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Navigating Regulatory Challenges in Assay Development

Human Health In Vitro Diagnostics

Documentation, Early FDA Engagement, and Understanding of Regulations All Critical

Based on our observations, approximately 75 percent of the market has experienced a lack of clarity about regulatory requirements or FDA expectations for study designs. Our expertise in working with the FDA can help ensure clarity in study design and navigate associated regulatory challenges.  

The design and development process for IVDs typically involves the preparation of key planning documents such as the Design and Development Plan, Regulatory Plan, Risk Management Plan, and Verification and Validation Plan. The draft documents that are created early on should be revisited throughout the development process, adding details, especially as the design of the device evolves and feedback is received from a regulatory agency such as the FDA. For example, a Regulatory Plan may need to be updated following an FDA pre-submission meeting in which study designs, device requirements, and regulatory pathway are discussed. 

To Include in the Regulatory Plan
There are several important elements to include in the regulatory plan, many of which should be updated as the FDA is engaged.  

  1. Purpose  
  2. Scope 
  3. References list – Include regulatory guidance documents, standards, publications and project documents (e.g., clinical validation, design verification, and analytical validation plans)  
  4. Product Information (device description) 
  5. Proposed Intended Use
  6. Regulatory Strategy Summary – Request the FDA’s feedback and update your strategy accordingly. 
  7. Regulatory Classification Information
  8. Proposed Regulatory Path – Engage the FDA early in the process and update this path as feedback is received. 
  9. Predicate Comparison Table
  10. IDE (Investigational Device Exemption) Considerations 
  11. Tracker for FDA Interactions – Note your FDA interactions in a table including feedback.
  12. Table of Premarket Submission Deliverables and Responsible Parties 
  13. Analytical and Clinical Requirements List – Request feedback from FDA early on these requirements and plan accordingly.
  14. Labeling Description 
  15. Table of Regulatory Correspondence – Include subject, date, and specific feedback that is part of the specific device Q-submission (pre-sub) number; these are important to reference during future FDA communications.
  16. Abbreviations List 

Pathways to Market Entry
There are multiple ways that IVDs can enter the U.S. market. If looking for resources from the FDA, one of the best places to start is the Center for Devices and Radiological Health (CDRH) website. They oversee device regulation for IVDs. Assays that include a SARS-CoV-2 target can potentially go through an Emergency Use Authorization (EUA) pathway. Otherwise, IVDs often go through a 510(k) premarket notification or premarket approval (PMA) pathway. High-risk devices generally go through a PMA pathway for market approval, while a De Novo pathway is often for low-to-moderate risk devices that don’t have a predicate. The pathway is determined in part by the risk classification and whether a predicate device can be identified.  

A predicate, of course, is an existing legally marketed device with the same intended use and technological characteristics. Notably, there is some room for interpretation on what “same” is, which makes it important to get FDA feedback early in the process. Most IVDs for respiratory viruses will follow the 510(k) process to clearance. If there is not a predicate device, one option is the De Novo classification request pathway, which involves FDA assigning a classification to a new device and creating a new classification regulation. Once the device has this new classification regulation, it can then serve as a predicate for downstream 510(k) submissions for similar devices.  

The device classification and existence of a predicate will shape the regulatory pathway, the types of regulatory controls that will be needed, and the data that the FDA will look for as part of the medical device submission. One of the best ways to initiate the process of developing the regulatory strategy and gathering information is through a pre-submission to the FDA. To get the most out of an FDA “pre-sub”, it is best to have the device’s intended use and sufficient information about the device design for the Agency to advise on protocols and test methods. 

After receiving feedback from the FDA, be sure to reconcile their outstanding questions. If there is alignment, additional clarification as a supplement to the pre-sub may be necessary, though submitting a 510(k) or De Novo classification request directly is also an option.  

For more about the importance of “Point of Need” diagnostics like those for SARS-CoV-2, influenza, and RSV, listen to this episode of “Science Diction” from MRIGlobal.

Guidance Documents to Review and Follow
For each of these pathways, it is important to know which guidance documents to review and follow.  

  • The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications 
  • De Novo Classification Process (Evaluation of Automatic Class III Designation)  
  • Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program 

When pursuing a 510(k) submission, there are several resources that can help improve understanding of what kind of documentation is necessary, including quality management system requirements and analytical and clinical study data. One method is reviewing the labeling and 510(k) decision summaries for similar devices, including what might be the proposed device predicate.  

Paying close attention to FDA guidance documents is also important, as there have been key updates to regulatory guidance for IVDs in the past few years. These includes recommendations for the use of clinical data in premarket notification submissions and best practices for selecting a predicate to support the 510(k) submission – both of which came out as draft guidance in 2023. If targeting certain pathogens like influenza, look for specific guidance from CDRH for devices that include an influenza target. 

If pursuing an EUA for a multiplex device that includes SARS-CoV-2 as an analyte target, understand that the FDA is encouraging device manufacturers to transition to using traditional marketing authorization pathways. If interested in going down the EUA pathway, understand the current priorities of the FDA for the COVID EUA, which can be found in their guidance document titled “Policy for Coronavirus Disease 2019 Tests,” which was also updated in 2023. In brief, the FDA is prioritizing devices under this COVID EUA that would have a significant benefit to public health or fulfill an unmet need. Their priorities would include devices supported by a government stakeholder or submitted as a supplement to an EUA.  

And finally, it is essential for any device developer to understand regulations and standards for their desired market.  

  • ISO 13485 is a widely used international standard recently incorporated into the U.S. Quality System Regulation 21 CFR Part 820, and it is intended to harmonize U.S. regulation with requirements of other regular regulatory authorities.  
  • ISO 14971 is a standard recognized by the FDA and international regulatory bodies for risk management during medical device development.  
  • And if performing clinical studies, it is best to be familiar with Good Clinical Practices (GCP) that apply to IVDs.   

Using this guidance can help successfully navigate the regulatory process and attain market access for your IVD.

Additional expertise on this topic

MRIGlobal’s Yvette Girard, MPH, Ph.D., Joe Russell, Ph.D., and Jennifer Stone, MS, hosted a free webinar on the development of rapid, accessible, and portable infectious disease diagnostics for seasonal respiratory diseases like influenza, RSV, and SARS-CoV-2. Watch the webinar recording at “Infectious Disease Diagnostics for Influenza, RSV and SARS-CoV-2.” You can also read about considerations for developing a disease diagnostic at “Six Stages to Developing a Novel Infectious Disease Assay.” 


Contact MRIGlobal for further information about our work with infectious diseases. Through a multidisciplinary approach, we provide scientific and subject matter expertise for the development of medical countermeasures research against specific threats, while expanding and accelerating the delivery of high quality clinical diagnostic products.  

To discuss how we can help your project be successful, contact us today.  


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