The ACL TOP Family 70 Series (ACL TOP 370, ACL TOP 570 and ACL TOP 770 / 770s / 770 LAS) are bench top, fully automated, random access analyzers designed specifically for in vitro diagnostic clinical use by health care professionals in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The systems provide results for both direct hemostasis measurements and calculated parameters.

Device Description

The ACL TOP Family 70 Series are fully automated coagulation analyzers that utilize the same intuitive software, the same consumables, reagents, calibrators and controls, and provide the same analytical methodology for routine and specialty assay result reporting as the predicate ACL TOP Family 50 Series.

The ACL TOP Family 70 Series instrument performs the following types of tests, using the same optical measuring wavelengths and test parameters as the predicate ACL TOP Family 50 Series:

. Coagulometric (Turbidimetric) Measurements
Chromogenic (Absorbance) Measurements .
. Immunological Measurements

The ACL TOP Family 70 Series also offers the same pre-analytical features available on the ACL TOP Family 50 Series. These features alert the instrument operator to a potential HIL (Hemoglobin, Icteric and Lipemia) interference situation specific to the assays requested for a sample, underfilled sample tubes or a detected clog.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the ACL TOP Family 70 Series device, based on the provided document:

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for the ACL TOP Family 70 Series appears to be demonstrating equivalent analytical performance to its predicate device, the ACL TOP Family 50 Series, across various representative assays. This equivalency is assessed through precision and method comparison studies.

Table of Acceptance Criteria and Reported Device Performance:

Study Category	Acceptance Criteria	Reported Device Performance (ACL TOP Family 70 Series)
Precision	Precision (e.g., %CV) should be within acceptable limits as defined by established guidelines (CLSI EP05-A3) and comparable to the predicate device's expected performance.	Successfully met criteria. Examples: - HemosIL D-Dimer HS 500: Low Control Total %CV 4.8, High Control Total %CV 2.1 - HemosIL Factor VIII: Normal Control Total %CV 3.4, Abnormal Control Total %CV 4.8 - HemosIL RecombiPlasTin 2G (PT): Normal Control Total %CV 1.8, High Abn Control %CV 4.0 - HemosIL RecombiPlasTin 2G (Fibrinogen): Normal Control Total %CV 3.9, Low Fibrinogen Control %CV 8.1 - HemosIL Liquid Anti-Xa: UF Low Control Total %CV 1.8, LMW High Control Total %CV 2.2
Method Comparison	Linear regression analysis (slope, intercept, correlation coefficient 'r') between the subject device and predicate device should demonstrate equivalent performance across the analytical measuring range (AMR), according to established guidelines (CLSI EP09c. 3rd Ed).	Successfully met criteria. All studies showed strong correlation (r ≥ 0.998) and slopes close to 1 with intercepts close to 0, indicating equivalence. Examples: - HemosIL D-Dimer HS 500: Slope 1.022, Intercept 0.5575, r 0.998 - HemosIL Factor VIII: Slope 1.006, Intercept -0.0587, r 0.998 - HemosIL RecombiPlasTin 2G (PT): Slope 1.012, Intercept -0.0940, r 1.000 - HemosIL RecombiPlasTin 2G (Fibrinogen): Slope 0.9756, Intercept -1.1220, r 0.999 - HemosIL Liquid Anti-Xa: Slope 0.9804, Intercept -0.0145, r 0.999
Overall Conclusion	Updates introduced do not impact the labeled performance data of the current menu of FDA-cleared assays. Device is safe and effective for its intended purpose and equivalent in performance to the predicate device.	Analytical study results demonstrate that the ACL TOP Family 70 Series, with updated non-analytical features, is safe and effective for its intended purpose and equivalent in performance to the predicate device (K150877).

