In the dynamic world of biopharmaceutical development and manufacturing, the advent of gene editing and CAR-T therapy represents a monumental leap forward in medical innovation. However, with these advancements come the intricacies of regulatory document development—a landscape where precision, speed, and clarity are of utmost importance. By utilizing a global team of experienced Medical Writers, biopharmaceutical Sponsors can navigate these challenges with confidence. Medical Writers apply a wide variety of tools to anticipate and prepare for future demands, from utilizing Artificial Intelligence in their work to applying the latest industry guidances in their processes.

In this blog, we explore the critical role of Medical Writers in navigating the complexities of two recent FDA guidances—one on gene editing and another on CAR‑T therapies.

In biopharmaceutical development, Medical Writers leverage their flexibility to seamlessly integrate various, and at times, disparate elements. Beyond mere authors, they are orchestrators, combining and harmonizing components of scientific knowledge, technical requirements, and operational intricacies to create cohesive regulatory documents necessary for the success of clinical trials.

Early Engagement: Maximizing Opportunities

At the genesis of every clinical trial lies the critical phase of clinical document development (including deliverables such as Briefing Documents, Protocols, Operations Manuals, Investigator’s Brochures, etc.) —an arena where foresight and meticulous planning are essential.

During this stage, Medical Writers emerge as strategic partners, collaborating with Sponsors and stakeholders to shape documents that not only adhere to regulatory authority standards but also optimize trial efficiency, approval times, and patient centricity & engagement. To fulfill this role, Medical Writers need to be aware of a wide range of guidances. For example, ICH guidelines highlight purely technical specifications for various documents, while the Good Lay Summary Practice from the EC’s Directorate-General for Health and Food Safety sheds light on how lay summaries facilitate a better understanding of clinical trials for people without any scientific background. Medical Writers need to be conscious of these guidances and through early engagement, they need to align with the vision of Sponsors and KOLs. During early engagement, Medical Writers can leverage their expertise to anticipate challenges and proactively mitigate risks – both for individual deliverables and comprehensive programs.

Skilled Medical Writers understand that information contained in guidances from Regulatory Authorities, such as the FDA, can be turned into checklists that mirror the requirements outlined in sections such as, for example, Chemistry, Manufacturing and Controls (CMC), thus ensuring that Sponsors have a clear roadmap for compliance throughout the trial.

Crafting Aligned Checklists

Consider the intricate process of genome editing component design—a cornerstone of many biopharmaceutical interventions. Medical Writers have the ability to delve into the nuances of regulatory guidances, extracting key requirements related to component design, manufacturing, and testing. With precision, they can translate these requirements into comprehensive checklists that serve as a guide for the documents they author. From the description of design platforms to the detailed procedures for quality control and assurance, each element is meticulously aligned with the CMC sections of the guidances, providing Sponsors with a roadmap for compliance and success.

Having created in-house checklists, Medical Writers can verify that any of their deliverables meets the specifications as suggested by the FDA for the specific therapeutic area. Converting the FDA’s guidances into tangible checklists can be seen in the example of the CMC section of the GE guidance. Here, most notably, GE Component Design describes why chosen design platforms are selected based on:

• Genomic targets and intended modifications
• Rationale for design and screening processes
• Sequences of GE components and expression constructs
• Optimization strategies reducing off-target genome modification risk

Analogously, the FDA guidance on CAR‑T can be turned into checklists as well. For example, the Vector Manufacturing and Testing section, should cover items such as:

• Characterization and testing of the vector structure, master, and working cell banks
• Stability studies for vectors
• Vector lot release testing
• Safety measures (such as sterility, mycoplasma, endotoxin, and adventitious agent testing)
• Identity, purity, biological activity, and strength of the vector

In the same CAR-T FDA guidance, the Collection, Handling, and Testing of Cellular Starting Material section checklist should look like the following:

• Describing procedures for handling leukapheresis starting material
• Determine donor eligibility for allogeneic leukapheresis material
• Test starting material for microbial contamination (e.g., sterility)
• Optionally characterize starting material (e.g., CD4+ and CD8+ T‑cells, NK cells, monocytes, and B‑cells)
• Proper labeling and tracking throughout the CAR‑T cell manufacturing process

These checklists help ensure the Sponsors are equipped with a plan for success that comes from Medical Writers dissecting complex regulatory guidelines and distilling them into actionable insights.

Empowering Trial Success: Leveraging Expertise

By leveraging their deep understanding of industry best practices, Medical Writers empower Sponsors to optimize trial design and execution, ensuring that patient safety remains paramount at every stage.

In the ever-evolving landscape of biopharmaceutical development, the role of Medical Writers as stewards of clarity and compliance cannot be overstated. Through their expertise and dedication, they help bridge the gap between vision and execution.