PACIFIC HEMOSTASIS IMMUNODEPLETED FACTOR V DEFICIENT PLASMA (THROMBOSDREEN BRAND) (100056) by PACIFIC HEMOSTASIS

Pacific Hemostasis Immunodepleted Factor V Deficient Plasma is intended for use in a clinical laboratory for the quantitative measurement of Factor V activity. Factor V activity in patient or control plasma is assayed by the amount of Prothrombin Time (PT) correction produced by the test plasma when mixed with Factor V deficient plasma. Results are compared to the degree of PT correction of a reference plasma with known Factor V activity. A pool of normal plasma is considered to vield 100% correction in the PT time, and has 100% of the normal Factor V concentration.

Pacific Hemostasis Immunodepleted Factor V Deficient Plasma is intended for use in the quantitative determination of Factor V activity in patient plasma… Factor..V. activity in plasma is assayed by the amount of Prothrombin Time correction produced " The correction of the unknown by the test plasma when mixed with factor deficient plasma. is compared to that produced by a reference plasma of known normal activity.

Device Description

Pacific Hemostasis (PH) Immunodepleted Factor V Deficient Plasma is a lyophilized preparation of fresh human plasma with added buffers. PH Immunodepleted Factor V Deficient plasma is intended for use in a clinical laboratory for the quantitative measurement of Factor V activity. The product is prepared from pooled normal plasma depleted of factor V by immobilized, highly specific antibodies. The Factor V activity contained in the product is less than 1% of normal levels. All other coaqulation factors are within the normal range. The reconstitution volume is 1.0 mL (with deionized or distilled The product is available in packages containing 10 vials. The water). reconstituted plasma is stable for 8 hours when stored stoppered at 2-8°C. 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 HB Ag (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 Hepatitis. AIDS, or other infectious diseases, this product should be handled as potentially infectious biological material.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study data for the "Immunodepleted Factor V Deficient Plasma" device.

A significant limitation of this document is that it is a 510(k) summary from 1997, which means it pre-dates the modern standards for reporting clinical study details for medical devices, especially AI/ML-enabled devices. The focus here is on demonstrating substantial equivalence to a predicate device rather than strictly defining and proving acceptance criteria in the current sense. Therefore, certain requested information (like specific AI/ML study details, expert qualifications for ground truth, or MRMC studies) is not applicable or not provided in this type of document.

Device Name: Immunodepleted Factor V Deficient Plasma (Human, Dried)
Predicate Device: Dade® Immunoadsorbed Factor V Deficient Plasma (Human), K912679

1. Table of Acceptance Criteria and Reported Device Performance

Given the nature of a 510(k) (substantial equivalence), the "acceptance criteria" are implicitly met by demonstrating comparable performance to the predicate device within acceptable laboratory variability. The specific numerical targets for "acceptance" are derived from the performance of the predicate device and general good laboratory practice for coagulation assays.

