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Over the years there have been ad hoc agreements between the Center for Drug Evaluation and Research (CDER) and the Center for Devices and Radiological Health (CDRH) concerning the status of products, that is, whether they are regulated as devices or drugs. It has become clear that the two Centers need to reach agreement on generic categories of products and to put these agreements in a form that would be available as a guide to the industry on the proper Center to contact for products subject to the agreement. This document is the agreement which identifies those products subject to regulation as devices and those subject to regulation as drugs and supersedes all previous agreements and decisions except for the Transitional Device Notice published in the Federal Register (42 CFR 63472) in 1977. It also outlines the working relationship between CDER and CDRH for the categories of products subject to this agreement.

Inquiries regarding this Agreement should be addressed to:

address update

Richard Chastonay
Center for Drug Evaluation and Research (HFD�0)
Food and Drug Administration
7520 Standish Place (MPN)
Rockville, Maryland 20850
(301) 295�63

or

Leighton W. Hansel
Center for Devices and Radiological Health (HFZ�0)
Food and Drug Administration
1390 Piccard Drive
Rockville, Maryland 20850
(301) 427�11

I. EFFECTIVE DATE.

This document takes effect October 31, 1991.

II. GENERAL DESCRIPTION.

The Center for Devices and Radiological Health is designated the lead center in FDA for regulating medical devices and radiation璻elated medical devices to ensure their safety and effectiveness. CDRH will generally use the device authorities of the Federal Food, Drug, and Cosmetic Act (Acts) and the Electronic Product Radiation Control requirements of the Act, as appropriate, for devices regulated in that Center. The Center for Drug Evaluation and Research is designated the lead Center in FDA for regulating drugs to ensure their safety and effectiveness and will generally use authorities under the drug provisions of the Act.

Section VII provides details concerning the products covered by this agreement and Section VIII describes the criteria to be applied in making drug/device determinations. Under the provisions of the Safe Medical Devices Act of 1990 and regulations promulgated to implement the combination product provisions of that Act, CDER and CDRH each may use both the drug and device provisions of the Federal Food, Drug, and Cosmetic Act as appropriate to regulate a combination product. (See 21 CFR Part 3).

III. DEVICE PROGRAMS THAT CDRH WILL ADMINISTER.

The Center for Devices and Radiological Health is designated the Center for major policy development and for the promulgation and interpretation of procedural regulations for medical devices under the Act. The Center for Devices and Radiological Health regulates all medical devices inclusive of radiation璻elated devices, that are not assigned categorically or specifically to CDER. In addition, CDRH will independently administer the following activities (references to "Sections" are the provisions of the Act):

1. A. Small business assistance programs under Section 10 of the Amendments (See PL 94�5). Both CDER end CDRH will identify any unique problems relating to medical device regulation for small business;
   B. Registration and listing under Section 510 including some CDER administered device applications. The Center for Drug Evaluation and Research will receive printouts and other assistance, as requested;
   C. Color additives under section 706, with review by CDER, as appropriate;
   D. Good Manufacturing Practices (GMPs) Advisory Committee. Under Section 520(f) (3), CDER will regularly receive notices of all meetings, with participation by CDER, as appropriate; and E. Medical Device Reporting. The manufacturers, distributors, importers, and users of all devices, including those regulated by CDER, shall report to CDRH under Section 519 of the Act as required. The Center for Devices and Radiological Health will provide monthly reports and special reports as needed to CDER for investigation and follow璾p of those medical devices regulated by CDER.
   
   E. Medical Device Reporting. The manufacturers, distributors, importers, and users of all devices, including those regulated by CDER, shall report to CDRH under Section 519 of the Act as required. The Center for Devices and Radiological Health will provide monthly reports and special reports as needed to CDER for investigation and follow-up of those medical devices regulated by CDER.
   

