The Applied DNA Technologies Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests are rapid chromatographic immunoassays for the visual, qualitative detection of human chorionic gonadotropin (hCG) in serum or urine specimen to help in the early determination of pregnancy. The test kits are for health care professionals use including professionals at physician's office labs (POLs). For a final Diagnosis of pregnancy, a more specific alternative clinical method must be used to obtain a confirmed analytical result.

Device Description

The Bionexia™ hCG Pregnancy Serum/Urine Test are distributed in both Cassette and Dipstick formats. Each test reagent strip contains mouse monoclonal anti-u-hCG antibody coated membrane and a dried chemical pad containing mouse monoclonal anti-ß-hCG anybody colloidal gold conjugate. The control antibodies are goat anti-mouse IgG.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criterion	Reported Device Performance (Bionexia™ hCG Tests)
Accuracy (Serum)	100% agreement with predicate device (ACON One Step hCG Urine/Serum Test Card) for 95 clinical serum specimens.
Accuracy (Urine)	100% agreement with predicate device (ACON One Step hCG Urine/Serum Test Card) for 94 clinical urine specimens.
Sensitivity	Detects serum or urinary hCG at a concentration of 20 mIU/ml or greater.
Cross-reactivity	No cross-reaction observed for hLH (300 mIU/ml), hFSH (1000 mIU/ml), and hTSH (1,000 µIU/mL) at 0 mIU/ml hCG. 100% non-cross-reactivity for hCG at 20 mIU/ml (this is essentially a positive control).

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

Accuracy/Comparison Study (Test Set):
- Serum: 95 clinical serum specimens.
- Urine: 94 clinical urine specimens.
- Additional evaluation: 20 negative and 29 positive serum & urine specimens (total 49) were re-evaluated at a third site.
- Data Provenance: Clinical specimens. The study was conducted at two Physician's Office Labs (POLs) sites, with additional re-evaluation at a third site. The country of origin is not explicitly stated, but the submission is to the FDA in the USA. The data appears to be prospective in the sense that the new device was tested on these clinical specimens.
Sensitivity and Cross-reactivity Study (Test Set):
- Sensitivity: Standardized to the WHO Fourth International Standard 75/589, implying a controlled, possibly spiked, sample set. Specific sample count not provided, but it states detection at 20mIU/ml or greater.
- Cross-reactivity: Evaluated at 0 mIU/ml (negative) and 20 mIU/ml (positive) hCG specimens. Specific sample count for each cross-reactant not provided, but it implies tests performed with each substance at the specified level. Likely spiked control studies.
Reproducibility Study (Test Set):
- Serum Controls: 100 tests (25 tests across 4 lots) for each hCG concentration level (0, 10, 12.5, 15, 17.5, 20, 25, 30, 35, 40, 100 mIU/ml).
- Urine Controls: 100 tests (25 tests across 4 lots) for each hCG concentration level (0, 10, 12.5, 15, 17.5, 20, 25, 30, 35, 40, 100 mIU/ml).
- Data Provenance: This appears to be spiked control studies using prepared control samples rather than clinical specimens.

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

The document implies that the predicate device (ACON One Step Pregnancy Urine/Serum Test) results were used as the reference point (ground truth) for the accuracy/comparison study. It doesn't explicitly mention external experts adjudicating the Bionexia™ results against a separate "true" ground truth. The comparison is against an already legally marketed and accepted device.
For the POLs site study, it is implied that healthcare professionals (the intended users) performed the tests and interpreted the results. The specific number or qualifications of these professionals are not detailed, but they are referred to as "health care professionals use including professionals at physician's office labs (POLs)."

