Medical Affairs and Medical Writing
A Leading Role for Preparing and Submitting Clinical Documents in ICH Member China

he China National Drug Administration (CNDA, the former China Food and Drug Administration [CFDA]) joined ICH in 2017. This promises more opportunities for clinical development, which makes it important to accelerate the preparation of high-quality submission documents in China. In the Medical Writing Theme of the 10^th DIA China Annual Meeting, industry experts from numerous companies shared their experiences to better prepare participants to embrace the opportunities and challenges presented by this new regulatory environment.

Key Takeaways

• Medical writers should begin with the idea of “driving insights into action:” Simple steps on mapping a better review process and managing a disciplined review process can become giant leaps.
• The structure and content of annual Development Safety Update Reports (DSURs) on investigational products can follow ICH E2F; project management by a medical writer is critical to developing a high-quality DSUR.
• Electronic Common Technical Document (eCTD) submission is much more than electronic submission: eCTD implementation will be an opportunity to accelerate new drug approval in China, but also a challenge for industry; early planning and preparation are the keys for success.
• The purpose of preparing and submitting a CTD for clinical documents is to completely and clearly present clinical studies; consider the emphasis points and relationships of Modules 2 and 5 when preparing these documents.
• Collaboration between medical writing and translation teams, supported by artificial intelligence-based machine translation, makes simultaneous document development in both English and Chinese possible and further accelerates cross-regional submissions.
• While regulatory submission guidelines in China are largely harmonized with the ICH, how to maintain high quality submission dossiers across the regions and how to accelerate the preparation process remain critical questions. Medical writers should prepare to embrace rapid technological changes in the future.

Return on Investment in Document Review

It is time to re-examine the current review process and think how to drive insights into action. Mapping a better (more lean, clean, and streamlined) process means more return on investment. Medical writers should guide the process, lead team time management, set expectations, provide review practice training, and prepare the review team. Discipline in review remains the biggest challenge; keeping the review cycle short, focusing on essential functional areas, asking directly for reviewer attention and insights, and managing differences one-on-one, would help. Transformative actions include aligning standard operating procedures for review speed and quality, arranging for technical or process support, establishing partnerships, and keeping things simple and moving forward.

Introducing and Sharing DUSR Experience

ICH E2F introduced the DSUR structure and content. A quality DSUR focuses on the reporting period versus cumulative period, delivers concise content, and not only provides data but interprets and evaluates the product safety profile. Project management by a medical writer, including planning adequate time for preparation and review and ensuring team members understand their responsibilities, is critical to ensure efficient DSUR development. Common challenges include short timelines, availability of source information, and data quality.

Embrace eCTD: Lifecycle Management of Clinical Documents

In January 2018, the Center for Drug Evaluation (CDE) announced its plan to implement specific ICH standards. While this presents an opportunity to accelerate new drug review and approval, it also creates a challenge for industry due to technical issues specific to Chinese dossiers. eCTD submission is much more than electronic; it provides an XML backbone, and defines the granular submission structure. All documents in an eCTD must be part of its operational lifecycle (new, replace, delete, and/or append). Knowledge sharing, proper granularity, and guidance interpretation are other keys to successful eCTD implementation.

Preparing Clinical Modules in ICH CTD Structure

The CTD for clinical documents presents the methods, analyses, and results of clinical studies completely and clearly. For China subpopulation studies, this document has the same structure as global documents. CTD Module 2.7 provides the clinical summary (biopharmaceutics studies, pharmacology studies, efficacy, and safety). Module 2.5 is an overview that not only summarizes Module 2.7 but also evaluates the product’s overall benefit-risk within the context of other, similar products. Module 5 provides all clinical study reports in detail. Complete the submission and statistical analysis plans before statistical analyses are conducted.

Simultaneous Preparation of Submission Documents in English and Chinese

A new working model for simultaneous bilingual document preparation means that translation can begin once a relatively stable source document is ready. After the source document is finalized, translators can focus only on new or revised content, and update the translated version to match. Technical advances such as AI can help reduce the team’s manual workload. In the future, human experts and AI-based machine translation are expected to work together, and significantly shorten the overall timeline by overlapping the writing and translation processes.

Panel Discussion

Experts in this theme agreed that medical writers must be familiar with all functional operations, understand the overall contents, and educate the submission team to maintain high quality submission dossiers and accelerate the submission timeline across all regions. Medical writers must also understand regulatory requirements specific to China and if necessary remind global reviewers, too. We may have little experience with new technical requirements, but can make use of previous submissions to provide good experience and knowledge.

Boosting innovation and technology has changed medical writing in many respects. In such a dynamic environment, an internal translation center would help to ensure quality and priority. AI can help during document preparation, but translation memory should be built to help AI learning, with human experts responsible for “training AI” and validating documents.

Conclusions


We are in a time of revolution, and face both opportunities and challenges, but medical writers remain the key coordinators and contributors to dossier submission preparation. Re-thinking the current process, assimilating deep knowledge of pertinent guidelines, and taking advantage of new technologies, will greatly accelerate the submission preparation and maintain the quality of these documents.