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28 June 2024
EMA/923413/2022 – v. 4.0
Clinical Trials Informaon System (CTIS) Programme
Clinical Trials Informaon System (CTIS) - Sponsor Handbook
A compilaon of key guidance, technical informaon, recommendaons, and references for
geng ready for the use of CTIS
Execuve summary
The aim of the EMA CTIS Sponsor Handbook (‘Handbook’) is to provide clinical trial (CT) sponsors
represenng pharmaceucal industry, SME (small and medium-sized enterprises), academia, research
organisaons and other clinical trial sponsor organisaons with the informaon they need to navigate
the Clinical Trials Informaon System (CTIS) - to create and submit clinical trial informaon to the
member states of the European Union as required by the Clinical Trial Regulaon [CTR: Regulaon (EU)
No 536/2014]. The Regulaon harmonises the assessment and supervision processes for clinical trials
throughout the EU/EEA, via CTIS. CTIS contains the centralised EU portal and database for clinical trials
foreseen by the Regulaon.
The Handbook addresses key quesons on CTIS and provides a compilaon and references to key
guidance, technical informaon, recommendaons, training materials, and supporve documentaon to
facilitate the submission and assessment of CTAs and addional informaon during the lifecycle of a trial.
It has been developed by the European Medicines Agency (EMA) in collaboraon with representaves of
industry stakeholders.
The Handbook will be revised as more informaon becomes available, or system funconalies are
updated. It is best used in conjuncon with the many references to which it points, for example, Volume
10 of the publicaon ‘The rules governing medicinal products in the European Union’ that contains
guidance documents applying to clinical trials (EudraLex - Volume 10 - Clinical trials guidelines).
Clinical Trials Informaon System (CTIS) - Sponsor Handbook
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Document evoluon
Version
Date
1.0
This first version of the CTIS Sponsor Handbook contains
priorised topics. Addional topics will be inserted/completed
in the document and updates will be provided in the next
versions.
28 July 2021
2.0
Updated handbook secons:
- Editorial changes across the document
- OMS registraon process (secon 3.2.1) updated
- User personas and organisaon models (secon 4.5) updated
with new links
- Product management in CTIS (secon 5) updated
- Transion from Direcve to Regulaon (secon 6) updated
- Data fields and documents specificaons (secons 7.1.3) new
- SUSARs reporng (secon 8.1) updated
- Training environment for user training and organisaon
preparedness (secon 10.4) new
30 November
2021
3.0
This document has been revised to its third version since CTIS
went live.
Updated handbook secons follow:
- Editorial changes and reference updates across the document
- Execuve summary updated
- Overview of Clinical Trial Applicaon (CTA) process in CTIS –
from submission to decision and reporng (secon 1.2) updated
- CTIS go-live date (secon 1.3) updated
- Organisaon and Sponsor Administrator registraon (secon
2.2) updated
- Key user management concepts in CTIS (secon 3.1) updated
29 November
2022
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Version
Date
- Markeng Authorisaon Holder (MAH) group of users (secon
3.5) new
- How to get a clinical trial applicaon started in CTIS (secon 4)
new
- Transion from Direcve to Clinical Trial Regulaon (secon 5)
updated
- How to create a transional trial in CTIS (secon 5.3) new
- How to manage trials transioned to the CTR in CTIS (secon
5.4) new
- Data, documentaon, and processes (secon 7) updated
- Safety reporng obligaons (secon 9) updated
- Support (secon 10) updated
- Other references (secon 11) updated
3.01
- Minor editorial changes
- Update of melines due dates in CTIS in Secon 4.1
- Update of document upload size (secon 7.1.3.2)
- Clarificaons on dates for the transion period (secon 5.1,
5.2.2)
December 2022
3.02
- Recording sites locally in CTIS (secon 2.2.2) new
- CTIS Bitesize Talks links (mulple secons) new
- Mul-factor authorisaon in CTIS (secon 2.1.1) new
- Mulple Q&A reference links added (secon 10.6) updated
- Glossary (secon 12) updated
April 2023
3.03
- Module 7 video links (secon 2.2.3) updated
- Note added to Part II document 'Proof of insurance cover or
idenficaon' (secon 4.2, table 4.2.5) updated
- Addional reference materials for CTIS users link (secon 4.2)
updated
October 2023
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Version
Date
- CTCG guidance on transional trials link (secon 5.1) updated
- Added link to CTCG Cover leer template for transional trials
(secon 5.1) new
- added link to the Guidance for the Transion of clinical trials
from the Clinical Trials Direcve to the Clinical Trials Regulaon
new
- Link Eudralex 10 page - Set of documents applicable to clinical
trials authorised under Regulaon EU No 536/2014 (secons
5.1 and 9.1) update
- Maximum number of documents upload in one batch (secon
7.1.3.2, table 7.1.3.2.1) new
- CT Highlights newsleer subscripon link (secon 10.2)
updated
- CTIS online training modules page (secon 10.4) updated
- CTIS Training Environment Support Service link (secon 10.5)
updated
- Added link to Q&A on protecon of CCI and personal data in
CTIS (secon 10.6) updated
- added link to Conclusion of VHP Procedure (secon 11) update
- ACT EU website link added (secon 11) new
- Reference to EMA Medical Terms Simplifier added (secon 12)
new
4.0
- Multi-factor Authentication (MFA) in CTIS (section 2.1.1)
updated
- Transition Period (section 5.1) updated
- Reference document to Guidance for the Transition of
clinical trials from the Clinical Trials Directive to the Clinical
Trials Regulation (section 5.1) updated
- Trials that should not be transitioned (section 5.2.1) updated
- Links throughout the document updated
June 2024
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Table of Contents
Execuve summary ............................................................................................................................ 1
Table of Contents ............................................................................................................................... 5
1. What CTIS is and what it does ......................................................................................................... 7
1.1. A brief introducon to CTIS ..................................................................................................................................... 7
1.2. Overview of Clinical Trial Applicaon (CTA) process in CTIS – from submission to decision and reporng ............ 8
1.3. CTIS go-live date ...................................................................................................................................................... 9
2. Geng access to CTIS – registraons ............................................................................................. 10
2.1. User self-registraon ............................................................................................................................................. 10
2.1.1. Mul-factor authencaon in CTIS .................................................................................................................... 11
2.2. Organisaon and Sponsor Administrator registraon ........................................................................................... 11
2.2.1. Organisaon registraon in OMS ....................................................................................................................... 11
2.2.2. Organisaon registraon locally in CTIS for use in CTIS ...................................................................................... 13
2.2.3. Sponsor Administrator registraon in EMA Account Management portal for use in CTIS ................................. 13
3. Management of users and organisaons in CTIS ............................................................................ 15
3.1. Key user management concepts in CTIS ................................................................................................................ 15
3.2. User roles concept in CTIS ..................................................................................................................................... 15
3.3. Organisaon-centric approach - Sponsor Administrator ....................................................................................... 16
3.4. Trial-centric approach – Clinical Trial Administrator .............................................................................................. 17
3.5. Markeng Authorisaon Holder (MAH) group of users ........................................................................................ 18
3.6. CTIS user personas and organisaon models ........................................................................................................ 18
4. How to get a clinical trial applicaon started in CTIS ...................................................................... 19
4.1. Introducon ........................................................................................................................................................... 19
4.2. Draing of the clinical trial applicaon dossier ..................................................................................................... 19
4.3. Clinical Trial Applicaon under evaluaon ............................................................................................................ 24
4.4. Clinical Trial Applicaon aer decision .................................................................................................................. 24
5. Transion from Direcve to Clinical Trial Regulaon ...................................................................... 25
5.1. Transion period .................................................................................................................................................... 25
5.2. Points to consider on transional arrangements .................................................................................................. 27
5.2.1. What trials should not be transioned ............................................................................................................... 27
5.2.2. Can the trial be transioned? ............................................................................................................................. 27
5.2.3. What are the assessment melines of transional trials ................................................................................... 29
5.3. How to create a transional trial in CTIS ............................................................................................................... 29
5.4. How to manage trials transioned to the CTR in CTIS ........................................................................................... 29
6. Product management in CTIS ........................................................................................................ 30
6.1. Medicinal product registraon in XEVMPD ........................................................................................................... 30
6.2. Medicinal product in CTIS extracted from XEVMPD .............................................................................................. 32
6.3. Adding an authorised medicinal product in CTIS ................................................................................................... 32
6.4. Adding an unauthorised medicinal product in CTIS .............................................................................................. 34
6.5. Medicinal product details in CTIS .......................................................................................................................... 35
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7. Data, documentaon and processes .............................................................................................. 36
7.1. Clinical Trial Applicaon (CTA) and Noficaon Forms .......................................................................................... 36
7.1.1. Clinical Trial Applicaon Form overview of the data fields to be completed and documents to be provided ... 36
7.1.2. Noficaon and Results: overview of the data fields to be completed and documents to be provided ........... 37
7.1.3. Data fields and document specificaons ............................................................................................................ 37
7.2. Trial categorisaon ................................................................................................................................................ 39
7.3. Download opons ................................................................................................................................................. 39
7.3.1. Clinical trial page ................................................................................................................................................ 39
7.3.2. Clinical trial applicaon page .............................................................................................................................. 40
7.3.3. Clinical Trial Search Download of results ............................................................................................................ 41
7.4. How to apply a change to a clinical trial dossier.................................................................................................... 42
7.4.1. During the draing of the inial clinical trial applicaon ................................................................................... 42
7.4.2. Once the inial clinical trial applicaon has been submied ............................................................................. 42
7.5. Handling of Requests for Informaon (RFIs) in CTIS .............................................................................................. 45
7.6. Subming the Clinical Study Report (CSR) ............................................................................................................ 49
8. Data transparency ........................................................................................................................ 49
9. Safety reporng obligaons .......................................................................................................... 51
9.1. Suspected Unexpected Serious Adverse Reacons (SUSARs)................................................................................ 51
9.2. Annual Safety Report (ASR) ................................................................................................................................... 52
10. Support ...................................................................................................................................... 53
10.1. Release notes and known issues ......................................................................................................................... 53
10.2. CTIS Highlights Newsleers ................................................................................................................................. 53
10.3. CTIS informaon events....................................................................................................................................... 54
10.4. CTIS training ......................................................................................................................................................... 54
10.5. CTIS training environment for user training and organisaon preparedness ...................................................... 55
10.6. Quesons and answers on CTR, CTIS and other EMA IT systems ........................................................................ 56
10.7. Support for SME and academia sponsors ............................................................................................................ 57
11. Other references ......................................................................................................................... 59
12. Acronyms and Glossaries ............................................................................................................ 60
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1. What CTIS is and what it does
1.1. A brief introducon to CTIS
CTIS is the single-entry point for clinical trials informaon in the European Union (EU) and in the
European Economic Area (EEA).
This includes a single clinical trial applicaon dossier, covering clinical trial applicaons submied to
EU/EEA Member States, including submission to Naonal Competent Authories (NCAs) and Ethics
commiees (ECs) and registraon of the clinical trial in a public register; all in one integrated submission.
CTIS provides harmonised and simplified end-to-end electronic applicaon procedures over the lifecycle
of clinical trials across the EU/EEA.
CTIS is, however, not a clinical trial management system. It should therefore not be relied upon by
sponsors to store informaon on a clinical trial. CTIS provides a digital secured archive of documents,
decisions, and informaon on a clinical trial, but sponsors should ensure they ulise their own
informaon management system to store informaon needed for compliance purposes.
The exchange of informaon between sponsors and Member States is fully electronic in CTIS.
In CTIS, Member States collaborate and coordinate amongst themselves for the evaluaon and
supervision of clinical trials resulng in one single decision per Member State Concerned.