4. Adjudication Method for the Test Set

The primary method for the accuracy/comparison study was a direct comparison to the predicate device. A "blind-labeled" approach was used (meaning the testers likely didn't know which sample was which device), but there's no mention of a formal adjudication method (like 2+1 or 3+1 consensus) for discrepancies if they arose between the new device and the predicate. Given the 100% agreement, no adjudication would have been necessary in those specific cases.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve With AI vs Without AI Assistance

No, an MRMC comparative effectiveness study was not done. This document describes the performance of a rapid in-vitro diagnostic (IVD) test, not an AI-assisted diagnostic tool. Therefore, the concept of human readers improving with AI assistance is not applicable here. The device itself performs the detection, with visual interpretation by the healthcare professional.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance was done for the device. The accuracy, sensitivity, cross-reactivity, and reproducibility studies demonstrate the performance of the Bionexia™ hCG Pregnancy Tests themselves, irrespective of the human factor beyond the visual interpretation of the test line. The device is designed for visual qualitative detection, meaning the "algorithm" is inherent in the chemical reactions and visual indicators. The results presented are the device's performance in detecting hCG.

7. The Type of Ground Truth Used

Accuracy/Comparison Study: The ground truth was established by the results of a legally marketed predicate device (ACON One Step Pregnancy Urine/Serum Test). This serves as a comparative ground truth.
Sensitivity: The ground truth was based on the WHO Fourth International Standard 75/589 for hCG concentration, which is a standardized reference.
Cross-reactivity and Reproducibility: Ground truth was established by using controlled, spiked samples with known concentrations of hCG and other related hormones/substances.

8. The Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of machine learning or AI. For IVD devices like this, the development process typically involves internal testing and optimization (which could be considered analogous to training data for the device's design), but this is not typically reported as a formal "training set" with specific numbers in regulatory summaries. The data provided focuses on validation (test set) performance.

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

As a traditional IVD device, there isn't a "training set ground truth" in the AI sense. The development of the device (choosing antibodies, membrane materials, concentrations, etc.) would be guided by established biochemical principles and internal testing using known hCG standards and samples with confirmed values, which serves a similar function to establishing "ground truth" during product development. However, these specific details of the development process and internal testing are not provided in this 510(k) summary, which focuses on validation data for regulatory submission.

Summary

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510(k) SUMMARY AS REQUIRED BY SECTION 807.92(C)

The Assigned 510(k) number is K071030

JUN 2 9 2007

Date of Summary: June 26, 2007

Common Name: hCG (Human Chorionic Gonadotropin) Pregnancy Test

Regulatory Information:

1. Regulation section: 21 CFR part 862.1155, Human Chorionic Gonadotropin test system
1. Classification: Class II
1. Product Code: JHI, radioimmunoassay, human chorionic gonadotropin
1. Panel: Clinical Chemistry 75

Name of Submitter:

Applied DNA Technologies Inc. 6310 Nancy Ridge Dr. Suite 106 San Diego, CA 92121, USA

Contact Person:

Feng-Yu Lee

Identification / Product Name:

Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests

Description:

Intended Use:

The test kits are for health care professionals use including professionals at physician's office labs (POLs).

For a final Diagnosis of pregnancy, a more specific alternative clinical method must be used to obtain a confirmed analytical result.

Predicate Kit:

ACON One Step Pregnancy Urine/Serum Test is used as predicate device for ADT's Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests to compare their performance of required studies.

510(k) number for predicate devices is:

ACON One Step Pregnancy Urine/Serum Test

K 041946

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Performance:

The product performance characteristics of ADT's Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests were evaluated in the blind-labeled spiked control studies and blind-labeled clinical specimen correlation study including POLs site study. The results of these studies demonstrate ADT's Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests to be substantially equivalent to the performance characteristics of ACON's One Step Pregnancy Urine/Serum Test.

(I) Accuracy/Comparison study indicated 100% agreement in total of 95 clinical serum specimens and 94 clinical urine specimens evaluated, the study were conducted at two POL sites. (Additionally, 20 negative and 29 positive serum & urine specimens were reevaluated at a third site and similar results were obtained.)

1. Serum sample

	ACON One Step hCG Urine/Serum Test Card
	+	-	Total
BionexiaTM Panel	+	48	0	48
	-	0	47	47
	Total	48	47	95

2. Urine sample

	ACON One Step hCG Urine/Serum Test Card
	+	-	Total
BionexiaTMPanel	47	0	47
	0	47	47
	Total	47	47	94

(II) Sensitivity and Cross-reactivity

The Bionexia" hCG Pregnancy Serum/Urine Test detects serum or urinary hCG at a concentration of 20mIU/ml or greater. The test has been standardized to the WHO Fourth International Standard 75/589.

