Dual 510(k) + CLIA Waiver

Understanding the Dual 510(k) and CLIA Waiver by Application (Dual Submission) Pathway

The Dual Submission pathway is a unified approach that combines a full 510(k) and CLIA Waiver by Application package into one submission. This pathway was established under the Medical Device User Fee Amendments of 2012 (MDUFA III) and provides a simplified process for manufacturers who are seeking both 510(k) clearance and CLIA waiver for their in vitro diagnostic (IVD) tests.

Typically, a manufacturer would need to provide evidence to the FDA that a previously cleared or approved test, which was initially categorized as moderate complexity, meets the CLIA statutory criteria for waiver. This would involve a request to the FDA to categorize the test as waived, which usually follows the clearance or approval of an IVD test.

A key feature of this pathway is the integration of comparison and reproducibility studies, which are crucial components of both 510(k) clearance and CLIA Waiver by Application. Traditionally, these studies are conducted by trained operators for 510(k) submissions and by untrained operators for CLIA Waiver by Application submissions. However, to simplify the process, an applicant may choose to conduct a single set of comparison and reproducibility studies with untrained operators. This approach aims to meet the requirements for both substantial equivalence under section 513(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for 510(k) clearance and the demonstration of simplicity and an insignificant risk of erroneous results under 42 U.S.C. § 263a(d)(3) for CLIA waiver.

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.

Advantages of the Dual Submission Program

The Dual Submission program offers several benefits for manufacturers seeking both 510(k) clearance and CLIA waiver for their in vitro diagnostic (IVD) tests. These benefits include:

Efficiency: The Dual Submission pathway combines the 510(k) clearance and CLIA Waiver by Application into a single submission, reducing the overall review time compared to separate, sequential submissions and leading to faster market access for medical devices.
Cost-Effectiveness: By submitting both applications together, manufacturers can save on costs associated with preparing and submitting separate applications, as well as reduce the time and resources needed for regulatory compliance.
Simplicity: The program allows manufacturers to use a single set of comparison and reproducibility studies conducted by untrained operators, simplifying the process of demonstrating substantial equivalence for 510(k) clearance and the simplicity of use and low risk of erroneous results for CLIA waiver.
Compliance: The Dual Submission pathway ensures that manufacturers comply with both FDA regulations for medical device clearance and CLIA requirements for waived tests, providing a streamlined and comprehensive approach to regulatory approval.
Faster Market Access: With reduced review times and simplified requirements, the program facilitates faster market access for innovative IVD tests, benefiting patients by enabling timely access to new and improved diagnostic technologies.

Who is the Dual Submission Pathway For?

The Dual Submission pathway is particularly suitable for manufacturers of medical devices that meet certain criteria:

Simple Devices: Devices that are straightforward and easy to use are well-suited for Dual Submission. These devices typically have minimal pre-analytical steps and are designed for use by untrained operators in waived settings.
Fail-Safe and Failure Alert Mechanisms: Devices equipped with fail-safe mechanisms and failure alert systems are ideal candidates for Dual Submission. These mechanisms help mitigate the risk of errors and ensure the safety and reliability of test results.
Premarket Notification Requirements: Devices subject to premarket notification (510(k)) requirements can benefit from the Dual Submission pathway. This includes devices that have undergone clearance or approval and now seek CLIA waiver status.
Few Pre-Analytical Steps: Devices with a limited number of pre-analytical steps, such as sample preparation and handling, are well-suited for Dual Submission. Simplifying the workflow reduces the potential for errors and enhances the device’s suitability for waived settings.

Manufacturers who meet these criteria and are developing medical devices that align with the characteristics mentioned above should consider applying for Dual Submission. FDA’s guidance (Recommendations for Dual 510(k) and CLIA Waiver by Application Studies) aims to assist manufacturers in designing study protocols that support both 510(k) clearance and CLIA waiver, thereby streamlining the regulatory approval process and facilitating faster market access for innovative diagnostic technologies.