Documents can be uploaded but not created in CTIS.
CTIS offers searchable clinical trial informaon to the paent, the healthcare professional, and the
general public. Clinical trial results are available both as a technical summary and in lay language.
Informaon can be retrieved by searching for a parcular trial or across trials for treatment-related
details.
Paent safety in clinical trials is enhanced as CTIS provides an end-to-end electronic soluon for safety
reporng of trials.
CTIS facilitates a harmonised safety assessment in Europe, supported by agreed assessment report
templates.
The clinical trial module of EudraVigilance provides for the electronic reporng of Suspected Unexpected
Serious Adverse Reacons (SUSARs) by sponsors and re-roung to Member States.
CTIS delivers an electronic Annual Safety Reports (ASRs) repository.
Digitalisaon
& Improved
Efficiency
Increased
Transparency
Enhanced
Paent
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CTIS is a unique intuive tool that facilitates the submission of clinical trial applicaons including those
for mul-naonal trials and therefore facilitang invesgaon of e.g. rare diseases. It thereby also
supports academic innovave work.
CTIS offers search and export of structured clinical trial data to allow efficient reporng for sciensts.
A clinical trial can be extended to more Member States e.g. to enhance recruitment rates.
1.2. Overview of Clinical Trial Applicaon (CTA) process in CTIS – from submission to decision and
reporng
CTIS is structured in two restricted and secured workspaces (Sponsor and Authority), only accessible to
registered users, and a website openly accessible to the general public.
The sponsor workspace provides clinical trial sponsors with the funconalies for submission of CTAs to
Member States, and management of informaon throughout the lifecycle of clinical trials.
The sponsor funconalies include:
• assignment and management of users;
• compilaon of clinical trial dossiers;
• receiving of alerts and noces for ongoing trials;
• compilaon of responses to requests for informaon;
• view deadlines, search, and access clinical trials;
• compilaon of noficaons related to the life cycle of the trial including submission of a summary of
clinical study results.
Registered users with the appropriate permissions are able to access the following tabs for their affiliated
trials:
The clinical trials tab provides search funconalies that facilitate users to find specific trials and view
informaon (see module 9 of the CTIS training programme).
The noces and alerts tab shows the messages triggered by acvies that occur during the life cycle of a
clinical trial (see module 4 of the CTIS training programme).
The tab for requests for informaon –RFI– tab provides access to such requests made by Member States
Concerned (MSC) for clinical trials, and enables users to view their status, due dates, and other relevant
informaon (see modules 4, 5 and 11 of the CTIS training programme).
The User administraon tab allows management of roles and permissions for all users that are registered
in the system (see modules 3 and 7 of the online CTIS training programme).
The CTIS Training Material Catalogue Module 2 provides a high-level overview of CTIS workspaces.
Support to
Innovaon &
Research
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References
Locaon (area or document)
Clinical Trial Regulaon (EMA website)
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-trials/clinical-
trials-regulaon
CTIS Training Material Module 02 ‘High-
level overview of CTIS workspaces and
common system funconalies: User
Quick Guide’
hps://www.ema.europa.eu/documents/other/quick-
guide-overview-cs-workspaces-common-system-
funconalies-cs-training-programme-module-
02_en.pdf
CTIS Training Material Module 02 ‘High-
level overview of CTIS workspaces and
common system funconalies: CTIS
common funconalies, Part A’
hps://youtu.be/EgIRpL17WaU
CTIS Training Material Module 03 ‘User
access management’
hps://www.ema.europa.eu/documents/other/quick-
guide-user-access-management-cs-training-programme-
module-03_en.pdf
CTIS Training Material Module 04 ‘Support
with workload management - Noces &
Alerts’
hps://www.ema.europa.eu/en/learning-
module/workload-management-sponsor/story.html
CTIS Training Material Module 04 ‘Support
with workload management -RFIs’
hps://www.youtube.com/watch?v=6z-Q6-LK8Ws
CTIS Training Material Module 05 ‘Manage
a clinical trial through CTIS’
hps://www.ema.europa.eu/en/learning-
module/manage-ct/story.html
CTIS Training Material Module 09 ‘Search,
view and download informaon on clinical
trials and clinical trial applicaons: User
Quick Guide’
hps://www.ema.europa.eu/en/documents/other/quick-
guide-how-search-view-download-clinical-trial-clinical-
trial-applicaon-sponsors-cs_en.pdf
CTIS Training Material Module 11
'Respond to requests for informaon
received during the evaluaon of a clinical
trial applicaon'
hps://www.ema.europa.eu/documents/other/step-
step-guide-how-respond-requests-informaon-received-
during-evaluaon-clinical-trial_en.pdf
1.3. CTIS go-live date
CTIS was launched on 31 January 2022, and the Clinical Trial Regulaon has been applicable since then.
In April 2021, the EMA's Management Board confirmed that the system met the agreed requirements
following an independent audit of CTIS. On 31 July 2021, the European Commission confirmed 31 January
2022 as the date of entry into applicaon of the Clinical Trials Regulaon, and the go-live of CTIS, via
publishment of a noce in the Official Journal of the European Union.
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Since the launch of CTIS, there has been a 3-year transion period; this is covered in more detail in
Secon 5 ‘Transion from Direcve to Clinical Trial Regulaon’.
References
Locaon (area or document)
Informaon on clinical trials in the
context of Regulaon EU No 536/2014,
including the noce published in the OJ
(European Commission website)
hps://ec.europa.eu/health/human-use/clinical-
trials/regulaon_en
Informaon in the context of Regulaon
EU No 536/2014 (EMA website)
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-trials/clinical-
trial-regulaon
2. Geng access to CTIS – registraons
2.1. User self-registraon
In order to access the CTIS Sponsor workspace, a user needs to have an acve EMA Account.
If the user already uses other EMA applicaons (e.g. Eudralink, SPOR, IRIS, EudraVigilance, OMS), the
user already has an EMA Account and could access the CTIS Sponsor workspace using his/her exisng
EMA Account credenals.
If the user does not have an acve EMA Account, (s)he needs to create one, by self-registraon.
The self-registraon process is described on the EMA Account Management (IAM) homepage and in
Module 03 of the CTIS Training Material Catalogue.
References
Locaon (area or document)
EMA Account Management homepage
hps://register.ema.europa.eu/identyiq/home.html
Geng Started with CTIS: Sponsor Quick
guide
hps://www.ema.europa.eu/documents/other/geng-
started-cs-sponsor-quick-guide_en.pdf
CTIS Training Material Module 03 ‘User
Access Management: Quick Guide’
hps://www.ema.europa.eu/en/documents/other/quick-
guide-user-access-management-cs-training-programme-
module-03_en.pdf
CTIS Training Material Module 03 ‘User
Access Management: Frequently Asked
Quesons (FAQs)’
hps://www.ema.europa.eu/en/documents/other/faqs-
user-access-management-cs-training-programme-
module-03_en.pdf
CTIS Training Material Module 03 ‘User
Access Management: Videoclip’
hps://www.youtube.com/watch?v=VSLYv9l-LcE&ab
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2.1.1. Mul-factor authencaon in CTIS
The mul-factor authencaon (MFA) strategy for user logins to CTIS, for both Sponsor and Member
State workspaces, was launched on 1 June 2023. This process reinforced the security of CTIS user
accounts.
For the MFA, it is recommended that each user is equipped with a mobile or an office phone that can be
used for second factor authencaon. Instrucons on seng up MFA for EMA systems are available here
.
Please note that MFA is not acvated in the CTIS Training Environment.
2.2. Organisaon and Sponsor Administrator registraon
2.2.1. Organisaon registraon in OMS
CTIS ulises organisaon data from Organisaon Management Service (OMS). OMS provides a single
source of validated organisaon data that can be used as a reference to support EU regulatory acvies
and business processes. It stores master data comprising organisaon name and locaon address for
organisaons such as markeng authorisaon holders, sponsors, regulatory authories, trial sites and
manufacturers.
If an organisaon has already been successfully registered in OMS, its informaon is public and a user can
search and retrieve its details within CTIS to populate the CTA, submit noficaons, or to use it for other
sponsor-related acvies in CTIS (e.g. populate employer’s details in personal profile).
The possibility to search and retrieve an organisaon in CTIS is available in different areas across CTIS,
and these areas are provided in the following table. Users are recommended to register in OMS the
organisaons in advance to the populaon of their inial CTA.
Table 2.2.1.1. Search and retrieval of an organisaon from OMS in CTIS.
CTIS Locaon/Situaon
OMS data search & retrieval
(through pop-up windows)
Personal profile Update employer informaon
Request a role Add sponsor organisaon
Create new trial Add sponsor organisaon
Part I: ‘Trial details’ ‘Scienfic advice and Paediatric
Invesgaon Plan (PIP)’ secon
Add a Competent Authority
Part I: ‘Sponsor’ secon Add Sponsor Legal contact / Add Third party organisaon
Part II: Trial Sites Add site
Serious Breach noficaon form Add site (where the breach occurred)
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If an organisaon is not yet registered in OMS when starng to use CTIS, it is required first to register the
organisaon via a ‘change request’
1
directly on the OMS portal. OMS can register organisaons included
in a Naonal Business Registry.
It is paramount that requests are supported by valid documentaon to achieve a successful OMS
validaon. Therefore, it is expected that the enty in possession of the valid documentaon proceeds
with the registraon in OMS. Users are urged to access the OMS related training material stored in
OMS
portal document repository and view the document requirements to submit a change request found in
the document ‘E - OMS Change Requests’.
Sponsor organisaons that are not registered in any Naonal Business Registry and cannot provide EMA
with sufficient documentaon for their requests as per document ‘E - OMS Change Requests’, shall aach
to their requests a ‘CT registraon Headed leer’ found as a template in
OMS portal document
repository.
In case the request raised is incorrect, or it is not supported by the appropriate accompanying
documentaon, this will result in the OMS validaon failing, and the organisaon’s details will not be
retrievable in a subsequent search in OMS for that organisaon.
Of note, any party can create a new organisaon record in OMS e.g., for a clinical invesgator site, CROs,
vendors or other facilies etc., that would be required when compleng a CTA or subming a
noficaon in CTIS. Any request should be supported by valid documentaon, as explained above,
otherwise it will not be possible for the sponsor user to search, select and find that organisaon’s details
again if the OMS request has failed (e.g. to support the registraon in OMS of a clinical invesgator
site/facility, a headed leer document signed and dated by a representave of that organisaon, stang
the full company name and address, should be provided).
Sponsors should refer to OMS process to ascertain the validaon melines of change requests to be able
to search and select the organisaon with the address of interest in CTIS. Note that an organisaon can
have several addresses (linked to the same main ORG-ID) and only one can be selected in CTIS.
References
Locaon (area or document)
EMA Organisaon Management Service
(OMS) homepage
hps://www.ema.europa.eu/en/human-
regulatory/research-development/data-medicines-iso-
idmp-standards/spor-master-data/organisaon-
management-service-oms
Submission of change requests in OMS
hps://www.ema.europa.eu/en/human-
regulatory/research-development/data-medicines-iso-
idmp-standards/spor-master-data/organisaon-
management-service-oms#subming-change-
requests-secon
Industry Webinar Introducon to OMS
services and acvies
hps://www.youtube.com/watch?v=fxMpsgDnWZY&ab
1
The term ‘change request’ for OMS refers to an addion of new or modificaon of exisng records in OMS.
