A Clear Path to the Clinic and Beyond: Why Getting Your IND Submission Right Matters

Imagine this - you are doing a final review of your initial Investigational New Drug (IND) application. You carefully review every section of every module, confirm that each is complete and final, and validate that the submission conforms to eCTD technical requirements. Everything looks in order. The work of many weeks and hundreds of hours is metaphorically held in your hands. You pause one last time as you stand on the threshold and mentally prepare yourself to pass the point of no return. You give the approval to submit.  

Regulatory submissions are complex and involve a certain level of risk. FDA review of the data and information presented in the initial IND submission will be the first step in determining whether your drug will make it into the clinic and how quickly it could happen. The initial submission and the subsequent maintenance of the IND also impacts the timeline for when it will eventually (hopefully!) be approved.

To successfully navigate these challenges, clear, complete, and compliant documentation is essential. For submissions and amendments, fulfilling FDA requirements on the first try can mean the difference between a smooth path forward or a grueling cycle of Agency meetings and clinical hold responses. Each avoidable delay not only increases operational costs but also stifles innovation, drains resources, and keeps life-changing products from reaching the patients who need them most.

The Costly Impact of Delays

1. Financial Strain

When an IND submission for a novel therapeutic is placed on clinical hold due to incomplete or inaccurate data, sponsors can lose months (or more) in the clinical development timeline. For every day a new drug’s clinical trial is delayed, additional costs—such as site fees, investigator grants, and staffing—keep mounting. Recent research indicates that “a single day equals approximately $500,000 in lost prescription drug or biologic sales, with daily prescription sales for infectious, hematologic, cardiovascular, and gastrointestinal diseases among the highest.” Clinical holds can also cause significant reputational harm to a company when the hold is publicly disclosed.  

2. Missed Market Opportunities

A delay in securing IND clearance or starting a registration-enabling clinical trial for a promising therapy could derail its timeline, allowing competing drugs to advance further in clinical development and leading to lost partnerships or diminished investor enthusiasm. This impact can be significant in crowded development spaces like oncology, where timing is critical for a drug to be first- or best-in-class.

3. Regulatory Challenges

Incomplete or noncompliant submissions can negatively affect an organization’s relationship with the FDA. Multiple resubmissions or frequent amendments not only slow down the agency’s review process but can also signal potential gaps in a sponsor’s management of the development program or, for CMC issues, cGMP compliance. Maintaining a productive relationship with the Agency is important; if strained, the loss of credibility and reviewers’ confidence in the information being presented may lead the reviewers to be less flexible with a company’s proposals

4. Resource Drain and Team Burnout

Teams dealing with repeated Information Requests (IRs) or needing to revise numerous documents in the submission during the mandated 30-day IND review period often find themselves working overtime on increasingly tight timelines as the regulatory deadline approaches. Scientists, regulatory strategists, and project managers who continually rework data and documents are often pulled from other projects they are also supporting, which can have a ripple effect throughout the organization. Delays beget more delays, and the fatigue that builds can threaten morale and productivity.

(Check out our webinar series on team resourcing for more tips on how to manage this!)

Unique Complexities of IND Submissions  

An IND must be submitted when a sponsor wants to evaluate a new drug or biologic in clinical trials in the US. This dossier provides the FDA with information and data on the quality of the drug or biologic, the results of nonclinical studies, and the Investigator Brochure and protocol for the proposed clinical study. This is continually updated throughout the development lifecycle.  

• Scientific Rigor: INDs must demonstrate a compelling rationale for clinical testing, with adequate assurance of safe use of the product in human subjects for Phase 1 studies, and for later-phase clinical investigations, study designs of adequate scientific quality to support potential marketing approval. Gaps in data supporting safe use of the product in humans or poorly designed studies can cause the FDA to place the trial on clinical hold, forcing sponsors to resolve these issues prior to enrolling patients.

