Newsletter Winter 2019 - Susan Manley - Early NDA Planning for Small to Mid-sized Companies


Early NDA Planning for Small to Mid-sized Companies

By Susan Manley 

Project Management/Regulatory

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The final phase 3 studies are ongoing with a planned completion in 12 to 18 months. Your board is looking to the submission date with great excitement. Your company has made it this far – is time to relax? No, not yet! Your company has not prepared a US NDA in several years or, even more concerning, has never prepared an NDA. What can you do now to ensure a smooth trip to the submission and beyond?

As a first step, familiarize yourself with eCTD, which is the standard electronic organization and format that is required for a US NDA (see Brandon Jones’s Spring 2018 article for a brief overview). Establish a high-level eCTD timeline, section by section, to identify the critical path to the submission date. List the individual components with the planned completion date, then examine each component/completion date pair to determine dependencies and whether the component completion can be accelerated. This timeline should be used as the basis of a tracking sheet that specifies resources and completion dates. The level of detail needed for the tracking sheet depends on your organization. For example, if you have a robust clinical organization, you may delegate the detail of clinical study completion and report preparation to that group, while you only track the study report completion date. Of course, the items on the critical path will need to be carefully staffed and managed.

In order to complete NDA submission, smaller organizations often need contract staff to deal with the peak workload during the last year before submission. A critical strategy is to bring key contract staff on board early enough so they become familiar with the drug class, planned documents, key scientific and regulatory issues, and internal procedures. If this strategy is not implemented, several setbacks may arise. Too often has the situation occurred in which more medical writers are added at the last minute without proper time and attention to orientation. This rush usually results in senior document reviewer frustration with document content that can involve multiple, time-consuming draft cycles.  

The last item typically finalized is the product labeling. The last components that feed into the labeling are the clinical summaries: the Integrated Summary of Safety, the Integrated Summary of Efficacy, 2.7.3 the Summary of Clinical Efficacy, 2.7.4 the Summary of Clinical Safety, and 2.5 the Clinical Overview (which includes a key discussion of risks and benefits). These final items deserve careful attention and review.  

The NDA submission requires labeling components to be annotated to the source information. A good practice is to prepare and maintain an “emerging package insert” during development, rather than drafting the label at the end of development. This emerging package insert should be annotated with the planned source document and any relevant comments. As work progresses, the emerging package insert will be modified based on development findings.

Careful planning should also apply to the order in which individual modules of the NDA are completed. Module 1 (Administrative Information), Module 2 (Summaries), and Module 5 (Clinical Study Reports) are usually the last sections to be completed. Frequently, Module 3 (Quality) and Module 4 (Nonclinical Study Reports) can be completed and provided to e-publishers days or even months before the completion of the other sections. A best practice is to complete Module 3 and 4 as early as possible. If this practice seems feasible for your company, you should consider discussing a rolling submission with FDA.   

Other topics to be addressed early on include:

·       Timing and content of the pre-NDA meeting. A draft package insert is required for this meeting. The planning and timelines for the NDA preparation should allow flexibility for revisions based on the outcome of this meeting.  

·       Organization of team meetings to communicate the “storyline” and address critical issues based on internal knowledge and FDA communications. 

·       Definition of writing standards, such as product name, document headers, use of templates, and granularity of documents. These standards will facilitate eCTD writing and future updating. 

·       Specification of the process for completing submission components, including quality control, review, sign-off, and storage. Storage should include not only the PDFs for submission, but also the final Word files, for the Word files will be helpful for future NDA amendments or submissions to other health authorities.

All trips to NDA submission have a few traffic humps and even some pot holes. Planning early while keeping these strategies and best practices in mind will help you navigate the journey more easily.