The Pacific Hemostasis ThromboScreen® 400C is a photo-optical instrument used for the performance of in-vitro diagnostic coagulation testing of citrated plasma samples in the clinical laboratory. The ThromboScreen® 400C has both clot and chromogenic testing capabilities. Assays performed on the instrument include routine clotting tests such as Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (Clauss and Derived methods), and PT and APTT-based factor assays. Chromogenic tests include assays such as Antithrombin III, Protein C and Heparin Xa.

Device Description

The ThromboScreen® 400C (TS400C) is a photo-optical instrument used for the performance of in-vitro diagnostic clotting and chromogenic procedures in the clinical laboratory. The instrument utilizes photo-optical principles for both clotting and chromogenic assays. The ThromboScreen® 400C light source is provided by a halogen lamp. The incubator block is temperature regulated to 36.5 - 37.5℃ and contains four measuring positions, five reagent and 24 cuvette prewarming positions.

AI/ML Overview

Here's an analysis of the provided text regarding the ThromboScreen® 400C, structured to address your request:

Acceptance Criteria and Device Performance Study

The ThromboScreen® 400C (TS400C) is a manual coagulation instrument using photo-optical principles for in-vitro diagnostic clotting and chromogenic procedures. The study aims to demonstrate its substantial equivalence to the MLA-900C and MLA-1000C. The acceptance criteria are implicitly defined by the performance of the predicate devices (MLA-900C and MLA-1000C) in precision and method comparison studies. The TS400C's performance is deemed acceptable if its results are comparable to those of the predicate devices.

1. Table of Acceptance Criteria (as implied by predicate devices) and Reported Device Performance (TS400C)

Test	Metric (Implied Acceptance)	TS400C Reported Performance
Within-run Precision (%CV)
PT (Low/Normal/High)	Comparable to MLA-900C/1000C	Site 1: 1.9-2.5; Site 2: 4.3-5.2
APTT (Low/Normal/High)	Comparable to MLA-900C/1000C	Site 1: 3.1-5.4; Site 2: 2.4-4.1
Clauss Fibrinogen (Low/Normal/High)	Comparable to MLA-900C/1000C	6.4-7.2
Derived Fibrinogen (Low/Normal/High)	Comparable to MLA-900C/1000C	2.3-7.5
Factor V (Low/Normal)	Comparable to MLA-900C/1000C	4.0-4.5
Factor VIII (Low/Normal)	Comparable to MLA-900C/1000C	9.7-9.9
Chromogenic ATIII (Low/Normal)	Comparable to MLA-900C/1000C	4.9-6.9
Between-run Precision (%CV)
PT (Normal/High)	Comparable to MLA-1000C	3.4-6.0
APTT (Normal/High)	Comparable to MLA-1000C	1.8-2.5
Clauss Fibrinogen (Low/Normal/High)	Comparable to MLA-1000C	2.9-4.1
ATIII (Low/Normal)	Comparable to MLA-1000C	4.5-9.4
Method Comparison (Correlation Coefficient, r)
Prothrombin Time (seconds)	High correlation (e.g., >0.95)	0.99 (both sites)
Prothrombin Time (INR)	High correlation (e.g., >0.95)	0.98, 0.99
Derived Fibrinogen	High correlation (e.g., >0.95)	0.98
Activated Partial Thromboplastin Time	High correlation (e.g., >0.95)	0.98, 0.96
Clauss Fibrinogen	High correlation (e.g., >0.95)	0.98 (both sites)
Factor VIII	High correlation (e.g., >0.95)	0.97
Factor V	High correlation (e.g., >0.95)	0.97
Chromogenic ATIII	Moderate-High correlation (e.g., >0.85)	0.88

Summary of Device Performance:

Precision: The TS400C demonstrated within-run and between-run precision comparable to the predicate MLA instruments, as detailed in Tables 1 and 2. For instance, PT within-run %CV for TS400C ranged from 1.9-5.2%, while the MLA ranged from 1.1-3.8% (Site 1) and 1.5-2.0% (Site 2). APTT within-run %CV for TS400C ranged from 2.4-5.4%, while the MLA ranged from 0.8-0.9% (Site 1) and 2.2-3.3% (Site 2). While not identical, the presented data is used to support substantial equivalence.
Method Comparison: The TS400C showed high correlation coefficients (r-values ranging from 0.88 to 0.99) when compared to the MLA-900C/1000C for various coagulation tests (PT, APTT, Fibrinogen, Factor V, Factor VIII, Chromogenic ATIII), as shown in Table 3. This indicates a strong agreement between the results obtained from the TS400C and the predicate devices. The regression equations also suggest a close linear relationship.

