Navigating the maze of electronic submissions at EMA
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Navigating the maze of electronic
submissions at EMA
Maurice Bancsi, PhD and Beatriz Criado, MSc
The European Medicines Agency (EMA) facilitates a range of different
submissions and application processes using several submission systems for
electronic procedures, which have clear advantages over paper-based
submissions. At present, first-time applicants cannot proceed with a regulatory
submission unless they have set up several accounts and assigned roles and
registered their companies and their assets. However, there is no “one-stop-
shop” place on the EMA website for users to access guidance for setting up
properly for each separate system. In the absence of such a central point of
information, we provide here a step-by-step guidance for first-time applicants
to set up appropriately for using electronic submissions at EMA.
Introduction
Until recently, submission of any kind of application to health authorities was a
straightforward, but cumbersome, process. Originals were hand-typed on
paper, copies were either carbon or photocopies, and applications, depending
on the type and size, were sent by anything from regular mail to paper-filled
truckloads. Submission processes started to change with the introduction of the
©2021 Regulatory Affairs Professionals Society
February 2021
personal computer and advances in telecommunication, allowing limited-sized
submissions to be sent by fax machine, which could be regarded as the first
“electronic” submissions to health authorities. Documents could be drafted on
personal computers with word-processors and copies were saved on floppy-
discs and later, compact discs and digital video discs. These larger submissions
were still sent by mail or courier services.
The last 15 to 20 years have marked the rise of the internet and its huge
potential as fax machines were replaced by email systems, and higher data
transfer speeds facilitated the submission of large quantities of data using
dedicated electronic portals.
The EMA1 is the central European Union (EU) institute coordinating the
evaluation of medicines for central approval in the EU. At the EMA, the
Eudralink2 system – a secure email system for sending large documents – was
introduced as one of the first electronic submission systems, combining the use
of email and an electronic portal. Since Eudralink, the are continuous efforts to
facilitate electronic submissions in a secure and reliable electronic environment.
Several systems have been introduced in addition to Eudralink, email, and the
EMA Service Desk:3
• The eSubmission Gateway and the eSubmission Gateway Web Client,
which are secure electronic submission channels for electronic common
technical document and some nonstructured submissions,4
• The IRIS portal,5 a secure online platform for handling product-related
scientific and regulatory procedures with EMA,
• EudraCT,6 the EU database for all interventional clinical trials on
medicines, and
• EudraVigilance,7 a secure system for managing information on
suspected adverse reactions to medicines being studied in clinical trials
or already authorized.
However, as it stands now, there is a multitude of different submissions and
application processes and the existence of these apparently standalone
submission systems, make it hard, and sometimes seemingly impossible, for
first-time applicants to find their way in this maze of electronic submission
systems, outlined in Figure 1 (see p. 3).
In this paper, we will clarify the respective systems in use at EMA and propose a
stepwise approach to help new applicants unravel the maze and facilitate
proper use of the available EMA systems.
Setting up to use EMA electronic systems
When the development of a new project, whether it is a drug, device, or
diagnostic, has progressed to a point where there is a need for interaction with
EMA ‒ for example, for scientific advice or protocol assistance, an orphan
February 2021
FIGURE 1 The current maze of EMA e-submission systems
Source: EMA
medicinal product designation, or a pediatric investigation plan (PIP) ‒ or where
it is advantageous to have that option available, an applicant needs to set up
several accounts.
Step 1
As a first step, three accounts need to be set up as shown in Figure 2:
• An EMA account on the EMA Account Management portal8 – This is
required for access to multiple other systems, such as the EMA Service
Desk, Eudralink, the SPOR (Substance, Product, Organization and
February 2021
FIGURE 2 Setting up accounts at the EMA
Source: EMA
Referentials)9 portal, the IRIS portal, and EudraCT. Sponsors of clinical
trials and companies holding a marketing authorization in the European
Economic Area (EEA) also need an active EMA account to register with
EudraVigilance for the electronic reporting of suspected adverse drug
reactions and the electronic submission of information on authorized
medicinal products.
• An e-Sub account on the eSub registration webpage10 – This is required
for submissions through the eSubmission Gateway, such as a PIP
submission and a marketing authorization application (MAA).
• An EMA customer account number – This is set up through the EMA’s
accounts receivable inbox.11 The account is needed for payment of
invoices12 from EMA, but also for applications in the IRIS system, such as
scientific advice and protocol assistance.
Step 2
The second step involves SPOR, IRIS, Eudralink, and EudraVigilance (Figure 3).
February 2021FIGURE 3 Setting up systems at the EMA
Source: EMA
To have access to IRIS and to maintain Organizations Management Services
(OMS)13 data in SPOR, appropriate user access roles for IRIS and SPOR are
required. For both SPOR and IRIS, a first user admin role (SPOR industry
superuser, IRIS industry user admin, or IRIS parallel distribution user admin),
requested through the EMA Account Management portal, will need to be
approved by EMA. The user admin roles will manage and approve all
subsequent affiliations to the organization. These subsequent roles would
include second superuser/user admin, user, manager, and contributor role, and
would also be requested through the EMA Account Management portal. A
Eudralink account can be requested through the EMA Service Desk.