• Quality & Manufacturing Data: Sponsors must provide Chemistry, Manufacturing, and Control (CMC) information to assure the proper identification, quality, purity, and strength as appropriate for the proposed clinical study. Missing or poorly structured information in the CMC section of an initial IND can lead to multiple IRs with a risk of clinical hold if issues cannot be resolved within the required 30-day review period. CMC information must also be updated as changes are made to the manufacturing process, with increasing detail usually required as development proceeds.  

• Protocol Clarity: Unclear or inappropriate patient selection criteria, endpoints, risk mitigation strategies, or other aspects of the clinical study design will lead to IRs and revisions to the protocol. If the deficiencies represent a potential risk to the safety of human subjects and cannot be adequately resolved within the 30-day review for initial INDs, or before planned study start in later development, the Agency may place the IND on clinical hold.

How to Bolster Submission Quality

1. Assemble the Right Team Early

Experts who specialize in IND submissions—such as CMC clinical and /nonclinical regulatory strategists, medical and technical writers, and project managers—should be brought on board from the start. Their familiarity with FDA requirements and guidelines as well as the IND development process ensures that you will work toward a complete and well-organized IND or amendment, with all information and data clearly presented, to reach your target submission date.  

Read more about how to hire the right medical writer!

2. Conduct Thorough Document Reviews

Before submitting an IND to the FDA, all sections should go through multiple rounds of internal stakeholder reviews. Review by both scientific and regulatory experts can ensure that key messages are clearly presented and catch any gaps, contradictory statements, or misalignment with guidance documents. This helps you address potential issues proactively rather than waiting for an Agency reviewer to catch them when the submission is filed.  

3. Keep Up with Regulatory Changes

The FDA continually updates guidance documents and issues new ones, especially in fast-evolving fields such as digital health, oncology, cell and gene therapy, and combination products. Stay on top of new requirements through workshops, official FDA channels, and industry newsletters to ensure your submission reflects the most current regulatory thinking.  

4. Leverage Technology and Project Management Tools

Streamlining the process with document templates and Regulatory Information Management software supports efficient document development and review, keeps teams organized, and eliminates confusion. This approach also provides clear audit trails, ensuring you can trace every change throughout the document lifecycle.

5. Emphasize Clear Communication

The multidisciplinary nature of IND submissions means that you’ll be interfacing with clinicians, manufacturing experts, statisticians, and sometimes external partners. Early alignment is key: make sure everyone understands their roles, deadlines, and the regulatory requirements that must be met. Transparent, ongoing communication can help you avoid the cascade of minor errors that become major problems later.  

Choosing the Right Partners to Avoid Delays

No matter how strong your in-house capabilities are, the challenges of IND submissions often call for specialized external support. Here’s why partnering with an experienced submission team can make the difference:  

• Targeted Expertise: Professionals who’ve successfully navigated these processes bring tested strategies and a deep understanding of potential pitfalls.  

• Access to Best Practices: Reliable partners stay updated on the latest FDA regulations and can rapidly integrate new guidance into your submission planning and documentation.  

• Efficient Review Cycles: External experts offer a fresh perspective on your data and structure, spotting issues that internal teams—overly familiar with the content—might overlook.  

• Scalable Support: Whether you need end-to-end submission preparation or targeted help with specific elements (e.g., clinical protocols, the CMC dossier, eCTD publishing), a flexible partner can scale to your project’s needs.

Final Thoughts: Stay on Track, Protect your Budget, and Advance Innovation

Getting FDA submissions right the first time is crucial. Each back-and-forth with the FDA not only costs time and money but also risks eroding stakeholder confidence—internally and externally.  

By investing in a thorough, strategic approach and choosing trusted partners with FDA submission experience, you can keep your development timelines on track, optimize resources, and ensure your products reach the people who need them.  

If your organization needs specialized regulatory expertise or robust project management support, we’re here to help. Our experienced regulatory team understands the nuances of preparing a successful IND. From building a rock-solid data package to providing fresh, expert eyes for final review, we can help you navigate FDA requirements, avoid costly missteps, and move forward with confidence. Schedule a consultation today!

‍