Process and Content of a Dual Submission

A Dual Submission involves submitting a comprehensive application that combines the requirements for both 510(k) clearance and CLIA Waiver by Application. The process begins with a Pre-Submission to inform the FDA of the intention to pursue a Dual Submission. During this Pre-Submission, applicants discuss planned study designs for comparison and reproducibility studies that support both 510(k) clearance and CLIA waiver. The content of a Dual Submission mirrors that of a complete 510(k) and CLIA Waiver by Application, with certain elements emphasized by the FDA. These include:

Device Description and Determination of Simplicity: A detailed description of the device demonstrating its simplicity of use, aligned with FDA guidelines on CLIA Waiver Applications.
Risk Analysis: Results of a risk analysis identifying potential sources of error for the device, referencing FDA guidelines and ISO 14971 on risk management for medical devices.
Failure-Alert and Fail-Safe Mechanisms: Description of risk evaluation and control measures, along with validation studies showcasing the effectiveness of failure alerts and fail-safe mechanisms, particularly under stress conditions.
Flex Studies: Results of flex studies demonstrate the device’s insensitivity to environmental and usage variations, especially under stress.
Analytical Studies: Detailed design and outcomes of analytical studies conducted internally, covering aspects like sensitivity, specificity, linearity, precision, carry-over, reagent stability, and sample stability.
Comparison Study: Description of study designs and results for comparison studies, indicating an insignificant risk of erroneous results by untrained operators.
Reproducibility Study: Description of study designs and results for reproducibility studies, demonstrating consistent performance of the device when operated by untrained operators.
Clinical Performance Study: While not typically required, some devices may necessitate a clinical performance study. Manufacturers should engage in further discussion with the FDA through a Pre-Submission for guidance.
Labeling: Proposed device labeling, including instructions for use consistent with a device that is simple to operate.

Timeline and MDUFA Decisions for Dual Submission

The Substantive Interaction for a Dual Submission should occur within 90 FDA Days and applies to the complete Dual Submission. The FDA aims to make an MDUFA Decision for a Dual Submission within 180 FDA Days (320 FDA Days if an advisory panel is required). MDUFA Decisions for a Dual Submission encompass several outcomes:

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.

Study Design Recommendations for Dual Submission

When designing comparison and reproducibility studies to support a Dual Submission, the FDA advises applicants to assess test performance in settings that closely mimic actual CLIA-waived settings, patients/samples, and test operators. Therefore, study designs should incorporate the following elements:

Use testing sites that accurately represent the intended use of the waived test.
Include subject populations that are reflective of the intended patient population(s).
Employ the intended sample type and matrix in the studies.
Enroll untrained operators who are representative of those in the intended waived settings. It’s recommended to involve operators with minimal training similar to what might be encountered at the relevant sites.
Integrate testing into the daily workflow of the site where operators often multitask between patient care, testing, and other responsibilities.

By incorporating these design considerations, applicants can ensure that comparison and reproducibility studies align closely with real-world scenarios, providing robust data to support the Dual Submission process.

Why Choose us?

In the intricate world of medical device regulations, we stand as your reliable guide. Our team of experts is proficient in the complexities of the Dual 510(k) and CLIA Waiver by Application pathway. We understand that each in vitro diagnostic (IVD) test has unique characteristics and intended uses, and we tailor our approach to meet these specific needs.

Our commitment to the principles of efficiency, cost-effectiveness, simplicity, compliance, and faster market access ensures that we provide you with the most streamlined and effective route to achieve your regulatory goals. We stay updated with the latest changes in technology and regulations, allowing us to provide you with the most current and relevant advice.

Our expertise in designing study protocols that support both 510(k) clearance and CLIA waiver, streamlines the regulatory approval process and facilitates faster market access for innovative diagnostic technologies. Partner with us to navigate the regulatory landscape with ease and efficiency.

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.