IV. DEVICE PROGRAMS THAT CDER AND CBER EACH WILL ADMINISTER.

Both CDER and CDRH will administer and, as appropriate, enforce the following activities for medical devices assigned to their respective Centers (References to "Sections" are the provisions of the Act):

1. A. Surveillance and compliance actions involving general controls violations, such as misbranded or adulterated devices under section 301, 501, and 502;
   B. Warning letters, seizures, injunctions, and prosecutions under Section 302, 303, and 304;
   C. Civil penalties under Section 303(f) and administrative restraint under Section 304(g);
   D. Non璻egulatory activities, such as educational programs directed at users, participation in voluntary standards organizations, etc.;
   E. Promulgation of performance standards and applications of special controls under Section 514;
   F. Premarket Notification, Investigational Device exemptions including Humanitarian Exemptions, Premarket Approval, Product Development Protocols, Classification, Device Tracking, Petitions for Reclassification, post market surveillance under Sections 510(k), 513, 515, 519, 520(g) & (m), and 522, and the advisory committees necessary to support these activities:
   G. Banned devices under Section 516;
   H. FDA璻equested and firm璱nitiated recalls whether under section 518 or another authority and other Section 518 remedies such as recall orders:
   I. Exemptions, variances, and applications of CGMP regulations under Section 520(f);
   J. Government璚ide Quality Assurance Program; and
   K. Requests for export approval under Sections 801(e) and 802.

V. COORDINATION.

The Centers will coordinate their activities in order to assure that manufacturers do not have to independently secure authorization to market their product from oath Centers unless this requirement is specified in the Section VII.

VI. SUBMISSIONS.

Submissions should be made to the appropriate Center, as specified herein, at the addresses provided below:

address update

Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room (Room #2-14)
12420 Parklawn Drive
Rockville, Maryland 20852

or

Food and Drug Administration
Center for Devices and Radiological Health
Document Mail Center (HFZ�1)
1390 Piccard Drive
Rockville, Maryland 20850

For submissions involving medical devices and/or drugs that are not clearly addressed in this agreement, sponsors are referred to the product jurisdiction regulations (21 CFR Part 3). These regulations have been promulgated to facilitate the determination of regulatory jurisdiction but do not exclude the possibility for a collaborative review between the Centers.

VII. CENTER JURISDICTION.

The following subsections provide details concerning status, market approval authority, special label/regulatory considerations, investigational options, and inter璫enter consultations for the categories of products specified. Section VIII provides the general criteria that CDRH and CDER will apply in reaching decisions as to which Center will regulate a product.

A.1(a) Device with primary purpose of delivering or aiding in the delivery of a drug that is distributed without a drug (i.e., unfilled).

EXAMPLES

• devices that calculate drug dosages
• drug delivery pump and/or catheter infusion pump for implantation
• iontophoreses device
• medical or surgical kit (e.g., tray) with reference in instructions for use with specific drug (e.g., local anesthetic)
• nebulizer
• small particle aerosol generator (SPAG) for administering drug to ventilated patient
• splitter block for mixing nitrous oxide and oxygen
• syringe; jet injector; storage and dispensing equipment

Status: Device and drug, as separate entities.

Market Approval Authority: CDRH and CDER, respectively, unless the intended use of the two products, through labeling, creates a combination product.

Special Label/Regulatory Considerations: The following specifics procedures will apply depending on the status of the drug delivery device and drugs that will be delivered with the device:

