Practical suggestions for document conversion into eCTD form

Electronic monitoring of medicinal products

Only medicinal products with a marketing authorization issued by the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) or the European Commission may be marketed in Croatia. In addition to the marketing authorization application, the applicant is obligated to submit the dossier in the form of an Electronic Common Technical Document (eCTD).

The CTD (Common Technical Document) describes the organization of modules, sections, and documents in the dossier preparation which is compliant with The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).
The ICH is a global project which harmonizes regulatory bodies in Europe, the United States of America, and Japan as well as medicinal product manufacturers in the interpretation and implementation of technical guidelines and marketing authorization applications.

The submission of electronic dossiers in eCTD form is mandatory in all types of marketing authorization applications in the national (NP), centralized (CP), decentralized (DCP), and mutual recognition procedure (MRP).

Document preparation and medicinal product parameters required for eCTD input

Document preparation is the first step in creating documentation for eCTD input. When submitting a marketing authorization application, the applicant must ensure technical compliance of each submitted document with the requirements of the ICH and national agencies. Therefore, all documentation must be submitted as a PDF (excluding the documentation submitted in the folder “working documents”). This means that all hard-copy documents must be converted into an electronic format. When converting hard-copy documents into eCTD form, it is recommended to submit the baseline sequence in order to facilitate the assessment of regulatory procedures and the monitoring of the medicinal product’s lifecycle. The baseline sequence should include the compiled authorized dossier in the eCTD form previously submitted to the agency in a hard-copy or Nees form. The baseline sequence should contain at minimum Module 3.

Considering that the complete dossier must be in an eCTD form with advanced search options, all medicinal product parameters must also be in the same form, and all subsequent dossier variation applications must be submitted in the electronic format.

Tools for converting documentation into an electronic format

At present, numerous programs (tools) from various manufacturers are available on the market and used for eCTD creation. Not only do they enable compliance with regulatory requirements of different countries, but they also increase productivity and lower the possibility of errors due to advanced automation. Through their utilization, agencies and marketing authorization holders save time required for dossier review: they enable easier navigation to the latest updated document and the previous version via a hyperlink, which helps users to quickly skip to the specific sections (modules) of the dossier in question.

eCTD validation

National agencies for medicinal products and the European Medicines Agency (EMA) adopted a common set of technical criteria for the verification of all eCTDs using appropriate review and validation tools. All eCTDs must undergo technical assessment prior to content assessment. After the eCTD has been published, it should be reviewed using a software which checks its technical compliance with the ICH’s specifications and national agencies’ requirements. This step must not be skipped since any technical invalidity results in the agency’s rejection of the submitted eCTD. A valid technical validity testing of the eCTD sequence must be performed prior to its submission to the agency. Verification of technical validity of the electronic dossier and its scanning using an antivirus program is mandatory.

Once the eCTD sequence passes the validation test, it may be submitted to European agencies. To simplify the electronic submission process and facilitate safe and simple information transfer from the marketing authorization holder to European agencies, the method of submitting eCTD sequences via the Common European Submission Portal (CESP) for NP, MRP, and DCP has been introduced.

The EMA uses the eSubmission Gateway for centralized procedures, and the eSubmission Web Client for the submission of previously prepared sequences in eCTD form.

Size of documentation

The maximum size allowed for an individual document under a single eCTD sequence is 500 MB; however, it is recommended to prepare documents under 10 MB in size. The document size can be reduced using the original electronic documentation or converting document images into text using an Optical Character Recognition (OCR) tool.

Mistakes during documentation input into eCTD

During documentation input mistakes can occur, which complicate the overall input process. Listed under are the most common mistakes observed from experience that occur during documentation input into eCTD:

• PDFs with incorrect hyperlinks or bookmarks
• Attempts to create a new eCTD sequence without Module 1 or omission of completion of the required module sections
• PDFs in incompatible formats (i.e. they are not search-compatible)
• Older-version PDFs that are no longer accepted by the eCTD
• PDFs locked with a signature
• Folder names within the eCTD sequence longer than 64 characters
• File(s) misplaced in incorrect folder(s)
• Invalid file extensions (e.g. “cover-letter.PDF” instead of “cover-letter.pdf”).

To prevent the occurrence of these mistakes, it is recommended to perform at minimum two quality controls (QC) of all documents and data prior to input. It would be optimal that each QC is performed by a different person to increase chances of error detection: even a small one could lead to dossier rejection.

Price of eCTD conversion service

The process of eCTD creation and submission requires regular monitoring of regulatory changes concerning medicinal products. Marti Farm Ltd employs a team of professionals with many years of experience to support you in this process. We ensure a high-quality and accurate service of medicinal product authorization via all types of applications in the Republic of Croatia (marketing authorization, variations, renewal, transfer, and withdrawal). We have been providing this service since 2019 and have successfully submitted more than 350 eCTDs to date.

The eCTD conversion service includes all activities required for dossier conversion in accordance with applicable regulations. The price includes tasks such as sequence creation, input of PDFs into the program, editing of individual documents, final sequence review, validation, and correction of potential mistakes. The service is charged per hour according to the factual work performed, however short or long it may take.

If you require this type of service, feel free to contact us on: bd@martifarm.com thanks to our flexibility and expertise, Marti Farm Ltd will ensure a timely, high-quality, and complete service!

Martina Ivanišević, MSc / Registration Associate

References:

• http://www.martifarm.hr/
• https://www.halmed.hr/
• http://esubmission.ema.europa.eu/
• https://www.ich.org/