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Review of Agreements, Guidances, and Practices in Compliance with the Medical Device User Fee and Modernization Act of 2002 [PDF 72KB] (September 2006)
In 1990, Congress amended the Federal Food, Drug and Cosmetic Act (the Act) to introduce the concept of combination products and to begin to clarify product jurisdiction issues. Shortly thereafter, in 1991, the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), and the Center for Devices and Radiological Health (CDRH), entered into three Intercenter Agreements ( ICAs): a CBER – CDER Intercenter Agreement, a CBER – CDRH Intercenter Agreement, and a CDER – CDRH Intercenter Agreement.
Although they differ in content, format, and scope, the ICAs share a common purpose of explaining how various categories of both combination and single-entity medical products were classified 1 and assigned 2 at the time the agreements were written in 1991. As explained in 21 CFR § 3.5(a)(2), the ICAs constitute guidance that is not binding on the public or the Agency.
At the time the ICAs were written in 1991, they were the major jurisdictional statements issued by the Agency. The ICAs continue to provide helpful guidance related to product jurisdiction, but their usefulness is becoming increasingly limited as new products are developed that were not envisioned when the ICAs were established, as new uses are developed for existing products, and as additional laws, regulations, and guidance have been promulgated. Since 1991, FDA has continued to classify and assign many new products not specifically covered by the intercenter agreements. 3 In addition, some jurisdictional decisions made since that time cover products that appear to be part of a broad class of product covered by an intercenter agreement, but are classified and/or assigned in a way different from the class of product because of the particular product’s specific characteristics or use. For these reasons, the body of jurisdictional decisions has grown and over time, the ICAs have become incomplete statements.
The Agency believes it is very important to provide robust transparency in jurisdictional decision making. Such transparency in jurisdictional decision making should result in greater predictability and consistency of decisions, and decrease ambiguity and uncertainty about Agency perspectives. Moreover, as the bases for Agency decision making become clearer, the need for formal RFD’s and informal inquiries covering specific products may be diminished, which should conserve resources for both industry and the Agency.
The Agency has considered and is implementing a variety of mechanisms to provide greater transparency in jurisdictional decision making. One of the options considered was to update to ICAs. Upon reflection, however, the Agency believes that the goal of robust transparency will likely be better served by means other than updating the Agreements. The process of updating the ICAs would be time consuming, and given the quick pace of product development, the revisions would again soon be out of date. For these reasons, the Agency believes that transparency would likely be better served by clearly articulating the principles upon which jurisdictional determinations are based, and by providing specific examples of jurisdictional determinations that help illustrate these principles.
The Agency has implemented and is developing a number of approaches to provide more information and transparency about the jurisdictional process. These methods are described below.
Assignment of Combination Products. The Agency recently published a final rule defining "primary mode of action," which is the statutory basis for assigning a combination product to a lead center for review. The regulation includes an algorithm that will be followed when the most important therapeutic action of a combination product cannot be determined with reasonable certainty. The preamble to the final rule includes 11 examples illustrating the primary mode of action definition and the assignment algorithm. The final rule was published in the August 25, 2005, Federal Register, and is available online at www.fda.gov/oc/combination.
Jurisdictional Determinations. The Agency has recently made available on the Office of Combination Products (OCP) Web site approximately 140 capsular descriptions of selected RFD decisions. In selecting which jurisdictional determinations were appropriate to summarize and make public in this way, FDA considered the extent to which the product could be suitably described, the extent to which the existence and description of the product or similarly described products has been made public, and related factors. The capsular descriptions are available at www.fda.gov/oc/combination/determinations.html. FDA will continue to update the list of capsular descriptions as new decisions are made and as information on these products becomes publicly available.
Jurisdictional Updates. The Agency has also made available a number of jurisdictional updates on the OCP Web site. Jurisdictional updates are more detailed statements of the classification and assignment of product classes. They reflect past Agency decisions, and are not intended to be policy statements. Jurisdictional updates generally contain information about the basis for the assignment and classification decisions that have been made. The Agency selects product classes to be the subject of jurisdictional updates based on the Agency’s perceptions of the current level of interest in the jurisdictional issue, the extent to which the class of products can be clearly described, the extent to which the existence and description of the class of products has been made public, and related factors. Jurisdictional updates are available at www.fda.gov/oc/combination/updates.html. Additional jurisdictional updates will be issued as appropriate.
