In a clinical development world divided by phases, transitions are critical at every step. The transition from nonclinical testing to the first-in-human (FIH) Phase I clinical trial is among the most important, as sponsors undergo rigorous regulatory scrutiny while agencies seek to understand the safety of an Investigational New Drug (IND) before approving its progression to a FIH study.
In a review by Lapteva and Pariser, 8.9% of INDs were placed on clinical hold, significantly delaying programs and creating white space.[i] The study concluded that many of these scenarios could have been avoided through better adherence to the available guidelines for investigational product development.
Close collaboration with agencies is critical in the lead up to IND submission. A pre-IND meeting is generally recommended to help sponsors obtain early feedback on their clinical development plan and address any issues before they become potential regulatory roadblocks.
However, when sponsors aren’t well-versed with navigating these formal discussions, the all-important regulatory exchanges can themselves become a source of white space – often one that is characterised by prolonged back-and-forth, and periods of inactivity when waiting for a regulatory response. In a LinkedIn poll conducted by Fortrea in October 2025, 247 respondents were asked to identify the biggest opportunity to eliminate ‘white space’ in clinical development from the following four options: regulatory streamlining, faster site activation, better protocol design, and smoother phase handoffs. ‘Regulatory streamlining’ was selected by 34% of respondents, making it the second most popular choice.
Here are four common pitfalls to avoid during this quest:
Pitfall 1: Leaving it too late
When it comes to regulatory meetings, timing is crucial. The process starts with a written request being submitted to the agency, outlining key details of the proposed IND, along with specific questions for discussion, and proposed dates. A response can typically be expected within three weeks; however, the agency may decline the meeting if the submission does not comply with its guidelines.
For example, one meeting request was declined because it contained more than ten questions, several subdivided into a, b, c parts. The sponsor was required to submit a revised request with fewer questions, delaying the process.
It is generally recommended to submit meeting requests approximately two months before the desired date, which means preparations should begin even earlier. Because agency responses can be unpredictable, starting as early as possible can help prevent delays, and avoid white space at this critical stage.
Pitfall 2: Insufficient data in the briefing document
Once a meeting has been scheduled, sponsors must prepare a comprehensive briefing document that includes all relevant nonclinical and CMC data, along with questions and supporting rationale. During the meeting, sponsors should refrain from raising any points that are not covered in this document, as the agency cannot fully address questions without the necessary information.
In summary, a detailed briefing document is essential for a successful agency meeting, and ensures all key aspects of nonclinical, clinical, and CMC are addressed. Missing information will need to be submitted later, which can extend white space and delay progress.
Pitfall 3: Poorly prepared and inappropriate questions and responses
Well-structured questions are essential for a productive pre-IND meeting and should be drafted well ahead of the appointment. Vague or unclear questions often lead to unproductive responses, so sponsors should avoid open-ended queries. Instead, questions should be framed so regulators can clearly indicate whether they agree or disagree with the proposed plan.
A limited number of questions can be answered during each pre-IND meeting, so these should focus on key development information rather than non-essential details. At this early stage of development, sponsors should avoid asking questions relevant to later phases, as agencies typically consider these ‘premature’.
When responding to the agency’s comments, sponsors should avoid sweeping generalisations or statements that facts do not support.
Pitfall 4: Trying to hide concerns
Pre-IND meetings are opportunities to obtain important feedback on all aspects of a drug development plan, including potential risks and challenges. When sponsors attempt to conceal or omit issues during the meeting, problems may arise later, potentially leading to a clinical hold. It is important to be transparent and keep the agency informed of all relevant details. That way, potential roadblocks can be identified early on, and solutions can be better understood in collaboration with the agency.
Final thoughts
Pre-IND meetings can be a highly beneficial way to gain valuable input from regulators on early-stage drug development efforts, but proper preparation is essential, especially for inexperienced sponsors. By starting preparations early, setting clear objectives and questions aligned with regulator’s guidelines, and compiling a comprehensive briefing package that addresses concerns upfront, sponsors can increase the likelihood of a productive meeting. This approach can help reduce delays and support a smoother progression to clinical testing.
To learn more about minimising white space in early-stage development, please download the new whitepaper from Fortrea below.
[i] Lapteva L, Pariser AR. Investigational New Drug applications: a 1-year pilot study on rates and reasons for clinical hold. J Investig Med. 2016 Feb;64(2):376-82. doi: 10.1136/jim-2015-000010. PMID: 26911627.