To have access to EudraVigilance, an EU qualified person for pharmacovigilance
(QPPV) or responsible person (RP) role must be requested through the EMA
Account Management portal. A service desk request needs to be raised with the
required registration documents, including the Gateway (also called EV Post)
connection details if this is the electronic transmission platform that will be
used for reporting. An organization can alternatively use EVWEB14 (also known
as Webtraders) as transmission platform.
February 2021• SPOR provides users or will provide users with several data
management services:
o Substance management services (not currently activated)
o Product management services (not currently activated)
o Organizations Management Services – OMS is a central repository
of organization data. If the organization on whose behalf an
applicant will be acting is not listed in OMS, a change request needs
to be raised to have the organization registered. When the
organization has been successfully registered, the applicant will
receive an organization identification code. OMS support the
continuous exchange of data between information systems across
the European medicines regulatory network and across the
pharmaceutical industry.
o Referentials management services – RMS provides referentials lists
and terms, such as routes of administration and dosage forms, in
multiple languages. RMS supports the continuous exchange of data
between information systems across the European medicines
regulatory network and the pharmaceutical industry.
• IRIS provides a platform for the following procedures to be accessed:
o Orphan designation
o Scientific advice (human and veterinarian)
o Protocol assistance (scientific advice for orphan designated
medicines)
o Parallel distribution
o Innovation task force (ITF) consultation and general procedures
(e.g., requests for a research product identifier [RPI])
o Change of name and address of an applicant on regulatory
entitlements.
o Several quick links are accessible in the IRIS portal for guidance
through the IRIS registration process, information on parallel
distribution notices, organizations and substances, guidance and
support documents and latest news.
• EudraVigilance is the system for managing and analyzing information on
suspected adverse reactions to medicines that have been authorized or
are being studied in clinical trials in the EEA. The EMA operates the
system on behalf of the EU medicines regulatory network.
• Eudralink can be used for secure transfer of large documents.
Step 3
In step three, the user admins assign further roles in the individual systems
(Figure 4):
• The first SPOR industry superuser can approve a second SPOR industry
superuser (recommended by EMA) and the SPOR industry user role.
• The IRIS industry user admin can approve a second IRIS industry user
admin (recommended by EMA) and the IRIS industry manager,
contributor, and user roles.
February 2021FIGURE 4 Assigning roles in systems at the EMA
Source: EMA
• The IRIS parallel distribution user admin can approve a second IRIS
parallel distribution user admin (recommended by EMA), and the IRIS
parallel distribution manager, contributor, and user roles.
• The user admins are responsible for these approvals, and the EMA is not
involved.
• The QPPV/RP can approve new EudraVigilance user role requests.
Once SPOR and IRIS roles have been assigned, the applicant will need to verify
whether their active substances are registered and appear as “authorized” and
“current” on the official EMA list of all substances, the European Union
Telematics Controlled Terms.15 If an active substance is not listed, then a
request must be raised at the EMA Service Desk to have it registered. Once the
substance is registered, the applicant can proceed to create a request for an RPI
through IRIS, necessary to proceed with certain types of scientific procedures
(Figure 5).
February 2021FIGURE 5 Active substance registration at the EMA
Source: EMA
Sponsorship/authorization to act on behalf of a sponsor
Once accounts have been created, roles have been assigned and companies and
products have been registered, the final consideration concerns the accessibility
of procedures. When a company is not established within the EEA (or has no
affiliate), some procedures are not immediately accessible, such as the orphan
medicinal product designation or classification as small- or medium-sized
enterprise or MAA. In those instances, that company will need to establish a
presence (e.g., an affiliate) within the EEA or designate a third party (established
within the EU) as sponsor for their procedures. For other procedures, such as
PIP, scientific advice or protocol assistance, a company may appoint a third
party to act on their behalf, while retaining sponsorship.
Use of EMA eSubmission platforms
After the accounts have been created, roles assigned, and companies and
products registered, all eSubmission platforms should be accessible, as outlined
in Figure 6.
February 2021FIGURE 6 eSubmission platforms at the EMA
Source: EMA
There are two major submission platforms:
• The eSubmission Gateway/Web Client is the mandatory system for
submissions related to the authorization and maintenance of medicinal
products, such as the initial MAA, a postapproval safety study, a
postapproval efficacy study, a periodic safety update report, a risk
management plan, a postapproval measure, a plasma master file, a
variation and a renewal.
• IRIS is used mostly during product development, for orphan
applications, for ITF meeting documents, parallel distribution
February 2021applications, scientific advice/protocol assistance requests and general
request, such as related to RPIs. The exception is the PIP submission
(initiated early in clinical development and maintained throughout
development), which is also done through the eSubmission
Gateway/Webclient.
The remaining submissions still reside under legacy platforms/systems, such as:
• Eudralink (priority medicines, or PRIME, applications),
• Email (name recognition group submissions, advanced therapy
medicinal product classification requests,
• ITF briefing meeting requests, and reporting shortages of medicines,
• The EMA Service Desk (requests for accelerated assessment of an MAA,
eligibility for the centralized procedure requests and notification of
quality defects), and
• The EMA account for access to clinical data.
