Technical Rejection Avoidance

A recent global review conducted by Thomson Reuters revealed that 40 health authorities are accepting eCTD. A number of these agencies are mandating eCTD adoption, including the European Medicines Agency and U.S. Food & Drug Administration. As a result of the widespread use of the eCTD format, submission quality is gaining more attention from regulators. eCTD submissions containing technical errors are now more likely to be rejected.

Preventing technical rejection starts with a focused strategy and awareness of validation criteria.

The FDA developed a Specification for eCTD Validation reference guide to introduce validation criteria and improve the reviewability of electronic submissions. This guide provides examples of technical deficiencies and defines error severity levels.

Technical deficiencies may include issues such as

  • Failure to provide electronically readable 356h or 1571 form for submissions sent through the Electronic Submissions Gateway
  • Providing an eCTD submission using a previously submitted sequence number
  • Failure to provide the required index.xml and us-regional.xml files
  • Presence of a virus
  • File format incompatibility

Best Practices

Based on our review of more than 500,000 electronic submissions, and conversations with publishers who assemble submissions daily, GlobalSubmit has developed a number of recommendations proven to avoid time consuming technical rejections.

Always Validate Prior to Submitting to the Agency

Failure to validate your eCTD prior to submission introduces risk of technical rejection. To speed the approval process you should always assess the quality of your submission before handing it over to the Agency. The FDA relies on GlobalSubmit VALIDATE™ for eCTD validation. This application runs a comprehensive error analysis based on regional criteria, and maps errors in terms of High, Medium, and Low severity. By using VALIDATE, you have the identical submission validation rules that are applied to your submission by the FDA.

Select Software that Builds Synchronicity with the Agency

When compiling an electronic regulatory submission, confidence in your output is at a premium. Any discrepancies between the version you see and the version reviewers ultimately evaluate can extend the overall process, and in some cases, lead to outright rejection. Working in the same interface as your regulatory agency eliminates any inconsistencies. GlobalSubmit REVIEW™ is used exclusively by the FDA to assess submissions, and thus, is the only platform to offer such peace of mind.

Establish Quality Processes and Procedures

Establishing quality processes and procedures is essential to successful eCTD implementation. It is important to harmonize your operations and technology to ensure compliance. We recommend a thorough assessment of existing processes to determine what works and what needs improvement.

Quality Check your Form and Cover Letter

The most frequent issues seen by the FDA involve inconsistency between application and submission numbers in the US regional XML backbone, application form, and cover letter. Your process should include a final quality check of these components for correctness and consistency.