Study Details:

Sample size used for the test set and the data provenance:
- Precision Studies:
  - For each material/control for the selected representative assays, samples were run for 20 days at two runs per day, 2 replicates per run, resulting in a total of n=80 data points per material.
  - Provenance: Not explicitly stated, but based on the context of an FDA submission for an in vitro diagnostic device, these would typically be laboratory-generated samples or commercial control materials. The studies were performed internally by the manufacturer ("Instrumentation Laboratory Company").
- Method Comparison Studies:
  - Sample sizes varied per assay:
    - HemosIL D-Dimer HS 500: N = 116 clinical samples
    - HemosIL Factor VIII: N = 104 clinical samples
    - HemosIL RecombiPlasTin 2G (PT): N = 116 clinical samples
    - HemosIL RecombiPlasTin 2G (Fibrinogen): N = 114 clinical samples
    - HemosIL Liquid Anti-Xa: N = 207 clinical samples
  - Provenance: The studies included "clinical samples spanning each assay's analytical measuring range (AMR)." The country of origin of these clinical samples is not specified, but they are prospectively collected or selected for the study based on their span across the AMR.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This being an in vitro diagnostic (IVD) device for laboratory analysis, the "ground truth" for the test set is established by the measurement itself on a recognized, cleared, and well-characterized comparator device (the predicate ACL TOP Family 50 Series), or by the known concentrations/activity of control materials. It's not a subjective interpretation task that requires human adjudication or expert consensus in the same way as, for example, image-based diagnostic AI. Therefore, no human experts are explicitly mentioned as establishing a subjective ground truth for these analytical performance studies. The "ground truth" for method comparison is the performance of the predicate device.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- None. Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective human interpretation (e.g., radiology reads) where discrepancies need to be resolved. For analytical performance studies of a medical device measuring quantitative analytes, the ground truth is objective (the measured value from the predicate device or a known concentration in a control).
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. An MRMC study is not applicable here as this is an in vitro diagnostic instrument, not an AI-assisted diagnostic tool that involves human readers interpreting cases. The device automatically performs coagulation and/or fibrinolysis testing.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, effectively. The entire study evaluates the analytical performance of the device itself (the ACL TOP Family 70 Series) in a standalone manner. While trained lab personnel operate the instrument, the performance metrics (precision, method comparison) are about the instrument's ability to produce accurate and precise results, independent of human interpretive intervention for the results themselves. The device's "algorithm" (its internal measurement and calculation processes) is being evaluated.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For precision studies, the ground truth is the known concentration/activity of control and plasma pool materials.
- For method comparison studies, the ground truth is the measured values obtained from the predicate device (ACL TOP Family 50 Series) for the same clinical samples. The principle is to see if the new device produces equivalent results when compared to an already accepted diagnostic method.
The sample size for the training set:
- The document does not mention a training set in the context of machine learning or AI model development. This device is an IVD instrument that utilizes established analytical methodologies (coagulometric, chromogenic, immunological measurements) and software, rather than a machine learning model that requires a discrete training phase with labeled data. The studies performed are verification and validation studies to demonstrate performance and equivalency to a predicate.
How the ground truth for the training set was established:
- As there is no mention of a "training set" in the context of an AI/ML model, this question is not applicable. The device's operation is based on pre-defined analytical principles, not on learning from a training dataset to establish a ground truth.

Summary

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June 21, 2023

Instrumentation Laboratory Company Carol Marble Senior Director of Regulatory Affairs 180 Hartwell Road Bedford, Massachusetts 01730

Re: K231031

Trade/Device Name: ACL TOP Family 70 Series Regulation Number: 21 CFR 864.5400 Regulation Name: Coagulation Instrument Regulatory Class: Class II Product Code: GKP Dated: April 10, 2023 Received: April 11, 2023

Dear Carol Marble:

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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 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 (OS) 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 mediation-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,

Min Wu -S

Min Wu, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K231031

Device Name ACL TOP Family 70 Series

Indications for Use (Describe)

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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510(k) Summary

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

Submitter's Information	Instrumentation Laboratory Company180 Hartwell RoadBedford, MA 01730-2443 (USA)
-------------------------	-----------------------------------------------------------------------------------------

Contact Person	Carol Marble
	Senior Director of Regulatory Affairs
	Phone: 781-861-4467
	Fax: 781-861-4207
	Email: cmarble@werfen.com

Preparation Date	June 15, 2023
------------------	---------------

Device Trade Names	ACL TOP Family 70 Series models:
	• ACL TOP 370
	• ACL TOP 570
	• ACL TOP 770
	• ACL TOP 770s
	• ACL TOP 770 LAS

Predicate Device	ACL TOP Family 50 Series	K150877
------------------	--------------------------	---------

Regulatory Information
Regulation No.	Regulation Description	Classification	Product Code	Panel
21 CFR 864.5400	Coagulation Instrument	II	GKP	Hematology (81)

