The electronic transfer of regulatory information and subsequent review of drug applications is now more streamlined after decades of paper-based procedures. The electronic version of the Common Technical Document (CTD), or the eCTD, is now becoming more and more common in life sciences contexts worldwide, particularly in the regulatory landscape. Therefore, organizations must get ready for this new method of working as this implementation continues. While this will require more work in the short term, organizations should use the benefits offered by eCTD by making sure that technology and tools are consistently updated and improved. Although this may seem straightforward, the intricate technological process imposes risk of application rejection if one lacks preparation in regulatory submission and publishing [1].
In this blog post, we will discuss some of the solutions regarding the common challenges encountered during electronic regulatory publications and submissions and throw some light on the best practices that could be followed for successful submissions.
It frequently occurs that documents are not reviewed for clarity and legibility before being submitted to the regulatory agencies, such as the US FDA. This can lead to ‘Refuse to Receive’ (RTR) for drug applications. We cannot reasonably expect the reviewer to read a paper that we are unable to understand owing to a lack of legibility. Thus, organizations implement in-house processes or liaise with vendors to conduct meticulous legibility checks to avoid RTR situations. For example, conducting a comprehensive review per a legibility checklist that addresses all the necessary parameters for functionality checks can be created on Microsoft Excel which could help in preventing errors that could lead to RTRs[2].
Moving ahead it is evident that bookmarking and hyperlinking enhance the navigation within the dossier; however, these tasks, when done, manually can be repetitive and time-consuming. Also, errors while drafting can prevent the document from being hyperlinked. In such scenarios publishing software programs are useful as they streamline and accelerate critical processes such as hyperlinking and bookmarking by way of one-click automation which can avoid repetition and save time. Moreover, a good practice would be to use validation software or tools to validate the source files before final publishing [3].
Uploading and publishing large-size documents into the regulatory portal could present challenges due to the document size restrictions. In such a situation, segregating sections of the files into multiple smaller file size slots and communicating the issue with the authorities at the same time could help resolve the issue [4].
Precautionary measures should be used to avoid regenerating a UUID number for a dossier that has already been filed to the authorities as UUID numbers can be created relatively readily. By conducting a check against the UUID number to the sequence prior, some of the validator tools available today can identify this issue before submission. However, if the UUID number was modified two sequences earlier and the submissions are made close together, it is still feasible to make a valid submission on the last sequence. A possible solution to this could be that the UUID number issue should be reported to the authorities right away, who would then make recommendations as appropriate. . In many instances, the sequence that had an incorrect UUID number can be corrected, and then re-uploaded to the authorities [5].
It can be tough for the eCTD structure to reflect changes that take place during the product lifecycle, such as manufacturing changes. The level of granularity selected at the start of the product lifecycle may prove to be challenging later. As eCTD standards are relatively stringent, this leaves little flexibility for document organization which can be challenging for applicants. A possible way to solve this issue could be to engage in two-way communication between the submitter and the regulatory agency at the earliest while consistently referring to guidelines [6]. For example, the ICH published comprehensive guidelines on the Organization of the Common Technical Document that provide detailed information on granularity [7].
To summarize, eCTD has become an integral part of the life sciences industry for the transfer of regulatory information between the submitter and the health authorities. With more and more countries adopting the eCTD structure, it is advisable to learn from the challenges that occurred and focus on the best practices. Lastly, it is evident that team collaborative efforts, performing validation checks, staying updated with the health authorities’ changes, and creating checklists are a few good practices to follow for successful publishing and submission.
References and Further Reading:
- White Paper: An introduction to eCTD [Internet]. Extedo.com. [cited 2022 Oct 12]. Available from: https://www.extedo.com/software/ectd-submission-management-publishing-software/white-paper/an-introduction-to-ectd
- Case study-Legibility checks to avoid ANDA rejection. DDReg Pharma. 2022. Available from: Legibility checks to avoid ANDA rejection – DDReg Pharma
- Ahammad N, Reddy N, Nagabhushanam MV, Ramakrishna B. Challenges faced during eCTD and CTD filling procedures for USFDA and Canada. J Drug Deliv Ther [Internet]. 2019 [cited 2022 Oct 11];9(4-s):673–9. Available from: http://jddtonline.info/index.php/jddt/article/view/3334
- Case study-Gulf Health Council file upload for biosimilar product. DDReg Pharma. 2022. Available from: Gulf Health Council file upload for biosimilar product – DDReg Pharma
- ema. 2020. Available from: QandA on UUID for eCTD_Feb 2020_final for adoption (europa.eu)
- Ross C. The History Of Electronic Regulatory Submissions Technologies: A Focus On Ectd (Electronic Common Technical Document) And Its Challenges And Benefits [Internet]. 2000. Available from: https://getd.libs.uga.edu/pdfs/ross_charnelle_201008_ms.pdf
- 2016. Organisation of the Common Technical Document for the Registration of Pharmaceuticals for Human Use. June 2016.