In 1982, an agreement detailed the working relationships between the organization previously identified as the Bureau of Medical Devices (BMD), the Bureau of Radiological Health (BRH) and the Bureau of Biologics (BoB) to identify the responsibilities of each for medical device activities.
Since then there have been several major organizational changes within the Food and Drug Administration (FDA). In 1982, BMD and BRH were joined administratively to form the Center for Devices and Radiological Health (CDRH). Also in 1982, BoB and the Bureau of Drugs were merged to form the Center for Drugs and Biologics (CDB), with biological products regulated by the Office of Biologics Research and Review (OBRR). In 1987, however, CDB was split into two major Centers, with biological products regulated by the Center for Biologic Evaluation and Research (CBER).
There also have been major advances in medical device technology and significant changes in the applications for existing technologies. New categories of in vitro diagnostics products have been developed to detect evidence of transfusion transmitted agents that were not recognized in 1982; use of "cellular" biologicals has continued to evolve as a therapeutic practice; and monoclonal antibodies are used in conjunction with medical devices for therapeutic purposes. Thus, this agreement has been updated to include medical devices which were not specified in the previous agreement and developing medical devices and device technologies for which there are no previous jurisdictional guidelines.
This document, which supersedes all prior agreements, outlines the working relationships that exist between CBER and CDRH for certain categories of medical devices or specified medical devices.
Submissions and inquiries should be made directly to the lead Center identified throughout this document.Inquiries regarding this Agreement should be addressed to: address update
Jerome A. Donlon, M.D., Ph.D.
Center for Biologics Evaluation and Research (HFB200)
Food and Drug Administration
8800 Rockville Pike
Bethesda, MD 20892
Leighton W. Hansel
Center for Devices and Radiological Health (HFZ340)
Food and Drug Administration
1390 Piccard Drive
Rockville, MD 20850
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 radiationrelated medical devices to ensure their safety and effectiveness. The Center for Devices and Radiological Health will use the device authorities of the Food, Drug and Cosmetic Act (FD&C Act) and the Electronic Product Radiation Control requirements of the Act, as well as any other authorities delegated to it, as appropriate, for devices regulated in that Center.
The Center for Biologics Evaluation and Research is designated the lead Center in FDA for regulating certain medical devices utilized in or indicated for the collection, processing or administration of biological products to ensure their safety and effectiveness and will use authorities under the Public Health Service Act (PHS Act) and the FD&C Act, as well as any other authorities delegated to it, as appropriate. Specific criteria for identifying medical devices regulated by CBER may be found in Section VI. For products that are combinations of biologicals and devices, the designation of the Center with primary jurisdiction is based on the product's primary mode of action.
The Centers will coordinate their activities in order to apply the Medical Devices Authorities in a consistent manner.
III. 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 FD&C Act. The Center for Devices and Radiological Health regulates all medical devices, inclusive of radiation-related devices, that are not assigned categorically or specifically to CBER. In addition, CDRH will independently administer the following activities (references to "Sections" are the provisions of the FD&C Act):
- Small business assistance programs under Section 10 of the Amendments (See PL 94295). Both CBER and CDRH will identify any unique problems relating to medical device regulation for small business;
- Registration and listing under Section 510. CBER will receive printouts and other assistance, as requested;
- Color additives under Section 706, with review by CBER, as appropriate;
- Good Manufacturing Practices (GMP) Advisory Committee. Under Section 520(f)(3), CBER will regularly receive notices of all meetings, with participation by CBER, as appropriate;
- Medical Device Reporting. The manufacturers, distributors, importers, and users of all devices including those regulated by CBER, shall report to CDRH under Section 519 of the FD&C Act as required. CDRH will provide monthly reports and special reports as needed to CBER for investigation and followup of those medical devices regulated by CBER.
IV. PROGRAMS THAT CBER AND CDRH WILL ADMINISTER
Both CBER and CDRH will administer and, as appropriate, enforce the following activities for medical devices, including their components, parts, and accessories, assigned to the respective Centers (references to "Sections" are the provisions of the FD&C Act):
- Surveillance and compliance actions involving general controls violations, such as misbranded or adulterated devices under sections 301, 501, and 502;
- Warning letters, seizures, injunctions, and prosecutions under Sections 302, 303, and 304;
- Civil penalties under Section 303(f) and administrative restraint under Section 304(g);
- Nonregulatory activities, such as educational programs directed at users, participation in voluntary standards organizations, etc.;
- Promulgation of performance standards and application of special controls under Section 514;
- Premarket Notification, Investigational Device Exemptions including Humanitarian Exemptions, Premarket Approval, Product Development Protocols, Classification, Device Tracking, Petitions for Reclassification, Postmarked Surveillance under Sections 510(k), 513, 515, 519, 520 (g) & (m), and 522, and the advisory committees necessary to support these activities;
- Banned devices under section 516;
- FDArequested and firminitiated recalls whether under section 518 or another authority and other Section 518 remedies such as recall orders;
- Exemptions, variances, and application of CGMP regulations under Section 520(f);
- GovernmentWide Quality Assurances Program; and
- Requests for export approval under Sections 801(e) and 802.