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Device Description

The ACL TOP Family 70 Series instrument performs the following types of tests, using the same optical measuring wavelengths and test parameters as the predicate ACL TOP Family 50 Series:

. Coagulometric (Turbidimetric) Measurements
Chromogenic (Absorbance) Measurements .
. Immunological Measurements

Intended Use / Indications for Use

Special Conditions for Use Statement

For prescription use only. ●

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Summary Comparison of Technological Characteristics (Predicate)
Item	Predicate Device (K150877)	Subject Device
Similarities
Trade Names	ACL TOP Family 50 Series	ACL TOP Family 70 Series
Model Trade Names	ACL TOP 350 CTSACL TOP 550 CTSACL TOP 750 CTSACL TOP 750ACL TOP 750 LAS	ACL TOP 370ACL TOP 570ACL TOP 770ACL TOP 770sACL TOP 770 LAS
Manufacturer	Instrumentation Laboratory Co.	Same
Classification	Class II	Same
Review Panel	Hematology (81)	Same
Regulation Description	Instrument, Coagulation, Automated	Same
Product Code	GKP	Same
Regulation Section	21 CFR 864.5400	Same
Indications for Use /Intended Use	The ACL TOP Family 50 Series (ACL TOP 350 CTS, ACL TOP 550 CTS, ACL TOP 750, ACL TOP 750 CTS, ACL TOP 750 LAS) are bench top, fully automated, random access analyzers designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The systems provides results for both direct hemostasis measurements and calculated parameters.	The ACL TOP Family 70 Series (ACL TOP 370, ACL TOP 570 and ACL TOP 770 / 770s / 770 LAS) are bench top, fully automated, random access analyzers designed specifically for in vitro diagnostic clinical use by health care professionals in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The systems provide results for both direct hemostasis measurements and calculated parameters.
Test Methodology	Coagulometric measurement Chromogenic measurement Immunological measurement	Same
Wavelengths	405 nm 535 nm 671 nm	Same
Summary Comparison of Technological Characteristics (Predicate) (Cont.)
Item	Predicate Device (K150877)	Subject Device
	Similarities (Cont.)
Test Menu	Clotting Assays Chromogenic Assays Immunological Assays	Same
Test Parameters	Assay volumes, rinse and clean cycles, timing, optical parameters, data algorithms, material definition	Same
Reagents, Controls and Calibrators	Packaging, formulation, performance claims in labeling	Same
Fluidic Handling	Aspiration, dispense, mixing, rinse, clean, temperature control, bulk fluids	Same
Sample Handling	Cap piercing, onboard storage	Same
Onboard Reagent Storage	Stirring, temperature control	Same
Reaction and Detection	Optics, temperature control	Same
System Software	Hardware control, user interface except as noted in the Differences section below	Same
Quality Control	Automated QC	Same
Pre-Analytical HIL Check	Standard for all models:Third measurement wavelength @535 nmand an additional emitter control channel	Same
Tube Fill Height Check	Standard for all models	Same
Clog Detection	Standard for all models	Same
Summary Comparison of Technological Characteristics (Predicate) (Cont.)
Item	Predicate Device (K150877)	Subject Device
Differences
External Skins and Chassis	On-market instrument appearance	Updated instrument appearance
Control Module Monitor	17-inch color touchscreen monitor	22-inch color touchscreen monitor
Software / Cybersecurity	On-market instrument software andcybersecurity	Updated Graphical User Interface (GUI)for aesthetics (e.g., higher resolutionicons)
		Added the Study Mode internal functionto support laboratories in more efficientlymeeting their Quality Systemrequirements. The Study Mode providesthe interface for laboratories to organizeand execute their internal performancestudies, including collection of data for lotcomparison, instrument comparison, orreference intervals.
		Added permission-based remote-controlfunction for desktop sharing and remotesoftware delivery and upgrades, utilizingsecurity and privacy controls by designand installed by default.

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Performance Summary

Analytical studies (specifically internal precision and method comparison) were performed on one lot of selected representative assays to establish that the updates introduced with the ACL TOP Family 70 Series do not impact the labeled performance data of the current menu of FDA-cleared assays claimed for the ACL TOP Family 50 Series. These studies followed recognized guidelines:

CLSI EP05-A3
. CLSI EP09c. 3rd Ed

All analytical studies were performed in accordance to established plans and protocols and design control procedures. Testing verified that all acceptance criteria were met and results equivalent to the predicate device.

