Iontophoretic drug delivery electrodes are indicated for the administration of soluble salts or other drugs into the body for medical purposes as an alternative to hypodermic injections. They are also indicated for iontophoretic dermal administration of IONTOCAINE® (Lidocaine HCl 2% and Epinephrine 1:100,000 Topical Solution).

Device Description

An iontophoresis device is a device that is intended to use a direct current to introduce ions of soluble salts or other drugs into the body for medical purposes. Iontophoresis technology is based on the principle that an electric potential will cause ions in solution to migrate according to their electrical charges. The quantity and distribution of a drug delivered into and across the skin by iontophoresis is dependent on the charge and molecular weight of the ion, the strength of the electrical current applied, electrode composition, duration of current flow, and numerous other factors.

The RH-900 consists of an active delivery electrode and a passive return electrode. Both electrodes have buffering capability for up to an 80mA-min treatment. These electrodes are designed for a single-patient, one-application use.

This electrode is recommended for use with the Phoresor® Iontophoretic Drug Delivery Systems (Iomed, Inc., Salt Lake City, UT 84120). This system is a 9-volt battery powered, solid state, microprocessor-controlled device that controls current levels and duration, calculates total charge delivered and monitors current flow and electrode/skin impedance.

The RH-900 electrode consists of a dry, monolithic, impregnated nonwoven polyester fabric liquid containment element designed to be hydrated with an aqueous solution immediately prior to use. It also has a carbon conductive element and an adhesive tape border for skin fixation. All components in contact with the skin are known GRAS materials and/or are listed in the National Formulary.

AI/ML Overview

The provided document describes the RH-900 Iontophoresis Electrode and its comparison to predicate devices, focusing on drug delivery capabilities and biocompatibility. The document does not describe a clinical study in the typical sense with patient outcomes, nor does it involve an AI/ML device. Therefore, it does not contain information about acceptance criteria in the context of clinical performance metrics like sensitivity, specificity, or accuracy, and does not provide details like sample sizes for test sets, expert qualifications, or MRMC studies for AI/ML devices.

However, I can extract the acceptance criteria (or rather, performance benchmarks) and the study (technical testing) used to demonstrate the device meets those benchmarks based on the information provided for this medical device (an iontophoresis electrode).

Here's the information structured to best fit your request, with strong caveats that this is not an AI/ML device study:

Acceptance Criteria and Study for Iomed RH-900 Iontophoresis Electrode

This document describes the safety and effectiveness of the RH-900 Iontophoresis Electrode by comparing its drug delivery and biocompatibility to predicate devices. It establishes performance through in vitro drug transport studies and in vivo dermal irritation studies.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Aspect	Acceptance Criteria (Benchmark/Goal)	Reported Device Performance (RH-900)
Drug Delivery	Comparable transport of both negative and positive charged drugs to currently marketed electrodes (specifically, K932620 Iomed RH-806/GS and K983484 Empi Dupel B.L.U.E.™).	"The testing shows that these model drugs can be comparably delivered using the RH-900." (tested with radiolabeled dexamethazone sodium phosphate (-) and lidocaine hydrochloride (+) in hairless mouse skin in vitro).
Biocompatibility (Primary Dermal Irritation)	Negligible to slight dermal irritation (scores of 0.0 to 1.9 on an 8.0 scale), comparable to the predicate Iomed RH-806/GS (TransO2/GS) which was rated in the lowest range ("mild irritant").	Negative polarity: rated negligible (0.4). Positive polarity: rated slight (0.6). "These scores are comparable to the Iomed, Inc. RH-806/GS (TransO2/GS) marketed electrode... rated in the lowest range (mild irritant)."
Biocompatibility (Cytotoxicity)	Overall materials of construction (including the unique hydratable non-woven material) must meet USP and ISO 10993-10 requirements, demonstrating safety for limited contact with intact patient skin. Specifically for the hydratable non-woven material, test results should indicate acceptable reactivity (e.g., mild reactivity or better).	Hydratable non-woven material: Cytotoxic grade of 2 (on a 0 to 4 scale), indicating 'mild' reactivity. "This meets USP and ISO 10993-10 requirements and shows that all the materials used in the RH-900 are safe to come in limited contact with intact patient skin."

