CLIA Waiver by Application
Under CLIA, the FDA categorizes in vitro diagnostic (IVD) tests by their degree of complexity: waived, moderate complexity, and high complexity. Tests that are waived by regulation under 42 CFR 493.15(c), or cleared or approved for home use, are automatically categorized as waived following clearance or approval. Otherwise, following clearance or approval, tests may be categorized either as moderate or high complexity according to the CLIA categorization criteria listed in 42 CFR 493.17.
A manufacturer of a test initially categorized as moderate complexity may request categorization of the test as waived through a CLIA Waiver by Application (CW) submission to the FDA. When a test is categorized as waived, it allows that test to be performed by laboratories with a Certificate of Waiver (CoW) or a Certificate for Provider Performed Microscopy (PPM) in addition to the other CLIA Certificate types. In a CW submission, the manufacturer provides evidence to the FDA that a test meets the CLIA statutory criteria for waiver, 42 U.S.C. § 263a(d)(3). The statute states that:
"The examinations and procedures [that may be performed by a laboratory with a Certificate of Waiver] are laboratory examinations and procedures that have been approved by the Food and Drug Administration for home use or that, as determined by the Secretary, are simple laboratory examinations and procedures that have an insignificant risk of an erroneous result, including those that — (A) employ methodologies that are so simple and accurate as to render the likelihood of erroneous results by the user negligible, or (B) the Secretary has determined pose no unreasonable risk of harm to the patient if performed incorrectly."
How to Prepare a CLIA Waiver by Application
- Review the following guidances:
- Administrative Procedures for CLIA Categorization
- Recommendations: Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices
- Consider submitting planned protocols or study designs though a Pre-Submission to obtain the FDA’s feedback prior to conducting a clinical study to support a CW. Please see the following guidance for more information about Pre-Submissions:
- Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
- Assemble the application. Recommended contents of a CW include, but are not limited to, the following:
- A signed and dated cover letter that:
- identifies the submission as a CW,
- references a cleared/approved marketing application (e.g., 510(k), PMA, BLA), and
- identifies at least one contact person, include name, title, phone number, and email address.
- A description of the device that demonstrates it is simple to use.
- The results of risk analysis including the identification of potential sources of error for your device.
- The results of risk evaluation and control including a description of (1) measures you have implemented to mitigate the risk of errors, and (2) validation and/or verification studies demonstrating the ability of failure alert, fail-safe mechanisms, and other control measures that you have incorporated into your device to mitigate the risk of errors, even under conditions of stress.
- The results of flex studies demonstrating insensitivity of the test system to environmental and usage variations under conditions of stress.
- A description of the design and results of clinical studies you conducted to demonstrate that the device has an insignificant risk of erroneous result in the hands of the intended user, at intended use sites.
- Proposed labeling with instructions for use consistent with a device that is "simple."
- Submit the application:
CW submissions for in vitro diagnostic devices are reviewed by FDA’s Center for Devices and Radiological Health (CDRH), specifically by the Office of In Vitro Diagnostics (OHT7). A CW submission package should be submitted via the CDRH Portal or sent to CDRH’s Document Control Center (DCC). The current mailing address for CDRH’s DCC is provided on the eCopy Program for Medical Device Submissions webpage. To expedite review, the FDA strongly encourages submission of a validated eCopy.
FDA Actions on CLIA Waiver by Application Submission
- Email Acknowledgment Letter
Within one week of the FDA’s receipt of the submission, the FDA will issue an email acknowledgment letter. The acknowledgment letter will include the date the FDA received the application and the assigned CW tracking number. The CW tracking number begins with the letters "CW" followed by 6 digits. The first two digits designate the calendar year the submission was received; the last four digits represent the submission number for the year, starting with 0001 (e.g. CW170001).
- Substantive Interaction (SI)
The FDA will engage in a Substantive Interaction (SI) within 90 FDA review days. The SI may be an email or letter notifying the applicant that the CW has been Approved, the review will Proceed Interactively, or Additional Information is requested.
- Proceed Interactively: the FDA has not identified substantive deficiencies in the initial submission review and any further minor deficiencies will be communicated through interactive review (email, phone, etc.).
