IDE Guidance Memorandum - #D01-1
Date: October 26, 2001
From: Director, Office of Device Evaluation (HFZ-400)
Subject: Procedures for Handling Inquiries Regarding the Need for an Investigational Device Exemptions Application for Research Involving Medical Devices
To: ODE Review Staff
The purpose of this memorandum is to establish written procedures for handling inquiries regarding the need for an investigational device exemptions (IDE) application for research involving medical devices.
As stated in Section 520(g) of the Federal Food, Drug, and Cosmetic Act, the protection of the rights, safety, and welfare of subjects participating in clinical investigations of medical devices is of utmost importance. The Food and Drug Administration (FDA), the local institutional review boards (IRBs), and clinical investigators have a critical role in helping to provide this protection. Recently, the death of a healthy volunteer participating in medical research conducted by Johns Hopkins University has been the subject of much discussion. One issue that has been raised is whether the clinical study should have been conducted under FDA’s purview given that the investigation involved an unapproved drug.
This and similar events have caused the Office for Good Clinical Practice (OGCP), Office of the Commissioner to take a closer look at the Agency’s handling of issues involving human subject protection, including inquiries into the need to submit an application to FDA for clinical research. Every year, the Office of Device Evaluation (ODE) handles numerous inquiries regarding the need to submit an IDE application for research involving medical devices. These inquiries are received through a variety of means - in meetings, by telephone, e-mail, fax or letter. Such inquiries are initiated by a wide variety of entities, including device manufacturers, clinical investigators, and IRB members. In order to respond to these inquiries, we may refer to the IDE regulation (21 CFR 812)1, particularly sections 812.1 (Scope), 812.2 (Applicability), and 812.3 (Definitions), and the FDA Information Sheet entitled, "Significant Risk and Nonsignificant Risk Medical Device Studies" (hereafter referred to as SR/NSR guidance)2.
Often, the inquiries we receive can be easily answered by referring to the sources identified above. Occasionally, inquiries will involve new technologies, new uses of existing devices, or otherwise present new situations not clearly identified in the regulation or the SR/NSR guidance. A few inquiries involve the scope of the IDE regulation and/or jurisdictional issues that may require consultation with the other FDA centers.
When responding to these inquiries, there are three possible responses: the research is exempt from the IDE regulation; the abbreviated IDE requirements must be met (nonsignificant risk [NSR] study); or the full requirements of the IDE regulation must be met, that is, an IDE application must be submitted to FDA (significant risk [SR] study). Our responses to these inquiries also determines the extent to which FDA regulations, including those for the protection of the rights, safety and welfare of human research subjects, must be complied with for the conduct of the research.
Although ODE has had procedures for handling these requests, these procedures have not previously been placed in writing. In order to ensure that these requests are handled appropriately and consistently, written procedures are now being provided.
All inquiries regarding the need for an IDE application in which a written response is being requested should be received in writing. By obtaining the request in writing, ODE will be better able to assess the purpose of the investigation, the potential risks to subjects, and therefore, the applicability of the IDE regulation. The inquiry may be submitted to the Agency in the form of an e-mail, a fax or a letter and should include a description of the device and the clinical protocol. A summary of the protocol may be acceptable if it has sufficient detail to describe the potential risks to subjects.
In order to ensure that the inquiries we receive are addressed in a timely manner, all written inquiries should be responded to within two weeks of receipt. There are several boilerplate letters on the H drive for use by ODE staff in responding to these inquiries. These include the exempt, nonsignificant risk, and significant risk boilerplate letters3. Once a decision has been reached, copies of the inquiry and the response are to be provided to the IDE Staff if the response was generated by the review division. The IDE Staff has developed a database to keep track of the number and nature of these inquiries.
Simple inquiries are ones that are specifically addressed by either the IDE regulation or the SR/NSR guidance. That is, the response to the inquiry is clear from looking at the regulation or guidance. If the inquiry is received by telephone or during a meeting, it should be noted in the routine documentation of such contacts. For example, the inquiry and the response may be noted in a log maintained for telephone contacts or in the minutes of the meeting that are shared with the IDE sponsor. As noted above under General Procedures, if a person requests a written response, the inquiry should also be submitted in writing.
Some examples of simple inquiries include:
A study of a device that is cleared for marketing and is being investigated in accordance with its cleared labeling. Such as study would be exempt from the IDE regulation (21 CFR 812.2(c)(2)).
A study of an investigational device of a type that is identified in the list of nonsignificant risk devices in the SR/NSR guidance.
Inquiries that are clearly addressed by the IDE regulation and/or the SR/NSR guidance only need to be reported to the IDE Staff if a written response is provided. (This would exclude routine documentation of a pre-IDE meeting or telephone call but would include any written issuance of a determination by letter, e-mail, or fax.)
Inquiries Requiring Interpretative Response
More often, ODE receives inquiries that require some interpretation of either the IDE regulation or the SR/NSR guidance. In these situations, it is important to document the inquiry, the decision making process, and the response provided. When such an inquiry is received by the review division, the IDE Staff needs to be contacted so the inquiry can be entered into the database. In addition, the IDE Staff should be consulted when interpreting the regulation and/or the SR/NSR guidance.
Some examples of inquiries requiring an interpretative response include:
A study of two legally marketed devices being investigated in combination but both devices are being used in accordance within their labeled indications. In this case, further evaluation would be needed to determine if the purpose of the study is to evaluate the safety and effectiveness of the combination of the two devices, and, if so, what risk is presented by the device combination.
A study of a device of a type identified in the list of nonsignificant risk devices that is used in a non-conventional way or has been modified to incorporate new features. The new use and/or features would need to be evaluated for the risk they present to research subjects.
As requested by OGCP, the IDE Staff will be maintaining a centralized repository for these types of decisions. Therefore, a copy of all documentation pertaining to the inquiry, the decision-making process, and the response is to be provided to the IDE Staff.
ODE also receives inquiries involving jurisdictional issues and/or the scope of the IDE regulation (e.g., basic physiological research). These inquiries should be made in writing and provided to the IDE Staff for entry into the database. The IDE Staff will coordinate the resolution of these inquiries with the review divisions, other FDA centers, and the Office of the Commissioner, as appropriate.
Some examples of complex inquiries include:
A study involving a cleared device which has been modified to allow use in the collection of data in a nutritional study.
A study involving a device that is used to collect basic physiologic information about the progression of a disease or condition.
Once a determination has been make, the IDE Staff will maintain copies of the inquiry, documentation of the decision-making process, and copies of the response.
This memorandum is effective immediately.
Bernard Statland, M.D., Ph.D.
1The IDE regulation can be found at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/showCFR.cfm?CFRPart=812
2The FDA Information Sheet "Significant Risk and NonSignificant Risk Medical Device Studies" can be found at: http://www.fda.gov/ScienceResearch/SpecialTopics/ RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm113709.htm.
3The exempt, nonsignificant risk, and significant risk letters are designated as G-45, G-43, and G-44, respectively.