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

Drug Delivery: The sample size for the in vitro hairless mouse skin model is not explicitly stated. The provenance is from a laboratory study ("in vitro by methods described by Petelenz et al., J Controlled Release 20 (1992), 55-56"). No country of origin is specified for the lab or samples.
Biocompatibility (Primary Dermal Irritation): Rabbits were used. The specific number of rabbits is not provided. The study was conducted in accordance with FDA regulations for Good Laboratory Practices (GLP) and ISO 10993-10:2002.
Biocompatibility (Cytotoxicity): The sample size for the in vitro cytotoxicity testing of the hydratable non-woven material is not specified. The testing followed GLP procedures and referenced USP and ISO 10993-10 requirements.

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

This type of information is not applicable as this is not a study assessing diagnostic performance by human experts. The "ground truth" for drug delivery was established by quantitative measurement of radiolabeled drug transport. The "ground truth" for dermal irritation and cytotoxicity was established by standardized laboratory testing protocols (GLP, ISO 10993-10) with objective scoring criteria, not by human expert consensus on images or interpretations.

4. Adjudication Method for the Test Set

Not applicable. This is not a study requiring adjudication of expert opinions.

5. 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 device is not an AI/ML product and does not involve human readers interpreting output.

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

Not applicable. This is a non-AI medical device. The "standalone" performance here refers to the device's inherent physical and chemical properties and interaction with biological systems, as tested in the laboratory.

7. The Type of Ground Truth Used

Drug Delivery: Quantitative measurement of radiolabeled drug transport across hairless mouse skin (in vitro model).
Biocompatibility (Primary Dermal Irritation): Objective scoring of dermal reactions in rabbits based on predefined scales (0.0 to 8.0), as per ISO 10993-10:2002 and GLP.
Biocompatibility (Cytotoxicity): Standardized in vitro cytotoxicity assays yielding a grade on a 0-4 scale, as per USP and ISO 10993-10.

8. The Sample Size for the Training Set

Not applicable. This is not an AI/ML device, so there is no training set.

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

Not applicable. As there is no training set for an AI/ML algorithm, this question is irrelevant to the provided document.

Summary

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Image /page/0/Picture/1 description: The image shows the word "IOMED" in a bold, sans-serif font. The letters are all capitalized except for the "i", which is lowercase. The word is slightly slanted to the right, giving it a dynamic appearance. The text is black against a white background.

JUL 1 0 2003

SUMARY OF SAFETY AND EFFECTIVENESS Iontophoresis Electrode

Date of Summary: 7 April 2003

A. General Provisions

Submitter's Name:	Iomed, Inc.
Submitter's Address:	2441 South 3850 West, Suite ASalt Lake City, UT 84120-9941
Contact Person:	Curtis JensenQuality and Regulatory Manager
Classification Name:	Iontophoresis Device21 CFR 890.5525
Proprietary Name:	RH-900
Common Name:	Iontophoresis Drug Delivery Electrode

B. Name of Predicate Device(s)

Iontophoresis Device K932620 Iontophoresis Drug Delivery Electrode Iomed, Inc. RH-806/GS (TransO2/GS)
. Iontophoresis Device K983484 Iontophoresis Drug Delivery Electrode Empi Dupel B.L.U.E.TM (Bi-layer Ultra Electrode)

C. Device Description

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levels and duration, calculates total charge delivered and monitors current flow and electrode/skin impedance.