According to the guidance presented in Section VI of this document, statutory submissions such as 510(k)s, IDEs, PMAs, are to be made directly to the appropriate Center. For those medical device systems that are identified in Section VI as involving more than one Center, the submission should be made to the lead Center. Submissions should be made to the appropriate Center at the addresses provided below: address update
For Devices Regulated by CBER:
Food and Drug Administration
Center for Biologics Evaluation and Research
Division of Product Certification (HFB 240)
8800 Rockville Pike
Bethesda, MD 20892
For Devices Regulated by CDRH:
Food and Drug Administration
Center for Devices and Radiological Health (HFZ 401)
1390 Piccard Drive
Rockville, MD 20850
For submissions involving medical devices and/or biological products that are not addressed in this Agreement, sponsors are referred to the product jurisdiction regulations (21 CFR Part 3). These procedural regulations have been promulgated to facilitate the determination of regulatory jurisdiction but do not exclude the possibility for a collaborative review between the Centers.
VI. MEDICAL DEVICES FOR WHICH THE CENTER FOR BIOLOGICS EVALUATION AND RESEARCH WILL HAVE LEAD RESPONSIBILITY
In general, CBER will have the lead responsibility for regulating medical devices used or indicated for the collection, processing, storage or administration of blood products, blood components or analogous products, as well as screening or confirmatory clinical laboratory tests associated with blood banking practices and other process testing procedures. In vitro tests which are required for blood donor screening and related blood banking practices (such as donor reentry) are licensed under the PHS Act (refer to the list in Section B1).
The Center for Biologics Evaluation and Research also has the responsibility for regulating all in vitro tests (including diagnostic tests which are not performed in association with blood bank practices) and any other medical devices intended for use for human immunodeficiency virus, type 1 (HIV 1) and type 2 (HIV 2) and other retroviruses. These devices, including (but not limited to) collection devices, specimen containers, test kit components or support materials and those used or indicated for the inactivation of these viruses, will be regulated by CBER under the Medical Device Authorities. For a product that is a combination of a device and a biological, the determination of the Center of primary jurisdiction is based on the primary mode of action.
A. Medical devices regulated by CBER through the use of the Medical Device Authorities:
- Medical devices which are dedicated systems intended for use with human subjects in the collection, processing, and/or administration of an in vivo use licensed biological or analogous product which are marketed separately from the licensed biological or analogous product. For example, this would include plasmapheresis machines used to collect, process and/or administer a licensed biological product and filters used to prepare a biological product. This category does not include blood administration sets, including those administration sets with filters, which are regulated by CDRH.
This category also excludes medical devices intended for direct therapeutic application, which will be regulated by CDRH. Direct therapeutic application is defined as the use of a particular medical device for a particular patient with a specific disease or medical condition where the application of such a device is intended to produce a direct clinical benefit to the patient. This would, for example, include medical devices applied to remove toxic substances or excess cells for a therapeutic benefit, blood administration sets and intraoperative blood salvage devices.
- Certain in vitro reagents including:
a. those intended for use in the processing of licensed biologicals and analogous products including but not limited to lectins, protectins, bovine albumin and potentiating media,
b. quality assurance reagents intended for use in conjunction with licensed biological reagents or in vitro tests,
c. leukocyte typing sera or other medical devices intended for use in the determination of tissue type.
- Medical devices other than reagents intended for use in the preparation of, in conjunction with, or for the quality assurance of a blood bank related licensed biological product or practice. Examples include: clinical laboratory devices with separate blood bank claims, software for clinical laboratory devices with separate blood bank claims, software programs for data management in a blood establishment, dosimeters and thermal indicators that are used for licensed biological products and microwave ovens used for thawing blood products. CDRH will continue to be responsible for administering the Electronic Product Radiation Control provisions of the Act.