- Additional Information (AI): Additional Information is requested, and the file is being placed on hold because substantive deficiencies were identified in the initial submission review.
- In this case, the applicant should submit the information requested to the CDRH DCC as a supplement to the CW with 180 days.
- If the FDA does not receive a complete response to all deficiencies in the AI request within 180 days of the date of the AI Request, the submission will be considered withdrawn and the applicant will need to submit a new application if they still wish to pursue a CLIA waiver.
- MDUFA Decision
The FDA will issue a MDUFA Decision within 150 FDA days (320 FDA Days if an advisory panel is required). For CWs, a MDUFA Decision may be a notification of Waiver Approval, a notification of Waiver Denial, or withdrawal by the applicant. If the CW is approved, the waived categorization of the test will also be included in the public CLIA Database at the next weekly update.
| Action | Review Time (FDA days) |
|---|
| Substantive Interaction | 90 days |
MDUFA Decision
No Panel
With Panel |
150
320 |
| Dual (510(k) and CLIA Waiver by Application | 180 |
Dual Submission Pathway
A Dual 510(k) and CLIA Waiver by Application (Dual Submission) is a single submission containing a complete 510(k) and CLIA Waiver by Application package. A Dual Submission is subject to 510(k) eCopy requirements, requires a 510(k) MDUFA User fee, and is subject to 510(k) Refuse to Accept (RTA) policies. An applicant should inform the FDA they plan to submit a Dual Submission through a Pre-Submission, and the cover letter for a Dual Submission should reference this Pre-Submission number. The Pre-Submission process provides a forum for the sponsor and the FDA to discuss proposed study designs for the Dual Submission. The Substantive Interaction for a Dual Submission should occur within 90 FDA Days and applies to the complete Dual Submission. The FDA goal to make a MDUFA Decision for a Dual Submission is 180 FDA Days (320 FDA Days if an advisory panel is required). MDUFA Decisions for a Dual Submission include:
- 510(k) SE and CLIA Waiver Approval
- 510(k) SE and CLIA Waiver Denial
- 510(k) NSE and CLIA Waiver Denial
- Withdrawal by the Applicant
For in vitro diagnostic test systems authorized under an emergency use authorization (EUA) for use in patient care settings operating under a CLIA Certificate of Waiver, the FDA intends to accept marketing submissions under the Dual 510(k) and CLIA Waiver by Application pathway, or Dual De Novo and CLIA Waiver marketing submissions modeled after the 510(k) and CLIA Waiver by Application pathway, as appropriate. (See Section 3301 of the Food and Drug Omnibus Reform Act of 2022, Title III of Division FF of the Consolidated Appropriations Act, 2023, Pub. L. No. 117-328 (“FDORA”).)
Please see the following guidance for study design recommendations for Dual Submissions:
- Recommendations for Dual 510(k) and CLIA Waiver by Application Studies - Guidance for Industry and Food and Drug Administration Staff
- For IVDs authorized under an EUA for use in patient care settings operating under a CLIA Certificate of Waiver, see the Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19)
Is there a User Fee for a CLIA Waiver by Application?
There is no MDUFA User Fee for a CLIA Waiver by Application.
Please note for the Dual Submission Pathway, you must pay the MDUFA User Fee for the 510(k) notification.
CLIA Waiver by Application Decision Summaries
Since 2017, the FDA has made CW decision summaries available on our website. For additional information, see CLIA Waiver by Application Decision Summaries.
Resources/Contact Us
- Webinar - CLIA Waiver Applications Final Guidance Documents
- Administrative Procedures for CLIA Categorization - Guidance for Industry and Food and Drug Administration Staff (PDF - 124KB)
- Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices - Guidance for Industry and Food and Drug Administration Staff
- Recommendations for Dual 510(k) and CLIA Waiver by Application Studies - Guidance for Industry and Food and Drug Administration Staff
- Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
- MDUFA IV Commitment Letter
- Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) Related to Coronavirus Disease 2019 (COVID-19)
- Questions? Contact us at CLIA@fda.hhs.gov