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2.2.2. Organisaon registraon locally in CTIS for use in CTIS
If users do not retrieve an organisaon further to a search in OMS or in CTIS, they can opt to create the
site in CTIS by clicking the buon ‘New Organisaon’, which will now appear enabled. It should be noted
that this funconality is only available for:
• Part I Sponsor secon – Third-party organisaons
• Part II – Trial sites
• Serious Breach noficaons – Details of the site where the serious breach occurred
• Third Country Inspectorate Inspecon – Third country inspecon site
• MS Inspecons – Inspected site
Organisaons that are created locally in CTIS are not validated by EMA. But users are encouraged to keep
in mind the OMS data quality standard set when they create their organisaons in CTIS, reducing then
the possibility to receive RFIs from assessing authories regarding inaccurate data.
Once users iniate the registraon of an organisaon in CTIS, it is in DRAFT status and the dra
organisaon is visible only within the scope of the dra CTA or dra noficaon, i.e. it does appear when
other sponsors (or even the same sponsors who created the organisaon) search in CTIS.
Once the CTA or noficaon, which contains this organisaon registered in CTIS (sll in DRAFT status) is
submied, the locally registered organisaon in CTIS changes from DRAFT status to ACTIVE status. This
implies that the organisaon is now searchable by other users, including users from different
organisaons such as other sponsors. Organisaons registered locally in CTIS with ACTIVE status are no
longer editable (to edit details of the organisaon such as address or name or country etc). If users need
to update the organisaon details whilst responding to an RFI or draing a substanal modificaon, they
will need to remove the inially created organisaon from their applicaon/noficaon and add a new
one by following the process described above.
More details can be found in the Module 03 of the CTIS Training Material Catalogue in
Step-by-step guide
(Create organisaons locally in CTIS).
2.2.3. Sponsor Administrator registraon in EMA Account Management portal for use in CTIS
The CTIS Sponsor Administrator is a high-level administrator role requested and managed through the
EMA Account Management portal.
A sponsor administrator is required to iniate the management of users in the sponsor workspace.
The request for the Sponsor Administrator role is submied by the user that will become the Sponsor
Administrator for an organisaon with a specific organisaon idenfier (ORG-ID) and will be handled via
EMA Account Management portal.
The registraon process for the Sponsor Administrator (‘Sponsor Admin’) role, via the EMA Account
Management portal, started on 1 September 2021 and needs to be supported by an appropriate
‘Affiliaon leer’ submied to EMA at the me of registraon. There is also the alternave route of the
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External Organisaon Administrator, described in the EMA Account Management portal (last link in
‘References’ table below).
It should be noted that the appointment of the high-level administrator for a sponsor, namely the
Sponsor Admin for an organisaon, is processed in IAM based on the organisaon idenfier (Org-ID).
If different Org-IDs for the same organisaon exist, they cannot be grouped together in the request to
appoint a Sponsor Admin for the purpose of using CTIS, and therefore, each request should be raised
individually. However, the same affiliaon leer can be used and aached for each individual request.
Once the Sponsor Administrator role is assigned to one person by EMA (or by the External Organisaon
Administrator of the organisaon) on the basis of the validaon of the request, the Sponsor
Administrator (or the External Organisaon Admin) receives automated e-mail noficaons of requests
from other users wishing to become Sponsor Administrators for the same organisaon. The first Sponsor
Admin (or the External Organisaon Admin) manages such requests in the EMA account Management
portal.
EMA does not handle these requests once the first Sponsor Administrator (or an External Organisaon
Administrator) has been assigned by EMA. The necessity of an ‘Affiliaon leer’, or any other supporng
documentaon, for these subsequent requests are decided by each organisaon internally
2
.
Explanatory training material is available in the CTIS Training Material Catalogue, in Module 07
‘Management of registered users and Role matrix’ and on the EMA Account Management homepage.
References
Locaon (area or document)
EMA Account Management homepage
hps://register.ema.europa.eu/identyiq/home.ht
ml
Affiliaon leer template
hps://register.ema.europa.eu/identyiq/help/affili
aon template.docx
CTIS Training Material Module 07 ‘Management
of registered users and Role matrix: Step-by-
step Quick Guide (high level Admin)’
hps://www.ema.europa.eu/en/documents/other/
step-step-guide-high-level-cs-administrator-
management-roles-permissions-cs-training-
programme_en.pdf
CTIS Training Material Module 07 ‘Management
of registered users and Role matrix: Frequently
Asked Quesons (FAQs) – specific ones’
hps://www.ema.europa.eu/en/documents/other/
faqs-management-roles-permissions-cs-training-
programme-module-07_en.pdf
CTIS Training Material Module 03 ‘Frequently
Asked Quesons (FAQs)’
hps://www.ema.europa.eu/documents/other/faq
s-user-access-management-cs-training-
programme-module-03_en.pdf
CTIS Training Material Module 07 ‘How to
request roles and how to assign roles to
registered users in CTIS’ and ‘How to amend
hps://www.youtube.com/watch?v=CBLVMFC4JeA
hps://www.youtube.com/watch?v=1CUyQcICyl8
2
However, proof of affiliaon leer is not required once an External Organisaon Administrator has been validated in EMA Account Management for a
certain organisaon.
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and revoke roles of registered users in CTIS’
Videoclips
External Organisaon Administrator
hps://register.ema.europa.eu/identyiq/help/user
admin.html#OrganisaonAdmin
3. Management of users and organisaons in CTIS
3.1. Key user management concepts in CTIS
There are two approaches to user management in CTIS: the organisaon-centric approach and the trial-
centric approach.
These approaches have been designed according to the needs of the different types of sponsor
organisaons that will use CTIS.
Before using CTIS, sponsors should carefully consider which user management approach best fits their
organisaon.
A full descripon of each of these approaches, including their advantages and disadvantages, are
explained in the reference documents listed below, as well as in Secon 3.3 (‘Organisaon-centric
approach - Sponsor Administrator’) and secon 3.4. (‘Trial-centric approach – Clinical Trial
Administrator’) of this document. Based upon the current experience with user administraon for non-
commercial sponsors, we recommend considering following the organisaon centric approach and to
request the help of your Clinical Trial Centre for CTIS operaons and CTR compliance.
References
Locaon (area or document)
CTIS Training Material Module 07 ‘Creang a
clinical trial: Clinical trial centric approach vs
organisaon centric approach’ (Video)
hps://www.youtube.com/watch?v=hfzZxwX2W-Y
CTIS Training Material Module 07 ‘Management
of registered users and role matrix’
hps://www.ema.europa.eu/en/learning-
module/management-roles/story.html
3.2. User roles concept in CTIS
In order to perform an acon in CTIS, such as preparing, subming or viewing a CTA, noficaons,
summary of results or clinical study reports, a user must be assigned with a CTIS user role to obtain
appropriate permissions.
Up to 18 sponsor user roles are foreseen for CTIS. The profile of a user can be built with a combinaon of
different roles, to allow the user to complete various acons in CTIS. Users with administrator roles (high-
level administrator, clinical trial administrator) can assign roles to other users, enabling them to perform
acons.
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Each role in CTIS comes with a specific set of permissions, which are predefined levels of acons that
users can perform on data and documents stored in CTIS. These permissions are at user management
level (reserved for administrator user roles) and access level, ranging from viewing to creang, preparing
and subming clinical trial informaon in CTIS.
EMA has prepared a document to describe the concept of user roles and permissions in detail, a Role
Matrix, which outlines the permissions linked to each user role, and a summary of roles document. These
documents can be found at the links below.
References
Locaon (area or document)
CTIS Training Material Module 07
‘Management of registered users and role
matrix’
hps://www.ema.europa.eu/en/learning-
module/management-roles/story.html
Sponsors Business Processes and Roles
hps://www.ema.europa.eu/documents/other/sponsors-
business-processes-roles-cs-training-programme-
module-07_en.pdf
Sponsor workspace: summary of role
permissions - Sponsor Workspace Roles -
permission matrix summary
hps://www.ema.europa.eu/documents/other/roles-
permissions-matrix-summary-sponsors-workspace-cs-
training-programme-module-07_en.pdf
3.3. Organisaon-centric approach - Sponsor Administrator
The organisaon-centric approach is one of two user management approaches in CTIS that can be used
by sponsors of a clinical trial. It is intended to serve the needs of organisaons and/or sponsors that run
mulple clinical trials.
The organisaon-centric approach means that user management is done at organisaon level.
Under the organisaon-centric approach, the sponsor needs to appoint a high-level administrator
(Sponsor Administrator). The Sponsor Administrator must be registered in EMA Account Management
plaorm (see Secon 2.2.2 on ‘Sponsor Administrator registraon in EMA Account Management portal
for use in CTIS’).
Before a user can register as a high-level administrator for a sponsor organisaon, this organisaon needs
to be registered with the Organisaon Management Service (OMS); see Secon 2.2.1 on ‘Organisaon
registraon in OMS for use in CTIS’.
Management of users within the organisaon is done at the organisaon level with a top-down model.
Once appointed, sponsor administrators can assign medium-level administrator (i.e. clinical trial
administrator) and business roles to users in CTIS to perform user management or business acvies. In
the organisaon-centric approach, users become affiliated to the organisaon (in parcular, the user
becomes affiliated to the ORG-ID number as registered in OMS) of the sponsor administrator in CTIS
when they are assigned with a role by this administrator.
The organisaon-centric approach is parcularly useful for organisaons that (will) conduct trials on a
regular basis, even if the frequency is low. The advantages of this approach are that it allows the
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management of access and roles across trials within one organisaon thus, supporng data quality and
integrity through a top-down validaon process, as well as ensuring security as a user can only create a
new CTA for that organisaon-ID, as registered in OMS, if it has been previously assigned the clinical trial
administrator (CT Administrator) role by the sponsor administrator.
Note: a user needs to be given the role of CT Administrator with scope ‘all trials’ in order to be able to
create one or more new CTAs, copy or resubmit a trial for that organisaon-ID.
Addional informaon is published on the EMA Corporate website under the Training Programme - User
access management (Module 03).
References
Locaon (area or document)
EMA Account Management homepage
hps://register.ema.europa.eu/identyiq/home.html
CTIS Training Material Module 03 ‘User
access management: User Quick Guide’
hps://www.ema.europa.eu/en/documents/other/quick-
guide-user-access-management-cs-training-programme-
module-03_en.pdf
3.4. Trial-centric approach – Clinical Trial Administrator
The trial-centric approach is one of two user management approaches in CTIS. A user is automacally
guided to use this approach in CTIS only in the case a sponsor administrator has not been registered and
appointed in the EMA account management system for a specific organisaon.
In this approach, when the user iniates the creaon of a new CTA, the system checks if a sponsor
administrator has been appointed for the sponsor organisaon selected for that inial CTA . If that is not
the case, the user will be able to proceed becoming the clinical trial administrator for that parcular trial.
Further allocaon of other CT Administrator or business roles to users is then done at trial level. The
clinical trial administrator can manage users only for the trial(s) of his/her concern and can perform all
sponsor business acvies in CTIS related only to that parcular trial(s).
In the trial-centric approach, users follow a boom-up model that supports an easy way of subming a
limited number of CTAs and straighorward management of a small number of users at trial level, not
organisaon level.
This approach is intended to serve the needs of small organisaons and specifically academic sponsors,
which may iniate trials on an ad hoc basis. It allows for the management of a smaller number of users
and one or very limited numbers of clinical trials. This allows a faster process (no need for registraon of
a high-level sponsor administrator) when subming a first inial, and subsequent applicaons, as
applicable. However, it is less secure as any user can, potenally, create a trial on behalf of a sponsor
organizaon that has not previously registered a sponsor administrator. Moreover, no individual user will
have a centralised oversight of the trials being conducted for that sponsor organizaon nor the users
involved.
