
phosphatidylethanolamine (HPE)
(Reagent 2); next, an APTT is
performed on both tubes using an
LA sensitive reagent (Reagent 4); if
LA were present in the test plasma,
they would be neutralized by HPE
in tube 2, and this would result in a
shortening of the clotting time of
tube 2 compared with that of tube
- By comparing the difference
between the two clotting times, the
presence of LA antibodies in the
test plasma can be identified.
The Reagent 3 contains a heparin
inhibitor which makes the test
system insensitive to heparin levels
up to 1 IU/mL. Furthermore, the
Staclot LA procedure calls for the
addition of a normal plasma
(Reagent 3) to the test system to | CRYOcheck Hex LA is a
hexagonal-phase phospholipid
neutralization test (HPNT),
which is an integrated test that
combines screening,
confirmatory and mixing test
procedures into a single assay.
CRYOcheck LA works on the
principle that LA are neutralized
by hexagonal phase
phospholipids that are present in
the assay's confirmatory
reaction mixture and not the
screening reaction mixture. The
presence of LA in plasma
samples is confirmed by the
correction of APTT clot times in
the presence of a reaction
mixture containing hexagonal
phase phospholipids.
In the CRYOcheck Hex LA assay,
the test plasma suspected to
contain LA is incubated in two
reaction cuvettes, both of which
entail dilution with pooled normal |
| | Comparison to Predicate | | | | | |
| Item | Predicate | | New Device | | | |
| Proprietary and
Established Names | Staclot LA | | CRYOcheck Hex LA | | | |
| Manufacturer | American Bioproducts Inc (original
applicant); Diagnostica Stago
(current manufacturer) | | Precision BioLogic Inc | | | |
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5
| Similarities | ||
|---|---|---|
| Staclot LA | CRYOcheck Hex LA | |
| clotting time due to factor | ||
| deficiencies that might be present. | ||
| If the Staclot LA does not produce | ||
| a shortening of the clotting time, | ||
| then the presence of anti-factor | ||
| antibodies should be suspected; in | ||
| this case, use an appropriate test | ||
| for anti-factor antibodies. |
Compare the clotting time of tube 1
(CT1) with that of tube 2 (CT2). A
shortening of clotting time of 8
seconds or more of tube 2
compared with that of tube 1 is
significant of a neutralization of
anti-phospholipid antibodies (this 8-
second cut-off in clotting times has
been determined with the ST4/ST
art® instrument - Diagnostica
Stago). | neutralizer), thus satisfying the
mixing test requirement. In the
first cuvette, the screening test
reaction is performed by mixing
the test plasma with the LA Start
reagent (pooled normal plasma).
In the second cuvette, the
confirmatory reaction is
performed by mixing the test
plasma with the LA Correct
reagent (pooled normal plasma
with hexagonal phase
phospholipid). The LA APTT
reagent is then added to each
cuvette, followed by 0.025 M
CaCl2 to activate clotting via the
intrinsic pathway. Clot times are
recorded for the screening
reaction mixture containing LA
Start and the confirmatory
reaction mixture containing LA
Correct. The result is reported
as the difference in clot time in
seconds ("delta correction")
between LA Start and LA
Correct cuvettes.
