By Albert Yehaskel
Completing a successful electronic Common Technical Document (eCTD) submission can be daunting, even with the help of guidance documents from the International Conference on Harmonization (ICH) – which developed the eCTD – or from the Food and Drug Administration.
The success or failure of an eCTD submission depends greatly on processes put in place prior to beginning the process. First, it is necessary to ensure that the company has what’s needed to assemble an eCTD. If the manpower, knowledge, experience and hardware/software are not in place, failure is almost a certainty. These should be sourced from outside if necessary.
Once these are in place, it is imperative to set a timeline. The timeline is constructed by picking a realistic filing date and working backwards to see what needs to get accomplished to meet that deadline. The timeline will be part of a Global Development Plan that will change and be revised but will remain your “road map” for several years.
The eCTD is made up of five modules:
- Module 1 provides for administration information and is country specific. For example, submissions in the United States require a Form FDA 356h with specific information. Other required forms include Field Copy Certification, Patent Certifications, Financial Disclosures, and Environmental Assessment, to name a few. In the EU, different information is required, such as Consultation with Patient Groups, Pharmacovigilance, Risk Management, and other information associated with the EU Region. Canada also has its own specific requirements.
- Module 2 provides for quality, non-clinical and clinical summaries.
- Module 3 provides for CMC information on the drug substance and drug product.
- Module 4 provides for non-clinical data and reports.
- Module 5 provides for clinical data and reports (including the ISE and ISS).
In beginning to populate Module 3 and subsequently Module 2, some of the challenges that you will be faced with will include the following:
- Key API characteristics.
- Pre-formulation and formulation development programs.
- Ensuring that your specifications and analytical assays are well developed.
- Ensuring that your early and later batches of clinical trial material and commercial material are produced pursuant to Good Manufacturing Practices.
- Having a good stability program in place with established stability protocols.
For your non-clinical program you will need to ensure that all the appropriate animal studies have been completed pursuant to good clinical practices and each non-clinical document signed off. Once Module 4 has been populated, you will need to provide a summary of your non-clinical data in Module 2.
For your clinical program, you will need to ensure that all the requisite trials are completed on time, Clinical Study Reports (CSRs) are written and signed off and that you begin the process of writing the Integrated Summary of Effectiveness (ISS) and the Integrated Summary of Safety (ISE). Gathering all the adverse events that transpired through your program is essential. When Module 5 is completed, you will need to provide a summary of the clinical information in Module 2.
As you begin to accumulate information, data reports, you will need to identify, in synch with your development plan, potential issues that could put your program at risk. When these risks have been identified and prioritized, you will need to find ways to mitigate the risks in order to meet your timeline.
It is advisable to form an eCTD Dossier Team early on in the process and assign responsibilities to each member with deliverable dates. For example, who will be responsible for writing the various Drug Substance and Drug Product templates in Module 3? Will the same person be writing the overall summary in Module 2? Will this be an individual or a team effort? Who will write the overall nonclinical and clinical summaries once all the data and reports are in? The same applies for the ISE and ISS which are among the final documents in the process.
Careful coordination is needed to ensure on-time delivery of all the moving parts within the eCTD. It is important to keep the following documents in mind:
- A time line chart that needs to be reviewed and possibly modified often.
- A Development Plan.
- A list of risks and mitigation strategies
- A Gap Analysis
- Identifying documents, information and data missing in each module
- Prioritizing and establishing a timeline for how the missing information will be obtained and when the information will be available
- Identifying key issues that could derail your submission and resolving these issues quickly
- A tracking chart of the status of all components of the eCTD. This can include a detailed eCTD Table of Contents as well as separate tables of contents for each of the modules.
As you move forward with the eCTD process, be sure to communicate often with the FDA or Boards of Health in discussions that help address any issues that arise. Don’t leave these interactions for the end, because this will just guarantee setbacks.
As a final tip, make sure to version all your documents. There will be hundreds of them. This is a great tracking tool and will have big pay offs.
Posted in Issue of the Month and tagged Albert Yehaskel.