The Audit® MicroControls™ Linearity FD Tumor Markers II is intended to simulate human patient samples for use as assayed quality control material, determining linearity, callbration verification of reportable range for the HE4 and HER2 analytes.

The Audit® MicroControlsTM Linearity FD Tumor Markers II is for In Vitro Diagnostic use only.

Device Description

The Audit® MicroControls™ Linearity FD Tumor Markers II is an in-vitro diagnostic device consisting of sets of 5 levels of freeze-dried, linearity material and additives in human based serum. The product contains the following analytes: HE4 and HER2. Each set consists of 5 levels labeled Level A, B, C, D and E. Each level has a fill size of 1ml. Materials of human origin used in the manufacture of this linearity set have been tested using FDA approved methods and are found to be non-reactive for HbsAg and antibodies to HCV and HIV-1/2.

AI/ML Overview

This document describes the Audit® MicroControls™ Linearity FD Tumor Markers II, an in-vitro diagnostic device. The provided text, however, focuses on the substantial equivalence review for a regulatory submission (510(k)) and details the device's characteristics, intended use, and performance data from stability studies. It does not present a study designed to prove the device meets specific acceptance criteria in terms of diagnostic accuracy or clinical effectiveness, as it is a quality control material.

The "acceptance criteria" discussed here relate to the stability and value assignment of the control material, not to diagnostic performance metrics like sensitivity or specificity for a medical imaging device. The "performance" refers to the stability of the control material and its ability to provide target values.

Therefore, many of the requested points are not applicable to this type of device and submission. I will address the relevant points based on the provided text.

Acceptance Criteria and Reported Device Performance

As this device is a quality control material, the acceptance criteria relate to its stability and the establishment of target values for its analytes (HE4 and HER2).

Acceptance Criteria Category	Specific Criteria/Study Type	Reported Device Performance/Findings
Shelf Life Stability	Accelerated Stability Study: To establish a claimed shelf life. (Specific numerical criteria for % deviation or other metrics are not provided in this summary but are stated as "Acceptance criteria were met to support the product claims.")	Shelf Life: 2 years, when stored unopened at 2-8º C. (Supported by accelerated stability studies; real-time studies are ongoing.)
Open Vial Stability	Real-Time Stability Study: To establish a claimed open vial stability period. (Specific numerical criteria for % deviation or other metrics are not provided in this summary but are stated as "Acceptance criteria were met to support the product claims.")	Open Vial Stability: 7 days, when stored tightly capped at 2-8º C. (Supported by real-time stability studies.)
Value Assignment	Multiple Measurements: Each analyte at each level was measured multiple times to establish mean target concentration values.	HE4/Roche Cobas e411 (pmol/L) Target Values and Ranges: Level A: 20.5 (Range 16.4-24.6)Level B: 380.6 (Range 304.5-456.7)Level C: 783.9 (Range 627.1-940.7)Level D: 1217.8 (Range 974.2-1461.4)Level E: 1461.0 (Range 1168.8-1753.2)HER2/Siemens Centaur XP (ng/ml) Target Values and Ranges:Level A: 5.1 (Range 4.1-6.1)Level B: 74.0 (Range 59.2-88.8)Level C: 146.0 (Range 116.8-175.2)Level D: 241.3 (Range 193.1-289.6)Level E: 303.0 (Range 242.4-363.7)
Linearity (expected)	The "Levels B, C and D produced according to the following dilution scheme:" suggests that the material is designed to demonstrate a linear relationship between levels.	The dilution scheme is provided: Level B = 0.75(Level A) + 0.25(Level E)Level C = 0.5(Level A) + 0.5(Level E)Level D = 0.25(Level A) + 0.75(Level E)

Additional Information based on request:

Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Test Set Sample Size: Not explicitly stated in terms of number of distinct samples for the stability studies or value assignment. The studies involved analyzing "vials representative of the entire lot" and "multiple times" for value assignment.
- Data Provenance: The studies were conducted by Aalto Scientific, Ltd. in Eatonton, GA, USA. The data would be considered prospective for the stability studies. The origin of the human serum matrix is not specified beyond "human serum."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- Not Applicable. The "ground truth" for this device refers to the assigned target values and stability characteristics of the quality control material itself, determined through laboratory measurements, not human expert interpretation of clinical data.
Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Not Applicable. This is not a study requiring adjudication of diagnostic interpretations. The value assignment was based on "mean value" from "multiple measurements" using specific laboratory analyzers and reagents.
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
- Not Applicable. This is a quality control material, not an AI diagnostic device that assists human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not Applicable. This is a quality control material. However, the performance assessment of the control material (stability, value assignment) is done in a "standalone" laboratory setting by measuring it on specified clinical chemistry analyzers.
The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- The "ground truth" for this quality control material is the assigned target concentration values for HE4 and HER2 established through repeated measurements on specific reference instruments (Siemens Centaur XP for HER2 and Roche Cobas e411 for HE4) using their corresponding reagents. This is a form of analytical reference measurement.
The sample size for the training set
- Not Applicable. This device is a quality control material and does not use a "training set" in the context of an AI/machine learning algorithm. The "value assignment" uses multiple measurements on specific instruments to determine the target values for each level.
How the ground truth for the training set was established
- Not Applicable. As there is no training set, this question is not relevant. However, the target values for the control material were established by measuring each analyte multiple times on the specified analyzers, and the mean value was used as the target concentration. "All supporting data is retained on file at Aalto Scientific, Ltd." (Page 6).

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

March 10, 2017

AALTO SCIENTIFIC, LTD. ROBERT BURDA REGULATORY AFFAIRS DIRECTOR 230 TECHNOLOGY PARKWAY EATONTON GA 30642

Re: K163629

Trade/Device Name: Audit® MicroControls™ Linearity FD Tumor Markers II Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I, Reserved Product Code: JJX Dated: December 21, 2016 Received: January 11, 2017

Dear Mr. Robert Burda:

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Kelly Oliner -S

For

Leonthena Carrington, MBA, MS, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health] Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K163629

Device Name Audit® MicroControls™ Linearity FD Tumor Markers II

Indications for Use (Describe)

The Audit® MicroControlsTM Linearity FD Tumor Markers II is for In Vitro Diagnostic use only.

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: K163629

A. Submitter

Aalto Scientific, Ltd. 230 Technology Parkway Eatonton, GA 31024 Telephone: (760) 431-7922 Fax:

Contact Person

Robert Burda Regulatory Affairs Director Telephone: (760) 444-8756 Email: rburda@aaltoscientific.com

Date of Summary Preparation

March 06, 2017

B. Device Identification

Product Trade Name:	Audit® MicroControls™ Linearity FD Tumor Markers II
Common Name:	Multi-Analyte Controls (Assayed and Unassayed)
Review Panel:	Clinical Chemistry
Device Classification:	Class I, Reserved
Product Code:	JJY
Regulation Number:	21CFR862.1660

C. Device to Which Substantial Equivalence is Claimed

K130762: Audit® MicroCV ™ Therapeutic Drug (TDM) Linearity Set

D. Intended Use

The Audit® MicroControls™ Linearity FD Tumor Markers II is intended to simulate human patient samples for use as assayed quality control material, determining linearity, calibration verification, and the verification of reportable range for the HE4 and HER2 analytes.

The Audit® MicroControls™ Linearity FD Tumor Markers II is for In Vitro Diagnostic use only.

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E. Technical Characteristics Compared to Predicate Device

Characteristics	(New Device, K163629)Audit® MicroControls™Linearity FD Tumor Markers II	(Predicate Device, K130762)Audit® MicroCV™Therapeutic Drug (TDM)Linearity Set
Intended Use	The Audit® MicroControls™Linearity FD Tumor Markers IIis intended to simulate humanpatient samples for use asassayed quality controlmaterial, determininglinearity, calibrationverification, and theverification of reportablerange for the HE4 and HER2analytes.The Audit® MicroControls™Linearity FD Tumor Markers IIis for In Vitro Diagnostic useonly.	The Audit® MicroCV™Therapeutic Drug (TDM)Linearity Set is an assayedquality control materialconsisting of five levels ofhuman based serum. Eachlevel contains:Acetaminophen, Amikacin,Carbamazepine, Digoxin,Gentamicin, Lithium,Methotrexate, Phenobarbital,Phenytoin, Quinidine,Salicylate, Theophylline,Tobramycin, Valproic Acidand Vancomycin. These fivelevels demonstrate a linearrelationship to each other fortheir respective analytes. It isintended to simulate humanpatient serum samples forpurpose of determininglinearity, calibrationverification and verification ofreportable range forAcetaminophen, Amikacin,Carbamazepine, Digoxin,Gentamicin, Lithium,Methotrexate, Phenobarbital,Phenytoin, Quinidine,Salicylate, Theophylline,Tobramycin, Valproic Acidand Vancomycin. Theproduct is intended for usewith quantitative assays onthe indicated analyzerprovided in the labeling andmay be used as qualitycontrol material for theseanalytes. When used forquality control purposes, it isrecommended that eachlaboratory establish its ownmeans and acceptable