Addional informaon is published on the EMA corporate website under the Training Programme - User
access management (Module 03).
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References
Locaon (area or document)
CTIS Training Material Module 03 ‘User access
management: User Quick Guide’
hps://www.ema.europa.eu/en/documents/other/q
uick-guide-user-access-management-cs-training-
programme-module-03_en.pdf
3.5. Markeng Authorisaon Holder (MAH) group of users
A MAH Administrator role is also available to support the submission of clinical study reports into CTIS
when a trial has been included in a markeng authorisaon applicaon. The registraon process for MAH
Administrator takes place via CTIS Service Desk, with the submission of a valid cover leer, including the
required informaon. More details on this process can be found in the CTIS Training Material Module 13
‘Clinical study reports submissions’.
References
Locaon (area or document)
CTIS Training Material Module 13 ‘Clinical
study reports submissions’
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-cs-online-
modular-training-programme#sponsor-workspace-
secon
3.6. CTIS user personas and organisaon models
Sponsors have various processes, structures and partnerships for managing clinical trials. In order to
facilitate the compleon of processes in CTIS, sponsors must understand the CTIS User Management
funconalies and how to best make use of these funconalies in their organisaonal environment.
Sponsors also need to understand user roles so that they can ensure that they have the correct
confidenality agreements in place.
To assist sponsors in understanding the CTIS User Management funconalies and how to organise in
CTIS, EMA has published CTIS user personas linked to CTIS user roles and permissions, and example
sponsor organisaon models in CTIS.
References
Locaon (area or document)
CTIS sponsor user personas
hps://www.ema.europa.eu/documents/other/clinic
al-trial-informaon-system-cs-sponsor-user-
personas_en.pdf
Principles for sponsor organisaon modelling
in CTIS
hps://www.ema.europa.eu/documents/other/princ
iples-sponsor-organisaon-modelling-cs_en.pdf
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4. How to get a clinical trial applicaon started in CTIS
4.1. Introducon
Under the organisaon-centric approach, the Sponsor Administrator needs to organise access for the
users based on the interacons that they will have in the system. It is essenal that the permissions
granted, and the scope of the role (trial specific or all trials) are understood to enable the relevant
navigaon, access to data and documents accordingly but also to enable acvies in the system as
required. Refer to Secons 2. and 3.
In case, the trial centric approach is selected, the CT administrator needs to organise user access based
on the interacons users should have in the system to fulfil the sponsor’s obligaons.
It is important that in advance of any interacons with the system, sponsor users get familiarised with the
use and navigaon in CTIS. It is recommended that inially a small team of users is assigned to navigate
to perform acvies in CTIS for a given trial/applicaon. These users are strongly recommended to get
experience first on the CTIS Training environment (see Secon 10.5. ).
This approach enables familiarisaon with CTIS and facilitates readiness and preparaon of dossier to
ease member state assessment.
To create and prepare any type of clinical trial applicaons in CTIS, several training materials including
step-by-step, e-learning and videos can be consulted (module 10). Secon 4.2 presents the various
subsecons of the clinical trial applicaon tab as they need to be completed and their corresponding
dedicated training materials. An overview of the documents available to be submied in CTIS is also
presented. Secon 4.3 presents the navigaon of the evaluaon tab and the melines that provide
informaon on the assessment acvies once the clinical trial applicaon has been submied. All
melines due dates in CTIS follow Central European Time (CET), regardless of the seasons of the year.
4.2. Draing of the clinical trial applicaon dossier
Table 4.2.1. Create a CTA
Step process 1: Create a CTA
Locaon (area or document)
Create a clinical trial applicaon (Step-by-
step guide)
hps://www.ema.europa.eu/en/documents/other/ste
p-step-guide-create-submit-withdraw-clinical-trial-
applicaon-nonsubstanal-modificaons-cs_en.pdf
Create a clinical trial applicaon (E-learning)
hps://www.ema.europa.eu/en/learning-
module/create-ct-applicaon/story.html
Table 4.2.2. Populate MSC & Form secons
Step process 2: Populate MSC & Form secons
Locaon (area or document)
Complete the MSC and Form secons (video)
hps://www.youtube.com/watch?v=1du3VUq4K5g
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Table 4.2.3. Populate Part I secon
Step Process 3: Populate Part I secon
Locaon (area or document)
Complete the Part I secon (video)
hps://www.youtube.com/watch?v=piRl9ZGTe-Y
Fill in the trial details of Part I secon (video)
hps://www.youtube.com/watch?v=q2Qn6p9VnXs
Complete sub secon Sponsor details (video)
hps://www.youtube.com/watch?v=4HtR_Xtn7pc
Complete sub secon Product details (video)
hps://www.youtube.com/watch?v=e-JTvFoBlCs
Sponsor Handbook v.3.0.3: Secon 6 ‘Product
management in CTIS’
Table 4.2.4. Populate Part II secon
Step Process 4: Populate Part II secon
Locaon (area or document)
Complete Part II secon (video)
hps://www.youtube.com/watch?v=jmylMwZFroc
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Table 4.2.5. Overview of documents and data available to be submied in CTIS for an inial CTA.
CTA tabs
subsecons
CTA placeholders
Document types available
for upload
3
,
4
,
5
Note
Form
Cover leer
Cover leer
Refer to the EudraLex
vol.10 CTR Q&As and CTR
document on content
requirements
Proof of payment
Proof of payment
Where applicable
Compliance with regulaon
Compliance with Regulaon
(EU) 2016/679
Trial category
Complete the relevant data
field, see secon 7.2.
MSC
Member states concerned
Indicate the proposed RMS
Part I
Trial specific informaon
(Part I) – Trial details
Trial idenfiers
Provide idenfiers of the
trial
Trial informaon
Low Intervenon
jusficaon
Protocol informaon
• Protocol
• Protocol synopsis
• DSMB
• Study design
Scienfic advice and
Paediatric Invesgaon Plan
(PIP)
•
Summary of scienfic
advice
• Scienfic advice–Quality
• PIP opinion
Associated clinical trials
Sponsor agreement
3
Include a document ‘not for publicaon’ alongside the document ‘for publicaon’ is needed.
4
Include translaons if required; refer to the CTR Q&As (Eudralex vol.10 chapter V)
5
Only include signed documents if required as per the CTR Q&As (Eudralex vol.10 chapter V)
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CTA tabs
subsecons
CTA placeholders
Document types available
for upload
3
,
4
,
5
Note
References
Provide the PMID
6
number
if available
Countries outside the EEA
Add non-EEA country if
applicable
Trial specific informaon
(Part I) – Sponsor details
Refer to the Eudralex
vol.10 CTR Q&As on
content requirements
Trial specific informaon
(Part I) – Product details
Reference to content (CTA)
Role: test
• IB or SmPC
• IMPD safety and efficacy
• IMPD Quality
Include comparator,
placebo or auxiliary
product as necessary
Content labelling
Content labelling of IMP
Part II
Trial site
Recruitment arrangements
Recruitment arrangements
Refer to ‘Part II applicaon
document templates’,
available under chapter I of
Eudralex vol.10
Subject informaon and
informed consent form
Subject informaon and
informed consent form
Refer to naonal
requirements
Suitability of the
invesgator
• Invesgator CV
• Suitability of the
invesgator
• Declaraon of Interest
Suitability of the facilies
Suitability of the facilies
If signed, consider
redacon
6
PubMed Idenfier
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CTA tabs
subsecons
CTA placeholders
Document types available
for upload
3
,
4
,
5
Note
Proof of insurance cover or
indemnificaon
Proof of insurance cover or
indemnificaon
Only the cerficate of
insurance (avoid adding
CCI in these documents)
Financial and other
arrangements
Financial and other
arrangements
Naonal requirements, e.g.
some MS require signed
Clinical Trial agreements
Compliance with naonal
requirements on Data
Protecon
Compliance with naonal
requirements on Data
Protecon
Oponal only, required by
some countries
Compliance with use of
Biological samples
Compliance with use of
Biological samples
Oponal, only if biological
samples are collected
References
Locaon (area or document)
Technical requirements for opmal use of CTIS
hps://www.ema.europa.eu/en/documents/other/
clinical-trials-informaon-system-cs-technical-
requirements-opmal-use_en.pdf
CTIS training material module 10 ‘Create,
submit, and withdraw a clinical trial'
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-cs-online-
modular-training-programme#sponsor-workspace-
secon
Addional reference materials for CTIS users
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-training-
support#addional-reference-materials-for-cs-
users-secon
CTIS Structured data form Instrucons - inial
applicaon, addional MSC, substanal and
non-substanal modificaons
hps://www.ema.europa.eu/documents/template-
form/clinical-trial-informaon-system-cs-
structured-data-form-inial-applicaon-addional-
member_en.xlsx
List of data and documents requested as a
minimum in CTIS to proceed with submission of
the different applicaon types
hps://www.ema.europa.eu/en/documents/other/
checklist-required-fields-applicaon-type-cs-
training-programme-module-10_en.pdf
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4.3. Clinical Trial Applicaon under evaluaon
Table 4.3.1. Evaluaon Tab
The Evaluaon tab includes several subsecons presenng the assessment overview for the validaon,
the Part I and the Part II, and the decision for each MSC. The validaon, Part I, and Part II secons include
an RFI and a conclusion subsecon.
Evaluaon tab
Locaon (area or document)
View the tabs for validaon, Part I conclusion,
Part II conclusion, and decision of a clinical
trial applicaon
Search, view, and download informaon on a
clinical trial
hps://www.ema.europa.eu/en/documents/other/q
uick-guide-how-search-view-download-clinical-trial-
clinical-trial-applicaon-sponsors-cs_en.pdf
Access, view, and respond to an RFI
hps://www.youtube.com/watch?v=vbQVkYi3pGI
The metables give an overview and progress on the assessment of the parcular clinical trial
applicaon.
Table 4.3.2. Timetables and Timelines for CTA Assessment
CTA Assessment: Timetables and Timelines
Locaon (area or document)
View Timetable (video)
hps://www.youtube.com/watch?v=HN7zcQW81P0
CTIS Evaluaon melines
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-training-
support#evaluaon-melines-secon
4.4. Clinical Trial Applicaon aer decision
Once the clinical trial applicaon has been authorised, the conclusion to the validaon and the
assessment phases can be viewed in the evaluaon tab. At the boom of the page, in the assessment
overview table, the informaon is recorded for each member state and includes each MSC’s respecve
decision.
In the event that a MSC would have disagreed to the conclusion ‘acceptable’ or ‘acceptable with
condions’ to Part I, this informaon would be also recorded in that secon.
All documents and data authorised for the trial, as a result of the authorisaon of the latest applicaon,
can be consulted in the tab ‘Full Trial Informaon’.
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5. Transion from Direcve to Clinical Trial Regulaon
5.1. Transion period
There is a 3-year transion period that started on the CTIS go-live date.
Year 1 (31 January 2022 to 30 January 2023):
During the first year aer CTIS go-live, sponsors could choose whether to apply for a new CTA under the
Clinical Trial Direcve (CTD: Direcve 2001/20/EC), or to apply under the new legislaon, the Clinical Trial
Regulaon (EU) No 536/2014, using CTIS.
Member States were ready to use CTIS and accept applicaons under the new legislaon (CTR) from day
1 of CTIS go-live.
Years 2 and 3 (31 January 2023 to 30 January 2025):
From 31 January 2023, all new CTAs must be submied under the new legislaon (CTR) using CTIS.
Submission of new CTAs under the CTD in EudraCT is no longer be available for new CTAs. The addion of
new member states is also no longer be possible under the CTD as from 31 January 2023. Trials under the
CTD must first be transioned, and then an Addional Member Stated Concerned Applicaon can be
submied only once the clinical trial dossier has been updated through a substanal modificaon using
CTIS.