Cross-reactivity study (Specificity) evaluated at negative (0 mIU/ml) and positive (20 mIU/ml) hCG specimens showed no cross-reaction:

Substances (level)	% Non-cross-reactivity
hCG (20 mIU/ml)	100%
hLH (300 mIU/ml)	1,500%
hFSH (1000 mIU/ml)	5,000%
hTSH (1,000 µIU/mL)	5%

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(III) Reproducibility

Levels(mIU/ml)	0		10		12.5		15		17.5		20		25		30		35		40
Neg. / Pos.	-	+	-	+	-	+	-	+	-	+	-	+	-	+	-	+	-	+	-	+
Lot 1	25	0	25	0	20	5	11	14	2	23	0	25	0	25	0	25	0	25	0	25
Lot 2	25	0	25	0	22	3	14	11	4	21	0	25	0	25	0	25	0	25	0	25
Lot 3	25	0	25	0	21	4	12	13	2	23	0	25	0	25	0	25	0	25	0	25
Lot 4	25	0	25	0	23	2	11	14	1	24	0	25	0	25	0	25	0	25	0	25
Total No.	100	0	100	0	86	14	48	52	9	91	0	100	0	100	0	100	0	100	0	100
Percent. %	100	0	100	0	86	14	48	52	9	91	0	100	0	100	0	100	0	100	0	100

Table 1: Serum controls

Table 2: Urine controls

Levels(mIU/ml)	0		10		12.5		15		17.5		20		25		30		35		40
Neg. / Pos.	-	+	-	+	-	+	-	+	-	+	-	+	-	+	-	+	-	+	-	+
Lot 1	25	0	25	0	23	2	11	14	1	24	0	25	0	25	0	25	0	25	0	25
Lot 2	25	0	25	0	19	6	12	13	1	24	0	25	0	25	0	25	0	25	0	25
Lot 3	25	0	25	0	21	4	14	11	3	22	0	25	0	25	0	25	0	25	0	25
Lot 4	25	0	25	0	24	1	9	16	2	23	0	25	0	25	0	25	0	25	0	25
Total No.	100	0	100	0	87	13	46	54	7	93	0	100	0	100	0	100	0	100	0	100
Percent. %	100	0	100	0	87	13	46	54	7	93	0	100	0	100	0	100	0	100	0	100

Conclusion:

Results of Accuracy, POL site study demonstrate the substantial equivalency between ADT's Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests and the ACON One Step Pregnancy Urine/Serum Test panel. It is also demonstrated that ADT's Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests are safe and effective in detecting human chorionic gonadotropin (hCG) in serum or urine sample to aid in the early determination of pregnancy.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle with its wings spread, rendered in black. The eagle is positioned to the right of the text, which is arranged in a circular pattern around the logo. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".

Re:

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Applied DNA Technologies, Inc. c/o Feng-Yu Lee Vice President of Operation 26251 Verona Place Mission Viejo, CA 92692

JUN 2 9 2007

K071030 Trade/Device Name: Bionexia™ hCG Pregnancy Serum/Urine Cassette and Dipstick Tests Regulation Number: 21 CFR 862.1155 Regulation Name: Human Chorionic Gonadotropin (HCG) test system. Regulatory Class: Class II Product Code: JHI Dated: March 25, 2007 Received: April 11, 2007

Dear Feng-Yu Lee:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Jean M. Cooper, M.S., D.V.M.

Séan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K071030

Device Name: ADT's Bionexia" hCG Pregnancy Serum/Urine Cassette and Dipstick Tests

Indications For Use:

The test kits are for health care professionals use including professionals at physician's office labs (POLs).

For a final Diagnosis of pregnancy, a more specific alternative clinical method must be used to obtain a confirmed analytical result.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Page 1 of 1

Division Sign-Off

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K07/030

Regulation Number and Section

§ 862.1155 Human chorionic gonadotropin (HCG) test system.

(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.