Starting the process of submitting an Investigational New Drug (IND) application is a pivotal, high-stakes project, especially for early-stage organizations navigating uncharted territory. Each year, over 1,000 INDs are submitted, yet 20-30% encounter avoidable delays or setbacks. For sponsors and medical writing teams, this event is more than just submitting paperwork; it’s a critical milestone for program development, bridging pre-clinical research with clinical evaluation. When a single component of the submission is misaligned, it can cause delays, increase costs, and jeopardize the entire development timeline. That’s why getting it right the first time is imperative for ensuring your program’s success.
In this blog, we’ll explore the three most common challenges faced during IND submissions and share practical strategies that sponsors and partners can implement to overcome these obstacles, ensuring a smoother, more successful path forward.
Learn more about how the FDA formally defines INDs and their requirements in 21 CFR 312.
The Top 3 Challenges
A medical writer’s first exposure to a difficult IND comes from a familiar scenario: A sponsor advanced in its science, but inexperienced in regulatory submissions, is racing the clock.
They want to submit their IND as fast as possible. Time is money. Every week of delay inflates costs and postpones critical treatments for patients. But when development speed outpaces regulatory readiness, writing teams inherit disjointed data, reports in progress, and sections that don’t quite align. Therefore, the team will rush a submission that is poorly written.
This is where INDs often go off the rails—not because the science is weak, but because the sponsor underestimates the intricacies and coordination needed. Here are the most common pitfalls that derail INDs and why they matter:
1.) Submissions Are Not Concise or Cohesive – Even when the required scientific components exist, the pieces often don’t connect. We frequently see:
- Data summaries that are too brief or overly technical, with no interpretation
- Missing links across CMC → pre-clinical → clinical modules
- Different sections contradict each other (e.g., differing proposed doses or formulations)
- No clear development logic (e.g., Why this dose? Why this route? Why now?)
When a submission lacks focus, it raises reviewer concerns about the sponsor’s reliability and readiness.
2.) CMC Packages Are Poorly Developed – CMC deficiencies are among the leading causes of IND delays, especially for biologics and cell/gene therapies. Problem areas include:
- Packages that are too long, unfocused, or missing decision-making questions
- Characterization of the drug substance is incomplete
- Manufacturing process is not well-described or insufficiently controlled
- Inadequate stability data (e.g., too short relative to proposed clinical use)
- Poor impurity profile rationale (e.g., viral safety, adventitious agents)
These issues often trigger avoidable information requests or partial clinical holds that could have been mitigated months earlier.
3.) Lead Times Are Underestimated – Sponsors often push on getting the modules completed as soon as possible. Teams often fail to plan for:
- Availability of source reports
- Overlap of sponsor review periods
- Late-breaking, unexpected pre-clinical safety data
- GLP toxicology study scheduling and reporting timelines
- Analytical method validation
- Time to revise the protocol after pre-IND meeting feedback
Collectively, these delays routinely push IND dates 6–12 months. And the financial impact is massive. A single month of delay can cost:
- $2M–$5M for Phase 1 study hold-ups
- $20M–$50M+ in total trial cost inflation
- $1M–$10M+ per month in opportunity cost
Most importantly, delays mean hundreds of thousands of patients wait longer for a critical therapy that could change their lives.
3 Key Strategies for Your Next IND Submission
A strong IND requires not only understanding the science behind the submission, but also the regulatory requirements.
At Syner-G, our combined functional areas of CMC, medical writing, and regulatory strategy have supported thousands of sponsors and reviewed hundreds of IND submissions. We know the common bottlenecks that can arise. What sets us apart isn’t just our writing expertise, but our comprehensive understanding of the IND process; how we structure it and effectively manage the entire program to drive success. The key elements for a successful IND include:
1.) Understanding the Full Scope of the IND – Go beyond traditional kickoff meetings. At the start of a project, apply a structured discovery process to include:
- Conducting an IND deep-dive transfer meeting
- Creating a joint RACI that clarifies who owns each deliverable
- Asking high-value questions designed to expose risk early
- Using risk-based quality management (RBQM) to operationalize and track risk
- Maintaining a shared assumptions log to prevent “surprises” downstream
- Running strong governance with clear escalation paths
This ensures all functions—CMC, pre-clinical, clinical, regulatory, and medical writing—start aligned.
2.) Build a Realistic and Reliable Timeline – A strong regulatory roadmap isn’t optional, it is essential for every successful IND. Outline the full picture:
- Batch availability
- Pre-clinical study completions
- Manufacturing dependencies
- Review loops
- Module interconnections
- Room for fluidity to accommodate last-minute delays
Scheduling tasks strategically is key to preventing sponsor teams from becoming overwhelmed by overlapping reviews. With this approach time is respected, predictability improves, and stress decreases.
3.) Foster Collaboration with Sponsors – Beyond technical accuracy, successful INDs require clear communication and alignment with reviewer expectations. It is important to partner directly with sponsors on:
- Organizational strategy across modules
- Drafting for clarity, structure, and readability
- “Reviewer mindset” framing to anticipate concerns
- Harmonization across modules to avoid contradictions
- Consistent scientific storytelling across CMC, pre-clinical, and clinical components
Every module—protocols, summaries, reports— should be crafted with precision, credibility, and regulatory nuance to help sponsors avoid rework and maintain critical momentum.
An IND is not just a regulatory milestone—it’s the opening chapter of a product’s clinical journey. By ensuring that this first step is strong, cohesive, and compelling, you lay the foundation for future milestones and success. High-quality, compliant medical writing plays a vital role in accelerating development and turning promising science into life-changing therapies.
