Electronic Common Technical Document eCTD

The Electronic Common Technical Document (eCTD) is an interface for the pharmaceutical industry to agency transfer of regulatory information. The content is based on the Common Technical Document (CTD) format.

It was developed by the International Conference on Harmonisation (ICH) Multidisciplinary Group 2 Expert Working Group (ICH M2 EWG). As of January 1, 2008, the U.S. Food and Drug Administration announced that the eCTD is the preferred format for electronic submissions.



eSubscription in Europe and US

eSubscription is the process of registering medicinal products for marketing authorisation at the local authorities.

eSubscription requires in current regulations in the US and Europe substantially different technologies, terminologies and vocabularies for registration of medicinal products. In the US, the FDA requires a “Structured Product Labeling” (SPL). In Europe, the European Medical Agency (EMA) initiated a new standard called IDentification of Medicinal Products (IDMP). It is most likely that FDA will take-over these standards in near future. IDMP raised the bar significantly by requiring information be sent in specific form for each country and language and coded with an ISO Code.



Global Ingredients Archiving System (GINAS)

What is GINAS in relation to ISO 11238

GINAS and ISO 11238 specifically addresses the identification and exchange of regulated information on substances.  GINAS supports all substance types described in the 11238 standard and provide multiple language capability for the naming of substances and controlled terminology used within the IDMP.

Background of GINAS

Globalisation presents tremendous challenges and opportunities for national regulatory agencies, the pharmaceutical industry, and global health as a whole. Emerging diseases and the health impacts of catastrophic events respect no national boundaries, nor does the increasing volume of substandard, contaminated, and counterfeit products that overburdens national regulators. Ingredients for pharmaceutical products are typically sourced on a global basis and it is very rare that all ingredients for a single product are produced within one jurisdiction. To regulate the global supply chain efficiently and to better respond to and prepare for catastrophic events it is essential to have a global information system for pharmaceutical ingredients.

ISO 11238 specifically addresses the identification and exchange of regulated information on substances. Working closely with that standard’s authors and regulatory authorities from various countries, NCATS is developing an information system to register and store substance-related information and provide identifiers. This will ensure a robust substance registration system that supports the additional needs of national and regional authorities and is consistent with the ISO 11238 standard. The system will support all substance types described in the 11238 standard and provide multiple language capability for the naming of substances and controlled terminology used within the system.

GINAS Project Description

The Global Ingredient Archival System (GINAS) represents a major opportunity for regulators worldwide to tackle the challenges of sharing ingredient information. This tool makes it possible to create a global standard for defining substances and a common identifier to identify ingredients in medicinal products. This will enable the global health community to share and use information to significantly improve health care delivery, the proper use of medications, and the management of risks involved in their use.

The project’s main goal is to provide a consistent definition of substances globally, and a common identifier for all the substances used in marketed medicinal products as well as active substances under clinical investigation. It is envisioned that a consortium of regulators from different national and international agencies would operate and maintain the platform in a secure and trusted manner. This centralized database will result in higher quality data while still respecting confidentiality requirements.

The software tools used in this project are developed, maintained, and distributed to project members and other interested parties by the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). As well as containing definitional information and identifiers, the system is able to store a wide variety of structured information on the identification, analysis, use, manufacture, pharmacology, and toxicology of medical product substances.

Goal of the Program

GINAS is a solution to the costly, duplicative, and piecemeal approaches currently being used. It will enable regulators to more easily monitor the global marketplace. The system could play a vital role in facilitating a global approach to pharmacovigilance; identifying and tracking substandard products and ingredients; alleviating drug shortages; enhancing clinical development; and coordinating and streamlining regulatory actions worldwide. The project will benefit industry by offering a “one-stop shop” to deposit substance-related regulatory information. It will help in developing specifications of substances and products in a more consistent manner, and in coordinating facility inspections. Finally, the project should dramatically reduce the time and costs of information-gathering for both companies and regulators.
NCATS intends this software product to be a freely distributable, maximally self-contained system to register substances and related manufacturing, analytical, and relevant biological information on substances that are of interest to health product regulators, product sponsors, and health researchers. Consistency will be achieved through a common data model and synchronization with a central database.
Since February 2013, Canadian, Dutch, German, Swiss, and U.S. regulators have been working with NCATS to create this system. Health Canada is providing an environment for collaborative development. This environment  supports the initial curation and mapping of content used for global substance identification.
The project group welcomes participation and sponsorship by regulatory agencies and other public health organizations throughout the world. It aims to be a global resource that will benefit public health by facilitating the transfer of regulatory information and providing industry and other interested stakeholders with a uniform process for depositing substance-related information.


