Managing the product's life cycle

As sponsors work to develop a proactive plan that will set up documents for reuse and management chores throughout the life of the product, they must also find submission-publishing tools to ensure the proper integration of cross-application linking and associated lifecycle changes into the submission building process. Life-cycle management capabilities are enhanced by the eCTD granular format, allowing submissions to become ongoing as documents, and data can be submitted as it becomes available for an application or submission type.

"New," "append," "replace," and "delete" are operation attributes within the eCTD XML backbone that allow sponsors to replace only granules of information that need replacing. The cross-application linking function makes sure that changes made to any document in one application are also changed in all referencing submissions and applications.

Granularity is a key indicator of the ability to cross-reference documents across multiple submissions. However, granularity can be challenging when the level of granularity differs between the two applications. For example, the clinical documents in an IND typically are more granular because each 1572 and each investigator CV would be a separate PDF file. Although this granularity model makes it much easier to maintain life-cycle management in the IND, it may make it more cumbersome to link back from the NDA. In the NDA, on the other hand, quality documents are more granular because more CMC changes occur that require those documents to be upgraded or replaced. Other potential life-cycle problems include:

• Tag or placement errors in the IND, which later are corrected post-NDA. In this case, corrections may need to be made in both applications and cross-application links should be updated.
• Postmarketing commitments that add a new protocol to the IND after the NDA has been approved. You need to ensure synchronization between both submissions.
• Other IND updates made post-NDA.

Conclusion

In today's shrinking economy, life-science companies are looking for ways to cut costs, improve efficiency, and reduce time to market. With eCTD deadlines looming in the world's major marketplaces, sponsors must embrace eCTD submission formats. The good news is the eCTD format has built-in functionality that can help simplify and improve submission building and life-cycle management chores across all product lines. The caveat is, however, that the submission builder has to understand timesaving eCTD features such as cross-application linking and plan for their use before submission.

To best use cross-application linking functionality, sponsors need to have a plan that:

• Identifies product life cycle and global submission goals prior to IND
• Makes granularity decisions that support the flow of documents across applications (IND though NDA) and across regions when building the IND eCTD
• Asks regulators to test all cross-application links when building the NDA
• Gets expert help to use best practice eCTD strategies and processes (learn from the other guy's mistakes)
• Plans separately for each product (there's no cookie-cutter approach).

A September/October 2006 impact report released by the Tufts Center for the Study of Drug Development revealed that the companies best at organizing and executing the drug development process earn a billion-dollar advantage over their slowest competitors, bringing products to market 17 months faster. This research underscores the value of learning to squeeze the most out of tools and processes, and the importance of taking advantage of timesaving eCTD features, such as cross-application linking.

Michelle Perez is a manager of global regulatory consulting operations at ISI, which has offices in North America, Europe, and Asia, michelle.perez@imagesolutions.com

Reference

1. C. Robinson-Kuiperi, A New Look at eCTD Lifecycle Management: How Mapping from NDA back to IND Can Streamline Submission Lifecycle Chores, presented at the 2009 DIA conference (San Diego, CA).