How a Mid-Size Biotech Achieved 98% First-Time Submission Acceptance
Technical rejections are expensive. Not in the direct sense—the cost of reformatting and resubmitting is manageable. The real cost is time. A rejected eCTD sequence delays your regulatory timeline by weeks, sometimes months. For a mid-size biotech racing toward a market window, that delay can be the difference between being first-to-market and being second.
This is the story of how one 120-person biotech went from two technical rejections in twelve months to a 98% first-time acceptance rate—sustained over 18 months.
The Starting Point
The company had three products in late-stage clinical development, with regulatory filings planned across FDA, EMA, and Health Canada. Their submission volume was about to triple—from roughly 5 submissions per year to 15 or more. The regulatory operations team consisted of four people, and they were already stretched.
Their technology stack was typical for a biotech at this stage:
- Publishing: A desktop eCTD tool installed on two workstations. One license per machine. Publishing was sequential—one submission at a time.
- Review: PDFs circulated by email. Comments tracked in a shared spreadsheet. Version confusion was constant.
- Planning: Dossier plans maintained in Excel. Submission timelines on a PowerPoint slide updated monthly by the Senior Director.
This setup had worked—barely—for five submissions a year. But the cracks were showing. In the prior twelve months, the team experienced two technical rejections from the FDA. The root causes were familiar to anyone in regulatory operations:
- Broken hyperlinks. Cross-module links that worked in the publishing tool’s preview but failed validation at the gateway. The team’s QC process was manual: open each PDF, click each link, verify each target. At scale, links were inevitably missed.
- PDF/A compliance failures. Documents rendered from Word templates that looked correct but contained embedded fonts or transparency layers that violated ISO 19005. These failures are invisible to the human eye and only surface at gateway validation.
Beyond the rejections, the operational metrics were unsustainable for the planned volume increase:
- 6-8 weeks per publishing cycle. From document collection to final gateway submission.
- 2-day QC review cycles. Manual hyperlink checking and document-by-document review.
- No leadership visibility. The Senior Director had no real-time view of where any given submission stood in the pipeline. Status updates were verbal, delivered in weekly meetings.
The Decision to Change
The tipping point was not the rejections themselves—it was the realization that tripling submission volume with the same tools and process would triple the rejection risk. The Senior Director of Regulatory Affairs made the case to leadership: invest in a platform now, or hire three additional headcount and still accept an unacceptable error rate.
The team evaluated three options: upgrading their desktop tool to the vendor’s cloud version, implementing a large enterprise RIM suite, or deploying a purpose-built publishing and review platform. The enterprise RIM suite was ruled out on timeline—a 6-12 month implementation would not meet the upcoming filing schedule. The desktop tool’s cloud version addressed some issues but did not solve the review workflow or hyperlink validation problem.
They chose DnXT Publisher and DnXT Reviewer. Deployment took four weeks from contract signature to first production submission.
What Changed
Automated hyperlink validation replaced manual QC. DnXT Reviewer’s hyperlink validation checks every link in the submission—cross-document, cross-module, and external. Each link is surfaced in a structured workflow with accept/reject disposition, threaded comments, and a complete audit trail. The team no longer opens individual PDFs to click links. The system checks them all and flags failures before the submission reaches the gateway.
DnXT Render eliminated PDF/A compliance issues. The platform’s rendering engine converts source documents to PDF with intelligent parsing, automated bookmark generation, and hyperlink retention. Every output is validated against ISO 19005 (PDF/A) automatically. The team’s PDF/A failure rate dropped below 1%. Documents that previously required 6-8 hours of manual rendering per submission now process in under an hour through the batch pipeline.
AI Navigator automated hyperlink creation. The most time-consuming manual task in eCTD publishing—creating cross-reference hyperlinks—was reduced from 20-30 hours per submission to under 5 hours. DnXT’s AI Navigator uses intelligent source detection and target mapping via XML metadata to generate links with ALCOA+ traceability reports. The team reviews and approves links rather than manually creating them.
Centralized review workflow replaced email-based QC. DnXT Reviewer provided a structured workspace: TOC navigation across Modules 1-5, document annotations (highlight, underline, strikethrough, text notes), threaded comments with statistics, and a dashboard showing pending approvals, task completion, and comment resolution. The review cycle compressed from 2 days to 4 hours.
The Senior Director got a dashboard. For the first time, leadership had real-time visibility into the submission pipeline: which sequences were in preparation, which were in review, which were published, and which were submitted. No more weekly status meetings to learn what happened five days ago.
Results Over 18 Months
After deploying DnXT, the team tracked the following metrics across their subsequent submissions:
- First-time acceptance rate: 98%. One technical query in 18 months, related to a regional Module 1 form issue—not a publishing or rendering defect.
- Publishing cycle time: reduced from 6-8 weeks to approximately 2 weeks. The largest gains came from automated rendering and hyperlink creation.
- Hyperlink error rate: reduced from 3-5% to below 0.5%. Automated validation catches errors that manual review consistently misses.
- Rendering accuracy: 99%. Documents render correctly on the first pass, eliminating rework cycles.
- QC review cycle: reduced from 2 days to 4 hours. Structured review workflows with automated link checking replaced manual PDF inspection.
- Submission volume: scaled from 5 to 17 submissions per year without adding headcount to the regulatory operations team.
What This Means for Regulatory Leadership
For a Senior Director evaluating whether to modernize the publishing and review stack, this case illustrates three points:
First, technical rejections are a process problem, not a people problem. The team that experienced two rejections was competent and diligent. They were failed by tools that required manual verification of things that should be automated. No amount of training or checklists will reliably catch broken hyperlinks across a 500-document submission.
Second, the ROI is measured in risk reduction and timeline compression, not just cost savings. The financial case for the platform was straightforward. But the strategic case was stronger: the ability to triple submission volume without proportional headcount growth, while simultaneously reducing the rejection rate, gave the company confidence to pursue an aggressive regulatory strategy.
Third, deployment speed matters. A platform that takes 6-12 months to implement does not solve the problem for the next three filings. DnXT’s four-week deployment meant the team was publishing on the new platform before their next submission deadline.
If your team is scaling submission volume and your current tools require manual QC to catch errors that should never reach the gateway, the math is not complicated. The cost of one technical rejection—in timeline delay, team morale, and leadership confidence—exceeds the cost of a platform that prevents it.