delta correction = (CT LA Start)
- (CT LA Correct)
The result is then compared to
an established cut-off. A result
greater than or equal to the
established cut-off is considered
LA positive, while a result less
than the established cut-off is
considered LA negative. |
| Expression of results | Qualitative; results are reported as
clot time delta (seconds) and are
interpreted as positive or negative
relative to an established cut-off
value. | Qualitative; results are reported
as clot time delta (seconds) and
are interpreted as positive or
negative relative to an
established cut-off value. |
6
| Differences | ||||||||
|---|---|---|---|---|---|---|---|---|
| Staclot LA | CRYOcheck Hex LA | |||||||
| Format | Staclot LA is comprised of three lyophilized reagents and two reconstitution liquids as follows: | |||||||
| Reagent 1 : ready-for-use buffer | ||||||||
| Reagent 2 : lyophilized hexagonal phase phosphatidylethanolamine | ||||||||
| Reagent 3 : lyophilized normal human plasma containing a heparin inhibitor | ||||||||
| Reagent 4 : lyophilized PTT-LS reagent consisting of cephalin prepared from rabbit cerebral tissues and a particulate siliceous activator | ||||||||
| Reagent 5 : solvent for reconstitution of Reagent 4. | CRYOCheck Hex LA is comprised of three reagents supplied in a frozen format as follows: | |||||||
| LA Start : Pooled normal plasma with buffer and a heparin neutralizer. | ||||||||
| LA Correct : Pooled normal plasma with buffer, a heparin neutralizer, and inverted hexagonal phase phospholipid. | ||||||||
| LA APTT : Silica-based LA sensitive APTT reagent with stabilizer. | ||||||||
| Storage | 2-8°C until expiration | ≤-70°C until expiration | ||||||
| Instrument | Manual (ST4/ST art®) | STA-R Evolution® | ||||||
| Associated Controls | STA® - Control LA 1 + 2 | CRYOCheck Lupus Negative Control | ||||||
| CRYOCheck Weak Lupus Positive Control | ||||||||
| CRYOCheck Lupus Positive Control | ||||||||
| Cut-off | A shortening of clotting time of 8 seconds or more of tube 2 compared with that of tube 1 is significant of a neutralization of anti-phospholipid antibodies (this 8-second cut-off in clotting times has been determined with the ST4/ST art® instrument - Diagnostica Stago). |
Each laboratory should verify this 8-second cut-off by testing the plasma of at least 20 normal individuals, using its own methodology to obtain the mean delta T + 4 SD. | The cut-off for the assay delta correction was determined using pooled data from a normal range study conducted on Stago STA-R Evolution® analyzers and calculating the mean + 4 SD, with the following results:
Delta Correction Interpretation 1 Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, deGroot PG. Update of the guidelines for lupus anticoagulant detection. J. Thromb. Haemost. 2009;7(10):1737-1740.
7
| Differences | ||
|---|---|---|
| Staclot LA | CRYOcheck Hex LA | |
| testing the plasma of at least 20 | ||
| normal individuals. | ||
| Heparin Interference | No interference up to 1 IU/mL | Unfractionated heparin: no |
| interference up to 2 IU/mL | ||
| Low molecular weight heparin: | ||
| no interference up to 2 IU/mL | ||
| Direct Thrombin and | ||
| Xa Inhibitor | ||
| Interference | Thrombin inhibitors (e.g., hirudin, | |
| argatroban...) present in the | ||
| sample to be tested may interfere | ||
| in the test and lead to falsely | ||
| positive results. | Dabigatran, rivaroxaban, and | |
| fondaparinux do not interfere | ||
| with the interpretation of | ||
| CRYOcheck Hex LA results but | ||
| may increase the delta | ||
| correction of LA positive | ||
| samples. | ||
| Warfarin Interference | The Staclot® LA procedure was | |
| used to test plasmas from | ||
| stabilized coumadin patients (n = | ||
| 29). All plasmas gave negative | ||
| results with Staclot® LA. | Plasma samples with elevated | |
| INR (up to 4.5) do not interfere | ||
| with the interpretation of | ||
| CRYOcheck Hex LA results | ||
| Factor VIII Inhibitor | ||
| Antibody Interference | The presence of anti-factor | |
| antibodies does not normally | ||
| produce a correction in clotting | ||
| time with the Staclot LA test | ||
| procedure. However considering | ||
| the heterogeneity of these | ||
| antibodies, some may interfere in | ||
| the test. Consequently, when these | ||
| are suspected, use an appropriate | ||
| test for anti-factor antibodies | Factor VIII inhibitor antibodies | |
| do not interfere with the | ||
| interpretation of CRYOcheck Hex | ||
| LA results, but at titers above 15 | ||
| BU/mL may increase the delta | ||
| correction of LA positive | ||
| samples. | ||
| Factor Deficiency | ||
| Interference | A total of 21 factor deficient | |
| plasmas, comprising deficiencies of | ||
| F. VIII (n = 8), F. VIII with the | ||
| presence of anti-F. VIII-antibodies | ||
| (n = 5), F. IX (n = 4), F. XI (n = 2), | ||
| F. XII (n = 1) and F. II (n = 1), were | ||
| tested with the Staclot® LA | ||
| procedure. The observed CT1-CT2 | ||
| was found in all cases 10,000 platelets/μL) showed interference with cRYOcheck Hex LA . results when compared with platelet poor ( |