Pacific Hemostasis Control Plasma (Abnormal) Level Theta is intended for use in a laboratory program of quality assurance for activated partial thromboplastin time (APTT) and prothrombin time (PT) results with short clotting times. PT and APTT clotting times at the low end, or below the locally determined normal reference range are often related to the presence of elevated levels of fibrinogen and factor VIII. Both of these proteins are elevated in response to an inflammatory stimulus, malignant disease process or trauma. Control Level Theta Plasma provides a means for verifying the lower extent of the reportable range of the PT and APTT, particularly the imprecision of short clotting times often encountered with these screening tests.

Device Description

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the Coagulation Control Plasma (Abnormal) Level $\theta$ device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Required for Pacific Hemostasis Control Level Theta)	Reported Device Performance (Pacific Hemostasis Control Level Theta)	Comparative Performance (Dade® Ci-Trol® Level I)
Within-run Precision (CV)	PT: ≤ 5%	PT (Dade Reagents): 1.35%PT (PH Reagents): 1.23%	PT (Dade Reagents): 0.74%PT (PH Reagents): 0.82%
	APTT: ≤ 5%	APTT (Dade Reagents): 0.55%APTT (PH Reagents): 0.74%	APTT (Dade Reagents): 0.48%APTT (PH Reagents): 0.79%
Between-run Precision (CV)	Not explicitly stated as a separate acceptance criteria, but implied to be comparable to predicate.	PT: 1.46%APTT: 1.29%	PT: 1.87%APTT: 1.41%
Reconstituted Stability (6 hours at room temp)	≤ 5% change in clot time over 6 hours	PT: 1.39% changeAPTT: 2.43% change	PT: 1.37% changeAPTT: -0.19% change
Shorter Clotting Times	Control Level Theta should yield abnormally short PT and APTT compared to normal plasma with various end-point detection methods.	All reagent-instrument testing combinations yielded shorter PT and APTT clot times for Control Level Theta when compared to Pooled Normal Plasma.	Intended to yield clotting times within the normal reference range.

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

The document does not explicitly state a specific sample size for the test set in terms of the number of patient samples. Instead, the evaluations were performed using:

Two different instruments: MLA®-1000C™ & MLA®-1600 for within-run precision, and MLA®-1000C™ for between-run precision and stability.
Nine PT reagents and seven APTT reagents across four different coagulation analyzers (manual LAbor Fibrintimer®, semiautomated MLA®-700, fully automated ACL-3000™6 and MLA®-1000C™) for demonstrating shorter clotting times.
Data Provenance: The data appears to be from prospective studies/testing conducted by Pacific Hemostasis for the purpose of this 510(k) submission. There is no mention of country of origin for the data; it's presumed to be from the United States given the submission to the FDA.

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

Not applicable. This device is a coagulation control plasma, not a diagnostic device that requires expert interpretation for ground truth. The "ground truth" for its performance is analytical (clotting times, precision, stability) measured by laboratory instruments.

4. Adjudication Method for the Test Set

Not applicable. As this is not an interpretive diagnostic device, no adjudication by experts for ground truth was performed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is not an AI-powered diagnostic device, and therefore no MRMC study with human readers was conducted.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

The entire study is effectively a "standalone" performance evaluation of the control plasma itself, as it's an in-vitro diagnostic control material, not a software algorithm. Its performance is measured directly through laboratory instrument readouts.

7. The Type of Ground Truth Used

The "ground truth" for this device's performance is established based on:

Analytical measurements: Clotting times (PT and APTT), coefficient of variation (CV) for precision, and percentage change over time for stability.
Comparison to a legally marketed predicate device: Dade® Ci-Trol® Coagulation Control, Level I, which is a pre-amendment device.
Internal manufacturing specifications: E.g., "The manufacturing specification for Control Level Theta is for less than a 5% change in clot time over a 6 hour storage period."

8. The Sample Size for the Training Set

Not applicable. This is an in-vitro diagnostic control material, not a machine learning algorithm. Therefore, there is no "training set" in the context of AI/ML.