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

Test Set Sample Sizes:
- Within-run Precision (Table 1): Unspecified number of samples for each "Low," "Normal," and "High" category for each test. The table implies at least three distinct sample types (Low, Normal, High) for most tests.
- Between-run Precision (Table 2): Unspecified number of samples for each "Low," "Normal," and "High" category for each test.
- Method Comparison (Table 3):
  - Prothrombin Time (seconds & INR): 94 samples (Site #1), 139 samples (Site #2)
  - Derived Fibrinogen: 47 samples (Site #1)
  - Activated Partial Thromboplastin Time: 93 samples (Site #1), 117 samples (Site #2)
  - Clauss Fibrinogen: 50 samples (Site #1), 20 samples (Site #2)
  - Factor VIII: 49 samples (Site #1)
  - Factor V: 50 samples (Site #1)
  - Chromogenic ATIII: 58 samples (Site #1)
Data Provenance: The study was conducted at two sites, referred to as "Site 1" and "Site 2." Site 1 used the MLA-1000C as the predicate, and Site 2 used the MLA-900C. The data is from "specimens... from apparently healthy individuals and from patients with different pathological conditions." This indicates prospective and/or retrospective clinical samples, collected with a mix of healthy and diseased states, to ensure a wide range of values. The country of origin is not explicitly stated but implies testing within a clinical laboratory setting, likely in the US given the FDA submission.

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

The concept of "experts" and "ground truth" as typically applied to image analysis or diagnostic interpretation by human readers is not directly applicable here. For a coagulation instrument, the "ground truth" is typically established by:

The reference method (here, the predicate MLA-900C and MLA-1000C instruments).
Clinically validated reagents and controls.
Adherence to established laboratory assay protocols.

Therefore, no information on the number or qualifications of "experts" (e.g., radiologists) in this context is provided or expected. The expertise implicitly lies in the design and validation of the predicate devices and the laboratory personnel performing the assays.

4. Adjudication Method for the Test Set

Not applicable. As this is a comparison between two instruments measuring quantifiable analytes, there is no human adjudication process involved in establishing the "correct" measurement for each sample. The comparison is statistical (correlation, regression, precision metrics).

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This is not an MRMC study. MRMC studies are typically used to assess reader performance (e.g., radiologists interpreting images) with and without AI assistance. This study involves comparing the performance of a new instrument against established predicate instruments for quantitative laboratory tests. Therefore, there is no "effect size of how much human readers improve with AI vs without AI assistance" to report.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, this is essentially a standalone (algorithm only) performance study of the TS400C. The instrument, while "manual" in that samples are pipetted by a user, performs the measurement and calculation independently of human interpretation of the results themselves. The data presented demonstrates the instrument's intrinsic accuracy and precision when performing specified assays, without a human interpretation step that the AI assists. The comparison is between the standalone TS400C and the standalone predicate MLA instruments.

7. Type of Ground Truth Used

The "ground truth" for the test set is established by the measurements obtained from the legally marketed predicate devices, the MLA-900C and MLA-1000C. These devices serve as the reference standard against which the new device's performance is compared. The use of "clinically significant ranges" and "patients with different pathological conditions" ensures that the comparison covers the relevant analytical range encountered in clinical practice.

8. Sample Size for the Training Set

The document does not describe a separate "training set" in the context of machine learning or AI models with distinct training and test phases. This is a traditional medical device validation study where the instrument's performance is evaluated. The "training" in this context would have occurred during the development and calibration of the TS400C by the manufacturer (Pacific Hemostasis). No specific sample size for such internal development is provided.

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

As explained above, the concept of a separate "ground truth" for a training set (as in AI/ML) is not explicitly detailed. The TS400C instrument's calibration and optimization would have been performed by the manufacturer, likely using internal standards, reference materials, and comparing against established laboratory methods, much like the predicate devices themselves would have been developed. This "ground truth" for development would involve the known values of calibrators and controls used to ensure the instrument's accuracy and linearity across its measuring range.

Summary

{0}------------------------------------------------

PREMARKET NOTIFICATION 510(K) SUMMARY 10.0

Applicant:	Laura A. Worfolk, Ph.D.Pacific Hemostasis11515 Vanstory DriveHuntersville, NC 28078704-875-0494Fax # 704-875-2092
Contact:	Laura A. WorfolkPhone: 704-875-0494Fax #: 704-875-2092
Date:	June 21, 1999
Trade Name:	Pacific Hemostasis ThromboScreen® 400C
Common Name:	Manual Coagulation Instrument
Classification Name:	Instrument, Coagulation (per 21 CFR section 864.5400)
Equivalent Devices:	MLA-900C, #K884863 & the MLA-1000C, #K894052

Description of the ThromboScreen® 400C

Intended Use of the ThromboScreen® 400C

The Pacific Hemostasis ThromboScreen® 400C is a photo-optical instrument used for the performance of in-vitro diagnostic coagulation testing of citrated plasma samples in the clinical Coagulation testing capabilities of the device include routine clotting tests such as laboratory. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (Clauss and Derived methods), as well as PT and APTT-based factor assays. Chromogenic tests include assays such as Antithrombin III, Protein C and Heparin Xa.

