The eCTD is here! While many organizations have delayed their adoption of this format, the U.S. FDA and several other global agencies are pressing forward towards its mandate. As eCTD adoption increases, submission quality is gaining more attention from regulators – especially from the FDA. Regulatory officials have expressed a commitment to increase their diligence with respect to submission quality and intend to begin rejecting eCTD sequences containing significant technical issues.
The best way to sidestep technical rejection and ensure agency compliance is to develop clear, focused strategies for solving submission quality issues.
The U.S. FDA has provided written guidance that specifically defines technical eCTD validation criteria. The Specifications For eCTD Validation guidance document was developed to provide clear guidance to help improve the reviewability of electronic submissions once they reach the agency. The FDA validation criteria define the impact of a high severity error as “The error is a serious technical error which prevents the processing of the submission and will require resubmission. The submission is considered not received by FDA.”
The FDA emphasizes the importance of technical submission quality in their Guidance for Industry: Providing Regulatory Submissions in Electronic Format — Receipt Date document. In this document, the agency clearly stipulates that they will consider a technically deficient application NOT RECEIVED until technical deficiencies are resolved and the application is resubmitted. Technical deficiencies may include issues such as:
- Defect in the media (e.g., CD-ROMs)
- Failure to provide an electronically readable 356h or 1571 form for submissions sent through the ESG
- 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
Looking to avoid time-consuming technical rejections? Follow our top 4 best practices:
- ALWAYS VALIDATE PRIOR TO SUBMITTING TO GLOBAL AGENCIES
Validating your eCTD prior to submitting to the agency is crucial to quick and efficient drug approval. For eCTD validation the FDA employs VALIDATE 2009, which completes a comprehensive error analysis based on their specified criteria. The solution also includes mapping of their current guidance in terms of HIGH, MEDIUM and LOW errors. Using this unique application, you can assign the same criteria in the same manner as the FDA.
- ENSURE FDA COLLABORATION – USE THE SAME SOFTWARE
Avoiding technical rejections can be simple. Just be certain to review your submissions and ensure that your collaborating ability with agency reviewers. The FDA uses REVIEW 2009, especially designed for the review of their applications. They see your dossier through REVIEW 2009, so why shouldn’t you?
- 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 your existing processes to see what works and what needs tweaking.
- QC YOUR FORM AND COVER LETTER
The most frequent issues seen by the FDA involve inconsistency or errors in 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.