Figure 5.1.1. Schemac representaon of the Clinical Trial Regulaon transion period.
CTAs that were submied under the old legislaon (CTD), ulising EudraCT, prior to 30 January 2023, will
be able to connue to run unl compleon under that Direcve unl 30 January 2025. Processes will
remain unchanged, and sponsors will therefore be able to submit substanal amendments and end of
trial noficaons as needed under the Direcve. EudraCT will remain operaonal throughout the
transion period to enable these trials to connue.
As from 31 January 2025, clinical trials authorised under the CTD must either have ended in the EU/EEA or
have been transioned. They cannot connue operang under the old legislaon ulising EudraCT beyond
the end of the 3-year transion period (30 January 2025). Thus, if sponsors are running trials that they
expect to connue in EU/EEA beyond 30 January 2025, sponsors need to transion them to the CTR before
the transion period expires.
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Figure 5.1.2. Schemac representaon of the Clinical Trial Regulaon transion period from 31 January 2023.
EudraCT will remain acve beyond the end of the transion period for sponsors to nofy global end of the
trial and submission of summary results of trials completed under the Direcve.
Transion applicaons can be submied at any me during the 3-year transion period and sponsors are
urged to ensure that they complete the process early enough in the transion period to ensure connuity
of the clinical trial beyond 30 January 2025, taking account of statutory holidays and the two-week winter
clock stop.
References
Locaon (area or document)
Link to EudraLex - Volume 10 - Clinical trials
guidelines - Set of documents applicable to
clinical trials authorised under Regulaon EU No
536/2014
7
hps://ec.europa.eu/health/documents/eudral
ex/vol-10_en#fragment1
Guidance for the Transion of clinical trials from
the Clinical Trials Direcve to the Clinical Trials
Regulaon
hps://health.ec.europa.eu/document/downlo
ad/10c83e6b-2587-420d-9204-
d49c2f75f476_en?filename=transion_ct_dir-
reg_guidance_en.pdf
CTCG Best Pracce Guide for sponsors of
mulnaonal clinical trials with different Part I
document versions approved in different Member
States under the Direcve 2001/20/EC that will
transion to the Regulaon (EU) No. 536/2014
hps://www.hma.eu/fileadmin/dateien/HMA_j
oint/00-_About_HMA/03-
Working_Groups/CTCG/2024_03_CTCG_Best_Pr
acce_Guide_for_sponsors.pdf
Annex Cover Leer Template Declaraon vs. 4.0
hps://www.hma.eu/fileadmin/dateien/HMA_j
oint/00-_About_HMA/03-
Working_Groups/CTCG/2024_03_CTCG_Annex_
cover_leer_template_-
7
The latest published European Commission Clinical Trials Regulaon No 536/2014 Q&A document can be found under the ‘Set of documents applicable
to clinical trials authorised under Regulaon EU No 536/2014’ secon.
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_CTCG_Best_Pracce_Guide_for_sponsors_on_
transion_vs4.docx
5.2. Points to consider on transional arrangements
Some aspects have been included here of what the sponsor should consider when defining a submission
strategy for CTIS during the transion period.
5.2.1. What trials should not be transioned
• Trials that have already ended or will end before the end of the transion period in the EU/EEA
should not be transioned.
• If an end of trial noficaon has been submied in all EU/EEA member states, but the global end of
the trial has not been nofied, the trial should not need to be transioned. Global end of the trial
and trial summary results should be posted via EudraCT under the Direcve.
• Trials that are old and started prior to the Direcve 2001/20/EC coming into applicaon do not
benefit from the transion process. If they are truly intervenonal and need to connue to run aer
the end of the CTR transion period, then a new CTA under the CTR needs to be submied.
• Paediatric trials that are being conducted enrely outside the EU/EEA but for which a EudraCT
number has been created should also not be transioned.
5.2.2. Can the trial be transioned?
Only trials submied under the CTD and likely to be ongoing beyond 30 January 2025 need to be
transioned if they meet these criteria:
• are intervenonal clinical trials in humans;
• involve at least one acve site in the EU/EEA where the trial is sll ongoing;
• there are no substanal amendments ongoing in any Member State Concerned (MSC) under the
Direcve.
Details of the requirements for transioning of mono-naonal and mul-naonal trials are provided in
the EudraLex Volume 10 Q&A menoned in the References table above.
General consideraons:
Sponsors need to ensure that all current approved documents under the Direcve are available in
electronic format in compliance with CTIS upload requirements (see secon 7.1.3. ‘Data fields and
document specificaons’).
Retrospecve documents do not need to be submied to CTIS (e.g. earlier versions of IBs or Protocols
that have been superseded under the CTD). Only current approved versions should be included in the
transion applicaon.
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Where a mandatory document is expected to be uploaded into the CTIS that does not exist for the
transioning trial (e.g. site suitability documentaon), then a blank document is expected to be uploaded
with a comment that the document does not apply and it has been provided to allow transion from the
CTD to the CTR Regulaon.
When compleng the CTA, and providing the CT data and documents in CTIS, consideraon should be
given to the transparency requirements of the CTR, including the need to remove personal data from
submied documentaon, if applicable: see chapter 8. on transparency of data.
Mono-naonal trials:
The trial is transioned from the CTD to the CTR by subming a new applicaon in CTIS that reflects the
content of the dossier that is currently approved and has been assessed by the MSC. Documentaon
required is specified in the queson 9 to the
Guidance for the Transion of clinical trials from the Clinical Trials
Direcve to the Clinical Trials Regulaon the available in the EudraLex Volume 10
Mul-naonal trials:
Mul-naonal clinical trials (trials conducted under the same EudraCT number in different Member
States) should be transioned as a single mul-country CTA under the CTR, ulising a harmonised or at
least consolidated protocol Sponsors may need to consider harmonising the protocol by substanal
amendments under the CTD before they transion them as one trial under CTR with one EU Clinical Trial
number Consolidaon of a protocol, to reflect only what is already approved in each MSC prior to
submission of a transion applicaon, does not require prior approval via submission of a substanal
amendment under the Direcve since no changes to the protocol content are made during the
consolidaon process.
In addion, if a sponsor intends to transion a mul-naonal clinical trial as a mul-country CTA under
the CTR, only data field informaon and documents for the MSCs where the trial is sll ongoing need to
be entered in CTIS.
The trial is transioned from the Direcve to the Regulaon by subming a new applicaon in CTIS that
reflects the dossier that is currently approved and has been assessed by all the MSCs. If the protocol is
not consolidated, the sponsor should first submit a substanal amendment under the Direcve in order
to align and obtain a harmonised protocol authorised by all Member States before subming a transion
applicaon under the CTR.
Alternavely, for trials where full harmonizaon of the protocol to be submied in the Part I of the
applicaon cannot be achieved due to different naonal requirements, a sponsor needs to prepare a
consolidated protocol, reflecng the common core provisions and capturing the minor differences as
regards the naonally authorised trials (see Reference table above for CTCG’s ‘Best Pracce Guide for
sponsors of mulnaonal clinical trials’). The consolidated protocol must correspond to what is
authorised in each of the Member States concerned.
For VHP trials being transioned, the sponsor should propose as the RMS the country that acted as the
VHP Reference MS.
For more informaon regarding the condions for the transion of mul-naonal trials refer to the
queson 10 to the Guidance for the Transion of clinical trials from the Clinical Trials Direcve to the
Clinical Trials Regulaon the available in EudraLex Volume 10.
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5.2.3. What are the assessment melines of transional trials
In CTIS aer submission of the dossier, the assessment workflow is triggered and the MSC need to select
the RMS in the event of mul-naonal trials. The validaon, assessment Part I, Part II and decision
milestones are triggered in the system with the need for MSC to proacvely record their conclusions and
decisions. Therefore, transioning a trial from the Direcve to the Regulaon can take up to a period of
60 days.
It is unlikely that RFI are raised for transional trials unless the documentaon submied does not
correspond with the documents approved under the CTD. In such a case, the melines would be
extended by 15 days in the validaon or 31 days in the assessment phase.
5.3. How to create a transional trial in CTIS
To transion a trial from EudraCT to CTIS, sponsors need to submit an inial CTA marked as a transional
trial. On how to mark their inial CTA as transional trial, users may follow the instrucons of the Quick
Guide of CTIS Training Module 23 that is dedicated to transional trials. Once an inial trial is marked as
transional, addional fields will appear in the applicaon dossier, allowing users to add in their
transional trial the corresponding EudraCT trial number. If sponsors create the trial without marking it
as transional, they cannot correct it at a later stage. They shall create the trial from scratch, marking it
this me as transional.
References
Locaon (area or document)
CTIS Training Material Module 23 –
Transional trials: ‘Quick guide Transional
trials from EudraCT to CTIS’
hps://www.ema.europa.eu/en/documents/other/s
ponsors-guide-transion-trials-eudract-cs-cs-
training-programme-module-23_en.pdf
CTIS Training Material Module 23 –
Transional trials: ‘FAQs Transional trials
from EudraCT to CTIS’
hps://www.ema.europa.eu/en/documents/other/fa
qs-transion-trials-eudract-cs-cs-training-
programme-module-23_en.pdf
5.4. How to manage trials transioned to the CTR in CTIS
Once the trial has a recorded authorisaon in CTIS, all the requirements of the CTR apply from the date
of approval of the transion applicaon under the CTR. The sponsor needs to comply with their CTR
obligaons for the management of the trial and submit noficaon informaon as required. These
include start of trial noficaon and start of recruitment that can have occurred prior to authorisaon,
but could include further events as they are likely to take place.
Also, any changes to the dossier need to be reflected in line with the requirements of the CTR. Therefore,
any subsequent substanal modificaons submied to the MSC need to comply with the requirements of
the CTR.
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6. Product management in CTIS
6.1. Medicinal product registraon in XEVMPD
Before compleng the CTA in CTIS, the sponsors should ensure that the details of the medicinal products
used in the clinical trials are already registered in the eXtended EudraVigilance Medicinal Product
Diconary (XEVMPD). It should be noted that a placebo can be added manually in CTIS directly; sponsors
do not need to submit placebo’s informaon on the XEVMPD.
The diconary includes all medicinal products that are authorised in the EU/EEA and unauthorised
medicinal products (referred to in the XEVMPD as 'development' products) that are associated with
clinical trials. Unauthorised products include those that have not received a markeng authorisaon in
the EU/EEA for the strength and/or pharmaceucal form.
To submit medicinal product data in the XEVMPD, sponsor organisaons must be registered in the
Organisaon Management Service (OMS) and also with EudraVigilance either via Gateway or the
EudraVigilance web applicaon (EVWEB). This applicaon allows registered users to create and send
Extended EudraVigilance Product Report Messages (XEVPRMs), receive XEVPRM acknowledgements,
view medicinal product informaon and perform queries.
Consolidated guidance on the electronic submission of informaon on unauthorised medicinal products
for human use in the XEVMPD is now available on the
'Data submission on invesgaonal medicines:
guidance for clinical trial sponsors' webpage. The guidance was prepared based on the processes already
in use and on informaon available in exisng documentaon.
Some high-level details specific for the registraon of medicinal products in XEVMPD, to then be used in
CTIS, are also presented below to describe the business flow.
The acve substance for the development medicinal product must be available in EMA SMS (Substance
Management Service).
Substance data is entered and maintained in the XEVMPD by the EMA; when substance informaon is
successfully inserted in the XEVMPD, a substance EV Code is generated by the XEVMPD.
