What Really Slows Down a Dossier?

Insights on Avoidable Mistakes

In regulatory affairs, speed and accuracy matter. A well-prepared dossier can accelerate approvals, while a flawed one can stall for months — sometimes years. Many delays aren’t due to complex science or shifting regulations but to avoidable mistakes in planning, execution, or presentation. Here are some common pitfalls that regulators consistently flag, and insights on how to avoid them.

1. Inconsistent Data Across Modules

One of the most frequent causes of queries is data misalignment between the Clinical, Nonclinical, and CMC (Chemistry, Manufacturing, and Controls) sections. For example:

• Patient numbers differ between the clinical summary and the clinical study report.

• Batch sizes in Module 3 don’t match labeling or stability data.

• Analytical methods described in different sections are not harmonized.

Avoidable? Yes. A final cross-check for consistency across modules before submission can prevent needless questions and “clock-stops.”

2. Poorly Justified Variations or Deviations

Regulators expect clarity on why a certain approach was chosen. Missing or weak justifications (e.g., for deviations in manufacturing controls, analytical procedures, or protocol amendments) lead to back-and-forth clarifications.

Avoidable? Absolutely. Every deviation should be explicitly explained, supported with rationale, and backed by data. Silence invites scrutiny.

3. Gaps in Stability Data

Stability is a common stumbling block. Submissions often lack:

• Full data sets for all strengths, pack types, and manufacturing sites.

• Ongoing stability data that covers the claimed shelf life.

• Clear justification for extrapolating data.

Avoidable? Yes. Plan stability studies early, ensure representative coverage, and provide interim data with commitments where full data sets are not yet mature.

4. Over- or Under-Inclusion of Documents

Regulators do not appreciate “data dumps.” Submitting excessive, irrelevant documents can obscure critical content. On the other hand, omitting key certificates, validation reports, or appendices triggers immediate questions.

Avoidable? Yes. Follow the CTD (Common Technical Document) guidance strictly: provide exactly what is needed, no more, no less.

5. Sloppy Formatting and Technical Issues

It may sound minor, but poorly indexed dossiers, incorrect bookmarks in eCTD, or broken hyperlinks frustrate reviewers and increase the risk of misinterpretation.

Avoidable? Definitely. A robust quality check of formatting, navigation, and technical compliance (using validation tools) should be part of every submission plan.

6. Lack of Regulatory Intelligence

Sometimes delays occur because the dossier does not reflect country-specific expectations — for example:

• Using global templates without adapting to local pharmacopoeial requirements.

• Missing translations or failing to provide country-specific labeling.

• Ignoring new guidance updates.

Avoidable? Yes. Keeping up-to-date regulatory intelligence and engaging with local affiliates early can prevent painful “surprises” from authorities.

7. Last-Minute Changes Without Alignment

Rushed, uncoordinated changes (e.g., to manufacturing descriptions, stability commitments, or labels) often create discrepancies across the dossier.

Avoidable? Yes. Change control processes and clear communication between CMC, clinical, nonclinical, and publishing teams are essential.

Final Thought

Most dossier delays don’t arise from cutting-edge science or insurmountable hurdles — they stem from preventable missteps. Regulatory reviewers expect clarity, consistency, and compliance. By focusing on rigorous cross-checking, clear justifications, and proactive regulatory intelligence, companies can avoid the avoidable and keep timelines on track.

Bottom line: In regulatory affairs, discipline in the details is what speeds approvals.