Different pharmaceutical agencies, like PMDA in Japan or EMA in Europe follow standard format of eCTD for submitting regulatory information to health authorities globally (Patil et al., 2024). This format has several benefits, but at the same time, it comes with significant challenges too. eCTD publishing involves five steps as presented on Figure 1 (Wu et al., 2023). This article sheds light on various challenges encountered in eCTD publishing and submission management, and solutions and smart practices to overcome these challenges for the pharmaceutical, biotech and medical device companies.
Figure 1: Stages of eCTD Publishing
The most important element of eCTD submission is maintaining legibility of the documents and their adherence regulatory requirement. The authorities that deal with the submissions follow acceptance and rejection criteria which is strictly based on the documents to be presented in a professional manner and standard format. Thus, the challenges in maintaining legibility of the document include: i. Scanning Quality: Sometime the challenge comes up with the paper documents converted to electronic format often suffer from low resolution or improper alignment. ii. Non-Searchable PDFs: Some documents are submitted as scanned images that cannot be searched or indexed, causing issues during the review process. iii. Format Issues: Inconsistent font sizes, excessive use of colors, or inappropriate page layouts leads to non-compliance.
Smart Practical Solutions
To overcome these challenges the following practices can be helpful: i. Invest in high-quality scanning equipment and use Optical Character Recognition (OCR) technology to ensure documents are searchable. ii. Standardize document formatting with templates and guidelines that align with regulatory expectations. iii. Conduct regular quality checks to ensure all files meet legibility standards.
Making a user-friendly eCTD submission required a proper bookmarking and hyperlinking efforts. With the help of these features, a reviewer can quickly verify the large amount of data from external sources (Chaudhari and Badjatya, 2019). But the challenge comes up with the implementation of hyperlinking that can significantly stand in the way of the review process. These challenges include: i. Broken Links: Hyperlinks that do not lead to the correct destination of the document. ii. Bookmark Placement: Improper, missing or misplaced bookmarks that fail to guide reviewers correctively. iii. Manual Effort: Excessive creation of the bookmarks and hyperlinks manually is time taking and increase the chance of human error.
Smart Practical Solutions
Several solutions are there to overcome this challenge: i. Utilization of the publishing software that automates the creation of bookmarks and hyperlinks can be effective. ii. Before submission, validation checks can be effective in identifying and fixing error. iii. For accurate bookmarking and hyperlinking, staff should be trained accordingly and best practices should be utilized in this manner.
In Pharmaceutical industries, the manufacturing companies need to deal with large volume of data, including high-definition images, clinical investigations, and technical specifications (Lakings, 2016). In order to overcome these size constraints in eCTD submissions, it can have important challenges: i. File Size: Controlling agencies follow strict file sizing policies for submissions ii. Uploading Speed: In limited internet resources large files can be time a taking process in uploading. iii. Corrupt Files Issue: The transfer of large data files has more likely to have a chance of being corrupt.
Smart Practical Solutions
Following solutions are available to overcome these challenges: i. Utilization of the authentic tools for compressing files that cannot compromise the quality of the resolution of images while reducing their space. ii. If possible, divide large files into parts so that it can comply with the authoritative requirements. iii. Employ patterns that are reliable in maintaining the quality of uploads.
The competitive environment of pharmaceutical industry stresses rapid submission to secure the market approvals (Algorri et al., 2020). Balancing tight deadlines with reliability is a significant challenge. In this scenario common challenges are: i. Limitation of Resources: Small teams may struggle to handle the excessive workload. ii. Last Moment Changes: Last moment edits can interrupt the submission process significantly. iii. Compromising the Quality: To meet deadlines, many errors can be ignored.
Smart Practical Solutions
Handling deadlines and resource limitations, following practices can be utilized: i. In each stage, the submission timeline should be managed carefully and sufficient resources should be assigned. ii. Use project management tools to make progress and identify possible blockages timely. iii. Outsource eCTD publishing and submission management to specialized service providers if internal capacity is insufficient.
In eCTD submissions, companies often need to manage different versions of documents which include updates, modifications, and annual reporting during the product life cycle (Garg et al., 2017). The complexity to maintain consistency in this regard has some significant challenges: i. Confusion in Version: During document submission, different versions of single document can be the cause of duplication and inconsistencies. ii. Uncontrolled Modifications: Unapproved edits can compromise data reliability. iii. Document Overwriting: Accidentally overwriting critical documents during updates can create problems.