• (i) It may be determined during the design or conduct of clinical trials for a new drug that it is not possible to develop adequate performance specifications data on those characteristics of the device that are required for the safe and effective use of the drug. If this is the case, then drug labeling cannot be written to contain information that makes it possible for the user to substitute a generic, marketed device for the device used during developments to use with the marketed drug. In these situations, CDER will be the lead center for regulation of the device under the device authorities.
  (ii) For a device intended for use with a category of drugs that are on the market, CDRH will be the lead center for regulation of the device under the device authorities. The effects of the device use on drug stability must be addressed in the device submission, when relevant. An additional showing of clinical effectiveness of the drug when delivered by the specific device will generally not be required. The device and drug labeling must be mutually conforming with respect to indications, general mode of delivery (e.g , topical, I.V. ), and drug dosage/schedule equivalents.
  (iii) For a drug delivery device and drug that are developed for marketing to be used together as a system, a lead center will be designated to be the contact point with the manufacturer(s). If a drug has been developed and marketed and the development and studying of device technology predominates, the principle mode of action will be deemed to be that of the device, and CDRH would have the lead. If a device has been developed and marketed and the development and studying of drug predominates then, correspondingly, CDER would have the lead. If neither the drug nor the device is on the market, the lead center will be determined on a case璪y璫ase basis.

Investigation Options: IDE or IND, as appropriate.

Inter瑿enter Consultation: CDER, when lead Center, will consult with CDRH if CDER determines that a specific device is required as part of the NDA process. CDRH as lead center will consult with CDER if the device is intended for use with a marketed drug and the device creates a significant change in the intended use, mode of delivery (e.g., topical, I.V.), or dose/schedule of the drug.

(b) Device with primary purpose of delivering or aiding in the delivery of a drug and distributed containing a drug (i.e., "pre璮illed delivery system")

EXAMPLES

• nebulizer
• oxygen tank for therapy and OTC emergency use
• pre璮illed syringe
• transdermal patch

Status: Combination Product

Market Approval Authority: CDER using drug authorities and device authorities, as necessary.

Special Label/Regulatory Considerations: None

Investigation Options: IND

Inter瑿enter Consultations: Optional

2. Device incorporating a drug component with the combination product having the primary intended purpose of fulfilling a device function.

EXAMPLES

• bone cement containing antimicrobial agent
• cardiac pacemaker lead with steroid璫oated tip
• condom, diaphragm, or cervical cap with contraceptive or antimicrobial agent(including virucidal)agent
• dental device with fluoride
• dental wood wedge with hemostatic agent
• percutaneous cuff (e.g., for catheter or orthopedic pin) coated/impregnated with antimicrobial agent
• skin closure or bandage with antimicrobial agent
• surgical or barrier drape with antimicrobial agent
• tissue graft with antimicrobial or other drug agent
• urinary and vascular catheter coated/impregnated with antimicrobial agent
• wound dressing with antimicrobial agent

Status: Combination Product

Market Approval Authority: CDRH using device authorities.

Special Label/Regulatory Considerations: These products have a drug component that is present to augment the safety and/or efficacy of the device.

Investigation Options: IDE

Inter瑿enter Consultation: Required if a drug or the chemical form of the drug has not been legally marketed in the United States as a human drug for the intended effect.

3. Drug incorporating a device component with the combination product having the primary intended purpose of fulfilling a drug function.

EXAMPLES

• skin prep pads with antimicrobial agent
• surgical scrub brush with antimicrobial agent
  

Status: Combination Product

Market Approval Authority: CDER using drug authorities and, as necessary, device authorities.

Special Label/Regulatory Considerations: Marketing of such a device requires a submission of an NDA with safety and efficacy data on the drug component or it meets monograph specifications as generally recognized as safe (GRAS) and generally recognized as effective (GRAE). Drug requirements, e.g., CGMPs, registration and listing, experience reporting apply to products.

Investigation Options: IND

Inter瑿enter Consultation: Optional

4(a)Device used in the production of a drug either to deliver directly to a patient or for use in the producing medical facility (excluding use in a registered drug manufacturing facility).

EXAMPLES

• oxygen concentrators (home or hospital)
• oxygen generator (chemical)
• ozone generator

Status: Device

Market Approval Authority: CDER, applying both drug and device authorities

Special Label/Regulatory Consideration: May also require an NDA if the drug produced is a new drug. Device requirements, e.g., CGMPs, registration and listing, experience reporting will apply to products.

Investigation Options: IDA: or NDA, as appropriate.

