The goal of any regulatory submission whether it’s an IND, NDA, MAA, ANDA, or variation dossier is to pass the first review without queries or rework. This requires strategic planning, clear documentation, technical compliance, and deep understanding of regulatory expectations.
Auxochromofours offers expert support to help life sciences companies prepare high-quality submission dossiers through its Regulatory Publishing and Submission Services
In this guide, we’ll walk through proven steps to prepare regulatory submissions that stand up to first-round review by agencies such as the FDA, EMA, MHRA, Health Canada, TGA, and CDSCO.
1. Start With Clear Regulatory Strategy
Before you draft or compile anything, define the submission strategy. A strong regulatory strategy maps out:
What type of submission you are making (e.g., IND, NDA, MAA)
Which regions and agencies will review
Applicable guidelines and formats (eCTD, CTD, NeeS)
Data requirements across modules
This roadmap helps ensure you have the right data and documents ready reducing rework and late requests from reviewers.
2. Organize Data Consistently Across Modules
Regulatory submissions are structured into modules (e.g., CTD Module 2 and Module 3) that cover administrative, quality, nonclinical, and clinical data. Consistency across these sections is key.
For example, when preparing nonclinical toxicology data, standardized datasets like SEND (Standard for Exchange of Nonclinical Data) are required by agencies like the FDA. Understanding how regulators review these datasets helps prevent common pitfalls and review delays. Auxochromofours explains this in detail in
SEND submissions that are incomplete, inconsistent, or poorly aligned with study reports often trigger additional review questions.
3. Master SEND and Other Standard Format Requirements
Regulatory reviewers expect submission data in standardized formats. SEND compliance and familiarity with these expectations can significantly improve first-round outcomes.
Ensuring that SEND datasets are complete, use accurate controlled terminology, and are linked correctly to study reports will help reviewers validate nonclinical data more quickly. For more on how to effectively prepare SEND submissions, see:
This blog explains why SEND is not simply an add-on, but a core part of nonclinical regulatory strategy especially for IND and NDA submissions.
4. Embrace eCTD Best Practices in Publishing
Electronic Common Technical Document (eCTD) is now the global standard for regulatory submissions. Submissions that do not follow eCTD structure, metadata requirements, and validation rules risk rejection even before scientific review.
Understanding how eCTD works and how technology like AI is beginning to support publishing workflows can help teams avoid structural and technical errors that cost time and money. Auxochromofours explains the evolution and importance of eCTD in its blog on eCTD and AI
This article highlights how eCTD structures submissions in a way that reviewers expect, and how tools can automate checks such as bookmarks, hyperlinks, metadata, and technical validation.
5. Ensure Quality of Clinical and Nonclinical Reports
Regulatory reviewers scrutinize both clinical and nonclinical study reports for scientific validity and consistency. These reports must reflect accurate conclusions derived from raw data, supported by robust statistical analysis.
Poor summaries, mismatches between raw data and reports, or unclear interpretations often result in review questions. Always ensure reports are internally consistent and well supported by underlying data.
6. Validate Submission Files Before Filing
Technical validation before submission is essential. Common reasons for rejection during pre-submission checks include:
Missing bookmarks or hyperlinks
Incorrect metadata
Validation errors in XML
Incorrect module structure
Mismatched file formats
Running validation tools and internal quality checks before submission will save time and improve your likelihood of first-round acceptance.
7. Maintain Strong Document Control and Versioning
A consistent document control system ensures that:
Version histories are clear
Approvals are documented
Changes are tracked
Final signed documents are identifiable
This level of organization helps during audits and reduces the risk of confusion or errors during submission review.
8. Anticipate Common Review Queries
Study common reasons that submissions are questioned, including:
Nonclinical data gaps
Missing or unclear clinical endpoints
Inconsistent data summaries
Formatting or structural issues
Once you understand recurring themes in submission reviews, you can pre-empt these by strengthening your initial dossier.
Regulatory authorities streamline review through data standards and clarity and avoiding known pitfalls increases your chance of clearing first-round review with minimal questions.
9. Prepare Clear and Traceable Cross-References
Reviewers often jump between sections to validate conclusions. Clear cross-references such as linking study data to summaries or label claims helps reviewers connect information quickly and confidently.
This is particularly important for large datasets or multi-module narratives.
10. Train Your Team in Submission Best Practices
Regulatory submission quality is as much about people as it is about documents. Teams should be trained in:
eCTD and CTD structure
Data standards like SEND and SDTM
Regulatory agency expectations
Internal quality controls
Document formatting requirements
Well-trained teams are more consistent, absorb changes faster, and make fewer avoidable errors.
Conclusion
Passing a first-round regulatory review requires a combination of strategic planning, technical compliance, careful formatting, and data integrity. High-quality, consistent submissions not only avoid unnecessary delays but also build credibility with regulatory agencies.
By aligning with global submission standards, preparing clear reports, and validating submissions before filing, you can significantly improve your chance of success on the first try.
Auxochromofours’ regulatory publishing and submission expertise can help organizations implement industry best practices that meet global expectations with accuracy and efficiency.
Frequently Asked Questions (FAQs)
1. What is a first-round review?
A first-round review is the initial evaluation by a regulatory agency to determine if a submission is complete and ready for full scientific assessment.
2. Why do submissions fail first-round review?
Common reasons include incomplete data, missing documents, incorrect formats, or technical errors in electronic submissions.
3. What is eCTD?
eCTD, or Electronic Common Technical Document, is the global standard format for organizing and submitting regulatory dossiers.
4. Why is SEND compliance important?
SEND standardizes nonclinical data, making it easier for reviewers to analyze toxicology and safety information quickly.
5. Should validation be done before submission?
Yes. Technical validation ensures that formatting, metadata, and file structures meet agency requirements.
6. Can global agencies reject submissions for formatting errors?
Yes. Many agencies will reject or refuse to file submissions with structural or technical errors before scientific review begins.
7. How can training improve submission outcomes?
Training ensures teams are familiar with regulatory standards, formats, and validation tools, reducing errors and review queries.
8. What agencies use eCTD format?
Agencies including the FDA, EMA, PMDA, MHRA, Health Canada, TGA, and CDSCO accept or require eCTD submissions.