Performance Metric	Acceptance Criteria (Implicitly: Comparable to Predicate)	Reported Device Performance (Pacific Hemostasis)	Predicate Device Performance (Dade)
Standard Curve Precision (Day-to-Day)
Mean Slope CV (%)	Comparable (e.g., within a reasonable percentage of predicate)	0.83%	2.42%
R² Range	≥0.99 (high linearity)	0.996-0.999	0.996-0.999
Recovery of Factor V Activity (Day-to-Day Precision)
Normal Reference Plasma (%CV)	Comparable (e.g., ≤10% for typical lab values)	4.5% (UCRP)	5.6% (UCRP)
Abnormal Reference Plasma (%CV)	Comparable (e.g., ≤10% or clinically acceptable)	3.5% (ACRP)	4.8% (ACRP)
Low Abnormal Reference Plasma (%CV)	Comparable (with understanding of higher variability at low levels)	6.7% (Level 1), 7.4% (Level 2), 12.5% (Level 3)	5.6% (Level 1), 3.9% (Level 2), 4.0% (Level 3)
Correlation with Assigned FV Values
Slope	Close to 1.0	0.915	0.977
R² (Correlation Coefficient)	Close to 1.0 (very high correlation)	0.989	0.991
Reconstituted Stability (8 hours @ 4°C)
Standard Curve Slope Change	Minimal change (e.g., <5%)	-0.278 (fresh) vs -0.284 (8-hr)	-0.245 (fresh) vs -0.246 (8-hr)
Standard Curve R² Change	Minimal change	0.999 (fresh) vs 0.999 (8-hr)	0.999 (fresh) vs 0.998 (8-hr)
FV Activity Recovery Change (Normal)	Minimal change (e.g., <5% difference)	-3.6%	-1.9%
FV Activity Recovery Change (Abnormal)	Minimal change (e.g., <5% difference)	3.5%	2.0%
Factor VII & X Activity	No decrease observed	No decrease (both PH and Dade)	No decrease (both PH and Dade)
Instrument Compatibility
Slope (vs. Dade on each instrument)	Close to 1.0 (range 0.917-1.196)	0.917-1.196	(Reference is Dade)
R² (vs. Dade on each instrument)	Close to 1.0 (range 0.992-0.999)	0.992-0.999	(Reference is Dade)
Overall Combined Instrument Data Slope	Close to 1.0	1.068	(Reference is Dade)
Overall Combined Instrument Data R²	Close to 1.0	0.977	(Reference is Dade)

Note: The acceptance criteria are "implicitly" derived from demonstrating "substantial equivalence" to the predicate device, K912679. This means the new device's performance is expected to be comparable to or better than the predicate's performance within typical laboratory variability. The narrative specifically highlights cases like the higher CV for PH's Level 3 control not being "clinically significant" due to the very low FV activity level and its use for internal reference, indicating the clinical context for acceptance.

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

The "test set" here refers to the samples used to evaluate the performance of the new device relative to the predicate.

Day-to-Day Precision Studies:
- Standard Curves: n=10 runs (on 10 different days) for each product (Pacific Hemostasis and Dade).
- Factor V Activity Recovery: n=10 runs for each of the five reference plasmas tested with both products (Pacific Hemostasis and Dade). This totals 50 data points for PH and 50 for Dade for FV recovery.
Reconstituted Stability Study: "Several vials" of each brand were pooled for testing 8-hour stability. The comparison was between "freshly reconstituted" and "8-hour stored" plasmas, likely involving single or replicate runs for standard curves and reference plasma recovery at each time point.
Instrument Compatibility Study: For each of the five instruments, standard curves were generated (likely n=1) and Factor V activity was determined for the five different reference plasmas using both PH and Dade products. This implies 5 reference plasmas * 5 instruments * 2 products = 50 data points for FV recovery across instruments.

Data Provenance: The study appears to be prospective in nature, as it describes experiments conducted specifically for this submission (e.g., "Day-to-day precision studies were performed..."). The data is almost certainly domestic (USA), as the submitting company is based in Huntersville, NC, and the instruments mentioned (MLA®-1000C™, Amelung KC 4 ATM, BBL® Fibrometer, MLA®-700, and ACL-3000PLUS) are commonly used in US clinical laboratories. The document states these instruments "represent approximately 80% of the clinical analyzers currently used in this country."

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

This document is for a laboratory reagent; therefore, the concept of "ground truth" established by human experts (like radiologists) for a diagnostic image is not directly applicable.

Ground Truth: The "ground truth" for the Factor V levels in the reference plasmas (UCRP, ACRP, Abnormal Factor V Controls) was their "assigned Factor V values." These values would have been established by the manufacturer (Pacific Hemostasis) using validated methods and reference materials, likely against an international standard or a well-characterized normal plasma pool.
Experts: No external "experts" are explicitly mentioned for establishing the ground truth of these reference plasmas in the context of this 510(k) submission. The manufacturer is responsible for establishing these assigned values.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in clinical studies involving interpretation of subjective results or disagreements between readers. Since this is a laboratory reagent assay, there is no "adjudication method" in the traditional sense. The data is quantitative and objective (e.g., %CV, slope, R² values). Methodological consistency (e.g., running on an automated coagulator like MLA®-1000C™ to minimize human error) and established laboratory protocols are used to ensure data quality and reliability.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, this is not applicable. An MRMC study is designed for evaluating human performance on diagnostic tasks, often involving image interpretation, with and without AI assistance. This submission describes the performance of a laboratory reagent, not an AI-powered diagnostic tool, and involves instrument-based measurements rather than human interpretation of cases. Therefore, there is no "AI assistance" component or human reader improvement effect to measure.

