Even before the FDAʼs full review of a New Drug Application (NDA) or Biologics License Application (BLA), a filing review is conducted to ensure that the submission is acceptable for a full review. A “Refuse to Fileˮ (RTF) letter from the FDA can halt years of progress in the blink of an eye.
What are the most common reasons for an RTF letter?
- CMC deficiencies account for almost 20% of RTFs
- After clinical efficacy and safety deficiencies (accounting for over 25% of RTFs), application organization was one of the top 5 reasons for the FDA to refuse to file a sponsor’s submission
Equally as challenging as receiving an RTF letter are delays in your submission timeline. A recent analysis showed that delays in drug approval could be as much as $800,000 per day.
What are the stumbling blocks that can cause a delay in submission and approval?
- Internal team dynamics
- Building timelines without taking document inter-dependencies into account
- Setting overly aggressive review schedules
(Learn how to optimize and stagger your review schedules effectively here.)
Even well after submission, sponsors often face hurdles that can delay drug approvals:
- Quality control documentation
- Inspection readiness
Avoiding RTF letters and costly delays requires more than technical expertise. It demands foresight, alignment, and disciplined execution.
At Syner-G, we partner with sponsors to build documented, science-aligned, inspection-ready submissions from the earliest stages of development through post-submission support. From strengthening CMC packages and improving submission “reviewability,” to optimizing cross-functional workflows and ensuring inspection readiness, our team helps reduce regulatory risk and accelerate time to approval.
