Guidance for Industry and FDA Staff: Expedited Review of Premarket Submissions for DevicesFor questions regarding the use or interpretation of this guidance in the review of PMAs and PDPs, please contact the PMA Staff at (240) 276-4040.
For questions regarding the use or interpretation of this guidance in the review of 510(k)s, including the Evaluation of Automatic Class III Designation classification actions (de novo review), please contact Heather Rosecrans at (240) 276-4021 or by email at heather.rosecrans@fda.hhs.gov.
For questions regarding the use or interpretation of this guidance in the review of devices regulated by CBER, please contact Sayah Nedjar, Ph.D., at 301-827-3524 or by email at sayah.nedjar@fda.hhs.gov.
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U.S. Department of Health
and Human Services Center for Devices and Radiological Health |
Written comments and suggestions may be submitted at any time for Agency consideration to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852. Alternatively, electronic comments may be submitted to http://www.Regulations.gov . When submitting comments, please refer to the exact title of this guidance document. Comments may not be acted upon by the Agency until the document is next revised or updated.
Additional copies are available from the Center for Devices and Radiological Health (CDRH) through the Internet at: http://www.fda.gov/cdrh/mdufma/guidance/108.pdf or http://www.fda.gov/cdrh/mdufma/guidance/. You may also send an e-mail request to dsmica@fda.hhs.gov to receive an electronic copy of the guidance document or send a fax request to 240-276-3151 to receive a hard copy. Please use the document number (108) to identify the guidance document you are requesting.
Additional copies of this guidance document are also available from the Center for Biologics Evaluation and Research (CBER), Office of Communication, Training and Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at http://www.fda.gov/cber/guidelines.htm.
Attachment 1: Suggested Timeframes for Discussing Expedited Review with FDA
Attachment 2: Expedited Review Form
| This guidance document represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance document. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance document. |
This document has the following purposes: (1) develop a common understanding of the statutory criteria for granting expedited review to premarket submissions for medical devices, and (2) outline standard procedures that should be followed to achieve an efficient expedited review process. Furthermore, this updated version of the guidance document reflects the changes under the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public Law 110-85)1 and corresponding changes in our expedited review policy for premarket approval applications (PMAs),2 premarket reports,3 product development protocols (PDPs), and premarket notification submissions (510(k)s).
An expedited review process for medical devices was first developed in 1994 and explained in a General Program Memorandum (G94-2) entitled, “PMA/510(k) Expedited Review.” That document was revised and issued as a guidance document on March 20, 1998, to reflect the expedited review criteria in Section 515(d)(5) of the Federal Food, Drug, and Cosmetic Act (the Act).4 The revised guidance document, known as “PMA/510(k) Expedited Review – Guidance for Industry and CDRH Staff,” was superseded and replaced by the guidance document entitled, “Expedited Review of Premarket Submissions of Devices,” dated November 26, 2003, which reflected a decade of experience from administering an expedited review program for medical devices, as well as the performance goals set forth in the MDUFMA I Goals Letter.5 The 2003 version of this guidance document is superseded by this version, which incorporates changes under FDAAA. More specifically, f or PMAs, FDA will no longer require additional conditions in order for an expedited PMA to be measured against MDUFMA expedited performance goals. Therefore, this guidance document no longer includes information specific to the additional conditions described under MDUFMA I for expedited PMAs.6 In addition, if a PMA or 510(k) is granted expedited status, this status would not be revoked during its review should a device of the same type be approved or cleared.FDA's guidance documents, including this guidance document, do not establish legally enforceable responsibilities. Instead, guidance documents describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance documents means that something is suggested or recommended, but not required.
We believe we should consider the least burdensome approach in all areas of medical device regulation. This guidance reflects our careful review of the relevant scientific and legal requirements regarding premarket device submissions and what we believe is the least burdensome way for you to comply with those requirements. However, if you believe that an alternative approach would be less burdensome, please contact us so we can consider your point of view. You may send your written comments to the contact person listed in the preface to this guidance or to the CDRH Ombudsman. Comprehensive information on CDRH's Ombudsman, including contact information, can be found on the Internet at http://www.fda.gov/cdrh/ombudsman/ .
FDA considers a device, or combination product containing a device,7 appropriate for expedited review8 if the device or combination product:
Manufacturers who are working with a federal agency in the development of medical devices to address a national security issue should include a letter in the premarket submission from the federal agency (e.g., Department of Defense, Department of Homeland Security) identifying the specific device or device type and indicating that commercial availability is of particular importance to our national security. The letter should be printed on official agency letterhead and signed by an individual with appropriate authority for making the request.