		ranges and use the valuesprovided only as guides. TheAudit® MicroCV™Therapeutic Drug (TDM)Linearity Set should not beused for calibration orstandardization of theAcetaminophen, Amikacin,Carbamazepine, Digoxin,Gentamicin, Lithium,Methotrexate, Phenobarbital,Phenytoin, Quinidine,Salicylate, Theophylline,Tobramycin, Valproic Acidand Vancomycin assays.The Audit® MicroCV™Therapeutic Drug (TDM)Linearity Set is "For In VitroDiagnostic Use Only".
Matrix	Human Serum	Human Serum
Type ofAnalytes	Clinical Chemistry	Clinical Chemistry
Form	Freeze-dried powder	Freeze-dried powder
Storage	2-8°C	2-8°C
Shelf Life	2 years at 2-8°C	2 years at 2-8°C
Open VialStability	7 days at 2-8°C	7 days at 2-8°C
Sterile	No	No
Analytes	HE4, HER2	Acetaminophen, amikacin,carbamazepine, digoxin,gentamicin, lithium,phenobarbital, phenytoin,quinidine, salicylate,theophylline, tobramycin,valproic acid, andvancomycin

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F. Device Description

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G. Value Assignment/Linearity

The mean and expected range for each method shall be presented in each lot specific insert of Audit® MicroControls™ Linearity FD Tumor Markers II. The indicated values shall be derived from analysis of vials representative of the entire lot. Analyte value assignment for Level A through Level E was performed on Siemens Centaur XP for the HER2 analyte and the Roche Cobas e411 for the HE4 analyte using the corresponding reagents. The analytes were measured multiple times. The mean value of each analyte was used to establish a tarqet concentration value at each level. All supporting data is retained on file at Aalto Scientific, Ltd.

H. Summary of Performance Data

Stability studies have been performed to determine the open vial stability and shelf life for the Audit® MicroControls™ Linearity FD Tumor Markers II.

Shelf Life-Accelerated Stability

Accelerated stability studies were conducted to establish the shelf life stability claims. All supporting data is retained on file at Aalto Scientific, Ltd. Acceptance criteria were met to support the product claims as follows:

Shelf Life: 2 years, when stored unopened at 2-8º C.

Shelf Life-Real Time Stability

Real time studies are ongoing to support the shelf life of this product.

Open Vial Stability

Real time stability studies were conducted to establish the open vial stability claims. All supporting data is retained on file at Aalto Scientific, Ltd. Acceptance criteria were met to support the product claims as follows:

Open Vial Stability. Once a vial has been opened, the product will be stable for 7 days when stored tightly capped at 2-8º C.

-Expected Values

Analyte value assignment was performed for Audit® MicroControls™ Linearity FD Tumor Markers II using the corresponding reagents for HE4 and HER2. Each analyte was measured multiple times and the mean value was used to establish target concentration values at each level. The target ranges are shown below.

The expected range of the mean is provided to assist the laboratory until it has established its own mean and standard deviation. The indicated mean and expected range (target range) of the mean is provided to serve only as a quide in assessing the performance of the test method in laboratories.

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Approximate target values for HE4 and HER2 are given in the table below. Lot-specific target values may differ after value assignment.

HE4/Roche Cobas e411 (pmol/L)
Level A		Level B		Level C		Level D		Level E
Target value	Target Range	Target value	Target Range	Target value	Target Range	Target value	Target Range	Target value	Target Range
20.5	16.4-24.6	380.6	304.5-456.7	783.9	627.1-940.7	1217.8	974.2-1461.4	1461.0	1168.8-1753.2

HER2/Siemens Centaur XP (ng/ml)
Level A		Level B		Level C		Level D		Level E
Target value	Target Range	Target value	Target Range	Target value	Target Range	Target value	Target Range	Target value	Target Range
5.1	4.1-6.1	74.0	59.2-88.8	146.0	116.8-175.2	241.3	193.1-289.6	303.0	242.4-363.7

Levels B, C and D produced according to the following dilution scheme:

Level B = 0.75(Level A) + 0.25(Level E)

Level C = 0.5(Level A) + 0.5(Level E)

Level D = 0.25(Level A) + 0.75(Level E)

J. Traceability

Materials are obtained from internally qualified vendors and are subject to an internal quality control process. Raw material information is retained on file at Aalto Scientific, Ltd.

K. Conclusions

Based upon the purpose of the device, the descriptions and labeling of the predicate device, the safety and efficacy, and the stability data generated, the product is substantially equivalent to the predicate device.

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.