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

This is not applicable. The device is a laboratory reagent. Its performance is inherently "standalone" in the sense that it functions chemically in an assay, but it is always used within a human-operated laboratory workflow on an instrument. It is not an algorithm, so "algorithm-only" performance is not a relevant concept here. The data represents the performance of the reagent system in controlled laboratory settings.

7. The Type of Ground Truth Used

The ground truth used was "assigned Factor V values" of various reference plasmas (e.g., Universal Coagulation Reference Plasma (UCRP), Abnormal Coagulation Reference Plasma (ACRP), and Abnormal Factor V Controls). These assigned values represent the known or expected Factor V activity in these control materials, serving as a benchmark for accuracy and recovery.

8. The Sample Size for the Training Set

This is not applicable/not provided. The device is a chemical reagent, not an AI/ML algorithm that requires a "training set" of data. The manufacturing process and quality control methods ensure the product's characteristics, but it's not "trained" on data in the computational sense.

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

This is not applicable. As stated above, there is no "training set" for this type of device. The "ground truth" for the reference materials used in testing (as described in point 7) would have been established by the manufacturer through validated assays and traceability to recognized standards, but this is not a "training set ground truth."

Summary

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K972627

AUG 1 3 1997

Premarket Notification 510(k) Surnmary Immunodepleted FV Deficient Plasma

PREMARKET NOTIFICATION 510(K) SUMMARY 8.0

Submitter: Laura A. Worfolk, Ph.D. Pacific Hemostasis 11515 Vanstory Drive Huntersville, NC 28078 (704) 875-0494 Fax # (704) 875-6671
Contact Person: The same as above.

Date: 07/11/97

Trade Name: Immunodepleted Factor V Deficient Plasma (Human, Dried)
Common Name: Not applicable
Plasma, Coaqulation Factor Deficient Classification Name: (per 21 CFR section 864.7290)
Dade® Immunoadsorbed Factor V Deficient Equivalent Device: Plasma (Human), K912679

Description of Immunodepleted Factor V Deficient Plasma:

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tested by an FDA approved method and found non-reactive for HB Ag (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 Hepatitis. AIDS, or other infectious diseases, this product should be handled as potentially infectious biological material.

Intended Use of Immunodepleted Factor V Deficient Plasma

Pacific Hemostasis Immunodepleted Factor V Deficient plasma is intended for use in a clinical laboratory for the quantitative measurement of Factor V activity. Factor V activity in patient or control plasma is assayed by the amount of Prothrombin Time (PT) correction produced by the test plasma when mixed with Factor V deficient plasma. Results are compared to the degree of PT correction of a reference plasma with known Factor V activity. A pool of normal plasma is considered to vield 100% correction in the PT time, and has 100% of the normal Factor V concentration.

Summary of of Performance Data For Substantial Equivalence Comparisons

Pacific Hemostasis Immunodepleted Factor V Deficient Plasma was compared to Dade® Immunoadsorbed Factor V Deficient Plasma (K912679). Both products are lyophilized preparations of human plasmas. The Factor V fevel in both is less than 1%; all other coagulation factors are within the normal range. The intended use for both products is identical; for the quantitative measurement of Factor V activity in patient plasma.