To expedite the process, the letter should also be faxed to the Office of Device Evaluation’s Program Operation Staff (POS). The early fax to POS will allow for confirmation of the expedited status and will allow for better monitoring of the review status of the expedited submission.
While all device submissions granted expedited review status are subject to priority review, there is no assurance that a device will receive FDA marketing authorization in a more timely manner when compared with submissions not granted expedited status. The reasons for this outcome are varied, such as a device involves new technology or presents complex scientific and regulatory issues that warrant more in-depth review; a failure by the manufacturing facility to be prepared for inspection; or a failure of the applicant to provide adequate scientific data in its submission.
In order to reap a benefit from the expedited review process, the commitment on behalf of the applicant to resolve all scientific and regulatory issues should match that of FDA. It will only be through effective communication (i.e., interactive review) and a total commitment to fulfilling all regulatory and scientific requirements that FDA and the applicant can speed market authorization for safe and effective products.9
Although an expedited PMA will be assessed against the MDUFMA II expedited performance goals without a pre-filing meeting, FDA strongly recommends to industry to have such a meeting.10
Granting expedited review status means that a marketing application that is determined to be appropriate for expedited review is placed at the beginning of the appropriate review queue and receives additional review resources, as needed. If multiple applications for the same type of device offering comparable advantage over existing approved alternatives have been granted expedited review, they are reviewed with priority assigned on a first-in-first-reviewed (FIFR) basis for each review cycle.
Furthermore, if one of these applications is approved, the remaining expedited applications will retain their expedited status until a final decision is rendered. This is a change from our previous practice in which we would revoke the expedited status from all pending expedited submissions once we approve a submission of the same type. We are implementing this change in order to simplify our review process. Since MDUFMA provides different performance goals for non-expedited and expedited PMAs, switching the status during the review of an application requires the review staff to switch to a different review process and be accountable for meeting a different goal. For this reason, the status of the application should be decided at the time the submission is filed and will continue until the review is completed and a final decision is rendered.
Any new application filed after the approval or clearance of a device of the same type will not be given an expedited status unless covered under Section III (Special Considerations).
Under MDUFMA I, for a traditional PMA, modular PMA, or panel-track supplement to be tracked against the expedited PMA performance goals, the applications/supplement had to meet the statutory expedited criteria described in Section II (Devices Appropriate for Expedited Review) AND the PMA applicant had to meet the following conditions:
If a PMA met the expedited statutory criteria but did not satisfy all three of the conditions above, the application was still considered expedited and FDA prioritized review of the application. However, FDA was not obligated to meet the MDUFMA I expedited PMA performance goals for this application. Thus, there were actually two different categories for expedited review: a “statutory only” category and a “statutory and MDUFMA” category.
Having two different expedited categories led to implementation difficulties, such as how to determine whether a device manufacturing site was ready for inspection at the time a PMA was submitted. While a PMA applicant may have claimed in its PMA submission that its manufacturing site was ready to be inspected, FDA’s inspectors often discovered that sites were actually not ready for inspection. Likewise, there were no criteria for deciding whether or not a particular meeting that an applicant had with the FDA, regardless of the topic of discussion, constituted a pre-filing meeting.
Thus, because of the difficulty in implementing the expedited provision under MDUFMA I, FDA and the industry agreed to streamline the process and eliminate the three additional conditions above. Therefore, under FDAAA, FDA will now evaluate the expedited status of each PMA application based solely on the original statutory criteria defined in Section II (Devices Appropriate for Expedited Review) above. Furthermore, all expedited original PMAs and panel track supplements will be assessed against the MDUFMA II expedited performance goals.11
The responsibility for identifying devices that are appropriate for expedited review is a responsibility jointly shared by industry and FDA. A primary objective of this guidance document is to promote a common understanding of which device submissions may be granted expedited review status to facilitate an early recognition of devices that merit such review. (Refer to Attachment 1 for suggested timeframes for making expedited review determinations early in the device development process.)
Note: When granting expedited review, the review divisions should consider other pending submissions for the same intended use that may also be appropriate for expedited review. Likewise, the review divisions should monitor incoming submissions for devices of the same type that may also be appropriate for expedited review status. If more than one pending submission is appropriate for expedited review, both submissions should be granted expedited review status.
The review division, along with all other CDRH components that may be participating, incur specific responsibilities upon granting expedited review. The areas below warrant special consideration.