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

Not applicable, as there is no training set.

Summary

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PREMARKET NOTIFICATION 510(K) SUMMARY

Submitter:	Laura A. Worfolk, Ph.D.Pacific Hemostasis11515 Vanstory DriveHuntersville, NC 28078(704) 875-0494Fax # (704) 875-6671
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The same as above. Contact Person:

4/16/97 Date:

Coagulation Control Plasma (Abnormal) Level 6 Trade Name:

Not applicable Common Name:

Classification Name: Plasma, Coagulation Control (per 21 CFR section 864.5425)

Dade® Ci-Trol® Coagulation Control, Level I Equivalent Device:

Description of Coagulation Control Plasma (Abnormal) Level θ:

Control Level 6 Plasma is a lyophilized preparation of fresh human citrated plasma with added stabilizers and buffers. The reconstitution volume is 1.0 mL (with deionized or distilled water). Control Level Theta contains markedly elevated levels of human fibrinogen and factor VIII, and produces an abnormally short Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) with a variety of end-point detection methods. Each unit of source material used in the preparation of this product has been tested by an FDA approved method and found non-reactive for HBAg (Hepatitis B Surface antigen) and negative for antibodies to HIV and HCV. However, since no known test method can offer complete assurance that product derived from human blood will not transmit

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Hepatitis, AIDS, or other infectious diseases, this product should be handled as potentially infectious biological material.

Intended Use of Coagulation Control Plasma (Abnormal) Level 9:

Control Level 0 Plasma is intended for use in a laboratory program of quality assurance for activated partial thromboplastin time (APTT) and prothrombin time (PT) results with short clotting times. PT and APTT clotting times at the low end, or below the locally determined normal reference range are often related to the presence of elevated levels of fibrinogen and factor VIII. Both of these proteins are elevated in response to an inflammatory stimulus, malignant disease process or trauma. Control Level 6 Plasma provides a means for verifying the lower extent of the reportable range of the PT and APTT, particularly the imprecision of short clotting times often encountered with these screening tests.

Summary of Data Comparing Control Level 8 Plasma to Dade® Ci-Trol® Level I:

Pacific Hemostasis Control Level Theta was compared to Dade® Ci-Trol® Level I. a pre-amendment device. Both Control Level Theta and Dade® Ci-Trol® Level I plasmas are lyophilized preparations of human citrated plasmas with added stabilizers and buffers. The intended use for both products is indistinguishable: as a control plasma for Prothrombin and Activated Partial Thromboplastin Time testing in a clinical laboratory program of quality assurance. Control Level Theta contains elevated levels of human fibrinogen and Factor VIII. which result in clotting times below the normal reference range. In contrast, Dade® Ci-Trol® Level I yields clotting times within the normal reference range.

Within-run precision studies performed on two different instruments (MLA®-1000C™ & MLA®-1600) using both Dade and Pacific Hemostasis brand PT and APTT reagents yielded comparable data. The coefficient of variation (CV) for Control Level Theta and Dade® Ci-Trol® I was well below the

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performance specifications. (For Pacific Hemostasis Control Level Theta the CV for both PT and APTT must be ≤ 5%. The stated CV for Dade® Ci-Trol® I is ≤ 5% and < 9% for PT and APTT, respectively.) Testing performed using Pacific Hemostasis brand PT and APTT reagents yielded a 1.23% (PT) and 0.74% (APTT) CV with Control Level Theta. The CV's for Dade® Ci-Trol® Level I using Pacific Hemostasis brand reagents was 0.82% (PT) and 0.79% (APTT). Testing was also performed using Dade brand PT and APTT reagents. For Control Level Theta, a 1.35% and 0.55% CV was obtained for PT and APTT testing respectively. Dade Ci-Trol Level I yielded a 0.74% and 0.48% CV for PT and APTT testing respectively. The following table summarizes this data:

Table 14. Summary of Within-Run Precision Studies
	PT		APTT
	Theta Control	Dade Ci-Trol®	Theta Control	Dade Ci-Trol®
Dade Reagents	1.35	0.74	0.55	0.48
PH Reagents	1.23	0.82	0.74	0.79

Results are %CV.