B. Medical devices regulated by CBER under the PHS Act:
- In vitro reagents subject to licensure including:
Antibody to Hepatitis B Surface Antigen
Antibody to Human Immunodeficiency Virus Type 1
Blood Grouping Reagents
Hepatitis B Core Antigen
Hepatitis B Surface Antigen
Hepatitis C Virus Encoded Antigen
Human Immunodeficiency Virus Type 1
Human Immunodeficiency Virus Type 2
Human T-Lymphotropic Virus Type I
Limulus amebocyte lysate (LAL) for either manufacturing or clinical diagnostic use
Reagent Red Blood Cells
CDRH may also regulate, as a licensed biological, any in vitro biological test reagent or reagent test which may be required to ensure the safety of blood, blood products or analogous products, or to ensure the purity, potency and safety of other licensed products.
- Certain combinations of medical devices and biological products including:
a. medical devices intended to serve as delivery systems for licensed biologicals which are packaged with a licensed biological (e.g., allergen patch and "tine" tests),
b. medical devices which are filled with licensed biologicals as a part of the manufacturing process, (prior to marketing to the end user) that are intended to serve as the final container and delivery system for the licensed biological (e.g., syringes filled with RhoD immunoglobulin),
c. medical devices intended to serve as in vivo delivery systems or implants for licensed biologicals which are either impregnated with a licensed biological or combined with a licensed biological as part of the manufacturing process
C. Special Situations
- In vitro tests or reagents for the direct or indirect detection of infectious agents such as cytomegalovirus, Yersinia enterocolitica, those causing syphilis and chagas disease and any other infectious agents that are transmitted by blood, blood products or analogous products will be assigned to CBER and CDRH as follows:
a. when such tests or reagents are intended only for diagnostic use, CDRH will regulate under the Medical Device Authorities (MDA),
b. when such tests or reagents are intended only for blood and plasma donor screening, CBER will regulate under MDA,
c. when such tests or reagents are intended for both diagnostic use and blood and plasma donor screening, CDRH will have the lead. Each Center will review the data necessary to support the intended use claims for which they have regulatory authority. Consolidated responses will be made to submissions or inquiries.
d. when such tests or reagents are required by the Agency for use in blood banks and plasmapheresis centers, CBER will regulate under the PHS Act.
- Nonlicensed human source materials of blood and blood components, intended for use in the manufacture of unlicensed in vitro diagnostic devices (including reagents) will be regulated by CBER during collection, storage and initial processing. Once the component materials have been incorporated into a manufacturing step whereby they are irrecoverable as original material or are packaged in a device container, these component materials become the regulatory responsibility of CDRH and will be regulated as medical devices under the Medical Device Authorities.
- Automated cell separators and other blood processing equipment will be regulated as medical devices under the Medical Device Authorities.
a. CDRH will have the lead responsibility if the medical device is used for therapeutic purposes. Therapeutic purposes is defined as the application of a particular medical device to a particular patient with a specific disease where the application of such a device is intended to produce a direct clinical benefit through the removal of toxins or excess deleterious elements.
b. CBER will have the lead responsibility for those medical devices used to separate components for the production of blood products and biological products. This would include devices used to collect, process/manipulate, store or modify particular biological components or "cellular" biologicals such that the benefit to the patient or recipient is derived from the administration of the biological component or "cellular" biological.
c. If automated cell separators or other blood processing equipment may be used for either therapeutic purposes or for the purpose of separating components for the production of blood products, CDRH will have the administrative lead responsibility. Each Center will review respective clinical and scientific data according to claimed uses. Consolidated responses will be made to submissions or inquiries.
- Medical devices that are intended for use in the processing of blood and blood components where the medical devices either include or are used in conjunction with filters, columns and other matrices (such as magnetic beads) that are coupled with biological substances (such as monoclonal antibodies) will be regulated as follows:
a. CDRH will have the lead responsibility if the devices are used for therapeutic purposes (as discussed in A.1.) and CBER will be consulted for decisions involving the biological substance.
b. CBER will have the lead responsibility if the devices are used for the collection, separation or processing of components for the production of blood, blood products, biological products, analogous products or "cellular" biologicals.
Bone marrow is considered a biologic analogous to blood or blood components. Any device or reagent used in the collection, processing or storage of bone marrow will be regulated by CBER. CBER has the option of regulating bone marrow directly through the licensing process and/or regulating the devices and reagents associated with bone marrow processing by use of the Medical Device Authorities.
- Irradiators intended for use in the inactivation of immunologically active cells in whole blood, red blood cells and platelets will be regulated by CDRH with consultation by CBER on the safety and effectiveness of the irradiated product.
Irradiators intended for use in the inprocess inactivation of HIV viruses or other pathogens in all blood products, licensed biological products, or analogous products will be regulated by CBER with consultation by CDRH.