To request the addion of new substance informaon, or an amendment of exisng substance
informaon, in the XEVMPD, sponsors should follow the process described in the
'Changes to some
business rules of the eXtended EudraVigilance Medicinal Product Diconary (XEVMPD)' document. EMA
will validate the request and the substance EV Code will be provided to the sponsor via an e-mail
confirmaon from the
EMA ServiceNow within 4 working days.
If a development medicinal product needs to be entered in the diconary by the sponsor, the sponsor
should submit the medicinal product data in the XEVMPD via an XEVPRM with the operaon type 'Insert'.
The medicinal product data must be submied in accordance with the principles described in secon 1
‘Inial submission of a development medicinal product’ of the
'Guidance on the electronic submission of
informaon on invesgaonal medicinal products for human use in the Extended EudraVigilance
medicinal product diconary (XEVMPD)' document. The document also includes informaon on how to
add missing informaon (for example substance or sponsor details) in the XEVMPD. Providing that the
inseron was successful, an EV Code will be assigned to the medicinal product record by the XEVMPD
and sent automacally to the sponsors' sender organisaon ID via an XEVPRM acknowledgement.
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Once the EV Code assigned to the medicinal product record is available in the XEVMPD, the sponsor can
search and retrieve the product details in CTIS. More informaon on associang an unauthorised
medicinal product to a CTA can be found in Secon 6.4. ‘Adding an unauthorised medicinal product in
CTIS’ of this handbook.
When registering medicinal products in the xEVMPD, sponsors are advised to take into account the
publicaon requirements of the relevant CTIS product data fields, as specified in CTIS applicaon fields.
The publicaon modality and melines of product-related fields is defined in Annex I of the Guidance
document on how to approach the protecon of personal data and commercially confidenal
informaon while using the Clinical Trials Informaon System (CTIS). Note that fields taken from xEVMPD
cannot be further amended in CTIS before publicaon. As per the xEVMPD guidance, due to the CTIS
publicaon rules it is recommended that the product name created and entered in xEVMPD does not
include the pharmaceucal form nor the strength of the product.
Training for clinical trial sponsors on how to enter and maintain product informaon into the XEVMPD is
also available (links in the ‘References’ table below).
References
Locaon (area or document)
Data submission on invesgaonal medicines:
guidance for clinical trial sponsors webpage
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-trials/data-
submission-invesgaonal-medicines-guidance-
clinical-trial-sponsors
Guidance on the electronic submission of
informaon on invesgaonal medicinal
products for human use in the Extended
EudraVigilance medicinal product diconary
(XEVMPD)
hps://www.ema.europa.eu/en/documents/other/g
uidance-electronic-submission-informaon-
invesgaonal-medicinal-products-human-use-
extended_en.pdf
Electronic submission of invesgaonal
medicinal product (IMP) data to the Extended
EudraVigilance medicinal product diconary
(XEVMPD) - Frequently asked quesons and
answers (FAQs)
hps://www.ema.europa.eu/en/documents/other/el
ectronic-submission-invesgaonal-medicinal-
product-imp-data-extended-eudravigilance-
medicinal_.pdf
Extended EudraVigilance medicinal product
diconary (XEVMPD) training webpage
hps://www.ema.europa.eu/en/human-
regulatory/post-authorisaon/data-medicines-iso-
idmp-standards/extended-eudravigilance-medicinal-
product-diconary-xevmpd-training
eXtended EudraVigilance Medicinal Product
Diconary (XEVMPD) Data-Entry Tool (EVWEB)
user manual
hps://www.ema.europa.eu/en/documents/other/e
xtended-eudravigilance-medicinal-product-
diconary-xevmpd-data-entry-tool-user-
manual_en.pdf
eXtended EudraVigilance Medicinal Product
Report Message (XEVPRM) Step-by-Step
hps://www.ema.europa.eu/en/documents/other/e
xtended-eudravigilance-medicinal-product-report-
message-step-step-guide-insert-development_en.pdf
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Guide: Insert of a Development Medicinal
Product (DMP)
6.2. Medicinal product in CTIS extracted from XEVMPD
For each trial in CTIS, the sponsor has to associate at least one medicinal product with the role as ‘test’
and populate this informaon in the Part I of an inial CTA.
Other product roles that can be associated to a CTA, as applicable, are: comparator, placebo and auxiliary
medicinal product.
In CTIS, the product informaon (for test product, comparator and auxiliary medicinal product) is
retrieved from the XEVMPD and this is enabled by a search and selecon funconality available for an
authorised product (i.e. a product with a markeng authorisaon in the EU/EEA), an acve substance, an
Anatomical Therapeuc Chemicals (ATC) code and an unauthorised product.
6.3. Adding an authorised medicinal product in CTIS
Medicinal product details in an applicaon form are mandatory. The users can add product details in a
CTA for any product role in the trial (test, comparator, auxiliary) by searching and selecng the product
details from XEVMPD. Only for placebo, the product details can be specified locally in CTIS.
A user can add an authorised product by searching per product details, acve substance, or ATC code, as
applicable.
The following parameters are displayed to a user that can search in XEVMPD, via CTIS, for an authorised
medicinal product:
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Figure 6.3.1. Search for an authorised medicinal product.
Depending on the parameters used to run the search, the user can get a unique search result returned,
or mulple results can be retrieved.
For example, in case of search by EU MP number (i.e. EV Code assigned to a specific medicinal product
record) only one result will be returned.
However, if the user is searching for an acve substance, a pharmaceucal form or strength of a
medicinal product, then mulple results may be returned.
The following parameters are displayed to a user that can search in XEVMPD, via CTIS, for an acve
substance used in an authorised medicinal product:
Figure 6.3.2. Search for an acve substance.
The following parameters are displayed to a user that can search in XE
VMPD, via CTIS, for an ATC code
(level 3, 4 or 5) associated with an authorised product:
Figure 6.3.3. Search for ATC code (level 3, 4 or 5) associated with an authorised medicinal product.
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6.4. Adding an unauthorised medicinal product in CTIS
Unauthorised medicinal product details may contain confidenal informaon and therefore access to
this informaon is restricted.
As explained in Secon 6.1 ‘Medicinal product registraon in XEVMPD’ above, unauthorised products
include those that have not received a markeng authorisaon in the EU/EEA for the strength and/or
pharmaceucal form.
If an acve substance is used in a clinical trial in a new pharmaceucal dose form and/or new strength, a
new development medicinal product must be entered in the XEVMPD by the sponsor organisaon.
If a medicinal product not yet authorised in the EEA is used in a clinical trial for different indicaons
and/or routes of administraon(s), the sponsor can update their exisng development medicinal product
in XEVMPD with the new indicaon/route of administraon.
Registraon of development medicinal products in XEVMPD is independent of the role of the medicinal
product in the clinical trial (i.e. test, comparator etc.) before they can be used to populate dossier part I
of the CTA in CTIS.
Users can retrieve unauthorised products informaon in CTIS only by searching for EU MP number
(medicinal product EV Code) together with the EU substance number (substance EV Code) referenced in
this product in the XEVMPD.
A medicinal product EV Code is a unique number assigned by the XEVMPD to each medicinal product
record successfully inserted in the diconary; it is used to idenfy this medicinal product in the XEVMPD.
It should be noted that both parameters, namely the medicinal product EV Code and the substance EV
Code, are mandatory to run the search in CTIS for unauthorised medicinal product data.
Users have to be cognisant of the required informaon in order to be able to run the search for
development products in XEVMPD and add the product in the CTA of CTIS.
Figure 6.4.1. Search for an unauthorised medicinal product.
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Once the medicinal product of interest is idenfied, the user will see some pre-populated data, as it is
available in the XEVMPD. The strength and pharmaceucal form of the retrieved unauthorised product
are not displayed in the dra CTA dossier Part I. This informaon only becomes visible following the
submission of the applicaon to the MSCs.
More details on the registraon of medicinal products in XEVMPD are provided in Secon 6.1. of this
handbook.
6.5. Medicinal product details in CTIS
For both authorised and unauthorised products, once the desired medicinal product details are retrieved
from XEVMPD, users will see some pre-populated data in CTIS extracted from XEVMPD.
Some addional details, such as the dosage and administraon details, informaon about the medicinal
product, Advance Therapy Medicinal Product (ATMP) details (as applicable), and combinaon with
medical device (as applicable), will have to be populated in CTIS.
In addion to the populaon of the structured data fields in CTIS, for each product, users also have to
provide the documents foreseen in the Clinical Trials Regulaon, as applicable, namely:
• Invesgator Brochure (IB) or the Summary of Product Characteriscs (SmPC);
• Invesgaonal Medicinal Product Dossier (IMPD) Quality;
• Invesgaonal Medicinal Product Dossier (IMPD) Safety and Efficacy;
• GMP documentaon ;
• Content labelling.
Figure 6.5.1. Addional details for medicinal products (Part I).
For more informaon, see also training module 10.
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References
Locaon (area or document)
CTIS Training Material Module 10 ‘Create, submit
and withdraw a clinical trial’
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-cs-online-
modular-training-programme#sponsor-
workspace-secon
‘How to submit an inial CTA in the CTIS Sponsor
workspace – Fill in the Part I secon’ (video) -
CTIS Training Material Module 10
hps://www.youtube.com/watch?v=e-JTvFoBlCs
7. Data, documentaon and processes
7.1. Clinical Trial Applicaon (CTA) and Noficaon Forms
This secon intends to provide informaon on the data fields and documents that sponsors need to
complete, as applicable, in the context of clinical trial applicaons and noficaons to be submied to
CTIS. These forms provide an overview of the data fields to be completed, and documents to be provided
with the aim to help sponsors prepare in advance, the informaon required for the submission of an
inial CTA, adding Member State Concerned applicaon (MSC), Substanal Modificaon (SM), non-
Substanal Modificaon, (non-SM) and noficaons.
The forms referred to in this document include the aributes of the fields (e.g. character limit).
7.1.1. Clinical Trial Applicaon Form overview of the data fields to be completed and documents to be
provided
In the table below, there are references to four Excel documents that list the structured data fields and
the documents to be completed. Each data form addresses the informaon to be provided for any type of
clinical trial applicaon, for a mul-trial substanal modificaon, for the response to a request for
informaon, or for an annual safety report. Each document contains an overview with some relevant
instrucons followed by the list of the data fields to be completed, and documents to be uploaded for
each of the CTIS secons to be prepared for an applicaon: the ‘Form’ secon (4 tabs included, one per
applicaon type), ‘MSC’, ‘Part I’ and ‘Part II’ secons. Moreover, the documents include the different
searches that the sponsor will need to perform through interfaces with other systems.
References
Locaon (area or document)
CTIS structured data form - Applicaons (IN,
AMSC, SM, non-SM)
hps://www.ema.europa.eu/documents/template-
form/cs-structured-data-form-inial-applicaon-
addional-member-state-concerned-
substanal_en.xlsx
Clinical Trials Informaon System (CTIS) - Sponsor Handbook
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CTIS structured data form - Applicaons (Mul
trial SM)
hps://www.ema.europa.eu/documents/template-
form/cs-structured-data-form-mul-trial-
substanal-modificaon_en.xlsx
CTIS structured data form – Requests for
Informaon
hps://www.ema.europa.eu/documents/template-
form/clinical-trial-informaon-system-cs-
structured-data-form-request-informaon-
rfi_en.xlsx
CTIS structured data form – Annual Safety
Report
hps://www.ema.europa.eu/documents/template-
form/clinical-trial-informaon-system-cs-
structured-data-form-annual-safety-report-
asr_en.xlsx
7.1.2. Noficaon and Results: overview of the data fields to be completed and documents to be
provided
The document provided in the table below contains an overview with some relevant instrucons
followed by the overview of the data fields to be completed and to be uploaded for each noficaon
form present in the ‘Noficaons’ secon implemented in the system: start of trial, start of recruitment,
end of recruitment, end of trial, global end of trial, temporary halt, restart of trial, restart of recruitment,
ancipated date of summary of results, unexpected event, serious breach, urgent safety measure and 3
rd
country inspectorate inspecon.