Given that the scientific advice and protocol assistance procedures have
recently moved under the IRIS umbrella, it may be a matter of time before the
other processes linked to email, the EMA Service Desk and Eudralink will also be
transferred.
Summary
The EMA facilitates a range of different submissions and application processes,
using several submission systems for electronic procedures, which have clear
advantages over paper-based submissions. However, with the multitude of
different submissions and application processes and the existence of several
apparently stand-alone submission systems, it is hard for applicants to find their
way in this maze of electronic submission systems. Here we have described a
stepwise approach for new applicants to facilitate the use of the available
systems at EMA. These steps included setting up accounts (EMA account, eSub
account, EMA Account Number) and systems/platforms (SPOR, IRIS) and
registration of organization and active substances.
Abbreviations
EEA, European Economic Area; EMA, European Medicines Agency; EU, European Union; ITF,
innovation task force; MAA, marketing authorization application; OMS, Organizations
Management Services; PIP, pediatric investigation plan; QPPV, qualified person for
pharmacovigilance; RMS, referentials management services; RP, responsible person; RPI, research
product identifier; SPOR, substance, product, organization, and referentials.
References
1. European Medicines Agency website. https://www.ema.europa.eu/en. Accessed 12
February 2021.
2. European Medicines Agency. Eudralink homepage. https://eudralink.ema.europa.eu/.
Accessed 12 February 2021.
3. European Medicines Agency. Login page for service desk.
https://servicedesk.ema.europa.eu/jira/servicedesk/customer/user/login?destination=p
ortals. Accessed 12 February 2021.
4. eSubmission website. eSubmission gateway and eSubmission web client.
http://esubmission.ema.europa.eu/esubmission.html. Last updated 19 November 2020.
Accessed 12 February 2021.
February 20215. IRIS, a secure online platform for handling product-related scientific and regulatory
procedures with EMA. https://iris.ema.europa.eu/~/. Accessed 12 February 2021.
6. EudraCT, the EU database for all interventional clinical trials on medicines.
https://eudract.ema.europa.eu/index.html. Accessed 12 February 2021.
7. EudraVigilance system overview. https://www.ema.europa.eu/en/human-
regulatory/research-development/pharmacovigilance/eudravigilance/eudravigilance-
system-overview. Accessed 12 February 2021.
8. European Medicines Agency. EMA account management.
https://register.ema.europa.eu/identityiq/login.jsf?prompt=true#/accessRequestSelf/ad
d. Accessed 12 February 2021.
9. European Medicines Agency. SPOR https://spor.ema.europa.eu/sporwi/. Accessed 12
February 2021.
10. European Medicines Agency. eSubmission Registration – Step 1.
https://esubregistration.ema.europa.eu/registration/. Accessed 12 February 2021.
11. European Medicines Agency. Email address for accounts receivable inbox.
AccountsReceivable@ema.europa.eu. Accessed 12 February 2021.
12. European Medicines Agency. EMA invoicing portal.
https://fees.ema.europa.eu/bd/public/zindex.jsp. Accessed 12 February 2021.
13. European Medicines Agency. Organisations Management Service (OMS).
https://spor.ema.europa.eu/omswi/#/. Accessed 12 February 2021.
14. EudraVigilance website. EVWEB.
https://eudravigilance.ema.europa.eu/human/evweb01.asp. Last updated 26 October
2012. Accessed 12 February 2021.
15. European Union. European Union Telematics Controlled Terms (EUTCT) System.
https://data.europa.eu/euodp/en/data/dataset/the-european-union-telematics-
controlled-terms-eutct-system. Modified 14 December 2018. Accessed 12 February
2021.
About the authors
Maurice Bancsi, PhD, is a director of regulatory affairs at Regulatory Professionals, a division of
Premier Research. He has more than 24 years of experience with biologicals, as well as small
molecules developing EU regulatory strategies, leading cross-functional teams in health authority
interactions (both on national and EU level) and submission of regulatory applications. Bancsi has
a doctorate in medicines from the University of Leiden, Netherlands. He can be contacted at
Maurice.bancsi@regprofessional.com.
Beatriz Criado, MSc, is an associate director of regulatory affairs at Regulatory Professionals, a
division of Premier Research. She has more than 23 years of experience in regulatory affairs in the
pharmaceutical and biotech industry and has held a range of leadership positions in regulatory
affairs. Criado has broad experience in a variety of therapeutic areas, including immunology,
neuroscience, women’s health, rare diseases, and pediatric indications. She has a master of
science degree in pharmaceutical and parapharmaceutical industry from the CESIF [Centre of High
Studies of the Pharmaceutical Industry], Madrid, Spain. She can be contacted at
Beatriz.criado@premier-research.com.
Citation Bancsi M, Criado B. Navigating the maze of electronic submissions at EMA. February
2021. REGULATORY FOCUS. Regulatory Affairs Professionals Society.
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