- CDRH will regulate tissue processing equipment and solutions used for transporting, storing, or otherwise processing human tissues and organs except for the equipment and solutions related to biological products. Cultured skin will be regulated by CDRH under the Medical Device Authorities. Cellular and tissue implants, including infused cells and encapsulated cells or tissues. will be regulated by CBER under the PHS Act and the FD&C Act (as amended), as appropriate.
VII. GENERIC DEVICES FOR WHICH CBER WILL HAVE LEAD RESPONSIBILITY
CBER is the lead Center for the classified generic devices listed in the chart below. Under the chart headings, the "Product Code" is a five character code assigned to a device or generic group of devices for use by manufacturers to list devices with FDA. The first two characters identify the classification advisory panel which provided a classification recommendation to FDA. If a PMA number is noted, there is no classification regulation. A breakdown of panel codes is as follows:
"Name" is the name used by CDRH in its product code book to describe a generic category of device.
"Section" is the section in Title 21 of the Code of Federal Regulations under which the regulation classifying the device is codified.
"Regulation Name" is the name that was used in publishing the classification regulations.
|Product Code||Device Name||Section||Regulation Name|
|81 GKT||Automated Blood Cell Separators||864.9245||Automated Blood Cell Separator|
|81 KSB||Transfer Sets||864.9875||Transfer Sets|
|81 KSD||Heat Sealing Devices||864.9750||Heat Sealing Devices|
|81 KSE||Blood Storage|
Refrigerators and Freezers
|864.9700||Blood Storage Refrigerators and Freezers|
|81 KSF||Quality Control Kit for Blood Banking Reagents||864.9650||Quality Control Kit for Blood Banking Reagents|
|81 KSG||Potentiating Media for in vitro Diagnostic Use||864.9600||Potentiating Media for in vitro Diagnostic Use|
|81 KSH||Environmental Chambers for Storage of Platelet Concentrate||864.9575||Environmental Chamber for Storage of Platelet Concentrate|
|81 KSI||Lectins and Protectins||864.9550||Lectins and Protectin|
|81 KSK||Stabilized Enzyme Solutions||864.9400||Stabilized Enzyme Solution|
|81 KSL||Copper Sulfate Specific for Gravity Determination||864.9320||Copper Sulfate for Specific Gravity Determination|
|81 KSM||Automated Coombs Test System||864.9300||Automated Coombs Test System|
|81 KSN||Automated Cell-Washing Centrifuges for Immunohematology||864.9285||Automated Cell-Washing Centrifuges for Immunohematology|
|81 KSO||Blood Bank Centrifuges for in vitro Diagnostic Use||864.9275||Blood Bank Centrifuges for in vitro Diagnostic Use|
|81 KSP||CellFreezing Apparatus and Reagents||864.9225||CellFreezing Apparatus and Reagents for in vitro Diagnostic use|
|81 KSQ||Blood Mixing and Weighing Devices||864.9195||Blood Mixing Devices and Blood Weighing Device|
|81 KSR||Empty Containers for the Collection & Processing of Blood and Blood Components||864.9100||Empty Container for the Collection and Processing of Blood and Blood Components|
|81 KSS||Blood Bank Supplies||864.905O||Blood Bank Supplies|
|81 KST||VacuumAssisted Blood Collection Systems||864.9125||VacuumAssisted Blood Collection Systems|
|81 KSW||Processing Systems for Frozen Blood||864.9145||Processing System for Frozen Blood|
|81 KSX||Blood Grouping Substances of Nonhuman Origin for in vitro Diagnostic Use||864.9160||Blood Grouping Substances of Nonhuman Origin for in vitro Diagnostic Use|
|81 KSY||Blood Grouping View Boxes||864.9185||Blood Grouping View Boxes|
|81 KSZ||Automated Blood Grouping and Antibody Test System||864.9175||Automated Blood Grouping and Antibody Test System|
|81 KZL||Blood and Plasma Warning Devices Test, Hepatitis B Core (IgM)||864.9205|
|Blood and Plasma Warning Device|
VIII. INTERCENTER JURISDICTIONAL COMMITTEE
An intercenter jurisdictional committee is now formed. It is composed of one representative and one alternate from each Center. 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 jurisdiction assignments. Where this committee cannot agree upon jurisdictional assignment, or where the sponsor requests review of assignment at the agency level, the product jurisdiction procedures will be used.
Gerald V. Quinnan, Jr., M.D.
Center for Biologics Evaluation and Research
James S. Benson
Center for Devices and Radiological Health
David A. Kessler, M D.
Former Commissioner of Food and Drugs