CLIA Waiver

Understanding the CLIA Waiver by Application Process

A CLIA Waiver by Application (CW) is a formal procedure that a manufacturer initiates to seek a change in the classification of an in vitro diagnostic (IVD) test from its original moderate complexity category to a waived category under the Clinical Laboratory Improvement Amendments (CLIA) regulations. CLIA classifies IVD tests into three levels of complexity: waived, moderate complexity, and high complexity. Tests that are automatically classified as waived include those that are cleared or approved for home use or specifically waived under 42 CFR 493.15©. Tests that do not fall into these categories may initially be classified as moderate or high complexity based on the criteria outlined in CLIA’s 42 CFR 493.17.

The CW submission to the FDA requires the manufacturer to provide substantial evidence that the test meets the statutory criteria for waiver. This criterion states that waived tests are either approved by the FDA for home use or are simple laboratory examinations and procedures with a negligible risk of producing incorrect results. These tests must either use methodologies so simple and accurate that user error is highly unlikely, or pose no unreasonable risk of harm to the patient if performed incorrectly. Once a test is successfully classified as waived through the CW process, it can be conducted in laboratories holding a Certificate of Waiver (CoW) or a Certificate for Provider Performed Microscopy (PPM), in addition to other CLIA Certificate types. This reclassification expands access to the test while ensuring that it meets stringent criteria for accuracy and safety.

There is no MDUFA User Fee for a CLIA Waiver by Application.

How to Prepare a CLIA Waiver by Application

To prepare a CLIA Waiver by Application (CW) submission, follow these steps:

1. Review Guidelines: Begin by reviewing the following guidance documents:

   • Administrative Procedures for CLIA Categorization
   • Recommendations: Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices

2. Consider Pre-Submission: If applicable, consider submitting planned protocols or study designs through a Pre-Submission to obtain the FDA’s feedback before conducting a clinical study to support your CW. Refer to the guidance document “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program” for more information.

3. Assemble the Application: Compile the CW application with the following recommended contents (not limited to):

   • A signed and dated cover letter specifically identifying the submission as a CW, referencing a cleared/approved marketing application (e.g., 510(k), PMA, BLA), and providing contact information for at least one person.
   • A device description demonstrating its simplicity of use.
   • Results of risk analysis, including identification of potential error sources.
   • Results of risk evaluation and control, detailing measures implemented to mitigate errors and validation/verification studies for failure alerts, fail-safe mechanisms, and other control measures.
   • Results of flex studies showcasing the test system’s insensitivity to environmental and usage variations under stress conditions.
   • Description and results of clinical studies conducted to show the device’s low risk of erroneous results in the hands of intended users at intended use sites.
   • Proposed labeling with clear instructions for use consistent with a simple device.

4. Submit the Application: Submit the CW application package to the FDA’s Center for Devices and Radiological Health (CDRH), specifically to the Office of In Vitro Diagnostics (OHT7). You can submit it via the CDRH Portal or send it to CDRH’s Document Control Center (DCC). The FDA encourages the submission of a validated eCopy to expedite the review process.

FDA’s Actions on CLIA Waiver by Application Submission

Upon submitting a CLIA Waiver by Application (CW), the FDA follows a structured process:

1. Email Acknowledgment Letter: Within a week of receiving the submission, the FDA sends an acknowledgment email containing the received date and a CW tracking number that starts with “CW” followed by a six-digit number indicating the year and submission order.

2. Substantive Interaction (SI): Within 90 FDA review days, there’s a Substantive Interaction (SI). This could lead to:

   • Approval: The CW is approved.
   • Proceed Interactively: Minor deficiencies may be addressed interactively.
   • Additional Information (AI) Request: If substantive deficiencies are identified, an AI request is made, and the applicant has 180 days to submit the requested information.

3. MDUFA Decision: Within 150 FDA days (or 320 days if an advisory panel is needed), a MDUFA Decision is issued:

   • Waiver Approval: The CW is approved, and the waived categorization is added to the public CLIA Database.
   • Waiver Denial: The CW is denied.
   • Withdrawal by the applicant.

4. Missed MDUFA Decision: If the FDA misses the MDUFA decision deadline by 20 days, they issue a Missed MDUFA Communication to discuss outstanding issues and provide an estimated completion date.

Throughout this process, clear communication and adherence to timelines are crucial for efficient review and decision-making.

How to Obtain a CLIA Waiver

To obtain a CLIA waiver, follow these steps:

1. Review Guidelines: Start by thoroughly reviewing the official Regulations and Guidance document that outlines CLIA Waiver protocols, applications, and categorization procedures.

2. Check Eligibility: Verify if your laboratory and personnel meet the eligibility criteria for a waiver as per CLIA qualifications. Ensure that your lab adheres to the recommendations for Good Laboratory Practices for Waived Testing Sites set by the CDC.

3. Consider Pre-submission: If conducting a clinical study, consider submitting planned protocols through a pre-submission to receive early feedback from the FDA. This feedback can support your application for a certificate of waiver later on.

4. Assemble Application (CMS-116): Download and complete Form CMS-116 from the Centers for Medicare & Medicaid Services. Fill in details such as laboratory information, type, hours of testing, estimated number of waived tests annually, personnel involved, and multiple-site information. Review all sections carefully to ensure completeness, as incomplete applications are typically rejected.

5. Submit Application: Send the completed CMS-116 form to the respective State Agency via mail or email. Ensure all paperwork is in order and all fields are filled. For in vitro diagnostic devices, applications will be reviewed by the FDA’s Center for Devices and Radiological Health (CDRH).

6. Certificate Issuance: Once CMS reviews and approves the application, a Certificate of Waiver with a ten-character alpha-numeric CLIA number will be issued. This unique identification number is used for tracking the laboratory and signifies that the basic requirements for obtaining a CLIA waiver have been met.

Why Choose Us?

At our organization, we are committed to providing top-tier services in the field of in vitro diagnostics. Our expertise in navigating the complex landscape of CLIA waivers sets us apart. We offer comprehensive guidance throughout the CLIA Waiver by Application process, ensuring your diagnostic tests meet the stringent criteria for accuracy and safety. Our team is well-versed in regulatory requirements and stays updated with the latest industry trends. We provide personalized support, from reviewing guidelines to preparing submissions and managing communications with the FDA. Our goal is to broaden access to your tests, enabling quicker and more accurate diagnoses for patients. Choose us for our deep industry knowledge, commitment to service, and dedication to promoting better health outcomes. We’re not just your service provider—we’re your partner in making healthcare more accessible.

About Accel

Accel Groups is a dedicated team of seasoned professionals in regulatory, clinical and market access. We help medical device and IVD manufacturers with complete product life cycle solutions from preclinical, strategy, clinical evaluation and trial, regulatory submission, to post market surveillance. Our regional principals have a minimum of 10+ years’ experience in their specialty to enable us to provide the regional in-depth expertise but with global one-stop shop solutions. Ask us about our Start-up kits for start-up companies with key countries regulatory pathway.