Why So Many Teams Hesitate to Ask Regulators — And Why They Shouldn’t

In the world of drug development, one of the simplest tools for reducing risk is also one of the most under-used: asking regulators direct questions. Whether it’s a clarification on an FDA expectation, an EDQM CEP procedure nuance, or a grey-zone interpretation of ICH guidance, development teams often sit on important questions far too long.

This is repeated — smart teams hesitating to reach out, worried about “looking unprepared,” “triggering scrutiny,” or “committing to a position too early.” And yet, the fastest path to regulatory clarity is often a well-constructed question asked at the right time.

Why Are People Afraid to Ask?

Across programs and companies, the same themes appear:

1. Fear of Revealing Gaps

Teams worry that asking a question will highlight internal uncertainty. However, reviewers appreciate proactive engagement — it shows you’re committed to getting it right.

2. Concern About Receiving an Unfavorable Answer

Some groups avoid asking because they fear the response could limit their flexibility. But ambiguity is far more costly. A clear answer (even if restrictive) enables planning, resourcing, and risk-based decision-making.

3. Misconception That Only Formal Meetings Are “Allowed”

Many assume their only avenue is a pre-IND or scientific advice meeting. However, written inquiries are widely accepted across global agencies — and often the fastest route to a small but meaningful clarification.

4. Lack of Confidence in How to Phrase the Question

People worry about asking “wrong,” appearing too basic, or drafting something that could be interpreted as a regulatory commitment. This is exactly where an experienced CMC regulatory strategist adds value: framing the question so it’s targeted, neutral, and useful.

How to Ask Questions — And Where to Send Them

FDA offers several pathways for written questions outside of formal meetings. In most cases, the key is a clear, concise, single-question email focused on technical interpretation rather than hypothetical scenarios.

• CDER and CBER Regulatory Project Managers

  Each active IND, NDA, BLA, or DMF has an assigned RPM who can receive written queries for clarification.

• Controlled Correspondence for Generics (OGD)

  A structured mechanism for specific, product-development questions.

• General Inquiry Mailboxes

  Many offices maintain public email addresses for technical or policy-related questions.

EDQM welcomes written questions for both new and ongoing CEP submissions. EDQM is typically responsive, but questions must be specific, factual, and tied to a dossier action. Open-ended or speculative questions should be avoided. Options include:

• EDQM Helpdesk for general or procedural questions

• CEP Team Mailboxes for dossier-specific clarification

What Makes a Good Regulatory Question?

A strong question is:

• Context – brief background so reviewers understand the scenario

• Neutral – not arguing for a position

• Concise – one clear ask, not three

• Risk-based – explains why the clarification matters

• Traceable – references guidance, precedent, or agency statements

We help teams craft questions that reduce uncertainty without unintentionally locking you into commitments or disclosing more than necessary.

Why Asking Early Saves Time and Money

Silence is expensive. Delayed clarifications may lead to:

• Unnecessary rework

• Late-stage surprises

• Misaligned development decisions

• Packaging, stability, or process changes at the wrong time

• Meeting requests that could have been avoided with one short email

A 30-minute effort to draft a targeted question can save months of downstream remediation.

How Helvetica CMC Consulting Can Help

We support clients by:

• Drafting agency inquiry emails

• Identifying when a written question is better than a full meeting

• Reviewing agency responses and translating them into actionable CMC strategy

• Navigating grey-zone topics where guidance is unclear or conflicting

• Ensuring alignment across regulatory, quality, manufacturing, and supply chain