Precision

Precision studies were performed using one lot of the following selected representative assays tested on representative ACL TOP Family 70 Series models (ACL TOP 370, ACL TOP 570, and ACL TOP 770). These studies used samples and controls with each material run for 20 days at two runs per day, 2 replicates per run (n=80).

Summary results for a representative ACL TOP Family 70 Series model are shown in the table below:

Material	Mean	Within Run %CV	Total %CV
Low Control	676.9	4.5	4.8
High Control	2488.9	1.7	2.1
Cut-off Pool	569.9	6.4	6.5
High Pool	2486.6	2.0	2.0

HemosIL D-Dimer HS 500 (K172903) – D-dimer ng/mL FEU

HemosIL Factor VIII deficient plasma (K034007) – Factor VIII % Activity

Material	Mean	Within Run %CV	Total %CV
Normal Control	94.22	2.6	3.4
Abnormal Control	29.58	2.0	4.8
Plasma Pool 1	33.30	2.7	3.8
Plasma Pool 2	9.01	2.4	2.7

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Precision
HemosIL RecombiPlasTin 2G (K070005) – Prothrombin Time Seconds
Material	Mean	Within Run %CV	Total %CV
Normal Control	11.94	0.6	1.8
Normal Control	23.24	0.7	3.7
Low Abn Control	36.93	0.8	5.0
High Abn Control	38.10	0.9	4.0
HemosIL RecombiPlasTin 2G (K070005) – Fibrinogen mg/dL
Material	Mean	Within Run %CV	Total %CV
Normal Control	339.1	0.9	3.9
Low Fibrinogen Control	140.7	6.4	8.1
Normal Pool	284.5	2.1	3.8
Abnormal Pool	136.9	4.3	5.0
HemosIL Liquid Anti-Xa (K213464) – Heparin IU/mL
Material	Mean	Within Run %CV	Total %CV
UF Low Control	0.36	1.4	1.8
UF High Control	0.66	1.5	1.8
UF Pool	0.56	1.2	2.2
LMW High Control	1.50	1.9	2.2
LMW Low Control	0.58	2.2	2.6
LMW Pool	0.66	2.0	2.4

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Method Comparison

Method comparison studies were performed using one lot of the following selected representative assays to compare the performance on representative ACL TOP Family 70 Series models (ACL TOP 370, ACL TOP 570, and ACL TOP 770 or ACL TOP 770 LAS) to a representative ACL TOP Family 50 Series model (ACL TOP 750 CTS). The studies included clinical samples spanning each assay's analytical measuring range (AMR) to demonstrate the equivalent performance between the subject and predicate devices.

Summary results for a representative ACL TOP Family 70 Series model are shown in the table below:

HemosIL D-Dimer HS 500 (K172903) – ng/mL FEU
Subject System	N	Slope	Intercept	r	Predicate System
ACL TOP Family 70 Series	116	1.022	0.5575	0.998	ACL TOP Family 50 Series
HemosIL Factor VIII deficient plasma (K034007) – % Activity
Subject System	N	Slope	Intercept	r	Predicate System
ACL TOP Family 70 Series	104	1.006	-0.0587	0.998	ACL TOP Family 50 Series
HemosIL RecombiPlasTin 2G (K070005) – Prothrombin Time (Seconds)
Subject System	N	Slope	Intercept	r	Predicate System
ACL TOP Family 70 Series	116	1.012	-0.0940	1.000	ACL TOP Family 50 Series
HemosIL RecombiPlasTin 2G (K070005) – Fibrinogen (mg/dL)
Subject System	N	Slope	Intercept	r	Predicate System
ACL TOP Family 70 Series	114	0.9756	-1.1220	0.999	ACL TOP Family 50 Series
HemosIL Liquid Anti-Xa (K213464) – Heparin (IU/mL)
Subject System	N	Slope	Intercept	r	Predicate System
ACL TOP Family 70 Series	207	0.9804	-0.0145	0.999	ACL TOP Family 50 Series

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Conclusion

The technological and functional characteristics of the ACL TOP Family 70 Series (subject device) as described herein are substantially equivalent to that of the ACL TOP Family 50 Series (predicate device). The analytical study results demonstrate that the ACL TOP Family 70 Series with updated non-analytical features is safe and effective for its intended purpose and equivalent in performance to the predicate device (K150877).

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.