Since the results for the between-run precision studies were indistinguishable between the two manufacturer's reagents, day-to-day precision studies were performed using Pacific Hemostasis brand reagents only. Testing was performed on the MLA®-1000C™. Control Level Theta had a 1.46% and 1.29% CV for PT and APTT testing respectively; Dade® Ci-Trol® Level I yielded a 1.87% and 1.41% CV for PT and APTT testing.

The reconstituted stability claim for Control Level Theta is for 6 hours at room temperature. (The manufacturing specification for Control Level Theta is for less than a 5% change in clot time over a 6 hour storage period.) Stability studies support this claim; there was a 1.39% change for PT and 2.43% change for APTT over a 6-hour time period. Dade Ci-Trol® Level I was also tested at 6

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hours and yielded comparable data; 1.37% and -0.19% for PT and APTT respectively. (These studies were also run on the MLA®-1000C™.)

Control Level Theta yields an abnormally short PT and APTT (when compared to normal plasma) with a wide variety of end-point detection methods. Control Level Theta and Pooled Normal Plasma were tested for the PT and APTT using nine PT reagents and seven APTT reagents. Testing for both the PT and APTT was performed on four different coagulation analyzers. The instruments used for this analysis were the manual LAbor Fibrintimer®, the semiautomated MLA®-700, and the fully automated ACL-3000™6 and the MLA -1000C™. This combination of analyzers represents approximately 80% of the instruments currently in use (within the USA). All reagent-instrument testing combinations yielded shorter PT and APTT clot times for Control Level Theta when compared to Pooled Normal Plasma. This testing was not performed for Dade® Ci-Trol® Level I since it is intended primarily for use with Dade brand PT and APTT reagents.

In summary, within-run, between-run and reconstituted stability studies support the substantial equivalence claim for Pacific Hemostasis Coagulation Control Level Theta to Dade® Ci-Trol® Level I. The one new performance characteristic, shorter clotting times, is intended to extend the verifiable limits of PT and APTT testing with more precision than controls that have longer clot times. Therefore based on the data provided, it is our conclusion that Control Level Theta is substantially equivalent to Dade® Ci-Trol® Level I.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the circle is an emblem featuring a stylized eagle with three wavy lines extending from its wing.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 17 1997

Lisa A. Worfolk, Ph.D. · Research Scientist Pacific Hemostasis 11515 Vanstory Drive, Suite 125 Hunterville, North Carolina 28078

K971428 Re : Coagulation Control Plasma (Abnormal) Level θ Requlatory Class: II Product Code: GGN April 16, 1997 Dated: Received: April 17, 1997

Dear Dr. Worfolk:

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 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 Requlations, Title 21, Parts 800 to 895. ਰੇ substantially equivalent determination assumes compliance with the Good Manufacturing -Practice -for Medical Devices: - General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in requlatory 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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ન્દ્ર

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 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/dsmamain.html".

Sincerely yours,
Steven Sitman

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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Page 1 of 1

5 10(k) Number (if known): ___________________________________________________________________________________________________________________________________________________

Device Name: Coagulation Control Plasma_Abnormal Level Theta

ndications For Use:

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times. PT and APTT clotting times at the researce of olyves of times. Pr and APTI Cloceing cimes at the for char of elevated levels of norwal reference runge are of these proteins are elevated in response to an inflammatory stimulus, malignant disease process or trauma. Control Level Theta P inflamatory Scimaras) Marighant Girouse proven when of the reportable range of Flasma provent, particularly the imprecision of short clotting times often encountered with these screening tests.

IPLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF EDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

	Veronica Celuia for Dr. Montgomery (Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	0971428

scription Use		OR	Over-The-Counter Use
r 21 CFR 801.109)			(Optional Format 1-2-96)

Regulation Number and Section

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.