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GOOD REGULATORY PRACTICES · 01

Good Regulatory Practices #1: Building Your IND with the End in Mind

Build an IND strategy that supports your entire development program, from first dosing to approval.

Dr. Leona Saunders, IRSG · 6 min read

Introduction

Early in my regulatory career, I learned a hard lesson that I've seen repeated dozens of times since: the decisions you make during IND development don't just affect whether FDA lets you start dosing patients. They follow you, for better or worse, all the way to your NDA, BLA, or MAA submission years later.

Too often, sponsors treat the IND as a hurdle to clear rather than a foundation to build. The goal becomes "get to Phase 1" rather than "create a regulatory strategy that supports approval." This short-term thinking creates problems that are expensive, time-consuming, and sometimes impossible to fix downstream.

This is the first in a series I'm calling Good Regulatory Practices, practical guidance on regulatory strategy that was rarely shared with me during my career, and that I believe should be accessible to everyone navigating drug development.

The Core Principle: Your IND Is the Foundation of Your Regulatory Dossier

Think of your IND not as a standalone submission, but as Module 1 of a much larger story you're telling FDA over the next 5-10 years. Every study report, every specification, every protocol design decision becomes part of your permanent regulatory record.

When you eventually compile your NDA or BLA, you're not starting fresh, you're building on everything you submitted in your IND and subsequent amendments. If that foundation is solid, compilation is straightforward. If it's shaky, you'll spend months (and significant budget) remediating issues that could have been addressed upfront.

The sponsors who move fastest through development are the ones who asked the right questions before they filed their IND. Let’s dive right in….

Key Issues to Consider During IND Development

1. Chemistry, Manufacturing, and Controls (CMC)

The mistake: Developing a manufacturing process that works for Phase 1 material without considering commercial scale.

The forward-thinking approach:

  • Establish specifications that are tight enough to ensure quality but realistic for commercial manufacturing
  • Document your process development rationale, FDA will ask about it later
  • Consider your control strategy early: what critical quality attributes matter, and how will you ensure them at scale?
  • If you're working with a CDMO, ensure they understand your long-term needs, not just your immediate batch requirements

Why it matters: CMC is the most common source of FDA Complete Response Letters. Process changes between Phase 3 and submission require bridging studies and can delay approval by 6-12 months or more.

2. Nonclinical Program Design

The mistake: Conducting only the minimum studies required to support first-in-human dosing.

The forward-thinking approach:

  • Design your toxicology program with your full clinical development plan in mind
  • Consider what long-term safety signals might emerge and how you'll address them
  • For biologics, think carefully about immunogenicity assessment strategy
  • Ensure your studies are GLP-compliant and your reports are submission-ready

Why it matters: Gaps in your nonclinical package discovered during Phase 2 or 3 can halt your program while you conduct additional studies. Species selection, duration, and endpoint decisions made at the IND stage are difficult to revisit.

3. Clinical Protocol Design

The mistake: Designing your Phase 1 protocol in isolation from your Target Product Profile (TPP).

The forward-thinking approach:

  • Ensure your endpoints, even in early phases, generate data that supports your eventual label claims
  • Consider what comparators, if any, you'll need to address in your development program
  • Build in pharmacokinetic and pharmacodynamic assessments that inform dose selection for pivotal trials
  • Think about your patient population, inclusion/exclusion criteria established early set precedents

Why it matters: Your Phase 1 protocol establishes the clinical narrative. Inconsistencies between early and late-phase protocols raise questions during FDA review and can complicate your integrated summary of safety and efficacy.

4. Documentation and Data Management Practices

The mistake: Treating early-phase documentation as informal or "good enough for now."

The forward-thinking approach:

  • Establish electronic systems and data standards that meet FDA expectations for submission
  • Ensure study reports are QA-reviewed and formatted for eCTD inclusion
  • Create a regulatory archive from day one, every protocol, every amendment, every FDA communication
  • Document your decision-making rationale, not just your decisions

Why it matters: When you're compiling your NDA, you need to retrieve and reference documents that may be 7-10 years old. Poor documentation practices create gaps that require time-consuming reconstruction, or worse, leave questions you can't answer.

5. Regulatory Strategy and Agency Interactions

The mistake: Filing your IND without a Pre-IND meeting or clear understanding of FDA's expectations.

The forward-thinking approach:

  • Request a Pre-IND meeting for novel compounds, complex products, or unfamiliar therapeutic areas
  • Develop your regulatory strategy before you finalize your development plan
  • Consider international development early, ICH guidelines exist for a reason
  • Document all FDA interactions meticulously; their feedback shapes your entire program

Why it matters: FDA's input at the IND stage can save years of misdirected development. A Type B meeting is a small investment compared to a clinical hold or a Complete Response Letter.

Warning Signs You Need Expert Regulatory Input

Not every program requires extensive consulting support, but certain situations significantly increase regulatory complexity. If any of these apply to your program, consider engaging an experienced regulatory strategist before you finalize your IND:

Novel Science or First-in-Class

  • New mechanism of action with limited regulatory precedent
  • Novel biomarkers or surrogate endpoints
  • Gene therapy, cell therapy, or other advanced modalities

Complex Product Characteristics

  • Combination products (drug-device, drug-biologic)
  • Complex formulations (liposomes, nanoparticles, controlled release)
  • Biosimilars or interchangeable biologics

Accelerated Development Pathways

  • Breakthrough Therapy designation (or intent to pursue)
  • Fast Track, Accelerated Approval, or Priority Review strategies
  • Orphan Drug designation with small patient populations

International Development Plans

  • Parallel US/EU development requiring harmonized protocols
  • Parallel Meetings
  • Different regulatory requirements across target markets
  • Global CMC strategy with multiple manufacturing sites

Sponsor Experience

  • First IND submission for your organization
  • Limited in-house regulatory expertise, hiring an entire department is not required to move forward.
  • Previous FDA interactions that raised concerns

The Bottom Line

Your IND is not a checkbox; it's the architectural blueprint for your entire regulatory submission. The quality of your IND determines whether your NDA compilation takes three months or twelve.

I've seen programs lose a year or more to CMC remediation that could have been avoided with better upfront planning. I've seen clinical holds issued for nonclinical gaps that should have been identified before the IND was filed. These aren't failures of execution; they're failures of strategy.

The sponsors who succeed don't just ask "what do we need to file an IND?" They ask "what do we need to build an approvable product?"

An hour of strategic regulatory planning at the IND stage can save months and millions at the NDA stage. That's not a sales pitch. That's 25 years of experience watching programs succeed and fail based on the quality of their early decisions.

About This Series

Good Regulatory Practices is an educational series designed to share practical regulatory knowledge that helps sponsors navigate drug development more effectively. Topics are drawn from real-world experience and address the strategic questions that make the difference between efficient development and costly delays.

If you have questions about a specific regulatory challenge or topic you'd like to see addressed, feel free to reach out. regulatory@regsci.com

Dr. Saunders is the Founder and CEO of Innovative Regulatory Science Group (IRSG), a regulatory consulting firm with over 25 years of FDA regulatory experience. She also serves as adjunct faculty at Northeastern University, teaching regulatory strategy for product development.

She is the Founder and CEO of tBrexa Bio, a woman- and minority-owned next-generation CDMO specializing in biologics, gene therapies, and AI-enabled manufacturing. Through tBrexa, she integrates regulatory intelligence, CMC strategy, and advanced bioprocessing to support innovators from IND planning to commercial readiness.

Educational planning content, not regulatory advice. Program-specific decisions require qualified quality, manufacturing and regulatory review.