Day-to-day precision studies were performed to assess the reproducibility of the Factor V standard curve prepared with the immunodepleted plasmas. One lot of Pacific Hemostasis (PH) Universal Coagulation Reference Plasma (UCRP, with known FV Activity) was used to generate the Factor V standard curves. PH Thromboplastin-D was used as the Prothrombin Time reagent, and PH Diluting Fluid (Barbital Buffered

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Saline) was used as the diluent. All testing for the day-to-day precision studies was run on the MLA®-1000C™. This is an automated coagulation analyzer, thus minimizing imprecision introduced by human error (i.e. pipetting). Standard curves prepared with Pacific Hemostasis and Dade brand immunodepleted plasmas were run on 10 days. There was very little variation in the standard curves for both products as evidenced by the slope and R2 values obtained (range of R2 values was .996-.999). The following table summarizes the day-to-day standard curves obtained:

	PH Standard Curvesn=10	Dade Standard Curvesn=10
Mean Slope	-0.285	-0.245
1 SD	0.002	0.006
% CV	0.83	2.42

Table 16. Summary of Standard Curve Data

To determine the precision of the standard curves prepared daily, the recovery of Factor V activity contained in five reference plasmas was determined. The reference plasmas chosen for analysis contain Factor V in the normal, abnormal and markedly abnormal range, they are: 1) a different lot of PH UCRP, 2) PH Abnormal Coagulation Reference Plasma (ACRP), 3-5) PH Abnormal Factor V Controls, Levels 1, 2 and 3. The following table is a summary of the results obtained:

Table 17. Summary of Day-to-Day Precision Studies. Recovery of FV Activity Contained in Reference Plasmas

	UCRP		ACRP		Level 1Control		Level 2Control		Level 3Control
	PH	Dade	PH	Dade	PH	Dade	PH	Dade	PH	Dade
mean	118.5	125.5	51.7	49.8	48.2	47.5	24.1	22.9	5.9	6.5
1 SD	5.29	7.01	1.78	2.39	3.20	2.67	1.79	0.88	0.74	0.26
% CV	4.5	5.6	3.5	4.8	6.7	5.6	7.4	3.9	12.5	4.0

*n=10 for each reference plasma

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The day-to-day recovery of Factor V activity (%CV) contained in four of the five reference plasmas was equivalent for both PH and Dade standard curves (curves prepared using either PH or Dade brand FV immunodepleted deficient plasmas). A slightly higher CV was obtained for the FV Abnormal Level 3 control using the PH immunodepleted plasmas (12.5% versus 4.0%). However, the imprecision observed at this level of Factor V activity is not clinically significant. The assigned Factor V value for this control is 5%, a value that is in the very low abnormal range, and below the normal cut off for both standard curves. This control was included in the analysis to determine the accuracy of extrapolated values at the low end of the range (for internal reference only). It is not recommended to report patient values that fall outside of the linear portion of the standard curve. To determine a patient Factor V value in this range (which is very rare), testing of a different sample dilution would be required. Alternatively, a standard curve representing Factor V activity in the low range could be generated.

The Factor V values obtained for the reference plasmas, using both immunodepleted plasmas. were compared to the assigned Factor V values. The assigned reference Factor V values were plotted against the recovered Factor V values using either PH or Dade brand immunodepleted FV plasmas. Linear regression was done and the slope of the line calculated. A slope of 1.0 with a correlation coefficient of 1.0 indicates exact recovery of Factor V values to the assigned reference values. The recovery of Factor V activity using both immunodepleted plasmas was quite good. The slope and R2 values obtained using Pacific Hemostasis brand substrate were 0.915 and 0.989, respectively; for Dade, 0.977 and 0.991, respectively.

The reconstituted stability claim for both PH and Dade brand immunodepleted Factor V deficient plasmas is 8 hours at 4°C. To evaluate the reconstituted stability, several vials of each brand of immunodepleted substrate were reconstituted, pooled and stored at 4℃ for 8 hours. Standard

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curves were prepared utilizing the 8-hour stored plasmas and compared to freshly reconstituted immunodepleted plasmas. The standard curves obtained using fresh and aged plasmas were indistinguishable for both PH and Dade brand deficient substrates, as evidenced by the data in the following table:

	PH Standard Curve	Dade Standard Curve
Fresh ID Plasma:SlopeR2	-0.2780.999	-0.2450.999
8-Hour ID Plasma:SlopeR2	-0.2840.999	-0.2460.998

ID = immunodepleted plasma

In addition, the recovery of Factor V activity contained in two reference plasmas (normal and abnormal) was determined using the fresh and 8-hour aged immunodepleted Factor V deficient substrates. The Factor V activity determined in the two reference plasmas was equivalent for both fresh and aged plasmas, supporting the 8-hour reconstituted stability claim. (With PH immunodepleted plasma, the FV value contained in the normal and abnormal reference plasmas changed -3.6% and 3.5% respectively, over the 8-hour time period. With Dade, the FV value contained in the normal and abnormal reference plasmas changed -1.9% and 2.0%, respectively, over the same time period.)

To further assess the reconstituted stability of the immunodepleted plasmas, a guantitative measurement of the Factor VII and Factor X levels contained in freshly reconstituted and 8-hour aged immunodepleted plasma was determined. Factor VII and Factor X were chosen for evaluation since the PT based Factor V assay will also detect deficiencies in both. There was no decrease in Factor VII and Factor X activity observed for both immunodepleted plasmas over the 8-hour incubation time period. These

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combined data strongly support the reconstituted stability claim for Pacific Hemostasis Immunodepleted Factor V Deficient Plasma.

Last, the performance of PH and Dade brand immunodepleted Factor V deficient plasmas was evaluated on several different coaqulation analyzers. The instruments chosen for evaluation included two manual, one semiautomated and two fully automated coagulation instruments: the Amelung KC 4 ATM, BBL® Fibrometer, MLA®-700, MLA®-1000C™ and the ACL-3000PLUS These instruments represent approximately 80% of the clinical analyzers currently used in this country. All Factor V assays were performed following the instrument manufacturer's protocol. Standard curves were generated using both immunodepleted plasmas and the recovery of Factor V activity contained in the five different reference plasmas was determined.

For all instruments tested, the Factor V activity level recovered in the reference samples using PH immunodepleted plasma was equivalent to that obtained using the Dade product. The Factor V values recovered in the reference plasmas using PH substrate were plotted aqainst those obtained with Dade for each instrument analyzed. Linear regression was performed and the slope of the line calculated. Excellent correlation was obtained on all instruments, with the slope ranging from 0.917-1.196, and the R2 ranging from 0.992-0.999. When all instrument data was combined, linear regression vielded a slope of 1.068 and an R2 value of 0.977, suggesting equivalent performance for PH and Dade brand immunodepleted plasmas.

In summary, the indistinguishable intended use, technological characteristics and combined performance data support the substantial equivalence claim for Pacific Hemostasis Immunodepleted Factor V Deficient Plasma to Dade® Immunoadsorbed Factor V Deficient Plasma. Therefore based on the data provided, it is our conclusion that Pacific Hemostasis Immunodepleted Factor V Deficient Plasma is substantially equivalent to Dade® Immunoadsorbed Factor V Deficient Plasma.

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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 consists of a stylized eagle or bird symbol with three curved lines representing its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular fashion around the bird symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Laura A. Worfolk, Ph.D. Research Scientist Pacific Hemostasis . . ........................................... 11515 Vanstory Drive Huntersville, NC 28078

AUG 1 3 1997

K972627 Re : Pacific Hemostasis Immunodepleted Factor V Deficient Plasma (ThromboScreen® Brand) Requlatory Class: II Product Code: GJT Dated: July 11, 1997 Received: July 14, 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, Druq, 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 requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 620) 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 In addition, FDA may publish further announcements action. 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 Requlations.

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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 requlation (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/dsmamain.html".

Sincerely yours,
Steven Litman

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

510(k) Number (if known):____

Device Name:_Immunodepleted Factor V Deficient Plasma

Indications For Use:

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Lise ૮૮૫ Gver-The-Counter Use_.._______________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801,109) (Optional Format 1-2-96) ision "im-Off) vision of Clinical Laboratory () Neinker

Regulation Number and Section

§ 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).