From NeeS to eCTD: The Digital Transformation of Pharmaceutical Submissions

In the grand theatre of pharmaceutical regulation, paper dossiers are quickly becoming relics of the past. Today, the gold standard for global regulatory submissions is digital—and more precisely, structured digital content that adheres to the Common Technical Document (CTD) or its more dynamic evolution, the electronic Common Technical Document (eCTD).

But not so long ago, in the early years of digital migration, many companies relied on NeeS (Non-eCTD electronic Submissions)—a digital stopgap that helped bridge the gap between paper and fully structured electronic files. With global regulators now aligning around eCTD as the required format, many companies are finding themselves at a crossroads: continue supporting NeeS submissions in select markets, or fully transition to modern eCTD services?

Let’s explore how we got here, where the industry is headed, and why robust eCTD services are becoming mission-critical for pharmaceutical and biotech companies alike.

The Roots: CTD and the Birth of Global Harmonization

The Common Technical Document (CTD) was born out of necessity. Before its introduction by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in 2000, every country required pharmaceutical companies to submit applications in varying formats, making global development extremely resource-intensive.

The CTD solved that by introducing a standardized dossier format, organized into five core modules:

1. Module 1 – Regional Administrative Information

2. Module 2 – Summaries and Overviews

3. Module 3 – Quality (CMC)

4. Module 4 – Nonclinical Study Reports

5. Module 5 – Clinical Study Reports

While it unified structure, CTD was originally designed for paper. This meant large, printed submissions, manually assembled and delivered physically—time-consuming, expensive, and error-prone.

The First Digital Leap: Introducing NeeS

As digital technologies crept into every corner of pharma, NeeS emerged as a way to replicate the CTD format electronically. NeeS preserves the CTD’s modular format but delivers documents as PDFs, organized into folder structures, and sent on digital media such as CD-ROMs or via secure portals.

Importantly, NeeS lacks structured metadata, XML backbones, and validation schemas, making it a “lightweight” electronic submission. It was never intended as a permanent standard, but rather a transitional step toward the full eCTD.

Still, its simplicity meant that many countries, particularly within Europe, adopted NeeS for national and decentralized procedures before eCTD mandates were implemented. Even now, some countries in the EU, the Middle East, Africa, and parts of Asia continue to accept or require NeeS for certain submission types (e.g., renewals, variations, PSURs).

The Rise of eCTD: Digital Structure, Global Compliance

As regulatory authorities began to modernize, eCTD became the new frontier. First introduced in the early 2000s by the ICH, the eCTD format enhances the CTD structure by adding:

• An XML backbone that maps and organizes content

• Granular lifecycle tracking of documents and dossiers

• Automated validation tools to ensure technical compliance

• Hyperlinking and bookmarks for intuitive navigation

With these features, eCTD allows regulators to review submissions more efficiently and provides sponsors with tools for managing complex, multi-year regulatory lifecycles.

Global Adoption of eCTD

Today, the majority of high-regulation markets have mandated eCTD for specific types of submissions:

• United States (FDA): eCTD format is required for all NDAs, ANDAs, BLAs, and master files submitted to CDER or CBER.

• Europe (EMA and NCAs): eCTD is mandatory for all centralized procedure submissions and most national procedures.

• Canada (Health Canada): Requires eCTD for most new drug submissions and now accepts only eCTD for new clinical trials.

• Japan (PMDA): Has adopted eCTD format for nearly all regulatory submission types.

• Australia (TGA) and GCC, Swissmedic, Singapore HSA, Saudi FDA, and more are all increasingly transitioning to eCTD mandates.

This widespread adoption underscores the growing importance of eCTD services to support regional variations, formatting, compliance, and validation.

The Limitations of NeeS in 2025

Despite its simplicity, NeeS comes with a number of limitations that make it less attractive as a long-term solution:

• No lifecycle management: NeeS lacks the structured XML backbone that tracks document history and updates across multiple submissions.

• No automated validation: Submissions must be manually checked for errors, increasing review timelines and risk.

• Inconsistent regulatory support: Regulatory authorities are deprecating support for NeeS in favor of eCTD.

• Lack of scalability: For growing portfolios, NeeS quickly becomes difficult to manage and maintain.

In short, while still accepted in limited contexts, NeeS is increasingly seen as a legacy format—suitable only for companies operating in specific regional niches.

eCTD 4.0: The Next Evolution

Regulators and industry alike are preparing for eCTD version 4.0, which brings significant enhancements:

• Improved data granularity with new document types and element-based authoring

• Multiple application support within a single submission instance

• RESTful API support for easier integration with enterprise systems

• International harmonization of specifications for easier cross-border submissions

The EMA and FDA are both moving toward phased adoption of eCTD 4.0, and companies investing in eCTD services today are positioning themselves for smoother transitions tomorrow.

The Strategic Role of eCTD Services

As the eCTD becomes the global norm, eCTD services have emerged as essential tools for regulatory success. These services encompass:

• eCTD publishing: Assembling and compiling submission documents in compliant format

• Technical validation: Running automated checks against region-specific validation criteria (e.g., FDA’s ESG validator, EMA’s EU eCTD checker)

• Lifecycle management: Tracking document versions, managing sequences, and archiving updates

• Submission tracking and project management

• Regulatory strategy consulting: Navigating country-specific submission requirements and transitions from NeeS to eCTD

For small to mid-sized pharma and biotech firms, outsourcing eCTD services is often more efficient than building in-house teams and infrastructure.

The Transition from NeeS to eCTD: A Roadmap

Successfully transitioning from NeeS to eCTD requires a strategic approach:

1.

Gap Assessment

Evaluate your current NeeS dossier structure, document formats, and validation history.

2.

Content Remediation

Revise documents to meet eCTD granularity, formatting, and naming conventions.

3.

Tool Selection

Choose an eCTD publishing tool that aligns with your regulatory scope and internal workflows.

4.

Training & Resourcing

Ensure teams understand eCTD principles, validation tools, and region-specific requirements.

5.

Pilot Submission

Run a mock or parallel submission to identify and resolve technical issues before go-live.

Partnering with a provider of expert eCTD services can de-risk this transition and accelerate implementation.

Why This Matters Now

In 2025, the pharmaceutical regulatory environment is defined by data-driven decisions, automation, and speed. Delays in submissions due to format errors, non-compliance, or misaligned strategies can cost months—and millions.

Moreover, global collaboration in drug development, expedited pathways like the FDA’s fast track or EMA’s PRIME, and post-market obligations all depend on agile, compliant regulatory systems.

eCTD services are no longer optional; they are foundational to regulatory success.

Conclusion: Digital Now, Digital Next

The journey from NeeS to eCTD reflects the pharmaceutical industry’s broader digital transformation. As regulatory bodies adopt more sophisticated review technologies and eCTD 4.0 looms on the horizon, companies must move beyond legacy formats.

Investing in eCTD services today ensures readiness for tomorrow’s regulatory landscape—and gives pharma and biotech companies the agility, scalability, and compliance needed to succeed in global markets.