D. Intended Use

E. Drug Delivery and Biocompatibility

Drug Delivery

Iontophoretic transport with the RH-900 electrode of both negative and positive charged drugs was compared to transport with currently marketed electrodes in hairless mouse skin in vitro by methods described by Petelenz et al., J Controlled Release 20 (1992), 55-56 (see 'Performance' section of this document). Model drugs used for these comparisons were radiolabeled dexamethazone sodium phosphate (-) (corticosteroid) and lidocaine hydrochloride (+) (local anesthetic). The testing shows that these model drugs can be comparably delivered using the RH-900.

Biocompatibility

Primary dermal irritation studies were carried out in rabbits in accordance with FDA regulations for Good Laboratory Practices (GLP) using normal saline. The protocol was designed according to ISO 10993-10:2002, and the device was tested from both positive and negative polarities.

The results of the testing showed that the RH-900 was rated negligible (0.4) when operated from the negative polarity and slight (0.6) from the positive polarity. These scores are based on the following scale:

-0.0 to 0.4: negligible
0.5 to 1.9: slight -
2.0 to 4.9: moderate -
-5.0 to 8.0: severe

These scores are comparable to the Iomed, Inc. RH-806/GS (TransO2/GS) marketed electrode. The difference in scales from the testing of the predicate device makes an exact comparison difficult, but it was rated in the lowest range

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(mild irritant). Similar scores from the Empi B.L.U.E.™ are not available for comparison.

Although data is available showing that there are no known health hazards associated with the RH-900 hydratable non-woven material, cytotoxicity test results were not available. Therefore cytotoxicity testing was performed on the hydratable non-woven material following GLP procedures. This is the only material that is used in the RH-900 that has no cytotoxicity data available for it. All other materials are GRAS. Test results show a cytotoxic grade of 2 (on a 0 to 4 scale). This indicates 'mild' reactivity. This meets USP and ISO 10993-10 requirements and shows that all the materials used in the RH-900 are safe to come in limited contact with intact patient skin.

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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 consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird with three stylized wing-like shapes.

Public Health Service

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

JUL 1 0 2003

Mr. Curtis Jensen Ouality and Regulatory Manager lomed. Inc. 2441 South 3850 West, Suite A Salt Lake City, Utah 84120-1191

Re: K031115

Trade/Device Name: RH-900 Iontophoretic Drug Delivery Electrode Regulation Number: 21 CFR 890.5525 Regulation Name: Iontophoresis device Regulatory Class: II and III Product Code: KTB, EGJ Dated: April 7, 2003 Received: April 8, 2003

Dear Mr. Jensen:

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), as long as you comply with all of the Act's requirements relating to drugs labeled or promoted with the devices as described below. 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 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 Part 801); good manufacturing practice requirements as set

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Page 2 - Mr. Curtis Jensen

forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Our substantially equivalent decision does not apply to drugs for use with your device. Therefore, you may neither label nor promote your device for use with specific drugs other than Iontocaine (Lidocaine HCl 2% and Epinephrine 1:100,000 Topical Solution), nor package drugs with vour device prior to FDA having approved the drugs for iontophoretic administration. For information on the requirements for marketing new drugs, you may contact:

Director Division of Drug Labeling Compliance (HFD-310) Center for Drug Evaluation and Research Food and Drug Administration 5600 Fishers Lane Rockville, Maryland

As you are aware, iontophoresis devices that are intended to use a direct current to introduce ions of soluble salts or other drugs into the body and induce sweating for use in the diagnosis of cystic fibrosis or for other uses, if the labeling of the drug intended for use with the device bears adequate directions for the device's use with that drug, were classified into Class II. An iontophoresis device that is intended to use a direct current to introduce ions of soluble salts or other drugs into the body for medical purposes other than those specified for class II devices is classified into Class III (21 CFR 890.5525). We published our strategy for calling for premarket approval (PMA) applications in the enclosed Federal Register, dated May 6, 1994, and the enclosed memorandum, dated April 19, 1994, and the enclosed Federal Register, dated August 22, 2000.