Inter瑿enter Consultation: Optional

4(b) Drug/Device combination product intended to process a drug into a finished package form.

EXAMPLES

• device that uses drug concentrates to prepare large volume parenterals
• oxygen concentrator (hospital) output used to fill oxygen tanks for use within that medical facility

Status: Combination product

Market Approval Authority: CDER, applying both drug a and device authorities.

Special Label/Regulatory Considerations: Respective drug and device requirements, e.g., CGMPs, registration and listing, experience reporting will apply.

Investigation Options: IDE or NDA, as appropriate.

Inter瑿enter Consultation: Optional, but will be routinely obtained.

B. Device used concomitantly with a drug to directly activate or to augment drug effectiveness.

EXAMPLES

• biliary lithotriptor used in conjunction with dissolution agent
• cancer hyperthermia used in conjunction with chemotherapy
• current generator used in conjunction with an implanted silver electrode (drug)that produces silver ions for an antimicrobial purpose
• materials for blocking blood flow temporarily to restrict chemotherapy drug to the intended site of action
• UV and/or laser activation of oxsoralen for psoriasis or Cutaneous T瑿ell Lymphoma

Status: Device and drug, as separate entities

Market Approval Authority: CDRH and CDER, respectively

Special Label/Regulatory Considerations: The device and drug labeling must be mutually conforming with respect to indications, general mode of delivery (e.g., topical, I.V.), and drug dosage/schedule equivalence. A lead center will be designated to be the contact point with the manufacturer. If a drug has been developed and approved for another use and the development and studying of device technology predominates, then CDER would have lead. If a device has been developed and marketed for another use and the development and studying of drug action predominates, then CDER would have lead. If neither the drug nor the device is on the market, the lead center will be determined on a case璪y璫ase basis. If the labeling of the drug and device create a combination product, as defined in the combination product regulations, then the designation, of the lead Center for both applications will be based upon a determination of the product's primary mode of action.

Investigation Options: lDE or IND, as appropriate.

Inter瑿enter Consultations: Required.

2. Device kits labeled for use with drugs that includes both device(s) and drug(s) as separate entities in one package with the overall primary intended purpose of the kit fulfilling a device function.

EXAMPLES

• medical or surgical kit (e.g., tray) with drug component

Status: Combination Product

Market Approval Authority: CDRH, using device authorities is responsible for the kit if the manufacturer is repackaging a marketed drug. Responsibility for overall packaging resides with CDRH. CDER will be consulted as necessary on the use of drug authorities for the repackaged drug component.

Special Label/Regulatory Considerations: Device requirements, e.g., CGMPs, registration and listing, experience reporting apply to kits. Device manufacturers must assure that manufacturing steps do not adversely affect drug components of the kit.

If the manufacturing steps do affect the marketed drug (e.g., the kit is sterilized by irradiation), an ANDA or NDA would also be required with CDRH as lead center.

Investigation Options: IDA or IND, as appropriate.

Inter瑿enter Consultation: Optional if ANDA or NDA not required.

C. Liquids, gases, or solids intended for use as devices (e.g., implanted, or components, parts, or accessories to devices).

EXAMPLES

• dye for tissues used in conjunction with laser surgery, to enhance absorption of laser light in target tissue
• gas mixtures for pulmonary function testing devices
• gases used to provide "physical effects"
• hemo璬ialysis fluids
• hemostatic devices and dressings
• injectable silicone, collagen, and teflon
• liquids functioning through physical action applied to the body to cool or freeze tissues for therapeutic purposes
• liquids intended to inflate, flush, or moisten (lubricate) indwelling devices (in or on the body)
• lubricants and lubricating jellies
• ophthalmic solutions for contact lenses
• organ/tissue transport and/or perfusion fluid with antimicrobial or other drug agent, i.e., preservation solutions
• powders for lubricating surgical gloves
• sodium hyaluronate or hyaluronic acid for use as a surgical aid
• solution for use with dental "chemical drill"
• spray on dressings not containing a drug component

Status: Device

Market Approval Authority: CDRH

Special Label/Regulatory Considerations: None

Investigation Options: IDE

Inter瑿enter Consultation: Required if the device has direct contact with the body and the drug or the chemical form of the drug has not been legally marketed as a human drug.