RFD Decision Letters. The Agency plans to begin posting on the OCP Web site RFD decision letters for products that have been approved or cleared. These letters will be redacted to remove trade secret and confidential commercial information in accordance with the Freedom of Information Act. It should be noted that, in some cases, products undergo changes in name, sponsor, design or other key aspects following FDA’s issuance of an RFD decision. FDA will post RFD decision letters when it can be sure that the covered product has been approved or cleared, but it should be recognized that the posting may be incomplete. OCP will continue to post RFD decision letters as it becomes aware that products covered by past decisions have been approved or cleared. Posting of these letters, which generally include FDA’s reasoning behind the RFD decision, is intended to provide additional transparency on the jurisdictional process. The letters will be available at www.fda.gov/oc/combination.
Combination Product Regulation. For some types of combination products, the CDER – CDRH ICA addresses good manufacturing practices, registration and listing, labeling, and other product regulation issues. The Agency is developing guidance and/or regulations to address these and other significant areas of combination product regulation, and when final, these documents will ultimately update the limited information provided in the ICAs on these topics.
Chemical Action. The CDER – CDRH ICA contains information about the classification of certain products as single entity products (i.e., a drug or a device rather than a combination product), and their assignment to CDER or CDRH. This classification is based on which statutory definition (drug or device) the product meets. One of the distinctions between the drug and device definitions is that a device cannot achieve its primary intended purposes through chemical action within or on the body of man, or be dependent on being metabolized to achieve its primary intended purposes. FDA plans to develop guidance and/or regulations to further clarify what is meant by "chemical action within or on the body" or by "being metabolized." When final, such guidance and/or regulations should be helpful to sponsors in determining whether a product meets the definition of a drug or a device.
Devices Regulated by CBER and CDRH. With respect to single entity (i.e., non-combination) products, the main purpose of the CBER – CDRH ICA is to identify categories of devices regulated by CBER rather than CDRH. Many of the principles in the CBER – CDRH ICA are generally current; however, FDA believes that additional guidance describing the assignment of devices that process human cellular and tissue products would be helpful. This product area was not fully envisioned at the time the CBER – CDRH ICA was developed.
Drug and Biologic Products. Many of the principles in the CBER – CDER ICA are outdated, particularly since the transfer of regulatory responsibility for therapeutic biological products from CBER to CDER in June 2003. The document "Transfer of Therapeutic Biological Products to the Center for Drug Evaluation and Research," available at www.fda.gov/oc/combination/transfer.html, identifies the categories of products currently regulated by CBER and CDER. This document also contains information about products that were not covered by the original CBER – CDER ICA, such as gene therapy products. The Agency is working to further clarify the assignment of single entity products between CBER and CDER and plans to further update this document. Once this new statement of the assignment of single entity products between CBER and CDER is complete, the Agency plans to rescind the CBER – CDER ICA as fully obsolete.
In conclusion, FDA believes that, to some degree, the Intercenter Agreements are helpful nonbinding guidance relating to product jurisdiction, but they should not be independently relied upon as the most current, accurate jurisdictional statements. However, because the Agency believes the Intercenter Agreements may still be helpful in certain situations, they continue to be available at www.fda.gov/oc/combination/intercenter.html. FDA recommends that persons wishing to get the most current, accurate information about jurisdictional determinations consult the various sources of jurisdictional information described above. If the publicly available information does not provide sufficient information about the jurisdiction of a particular product, the Agency recommends that interested persons contact OCP at 301-427-1934, or by email at combination@fda.gov to obtain further information and discuss options for determining the classification and/or assignment of a product.
Footnotes
1. Classification refers to the determination of a product’s regulatory identity as a drug, device, biological product, or combination product.
2. Assignment refers to the determination of the Agency center that will have primary jurisdiction for the review and regulation of a product.
3. These decisions have been made through the formal Request for Designation (RFD) process, as well as through an informal process of jurisdictional determinations. For further information about RFDs and informal requests for jurisdictional determinations, see the Frequently Asked Questions on the Office of Combination Products Home Page.
Jurisdictional Updates: Office of Combination Products