Table 1. Suggested Timeframes for Discussing Expedited Review Status (shown in solid shading)
Legend for Table 1:
Criteria for Expedited Review 1. Condition is life-threatening or irreversibly debilitating AND 2. the device addresses an unmet medical need, demonstrated by any one of the following:
Pre-Submission Product Development Timeline
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Applicant: ____________________________________________________________________
Device: ______________________________________________________________________
Use/Indications: ______________________________________________________________
Document #: ________________________________________________________________
Justification for Expedited Review Check if YES (
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1. |
Does the device affect a condition that is life-threatening or irreversibly debilitating? |
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2. |
Does the device address an unmet medical need, as demonstrated by any one of the following:16 a. breakthrough technology b. no approved alternative c. significant clinically meaningful advantage d. in the best interest of patients. |
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3. |
Are the answers to 1 & any one part of 2 a YES response? |
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If yes, go to 4. |
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If no, skip to 5. |
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Expedited Review Assessment (check only one) |
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4. |
The application qualifies for expedited review status and is subject to MDUFMA Performance Goals |
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5. |
The application does not qualify for expedited review status |
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Identify review team leader & members:
Attach tentative review timeline.
Signature: ________________________________________________
Division Director & Date
1 FDAAA includes the Medical Device User Fee Amendments of 2007 (MDUFMA II).
2 PMAs involved are traditional PMAs, modular PMAs (after the last module is received), and panel-track supplements.
3 A premarket report is a PMA application for a reprocessed, single-use device (see section 515(c)(2) of the Federal Food, Drug, and Cosmetic Act (Act); 21 U.S.C. 360e(c)(2)).
4 While Section 515(d)(5) of the Act only applies to premarket approval applications (PMAs), because of the potential public health importance of devices warranting expedited review status, FDA also has applied the expedited review criteria to all premarket submissions, including devices evaluated under a PDP, the Evaluation of Automatic Class III Designation process (also known as the “de novo” or “risk based” classification process), and 510(k)s. For information on the de novo process, refer to Section 513(f)(2) of the Act and the guidance document entitled “Evaluation of Automatic Class III Designation” found at http://www.fda.gov/cdrh/modact/classiii.html.
5 For more information, please refer to the letter from the Secretary of Health and Human Services to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate (“Goals Letter”) dated November 19, 2002, http://www.fda.gov/cdrh/mdufma/pgoals.html and referenced in section 101(3) of the Medical Device User Fee and Modernization Act of 2002 (MDUFMA I).
6 A pre-filing meeting was one of the previous conditions under MDUFMA I for a PMA to have an expedited review status and be subject to MDUFMA performance goals. Although removed as a condition, CDRH intends to develop guidance on meetings with industry, including pre-submission meetings. For CBER submissions, please refer to CBER’s meeting procedures webpage at http://www.fda.gov/cber/regsopp/81011.htm.
7 Combination products are eligible for expedited review under the MDUFMA goals when CDRH or CBER has been designated as the lead Center.
8 FDA is required by statute, section 515(d)(5), to review only PMAs meeting certain conditions on an expedited basis. FDA, however, is using these criteria as guidelines for expedited review of PDPs, 510(k)s, and de novo classifications. For more information on de novo classification, refer to http://www.fda.gov/cdrh/devadvice/314c.html.
9 FDA has issued a guidance document on interactive review entitled, “ Guidance for Industry and FDA Staff: Interactive Review for Medical Device Submissions: 510(k)s, Original PMAs, PMA Supplements, Original BLAs, and BLA Supplements,” http://www.fda.gov/cdrh/ode/guidance/1655.html.
10 CDRH intends to develop guidance on meetings with industry, including pre-submission meetings. For CBER submissions, please refer to CBER’s meeting procedures webpage at http://www.fda.gov/cber/regsopp/81011.htm.
11 See the guidance document entitled, “FDA and Industry Actions of Premarket Approval Applications (PMAs): Effect on FDA Review Clock and Performance Assessment,” at www.fda.gov/cdrh/mdufma/guidance/1218.html.
12 See also FDA’s guidance document on interactive review entitled, “ Guidance for Industry and FDA Staff: Interactive Review for Medical Device Submissions: 510(k)s, Original PMAs, PMA Supplements, Original BLAs, and BLA Supplements,” http://www.fda.gov/cdrh/ode/guidance/1655.html.
14 See http://www.fda.gov/cdrh/ode/guidance/1341.html for information about the public availability of the advisory panel materials.
15 Any disclosures will be made in accordance with 21 CFR Part 20 and any other applicable laws protecting private, confidential commercial information, and trade secrets.
16 FDA will verify the applicability of any justification proposed.
Updated March 3, 2008
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