Lot Distribution Report LDR

Lot Distribution Report LDR

In US under 21 CFR 600.81, marketing authorisation applicants must submit to the Center for Drug Evaluation and Research (CDER), LDRs containing certain specified information every 6 months about the quantity of the product distributed under their Therapeutic Biologic Applications (BLAs).

Biologic Lot Distribution Data must be submitted in SPL XML format within eCTD submissions.

FDA requires applicants to submit Biologic LDRs in an electronic format that the agency can process, review, and archive. This reporting requirement is effective as of June 10, 2015.

Every six months, applicants must submit to the appropriate center, LDRs containing certain specified information about the quantity of the product distributed under their BLAs (including to distributors).

The lot distribution file should be included in eCTD Module 3, section 3.2.R Regional Information. The lifecycle for this file should be updated as appropriate, in accordance with the current eCTD specification.


Periodic Adverse Drug Experience Report PADER

Periodic Adverse Drug Experience Report PADER

Post-approval cumulative reports of safety include Periodic Adverse Drug Experience Reports (PADERs) in the U.S. and Periodic Safety Update
Reports (PSUR) in many other regions, including in Europe. Their purpose is to update and evaluate the worldwide safety experience with a medicine
at defined time points after approval. Generally speaking, the Periodic Adverse Drug Experience Report PADER provide succinct summary information together with an evaluation of the benefit-risk profile of approved medicines in the light of new or changing post-approval information. This evaluation is designed to help ascertain whether further investigations are necessary and whether changes should be made to the approval or to the medicine’s labeling. In summary, the aim of cumulative reports of safety is to:

  • Report all the relevant new information from appropriate sources
  • Relate these data to patient exposure to the medicine
  • Summarize the medicine’s approval status in different countries and any significant variations related to safety
  • Create periodically the opportunity for an overall reevaluation of safety
  • Indicate whether changes should be made to an approved medicine’s label in order to optimize the use of the product

FDA has started accepting PADER/PAER Submission in eCTD Format from June 10, 2015.

Electronic Format of the Periodic Adverse Drug Experience Report PADER

FDA requires Industries to submit Periodic Adverse Drug Experience Report PADER in electronic format
The descriptive information portion of the PADER should be submitted as a PDF file to section 5.3.6 of the Electronic Common Technical Document (eCTD)
PADER is a single pdf file with proper bookmarks, Table of Contents and hyperlinking Submission in Electronic Format for Post Marketing Safety Reports, applies to all post marketing safety report for human drug and biologic products, includes individual case safety reports(ICSRs) and periodic safety reports.

PSUR Repository

Planning and preparation of the PSUR

The use of the PSUR Repository has become mandatory in the European Union on 13 June 2016. The PSUR repository is a single, central platform for PSURs and related documents to be used by all regulatory authorities and pharmaceutical companies in the EU.

EMA´s  Introductory cover note to the PSUR submission defines the procedure and how PSURs should be prepared and submitted for medicinal products in Europe.

Information important for the submission of the PSUR

For more details on the submission process please refer to the page Periodic safety update reports: questions and answers in the EMA Website.

List of Union reference dates and frequency of submission of periodic safety update reports (PSURs)

The PSUR list is updated on a monthly basis and any changes in the EURD list, such as the PSUR submission frequencies, the dates of submission and the PSUR submission requirement for medicinal products referred to in Articles 10(1), 10a, 14 or 16a of Directive 2001/83/EC come into force 6 months after its publication.

Procedural Timetables of PSUR

This EMA page procedural timetables lists the timetables for the submission, start and finish dates of procedures, as well as other interim dates and milestones that occur during the various procedures.

Timetables are categorised according to the type of procedure (e.g. full applications, extensions and variations, as well as response timetables).

The dates for submission, start of the procedure and plenary meetings of the Committee for Medicinal Products for Human Use (CHMP), the Pharmacovigilance Risk Assessment Committee (PRAC) and the Committee for Advanced Therapies (CAT) are generally fixed, but the other dates may be subject to adjustment until the CHMP reaches the adoption of the final opinion for the individual application.

At the start of the procedure, the Agency will notify the applicant of the adopted final timetable in writing.

What will you find in this page?

  • Initial marketing authorisation and extension applications
  • Variations
  • Renewals and annual reassessments
  • Pharmacovigilance procedures
  • Referrals
  • Post-authorisation measures
  • Advanced therapy medicinal products (ATMPs) procedural timetables

PSUR Substances in the “Active Pharmaceutical Ingredients Dictionary”