{1}------------------------------------------------

Summary of Substantial Equivalence Comparisons

The ThromboScreen® 400C (TS400C) was compared to the MLA-900C and the MLA-1000C (K884863 & K894052, respectively). All three instruments have a similar intended use: for in-vitro diagnostic coagulation testing in the clinical laboratory. Further, the proposed device and the predicate devices utilize photo-optical measurement principles for both clot and chromogenic based assays,

The TS400C is a "manual" coagulation instrument, in that the user must pipet both sample and test reagent. In contrast, the MLA-900C is semi-automated, and the MLA-1000C is a fully-automated instrument. The MLA-900C requires manual sample addition, but has an automatic pipet for reagent addition. The MLA-1000C has an automatic pipetting system, which adds both sample and test reagent. The light source for the MLA instruments is a halogen lamp and the wavelength is set at 550 nm for clotting assays, and 405 nm for chromogenic assays. A halogen lamp is also utilized by the TS400C, however a 405 nm filter is used for both clotting and chromogenic assays. Although the TS400C utilizes a different wavelength for clotting assays compared to the MLA, it has been optimized for this specific light source/filter combination. The performance data generated support this statement (Tables 1-3).

Within-run and between-run precision studies were performed using Pacific Hemostasis (PH) brand reagents. Tables 1 and 2 summarize the data obtained from these studies. Comparison testing performed is shown in Table 3. Specimens were evaluated from apparently healthy individuals and from patients with different pathological conditions, which are expected to affect the results for a particular assav. For derived Fibrinogen comparison testing, extrapolated data was included in the Note: analysis. This was done so that a wide range of Fibrinogen results could be compared between the two instruments. In a normal clinical testing situation, patient values above the highest standard curve point are not reported. Rather, the user is advised to report the result as greater than the highest standard curve value, and use the Clauss methodology for Fibrinogen testing (page 48 of the Operator's Manual).]

{2}------------------------------------------------

	Test	TS400C			MLA
		Low	Normal	High	Low	Normal	High
PT	Site 1		1.9	2.5		1.1	3.8
	Site 2		4.3	5.2		1.5	2.0
APTT	Site 1		5.4	3.1		0.8	0.9
	Site 2		2.4	4.1		3.3	2.2
Clauss Fib. *		7.2	6.7	6.4	2.8	1.2	3.8
Derived Fib. *		7.5	2.6	2.3	4.4	3.4	2.1
Factor V*		4.0	4.5		1.2	2.0
Factor VIII*		9.9	9.7		5.3	4.7
ChromogenicATIII*		6.9	4.9		10.1	3.2

Table 1. Summary of Within-run Precision Studies, %CV

*Testing at Site 1 only. (Shaded areas, no testing performed. Only clinically significant ranges tested.) Note: MLA-1000C used at Site 1, MLA-900C used at Site 2.

		TS400C			MLA-1000C
Test	Low	Normal	High	Low	Normal	High
PT		3.4	6.0		1.4	4.5
APTT		2.5	1.8		1.4	1.2
Clauss Fib.	4.1	4.0	2.9	5.5	4.5	4.9
ATIII	9.4	4.5		9.9	5.1

Table 2. Summary of Between-run Precision Testing*

*Testing performed at Site 1 only.

{3}------------------------------------------------

Test	Site & Sample #	CorrelationCoefficient, r	Regression Equation
(Reagent, Unit)
Prothrombin Time (PT)	Site #1 - 94	0.99	y = 1.045x - 0.3358
(Thromboplastin DS,seconds)	Site #2 - 139	0.99	y = 1.141x - 1.5248
Prothrombin Time	Site #1 - 94	0.98	y = 0.9395x + 0.1153
(Thromboplastin DS, INR)	Site #2 - 139	0.99	y = 0.9955x + 0.0617
Derived Fibrinogen	Site #1 - 47	0.98	y = 1.0093x + 0.1442
(Thromboplastin DS,mg/dL)
Activated PartialThromboplastin Time	Site #1 - 93	0.98	y = 1.1449x + 1.3424
(APTT-LS reagent,seconds)	Site #2 - 117	0.96	y = 0.9955x + 0.0617
Clauss Fibrinogen	Site #1 - 50	0.98	y = 0.9366x + 27.28
(Thrombin reagent,mg/dL)	Site #2 - 20	0.98	y = 0.9843x + 3.2104
Factor VIII	Site #1 - 49	0.97	y = 1.04x - 0.8112
(APTT-LS, % activity)
Factor V,	Site #1 - 50	0.97	y = 1.0511 - 5.6923
(Thromboplastin DS, %activity)
Chromogenic ATIII	Site #1 - 58	0.88	y = 0.9417x + 7.6005
(ATIII Chromogenic Kit,%)

			Table 3. Summary of Method Comparison Studies Between the TS400C & the MLA-900C/1000C
--	--	--	---------------------------------------------------------------------------------------	--	--

Note: Site 1 used the MLA-1000C, Site 2 the MLA-900C.

