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.


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.



Master Data Management (MDM) is critical for IDMP compliance

In matching IDMP´s required data with customer´s data there will be several systems identified which hold IDMP relevant data.

In case of Marketing Authorisation Holders (MAHs) this will be Regulatory Information Systems (RIMs) which must be focused on. The RIM will be source for most of regulatory input, partly for substances, marketing and a small part of the packaging data. But more details may be needed from other systems.

Master Data Management will help assembling these data from the different sources, augmenting them by further data, preparing them for submission and matching the internaly used vocabularies against IDMP´s controlled dictionaries.

What impact will IDMP have on Providers of Structured Drug Information Systems?

IDMP will not only become standard for regulatory purposes. Furthermore it will also become the standard model used for systems in Pharmaceutical Information Systems, Drug Dictionaries, Clinical Decision Support, Hospital Information and Patient Information. So the impact of IDMP on providers of such systems is significant!

What are the key steps of a gap analysis and which next steps should be done?

It is important to create a common understanding for the project across the company. So typically all departments should be involved. The steps could be:

  1. Identify on a very high level the data sources and the owners that are candidates for extraction of idmp required data
  2. Define some test products which offers variations in product type, substances (mono, combi with different strength), in-licensed products etc., to be encoded and structured in IDMP
  3. Extract the required data manually out of the identified sources (step 1) and check if all needed information is available. Classify the quality of the extracted data in effort categories such as:
    a. single source which can be mapped to IDMP
    b. single source which requires significant effort to format data for mapping to IDMP
    c. available in multiple systems requiring harmonisation, or with poor data quality
    d. unstructured Data (Documentation)
    e. location not found; substantial manual effort to retrieve information
  4. Define (based on the outcome of step 3) your user requirements and potential high-level solution architecture. This can vary from an inhouse solution up to a wide range of solution scenarios with or without an integrated Master Data Management system
  5. The final step is the Request For Proposal (RFP) and the vendor selection and implementation

How can IDMP1 help you make your IDMP project a success?

The ISO IDMP standard will not only be the standard for regulatory affairs, but it will also become the standard model for pharmaceutical information systems used in in public information systems for patients, in clinical decision support in hospitals and in e-health.

IDMP1 offers structured data for medicinal products mapped against the IDMP´s required structure and controlled vocabularies. Its IDMP Drug Dictionary is an excellent starting point to define the structured representation of S(m)PC documents´content (e.g. for clinical particulars).


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”




Periodic Safety Update Report (PSUR)

The objective of the PSUR is to present a comprehensive and critical analysis of the risk-benefit balance of the product taking into account new or emerging safety information in the context of cumulative information on risk and benefits.

1 September 2015, companies should use the xml delivery file for all PSUR submissions to the EMA via the eSubmission Gateway/Web Client websites

The PSUR XML delivery file for EMA submission is introduced to harmonise the submission mechanism for all PSURs submitted to EMA and it will apply to all types of PSUR and PSUR supplementary information submissions.

PSUR Substances in the “Active Pharmaceutical Ingredients Dictionary”