If you’re a medical device manufacturer planning to introduce a new product to the U.S. market, obtaining clearance from the Food and Drug Administration (FDA) is crucial. One of the common routes to the market for moderate-risk medical devices is the 510(k) submission process. However, not all submissions get accepted in the first attempt. The FDA’s “Refuse to Accept” (RTA) policy can be a major roadblock if not addressed properly.

What is the Refuse to Accept Policy?

Most Class II and some Class I medical devices require 510(k) submission, demonstrating that the device is safe and effective and is substantially equivalent to a legally marketed predicate device.

The RTA Policy outlines the criteria and standards that a 510(k) submission must meet to be accepted for a substantive review.

RTA is a minimum threshold of acceptability, and submission that is accepted in this stage of administrative and preliminary technical review is accepted for a substantive review.

This early administrative review, as per the policy, takes place within 15 calendar days of the initial filing of your 510(k) application. The RTA policy can be a significant stumbling block if not proactively addressed.

In accordance with this policy, the FDA aims to:

⦿ Ensure the submission has the necessary information required
⦿ Allocate resources effectively
⦿ Reduce the chances of unnecessary delays during the substantive review
⦿ To make well-informed decisions

To understand more about FDA 510(k) submission and review process, check tips to successful 510(k) submission.

The RTA Policy is an integral part of the FDA’s efforts to improve the efficiency of the 510(k) review process.

What information is required by the RTA Checklist?

The RTA Checklist classifies the questions into the following buckets:

⦿ Administrative
⦿ Device Description
⦿ Substantial Equivalence Discussion
⦿ Proposed Labelling
⦿ Sterilization
⦿ Shelf-Life
⦿ Biocompatibility
⦿ Software
⦿ Cybersecurity
⦿ Electrical Safety and EMC
⦿ Performance Data General
⦿ Performance Characteristics – for In Vitro Diagnostic Devices

How the FDA performs RTA Screening?

During the Refuse to Accept (RTA) review process for 510(k) submissions, the FDA follows a checklist to assess the completeness of your 510(k) application.

The FDA reviewer will use the RTA checklist to go through your submission and mark each requirement as “Yes,” “No,” or “NA” (Not Applicable) to indicate whether the necessary information is present and meets the required standards.

While sending the RTA Hold letter, the FDA reviewer includes the completed RTA checklist, highlighting the deficiencies and providing feedback on areas that need improvement.

What does RTA review results in?

As a result of the RTA review, the following would be one of the outcomes:

Acceptance for Substantive Review

If your submission meets all the necessary requirements and contains the essential elements as per the FDA’s instructions, it will be accepted for substantive review.

This means that the FDA will proceed with a thorough evaluation of the submission to assess the device’s safety and effectiveness.

RTA Hold

If your submission lacks certain critical components or essential information, you will receive RTA Hold.

In this case, the FDA will provide detailed feedback outlining the deficiencies and missing elements that need to be addressed before the submission can be accepted for substantive review.

Typically you will have 180 calendar days to address the deficiencies identified in an RTA HOLD letter.

What are the common reasons for RTA Hold and its Solutions?

Let’s understand what are the common deficiencies manufacturers face during RTA Hold with examples.

Case Study 1

An ECG manufacturer did not include a comprehensive description of its proprietary signal processing algorithm in their 510(k).

Deficiency

Inadequate Device Description.

Why this deficiency

The submission does not provide a clear and accurate description of the device, and its technological characteristics for the FDA to evaluate its performance claims.

Case Study 2

The clinical trial data provided by the microneedling device manufacturer included only the summary of the results and doesn’t demonstrate statistically significant improvements over the predicate device.

Deficiency

Insufficient Performance Data.

Why this deficiency

The clinical study report included in the submission did not include the per-patient data and statistical analysis to facilitate the assessment of substantial equivalence.

Case Study 3

While drafting the user manual and designing labeling, Surgical Staplers and Staples manufacturers did not follow the device-specific FDA guidance document.

Deficiency

Inadequate Labeling and Instructions for Use.

Why this deficiency

The submitted labeling and instructions may not be clear, comprehensive, or in compliance with the FDA requirements.

This case is applicable even if the user manual lacks essential information on proper device calibration and maintenance, leading to confusion amongst the users.

You can always seek the FDA’s feedback via a Pre-Submission before you file your 510(k) application.

There are more such cases.