Smart Practical Solutions
For the management of multiple versions, the practices that can help are: i. Implementation of a strong document management system can help in tracking the version with its history and impose access to control sensitive documents. ii. To identify document versions easily a standardized naming technique can be utilized. iii. For document accuracy and maintaining recent versions regular audits should be conducted.
Worldwide, different regulatory agencies deal with exceptional requirement in submission which makes the process complicated for operating different companies in different regions (Krogulski, 2017). Some common challenges in this scenario are: i. Diverse Standards: Due to diversity in standards, it can make differences in module structure, file naming conventions, and metadata requirements. ii. Language Barriers: Language barriers can increase the risk of errors; hence the submissions may need to be translated into local languages. iii. Variations in Timelines: Expectations and review timelines may be different with respect to different authorities.
Smart Practical Solutions
The solution available for above challenges are: i. Stay updated on the latest guidance from each regulatory authority and tailor submissions accordingly. ii. Partner with experienced regulatory consultants who understand regional differences. iii. Use eCTD publishing tools that support different languages at a time.
Companies must be prepared to Address Agency Feedback and Rejections Even after submitting an eCTD (Suchanek and Ostermann, 2012). In this scenario Common Challenges are: i. Incomplete Submissions: Missing documents or inappropriate formatting can result in rejection. ii. Delayed Responses: Failing to respond to agency queries promptly can affect approval timelines. iii. Tracking Amendments: Keeping track of changes requested by agencies and ensuring they are correctly incorporated.
Smart Practical Solutions
Practices that can be adopted in post submission process are: i. Using tools that provide visibility in submission status and facilitate quick response to agency feedback. ii. Maintaining a detailed record of all correspondence and updates to make sure a clear audit trail. iii. Experienced staff on post submission requirements can also be helpful.
While eCTD has transformed the way regulatory submissions are managed, this process comes along with its various challenges. The challenges related to legibility of the document, manual errors, file management, regulatory variations, uploading large file and post submission challenges, can all make significant complications for different industries including pharmaceutical, biotech, and medical related device manufacturing companies. However, by implementing advanced technologies, standardizing processes, and exploiting industry expertise, these challenges can be effectively managed. Figure 2 visually presents best practices for eCTD submission. Addressing these points with proper dedication, companies can modernize their eCTD submissions, reduce the risk of delays or rejections, and focus on bringing innovative products to the market.
Algorri, M., Cauchon, N. S., & Abernathy, M. J. (2020). Transitioning chemistry, manufacturing, and controls content with a structured data management solution: streamlining regulatory submissions. Journal of Pharmaceutical Sciences, 109(4), 1427-1438.
Chaudhari, P. V., & Badjatya, J. K. (2019). Good Practices in Management of deficiencies in CTD dossier and comparative study for US, EU and Australia. International Journal of Drug Regulatory Affairs, 7(4), 40-55.
Garg, V., Chopra, S., Singh, S., Gulati, M., Kumar, B., & Mittal, N. (2017). A comparative study of common technical document in different regulated market. Journal of Pharmacy Research, 11(8), 1015-1024.
Krogulski, S. (2017). Best practices for submitting promotional 2253 submissions in the new module 1 specification. Therapeutic Innovation & Regulatory Science, 51(5), 645-650.
Lakings, D. B. (2016). The CTD and eCTD for the Registration of Pharmaceuticals for Human Use. In New Drug Approval Process (pp. 180-218). CRC Press.
Patil, N. S., Ranjan, A., Narang, R. K., & Singh, A. (2024). Evaluating the Imperative Role of Pre-and Post-eCTD Standards in Dossier Validation: An Inevitable Outlook. Current Pharmaceutical Design, 30(18), 1379-1381.
Suchanek, A., & Ostermann, H. (2012). The Electronic Common Technical Document (eCTD): An International Pro/Con Analysis of the Pharmaceutical Product Electronic Submission Process. Drug information journal: DIJ/Drug Information Association, 46(1), 124-139.
Wu, M., Xu, Y., Zhou, N., & Liang, Y. (2021). The Status of the Electronic Common Technical Documents Implementation in China: A Comparative Study Based on the USA and EU. International Journal Of Drug Regulatory Affairs, 9(3), 16-24.
Figure 2: Best Practices for a Successful eCTD Submission
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