Avoid delays and refusals by performing a pre-submission risk assessment. Use FDA RTA checklists, mock reviews, Pre-Submission meetings, and internal audits to identify and mitigate regulatory, technical, and quality risks before filing.
One of the most frustrating scenarios for a device company is investing time and money into a premarket submission (whether a 510(k), De Novo, or PMA) only to face an FDA refusal or significant delay because of preventable issues. That’s why performing a risk assessment before submission is critical. This involves scrutinizing your submission package and overall readiness through the eyes of FDA – essentially doing a mini “regulatory audit” of the submission to catch any shortcomings.
A key strategy is to leverage the FDA’s Refuse-to-Accept (RTA) checklists and guidance. FDA will not even begin substantive review of a 510(k) if certain administrative and content criteria aren’t met. Roughly 30% of 510(k) submissions (as of 2022) weren’t accepted for initial review due to such deficiencies. To avoid this, treat the RTA checklist (available in FDA guidance and on their website) as gospel during your pre-submission risk assessment.
Missing even a small item can result in an automatic RTA hold. Many companies create an internal submission review team separate from the authors to catch oversights. This is a form of risk mitigation akin to a quality inspection of the submission itself.
Beyond administrative completeness, technical completeness is another area for risk mitigation. Ask yourself: if you were the FDA reviewer, what questions or concerns might you raise? Have you provided justification for all claims? Is every piece of data backed by reports?
Common reasons FDA might refuse to file or later issue deficiency letters include:
A mitigation strategy is to perform a “mock review” – some companies even hire external experts or former FDA reviewers to evaluate the submission package. Identifying weaknesses early helps avoid FDA holds or delays.
Engaging with FDA before the official submission is a powerful mitigation strategy. The Q-Submission program allows you to ask FDA for feedback on specific questions or to have a meeting to discuss your plans. This can drastically reduce risk by clarifying expectations on clinical data, testing plans, or regulatory strategy.
For example, if unsure whether clinical data is needed, a Pre-Sub can provide FDA’s opinion, avoiding surprises during review. For novel technologies, Pre-Subs clarify evidence requirements. Incorporating FDA feedback into your submission mitigates risk of rejection on those points.
Manufacturing and quality readiness is another pre-submission risk. For PMAs and some 510(k)s, FDA may audit your manufacturing facility. A strong submission paired with a weak quality system can delay approval.
Conduct internal audits simulating FDA pre-approval inspections to ensure production processes, supplier controls, and design transfer are compliant and ready.
All documents referenced in your submission (SOPs, standards, testing protocols) should be current and correct. Inconsistencies, such as outdated protocols or mismatched Indications for Use statements, can raise FDA flags.
Mitigate this risk with thorough proofreading, version control, and possibly a “single source” approach where key statements are maintained in one master file and populated consistently throughout the submission.
Sometimes pre-submission risk assessment reveals that the planned regulatory pathway is too risky. Adjusting strategy—such as pursuing a De Novo instead of a 510(k), or adding a Breakthrough Device designation request—can reduce risk and improve communication with FDA.
Pre-submission risk assessment is about being one step ahead of FDA. It combines checklist-driven reviews, FDA engagement, and internal testing of submission strength. The goal is to minimize unknowns at submission, avoiding refusals, deficiency letters, or delays. An ounce of prevention before submission is worth a pound of cure afterward.