Details on the submission of results documents are also provided.
7.1.3. Data fields and document specificaons
Data fields and document specificaons can be found in the overview secon of each CTIS Structured
data form.
When populang clinical trial informaon in CTIS, the following points should be considered:
7.1.3.1. Limits of characters for free-text fields
Generally, there is a limitaon of 4000 characters for manual data free-text fields. Nevertheless, there are
certain fields following masked values, i.e. PIP number (EMEA-111111-PIP11-11) or fields with smaller
sizes. These are further detailed below.
References
Locaon (area or document)
CTIS structured data form – Noficaons and
Results
hps://www.ema.europa.eu/documents/template-form/cs-
structured-data-form-noficaons_en.xlsx
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Table 7.1.3.1. Number of characters allowed in free text fields in CTIS
Character limitaon
Manual data free-text fields (general rule)
4000
Phone number
15
Protocol code, registry idenfier, designaon number for
orphan drug, CAT reference number
20
Sponsor internal idenfier for unexpected event, serious
breach, urgent safety measure, 3
rd
country inspectorate
inspecon noficaons
20
Registry name, source of monetary support, period tle, arm
tle, sponsor contact person first name and last name, address,
town/city, department, email address, product code, gene of
interest, species origin for the xenogeneic cells, ssue-
engineered xenogeneic species of origin, device trade name,
device nofied body, authorisaon number of manufacturing
and import
100
Primary and secondary end points
500
Descripon of the device
2000
7.1.3.2. Characteriscs of documents upload
Every me users upload a document in CTIS, they should keep in mind that the system allows for storage
of clinical trial data with a maximum size of 220 GB and parcularly permits the following characteriscs
for document upload:
Table 7.1.3.2.1. Characteriscs of document upload in CTIS
Document details
System limitaon
Document file name
100 characters. None of these 7 special characters
(/,.;|) allowed
Document version
10 characters, it can be numerical or not
Document comment free text field
4000 characters
Document file size
50 MB
Maximum number of documents uploaded in
one batch
25
References
Locaon (area or document)
Clinical Trials Informaon System (CTIS) - Sponsor Handbook
EMA/923413/2022
Page 39/62
Guide on CTIS Common features
hps://www.ema.europa.eu/documents/other/clinic
al-trials-informaon-system-cs-common-features-
cs-training-programme-module-02_en.pdf
CTCG’s Best Pracce Guide for Sponsors of
document naming in CTIS
hps://www.hma.eu/fileadmin/dateien/HMA_joint/
00-_About_HMA/03-
Working_Groups/CTCG/2022_09_CTCG_Instrucon_
naming_documents_CTIS_EU_v1.4.pdf
7.2. Trial categorisaon
The trial category is chosen by the sponsor when filling in the ‘form’ secon of the applicaon, based on
definions provided in table V of Annex I of the
Guidance document on how to approach the protecon
of personal data and commercially confidenal informaon while using the CTIS. Refer to CTIS training
Module 10 e-learning presentaon and FAQs for instrucons on how to change the category of a trial.
References
Locaon (area or document)
CTIS Training Material Module 10 ‘Create,
submit and withdraw a clinical trial’
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-cs-online-
modular-training-programme#sponsor-workspace-
secon
7.3. Download opons
There are two ways for downloading CT and CTAs informaon; either from the clinical trial page or from
the clinical trial applicaon(s) of the trial. There is also an opon for CTIS sponsor users to download
search results when searching for clinical trials. The subsecons below provide users with more details
for each download opon.
7.3.1. Clinical trial page
By clicking on the trial number, users open the clinical trial page and may access all related informaon
submied via the applicaon(s) of the trial. On the upper right corner, users can use the download
buon and retrieve a zip file that includes any informaon related to the trial and its applicaons. The
users, once click on the ’Download’ buon, can view a tree menu from which they can select which data
(applicaon dossier –Form, MSC, Part I and Part II– or Evaluaon related) of an applicaon (only one
applicaon per me can be selected) they wish to include in the downloading zip file. Besides applicaon
related data, users may include in the zip file addional informaon regarding Noficaons, Correcve
Measures and Trial results.
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Figure 7.3.1.1: Downloading applicaon data from the clinical trial page.
By using the ‘Download’ buon, users can download the latest version of the structured data and
documents that have been submied per applicaon, provided they have permission to access. They can
access and retrieve previous submied versions of data and documents, by navigang through the CTA
pages, as it is described in the following subsecon (second download opon).
7.3.2. Clinical trial applicaon page
Users can download the documents submied in the various secons of a CTA or a non-SM. They can
download the files from the secons Form (e.g. cover leer), Part I (e.g. protocol) and Part II (e.g.
Recruitment arrangements), using the ‘Download’ icon, found on the right side of each document in its
placeholder. Another way to download the documents from the CTA page is to access them from the ‘All
documents’ le, found in the end of the Part I and II secons and use the respecve PDF icons, found on
the right side of all documents.
Figure 7.3.2.1: Downloading documents from the clinical trial applicaon page (‘All documents’ le).
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Previous versions of the documents (if any) can be downloaded also. You may access them using the
arrow next to ‘Previous versions’ found on the right side of the documents, and then the ‘Download’
icon.
Figure 7.3.2.2. Downloading previous document versions.
Previous versions of the applicaon and their respecve data can be accessed by using the ‘Versions’
buon, found on the upper right corner of the CTA page.
Figure 7.2.3.2.3: Accessing previous versions of a CTA and respecve data.
7.3.3. Clinical Trial Search Download of results
Within the clinical trial overview page, users can use the subtabs to access and view any data and
informaon related to that clinical trial. One of them, labelled ‘Trial results’, contains the placeholders for
summary of results, for lay person summary of results and for related clinical study reports. The
documents aached to those placeholders can be downloaded by users who have the appropriate
access, by using the respecve download icons. Users may download the data related to clinical trial
results by using the download funconality, found on the CT overview page. By clicking the download
buon, found on the upper right corner, users can select which data to include in their download zip file.
Among the main data groupings, users may retrieve the summary of results/Layperson summary.
References
Locaon (area or document)
Clinical Trials Informaon System (CTIS) - Sponsor Handbook
EMA/923413/2022
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Search, view and download informaon on
clinical trials and clinical trial applicaons –
Sponsor users
hps://www.ema.europa.eu/documents/other/step-
step-guide-how-search-view-download-clinical-trial-
clinical-trial-applicaon-authority-cs_en.pdf
7.4. How to apply a change to a clinical trial dossier
7.4.1. During the draing of the inial clinical trial applicaon
Users can edit the applicaon while it is in dra status (i.e. unl it has not been submied). To do so,
users can access the applicaon, from the CT summary page and select the ‘Applicaon ID’ under the
column' ID' of the 'Applicaon and Non-Substanal Modificaon' secon. In order to populate and
upload the relevant informaon and documentaon of an applicaon, users need to click on the padlock
buon of each subsecon. If users need to update documents of an applicaon that is sll in dra, they
need to remove the already aached document and re-upload the new version. They can also edit the
details pertaining to a document. By using the pencil icon, they can make many of the placeholder fields
editable (tle, date, version, comment), and the values populated to them may change. Aerwards, they
can either save the applicaon by clicking on the 'Save' buon in the upper-right corner of the page or, if
all the required fields are completed, submit the applicaon.
References
Locaon (area or document)
‘High-level overview of CTIS workspaces and
common system funconalies’ – CTIS Training
Material Module 02
hps://www.ema.europa.eu/documents/other/clin
ical-trials-informaon-system-cs-common-
features-cs-training-programme-module-
02_en.pdf
7.4.2. Once the inial clinical trial applicaon has been submied
Aer subming the CTA, if users want to update the dossier, they need to create a substanal
modificaon (SM) CTA or a non-substanal modificaon (non-SM), as applicable.
A sponsor can dra and submit a substanal modificaon (SM) or a non-substanal modificaon (non-
SM) to a MSC that does not have an assessment on-going in relaon to this clinical trial (see next table).
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Table 7.4.2.1. Allowed submissions whilst ongoing evaluaon of a CTA.
Submission of an
SM to Part I and Part
II
Submission of an SM
to Part I
Submission of an
SM to Part II
Submission of a
non-SM
Submission of an applicaon
for addional MSC
Inial
applicaon
Not unl a decision
is issued by all MSCs
Not unl a decision is
issued by all MSCs
Not unl a
decision is issued
by all MSCs
Not unl a
decision is
issued by all
MSCs
Not unl a decision is issued
by all MSCs
Evaluang Part
I & Part II SM
applicaon
No No No No No
Evaluang Part
I only SM
applicaon
No No No No No
Evaluang Part
II only SM
applicaon
No No Only to MS
who did not
receive the Part
II SM
No yes
Evaluang add
addional
member state
No No
Only to MS not
evaluang the
applicaon to
add an
addional MSC
No Only to MS
that is not an MSC or
evaluang an assessment to
become an MSC
Substanal modificaon (SM) - request by the sponsor for a change of a CT that is likely to substanally
impact the subjects' safety or rights or the reliability/robustness of the generated data. A substanal
modificaon will be evaluated by the MSC aer it has been submied.
The scope of a substanal modificaon can be Part I only, Part II only, or Part I and Part II. Aer selecng
the scope of the SM, users need to prepare the dossier of the SM, adding required informaon, eding
already submied structured data and updang submied documents. They can update a document,
using the ‘update’ icon. Once click on the update icon, users can aach the new version of the document,
indicang their version reference and adding any relevant comment (if needed) in the dedicated free text
field. They can change the informaon pertaining to the document by using the pencil icon and even
empty the document placeholder, by using the remove icon.
Non-substanal modificaon (non-SM) - any change to the CT dossier that is not likely to substanally
impact the safety or rights of the subjects, or the reliability and robustness of the data generated in the
CT but is relevant for the supervision.
Sponsors can submit non-SMs to keep the informaon of the dossier up to date. Non-SM changes can
also be provided as part of RFI responses where so required.
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A sponsor can only submit an SM or a non-SM to an MSC that does not have an on-going assessment of
an applicaon for the concerned trial. If users need to upload new versions of documents, they can
submit a clean version of the updated document, as well as the original document with tracked changes,
to facilitate the assessment of CTAs.
Table 7.4.2.2. Documents and Structured Data Fields that may be populated with an SM applicaon type.
Form
MSC
Part I
a
Part II
a
Document
for upload
Cover leer
Documents
Documents
Modificaon
descripon
Document
translaons
Document
translaons
Supporng informaon
Proof of payment
Structured
data field
Supporng informaon
Number of
subjects per MSC
Data
Trial site
SM reason
Data translaons
PI contact details
SM scope
Third party enty
Sponsor contact
details
Descripon of
changes
a
If there are any changes to the dossier
Table 7.4.2.2.3. Documents and Structured Data Fields that may be populated with a non-SM applicaon type.