D. Products regulated as drugs.

EXAMPLES

• irrigation solutions
• purified water or saline in pre-filled nebulizers for use in inhalation therapy
• skin protectants (intended for use on intact skin)
• sun screens
• topical/internal analgesic璦ntipyretic

Status: Drug

Market Approval Authority: CDER

Special Label/Regulatory Considerations: None

Investigation Options: IND

Inter瑿enter Consultations: Optional

E. Ad Hoc Jurisdictional Decisions.

Status: Device or drug

Market approval authority: CDRH or CDER as indicated.

Special label/regulatory considerations: None

Investigational options: IDE or IND, as appropriate

Inter-center consultation: Required to assure agreement on drug/device status.

VIII. GENERAL CRITERIA AFFECTING DRUG/DEVICE DETERMINATIONS.

The following represent the general criteria that will apply in making device/drug determinations:

A. Device Criteria:

1. A liquid, powder, or other similar formulation intended only to serve as a component, part, or accessory to a device with a primary mode of action that is physical in nature will be regulated as a device by CDRH.
2. A product that has the physical attributes described in 201(h) (e.g. instrument, apparatus) of the Act and does not achieve its primary intended purpose through chemical action within or on the body, or by being metabolized, will be regulated as a device by CDRH.
3. The phrase "within or on the body" as used in 201(h) of the Act does not include extra corporeal systems or the solutions used in conjunction with such equipment. Such equipment and solutions will be regulated as devices by CDRH.
4. An implant, including an injectable material, placed in the body for primarily a structural purpose even though such as implant may be absorbed or metabolized by the body after it has achieved its primary purpose will be regulated as a device by CDRH.
5. A device containing a drug substance as a component with the primary purpose of the combination being to fulfill a device function is a combination product and will be regulated as a device by CDRH.
6. A device (e.g., machine or equipment) marketed to the user, pharmacy, or licensed practitioner that produces a drug will be regulated as a device or combination product by CDER. This does not include equipment marketed to a registered drug manufacturer.
7. A device whose labeling or promotional materials make reference to a specific drug or generic class of drugs unless it is prefilled with a drug ordinarily remains a device regulated by CDRH. It may, however, also be subject to the combination products regulation.

B. Drug Criteria:

1. A liquid, powder, tablet, or other similar formulation that achieves its primary intended purpose through chemical action within or on the body, or by being metabolized, unless it meets one of the specified device criteria, will as regulated as a drug by CDER.
2. A device that serves as a container for a drug or a device that is a drug delivery system attached to the drug container where the drug is present in the container is a combination product that will be regulated as a drug by CDER.
3. A device containing a drug substance as a component with the primary purpose of the combination product being to fulfill a drug purpose is a combination product and will be regulated as a drug by CDER.
4. A drug whose labeling or promotional materials makes reference to a specific device or generic class of devices ordinarily remains a drug regulated by CDER. It may, however, also be subject to the combination products regulation.

IX. INTERCENTER JURISDICTIONAL COMMITTEE.

An intercenter jurisdictional committee is now formed. The committee members will meet on an ad hoc basis, will discuss all jurisdictional questions, and will be expected to handle the majority of requests for jurisdictional assignments. Where this committee cannot agree upon the jurisdictional assignment, or where the sponsor requests review of assignment at the Agency level, the product jurisdiction procedures will be used.

Signed:

Carl C. Peck, M.D., Director
Center for Drug Evaluation and Research
Dated: 10/31/91

Signed:
James S. Benson, Director
Center for Devices and Radiological Health
Dated: 10/31/91

Concur:
Signed:
David A. Kessler, M.D.
Commissioner of Food and Drugs

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