If you have any questions regarding this letter, you may contact:

Kevin Lee, M.D. Food and Drug Administration Center for Devices and Radiological Health Division of General, Restorative and Neurological Devices 9200 Corporate Boulevard (HFZ-410) Rockville, Maryland 20850 (301) 594-1296

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 advice for your device on our labeling regulation, please contact the Office of Compliance at (301) 594- 4659. Also, please note the regulation entitled, "Misbranding by

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reference to premarket notification" (21 CFR 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 (301) 443-6597, or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Mark A. Milheim

Celia M. Witten, Ph.D., M.D. Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosures

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Indications for Use Statement

Applicant: Iomed, Inc. KO31115 510(k) Number (if known): Device Name: RH-900 Indications For Use: Iontophoretic drug delivery electrodes are indicated for the administration of soluble salts or other drugs into the body for medical purposes as an alternative to hypodermic injections. They are also indicated for iontophoretic dermal administration of IONTOCAINE® (Lidocaine HCl 2% and Epinephrine 1:100,000 Topical Solution). eral, Restorative and Neurological Devices 510(k) Number. (PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE) (Per 21 CFR 801.109) (Optional Format 1-2-96)

Regulation Number and Section

§ 890.5525 Iontophoresis device.

(a)
Iontophoresis device intended for certain specified uses —(1)Identification. An iontophoresis device is a device that is intended to use a direct current to introduce ions of soluble salts or other drugs into the body and induce sweating for use in the diagnosis of cystic fibrosis or for other uses if the labeling of the drug intended for use with the device bears adequate directions for the device's use with that drug. When used in the diagnosis of cystic fibrosis, the sweat is collected and its composition and weight are determined.(2)
Classification. Class II (performance standards).(b)
Iontophoresis device intended for any other purposes —(1)Identification. An iontophoresis device intended for any other purposes is a prescription device that is intended to use a current to introduce ions of drugs or non-drug solutions into the body for medical purposes other than those specified in paragraph (a) of this section, meaning that the device is not intended for use in diagnosis of cystic fibrosis, or a specific drug is not specified in the labeling of the iontophoresis device.(2)
Classification. Class II (special controls). The device is classified as class II. The special controls for this device are:(i) The following performance testing must be conducted:
(A) Testing using a drug approved for iontophoretic delivery, or a solution if identified in the labeling, to demonstrate safe use of the device as intended;
(B) Testing of the ability of the device to maintain a safe pH level; and
(C) If used in the ear, testing of the device to demonstrate mechanical safety.
(ii) Labeling must include adequate instructions for use, including sufficient information for the health care provider to determine the device characteristics that affect delivery of the drug or solution and to select appropriate drug or solution dosing information for administration by iontophoresis. This includes the following:
(A) A description and/or graphical representation of the electrical output;
(B) A description of the electrode materials and pH buffer;
(C) When intended for general drug delivery, language referring the user to drug labeling approved for iontophoretic delivery to determine if the drug they intend to deliver is specifically approved for use with that type of device and to obtain relevant dosing information; and
(D) A detailed summary of the device-related and procedure-related complications pertinent to use of the device, and appropriate warnings and contraindications, including the following warning:

Warning: Potential systemic adverse effects may result from use of this device. Drugs or solutions delivered with this device have the potential to reach the blood stream and cause systemic effects. Carefully read all labeling of the drug or solution used with this device to understand all potential adverse effects and to ensure appropriate dosing information. If systemic manifestations occur, refer to the drug or solution labeling for appropriate action.(iii) Appropriate analysis/testing must demonstrate electromagnetic compatibility, electrical safety, thermal safety, and mechanical safety.
(iv) Appropriate software verification, validation, and hazard analysis must be performed.
(v) The elements of the device that may contact the patient must be demonstrated to be biocompatible.
(vi) The elements of the device that may contact the patient must be assessed for sterility, for devices labeled as sterile.
(vii) Performance data must support the shelf life of the elements of the device that may be affected by aging by demonstrating continued package integrity and device functionality over the stated shelf life.