In conclusion, the similar intended use, technological characteristics and the combined performance data support the claim that the ThromboScreen® 400C is substantially equivalent to the MLA-900C and the MLA-1000C.

{4}------------------------------------------------

11.0 ATTACHMENTS

ThromboScreen® 400C Operator's Manual. 1.
The Introduction section of the MLA-1000C Operator's Manual. (With the exception of the 2. Automatic Primary Tube Sampler, the MLA-900C is the same system as the MLA-1000C. Therefore Refer to page 1-1 of the MLA-1000C the MLA-900C Operator's Manual was not included. Operator's Manual.)
1. TS400C Power Supply approval certificates.
1. Manufacturer's Certificate of Software Traceability.
Manufacturer's Certificate of Y2K Compatibility. 5.

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three overlapping shapes that resemble birds in flight. The logo is black and white.

DEPARTMENT OF HEALTH & HUMAN SERVICES

3 1999 SEP

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Laura A. Worfolk, Ph.D. Principal Research Scientist Pacific Hemostasis 11515 Vanstory Drive, Suite 125 11315 Vanstory Dr. Program 28078-8144 ·

K992130 K992130
Trade Name: Pacific Hemostasis ThromboScreen® 400C (TS400C) Re: Regulatory Class: II Product Code: KQG Dated: June 22, 1999 Received: June 23, 1999

Dear Dr. Worfolk:

We have reviewed your Section 510(k) notification of intent to market the device referenced We have reviewed your Section 510(c) notification of the minent (for the indications for use
above and we have determined the devices marked in interstate commerce above and we have determined the devices marketed products (top interstate commerce
stated in the enclosure) to legally marketed previce Americal in interstate commence stated in the enclosure) to legally marketed predical Device Amendments, or to devices that
prior to May 28, 1976, the enactment date of the Federal Food, Drug, and prior to May 28, 1976, the enatment and on the Federal Food, Drug, and have been reclassified in accordance with the provisions of the Peneral controls
Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls Cosmetic Act (Act). You may, therefore, market the Act include requirements for annual
provisions of the Act. The general controls provisions of the Act include requirement provisions of the Act. The general controls provisions of the Host. For I
registration, listing of devices, good manufacturing practice, labeling, and prohibitions against
a misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III
n treass If your device is classified (see above) into elder class in (opertials major regulations)
(Premarket Approval), it may be subject to such additions. Title 21, Parts 800 to 8 (Premarket Approval), it may be subject to such auch as mile 21, marts 800 to 895.
affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 affecting your device can be found in the counds compliance with the Current Good
A substantially equivalent determination assumes compliance with the Current Regulation (C A substantially equivalent determination assumes compilation (QS) for
Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) Manufacturing Practice requirements, as ser form in the Quad that, through periodic QS
Medical Devices: General regulation (21 CFR Part 820) and that, through periodic of Medical Devices: General regulation (ZI CFK Fart 620) will verify such assumptions. Failure to
inspections, the Food and Drug Administration (FDA) will verify such assumpti inspections, the Food and Drug Administration (r bring basilion, FDA may publish
comply with the GMP regulation may result in regulatory action. Please note: this comply with the GMP regulation in the Federal Register. Please note: this further announcements concerning your device in the reasing and affect any obligation you might
response to your premarket notification submission does not affectronic Produc response to your premarket notification submission actives under the Electronic Product
have under sections 531 through 542 - The Act lows or reaulations have under sections 551 through of ID CFE Federal laws or regulations.

{6}------------------------------------------------

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may Onder the Chillour Baberatory Inspiration. 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 I his letter will and w Jour of substantial equivalence of your device to a legally marketed notification. The PDF Intellig of Gestion 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 additionally, 0071100111, 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

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

Page__of_

i10(k) Number (if known):	K992130
---------------------------	---------

Device Name: _________________________________________________________________________________________________________________________________________________________________

Indications For Use:

STATEMENT OF INDICATIONS FOR USE

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

	Concurrence of CDRH, Office of Device Evaluation (ODE)
	(Division Sign-Off) Division of Clinical Laboratory Devices
510(k) Number	K992130

Prescription Use
OR
Over-The-Counter Use

Prescri (Per 21 CFR 801.109)

ver-The-Counter osc.

(Optional Format 1-2-96)

Regulation Number and Section

§ 864.5400 Coagulation instrument.

(a)
Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies.(b)
Classification. Class II (special controls). A fibrometer or coagulation timer intended for use with a coagulation instrument is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.