Following are examples of some deficiencies that we have encountered with manufacturers when they came to us with an RTA HOLD Letter:

⦿ Incomplete or incorrect documentation
⦿ Inconsistent Indications for Use
⦿ Inadequate performance data such as biocompatibility testing, electrical safety testing, or software testing
⦿ Incorrect device classification
⦿ Insufficient software validation and verification
⦿ Unclear software hazard analysis and inadequate mitigation measures
⦿ Missing sterilization validation data
⦿ Insufficient clinical data and failure to provide clinical study protocols, as applicable
⦿ Failure to address predicate device differences
⦿ Issues with packaging and labeling validation
⦿ Inadequately following the applicable FDA guidance document

If any of the above issues resemble your deficiencies or you have any new deficiencies, reach out to us to assist in your RTA response.

It is important to note that preventing an RTA HOLD requires a dedicated accountable owner for 510(k) submission. Effective cross-functional collaboration, a thorough understanding of requirements, and efficient project management go a long way.

How to follow the RTA Checklist?

Thoroughly Review the Checklist

Take the time to go through the RTA Checklist thoroughly. It contains a list of all the required elements and information that your submission must include for a complete and acceptable review.

⦿ Organize Your Documentation

Ensure that all the required documentation and information are well-organized and easily accessible. Arrange your submission according to the structure provided in the checklist.

⦿ Check off Each Requirement

As you review your submission, mark off each requirement on the RTA Checklist to indicate whether you have included the necessary information. Use “Yes” for items that are added to your submission.

⦿ Say why if the requirement is NA/No

State “No” or “NA”, as appropriate, wherever the requirement is not required/not applicable to your device.

⦿ Provide Location References

For items marked “Yes” in the checklist, consider providing references to the specific locations in your submission where the information can be found. This can help the FDA Reviewer locate the relevant data easily.

How to Skip RTA Hold?

Below are the key steps that you can follow to increase your chances of passing the FDA Refuse to Accept (RTA) Process for your 510(k) submission and ensuring that your application is accepted for substantive review.

⦿ Choose the right RTA checklist based on 510(k) type
⦿ Familiarize yourself with the RTA Checklist
⦿ Prepare a comprehensive application
⦿ Provide the required data to substantiate your claims
⦿ Check for consistency and accuracy
⦿ Follow FDA Guidance and Standards
⦿ Provide clear references
⦿ Seek assistance from regulatory experts or consultants who have experience with 510(k) submissions and FDA requirements

By following these steps and paying close attention to the details, you can increase your chances of passing the FDA’s RTA Process and moving your 510(k) submission to the substantive review stage.

Conclusion

Navigating the FDA’s “Refuse to Accept” policy can be a challenging process, but by carefully preparing your 510(k) submission and by addressing all requirements, you can increase your chances of success.

Engage in open communication with the FDA, seek guidance of experts, follow the requirements, and ensure your submission is comprehensive and complete. By doing so, you can minimize the risk of RTA refusal and expedite the clearance process, bringing your innovative medical device to market faster.

How Elexes can be your guide when it comes to RTA?

We understand the FDA RTA process can be a daunting challenge. With our in-depth knowledge of FDA regulations and vast industry experience, we’ll expertly guide you through the submission, ensuring every “i” is dotted and “t” is crossed. From a stringent review of your package to addressing potential risks, we have got your back, leaving no room for RTA holds.

Can I appeal the FDA's decision if my 510(k) submission is refused under the RTA policy?

No, the RTA decision is not appealable.

What is the difference between the acceptance review and the substantive review for 510(k) submissions?

The acceptance review is an initial screening to determine submission completeness, while the substantive review assesses the device’s safety and effectiveness, including its substantial equivalence to predicate device(s).

If I get RTA Hold, does that mean my 510(k) submission is rejected?

An RTA letter does not mean that the FDA has rejected the application; instead, it indicates that the submission requires additional information to proceed with the review. Once you address the identified deficiencies and provide the necessary information, you can submit your RTA response for further evaluation. Need assistance in addressing your deficiencies. Book an appointment with us.

Is the eCopy program applicable for RTA response or can I submit via email to the FDA?

Yes, the eCopy program is applicable to an RTA response. Read more here about the eCopy program. You can check our article eCopy Medical Device Submission (How to create a successful eCopy?) for more details on this.

If the RTA responses are not submitted within the 180-day timeframe, what are the consequences?

If you fail to submit the responses to the RTA Hold Letter within the timeframe, the FDA will withdraw your application on the next day following the deadline. When the application is withdrawn, it means that the FDA will no longer consider the submission for further review.

Elexes Team

Elexes medical consulting is one of the leading regulatory & compliance consultant for several industries: Medical device, Pharmaceuticals, Cosmetics, Food, and Biologics.

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