Form
MSC
Part I
a
Part II
a
Document
for upload
Documents
b
Documents
Document
translaons
Document
translaons
Structured
data field
Modificaon
descripon
Number of subjects
per MSC
Data
b
PI contact details
Data translaons
Third party enty
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Form
MSC
Part I
a
Part II
a
Sponsor contact
details
Descripon of
changes
a
If there are any changes to the dossier
b
Document/Field can be modified with limitaons
References
Locaon (area or document)
How to Manage a CT – CTIS Training Material
Module 05 eLearning
Secon 3 - Update and withdraw other types of
noficaons slide
hps://www.ema.europa.eu/en/learning-module/manage-
ct/story.html
hps://www.ema.europa.eu/en/documents/other/s
tep-step-guide-how-search-view-download-clinical-
trial-clinical-trial-applicaon-sponsors-cs_en.pdf
Create, submit and withdraw a CTA – CTIS
Training Material Module 10 eLearning
Secon 2 – Edit and upload
hps://www.ema.europa.eu/en/learning-
module/create-ct-applicaon/story.html
‘Step-by-step guide’ – CTIS Training Material
Module 10
Page 4
hps://www.ema.europa.eu/en/documents/other/s
tep-step-guide-create-submit-withdraw-clinical-trial-
applicaon-nonsubstanal-modificaons-cs_en.pdf
FAQs - CTIS Training Material Module 10
Quesons
1.6. How can users edit a CTA?
2.3. How can users create & edit an Inial CTA?
hps://www.ema.europa.eu/en/documents/other/f
aqs-how-create-submit-withdraw-clinical-trial-
applicaon-cs-training-programme-module-
10_en.pdf
7.5. Handling of Requests for Informaon (RFIs) in CTIS
During the evaluaon of CTAs, MSC have the possibility to require clarificaons from the sponsors by
raising RFIs that should be addressed within the defined melines. It should be noted that failing to
provide responses within the melines will lead to the applicaon being lapsed. It is encouraged that
high-quality dossiers are submied in CTIS with each applicaon, to minimise, where possible, the need
to raise a request for informaon.
RFI can be idenfied by the sponsors via monitoring the noces and alerts tab and the RFI tab in CTIS
Sponsor workspace. For example, in an inial applicaon with Part I and Part II, an RFI can be raised by
the RMS as part of the validaon and assessment of Part I and by each MSC following art II assessment.
RFI can be raised by the RMS and MSC at any point in me during the evaluaon phase. There are no
predicted melines and period of me when RFI can be raised, therefore the sponsors should be vigilant
in monitoring the noces and alerts and the RFI tab.
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RFIs are raised by the RMS/MSC via the consideraons documented in the system as part of the
evaluaon. Documented consideraons are then consolidated by the RMS/MSC
(accepted/merged/adapted or rejected) directly in CTIS and used as the basis for the RFI. RMS/MSC can
also upload documents into CTIS as supporng documentaon to the RFI being raised.
Sponsors have the possibility to download from CTIS the consideraons part of the RFI, as well as any
supporng documentaon, so the RFI can be allocated to relevant team members to be addressed. Users
can also have access to the consideraons in the RFI and any documents directly from CTIS and provide
their reply directly in the system.
In order to address an RFI, the sponsor has to provide a response in the free text displayed aer each
consideraon raised by the RMS/MSC as part of the RFI, that can be complemented by supporng
documents. RFI responses can be saved as dras before submission.
Figure 7.5.1. Response to an RFI consideraon (free text with oponal supporng documents) can be saved as dra before submission.
The sponsor also has the possibility to apply changes to the dossier, both structure data and documents,
depending on the nature of the request raised. If changes to the dossier are applied, the sponsor should
also provide a document containing a descripon of the changes made.
Figure 7.5.2. Changes to a CTA dossier shall be described in a document.
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Previously uploaded documents can be deleted when responding to an RFI or a new version of a
document can be provided (in this case documents will have the same document type, language and
tle). When uploading a new document, the sponsor can specify the date and the version of the file, and
a system version will also be generated sequenally by the system, independently of the sponsor’s
version number.
Figure 7.5.3. An RFI response may include uploading, updang or deleng a document.
Completely new documents can also be submied when replying to an RFI, for the secon of the
applicaon dossier in queson and subject to the RFI.
Access to the RFI, as well as download funconality, depends on the user profile. For example, in Part I
users will only have access to RFI pertaining to Part I of the dossier. Each user can download the RFI and
RFI responses that the user has access to. It should be noted that CT Administrators can assign to
themselves access to Part I and Part II and therefore can have access to all RFIs.
CTIS enables sponsors users to address RFIs simultaneously in the different secons of the CTA, namely a
user can work on Part I RFI at the same me as users working on Part II RFI. Also, Part II RFIs raised by
different MSCs can be addressed simultaneously by different users, if needed. In case of simultaneous
RFIs, users should be mindful to work on their respecve RFIs.
Figure 7.5.4. New CTA dras are created to respond to RFIs simultaneously.
RFI raised in the course of evaluang a Clinical Trial Applicaon (CTA) and the responses provided are
subject to publicaon rules, except for RFI raised for secons of the applicaon that are exempted from
publicaon, such as the quality secon of the dossier or quesons related to quality in general.
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Training material on how to address incoming RFIs related to the evaluaon of a CTA has been published
on the CTIS Training Material Catalogue, Module 11.
As part of an ad hoc assessment, in case of evaluaon of an annual safety report (ASRs), or when a
sponsor opinion needs to be provided in the context of a correcve measure, an RFI can also be raised.
That RFI and its response are exempt from publicaon.
Training material on how to address other types of incoming RFIs (Ad hoc assessment, Correcve
measures) has been published in the CTIS Training Material Catalogue, Modules 04 and 05. Training
material on how to address incoming RFIs related to ASR is published in the CTIS Training Material
Catalogue, Module 18.
References
Locaon (area or document)
CTIS Training Material Module 04 ‘Support
with workload management in the sponsor
workspace: eLearning – RFI secon’
hps://www.ema.europa.eu/en/learning-
module/workload-management-sponsor/story.html
CTIS Training Material Module 04 ‘Support
with workload management in the sponsor
workspace: FAQs – RFI secon’
hps://www.ema.europa.eu/en/documents/other/faqs-
support-workload-management-workspace-cs-
training-programme-module-04_en.pdf
CTIS Training Material Module 04 ‘Support
with workload management in the sponsor
workspace: Videoclip’
hps://www.youtube.com/watch?v=6z-Q6-LK8Ws&ab
CTIS Training Material Module 05 ‘Manage
a CT through CTIS: eLearning – various
references to types of RFI’
hps://www.ema.europa.eu/en/learning-
module/manage-ct/story.html
CTIS Training Material Module 05 ‘Manage
a CT through CTIS: FAQs – various
references to types of RFI’
hps://www.ema.europa.eu/en/documents/other/faqs-
how-manage-ct-cs-training-programme-module-
05_en.pdf
CTIS Training Material Module 11 ‘Respond
to requests for informaon received during
the evaluaon of a clinical trial applicaon:
eLearning’
hps://www.ema.europa.eu/en/learning-
module/respond-to-rfis-cs/story.html
CTIS Training Material Module 11 ‘Respond
to requests for informaon received during
the evaluaon of a clinical trial applicaon:
FAQs’
hps://www.ema.europa.eu/en/documents/other/faqs-
how-respond-requests-informaon-received-during-
evaluaon-clinical-trial-applicaon-cs_en.pdf
CTIS Training Material Module 11 ‘Respond
to requests for informaon received during
the evaluaon of a clinical trial applicaon:
Videoclips’
hps://www.youtube.com/watch?v=vbQVkYi3pGI&ab
hps://www.youtube.com/watch?v=DXrQMStp2a0&ab
hps://www.youtube.com/watch?v=sO8YRSatsDA&ab
CTIS Training Material Module 18 ‘How to
create and submit an annual safety report
hps://www.ema.europa.eu/en/documents/other/step-
step-guide-how-create-submit-annual-safety-report-
respond-related-requests-informaon-cs_en.pdf
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and respond to related requests for
informaon: Step by Step guide’
7.6. Subming the Clinical Study Report (CSR)
Refer to the following Quick guide for informaon on how to submit a CSR.
References
Locaon (area or document)
CTIS Training Material Module 13 ‘Clinical
Study Reports submission Quick guide’
hps://www.ema.europa.eu/en/documents/other/quick-
guide-clinical-study-reports-submission-cs-training-
programme-module-13_en.pdf
8. Data transparency
The clinical trial informaon processes and flows in CTIS start with a CTA submied by the sponsor, or
delegated enes, via CTIS secure domain (see Secon 4. ‘How to get a clinical trial applicaon started in
CTIS ’), to carry out a clinical trial in the EU/EEA, and the corresponding evaluaon performed by the
MSCs.
Following this evaluaon, a decision is issued by each MSC for the CTA, on whether the trial is authorised,
authorised with condions, or not authorised. Aer a decision of any kind has been issued by the MSC,
data and documents submied to CTIS for the trial will be made available to the public as per the
modality and melines defined in the Annex 1 to the
Guidance document on how to approach the
protecon of personal data and commercially confidenal informaon while using the CTIS. The detailed
list of structured data that are, or are not subject to publicaon is specified in the files menoned in
Secon
7.1. of this document (specifically: CTIS applicaon fields and Noficaons and Results). A useful
summary of the rules can be found in the quick user guide. All the menoned reference documents
reflect the current publicaon rules for CTIS, defined in the Revised CTIS transparency rules, and provide
guidance on the protecon of personal data and commercially confidenal informaon (CCI) submied
to the system, in accordance with the requirements of Arcle 81(4) of Regulaon (EU) No 536/2014
(CTR). A Quesons and Answers (Q&A) document on this topic is also available to users, see Q&A o
n the
protecon of Commercially Confidenal Informaon and Personal Data while using CTIS.
The disclosure melines of data in CTIS depend on the trial category, on the populaon age (in case of
category 1 trials) and on the trial phase (in case of category 2 trials that are integrated phase 1 and 2).
The trial category is chosen by the sponsor when filling in the ‘form’ secon of the applicaon, based on
definions provided in Table V of Annex I
. Excepons to these disclosure rules apply to all trials submied
before 18 June 2024 (referred to as ‘historical trials’), which have only their structured data published;
moreover, for those trials documents submied through part I Non-Substanal Modificaons and
addional member state applicaons are also not published: see secon 2.3 of
Guidance document and
table IV of its Annex I.
For all documents that are in scope of publicaon (see Table II of Annex I of the guidance document),
users need to provide a document version ‘for publicaon’, where personal data and CCI should be
properly redacted or should not appear (see chapter 3 and 4 of the
Guidance document). Please note
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that any document inadvertently uploaded ‘for publicaon’ into the relevant CTIS document upload
secons will be published. For example, if an IB is uploaded into the SmPC secon of a Category 2 or 3
trial, the IB will be made public if the sponsor does not correct this oversight before the decision on the
applicaon.
The ability to upload a version ‘not for publicaon’ is made available to the sponsor, in order to provide
informaon on personal data and CCI that are deemed necessary for the assessment by the RMS/MSCs.
It is not expected that such a version is provided by the sponsor for all document types: this need
depends on the document content. This funconality allows the exchange of informaon in the CTIS
secure domain between users with regulated access depending on their profile, while at the same me
protecng personal data and the legimate interest of sponsors for what concerns CCI.
With respect to those documents that are not subject to publicaon, note that quality and non-quality
documents need to be submied as separate documents. This includes the IMPD-Q, Scienfic Advice -
Quality and Quality RFI response documents. CTIS user roles depend on maintaining separate quality
documents to ensure only authorised users can view quality informaon.
References
Locaon (area or document)
Regulaon (EU) No 536/2014 of the European
Parliament and of the Council of 16 April 2014 on
clinical trials on medicinal products for human
use, and repealing Direcve 2001/20/EC
hps://eur-lex.europa.eu/legal-
content/EN/TXT/?uri=celex%3A32014R0536
Revised CTIS transparency rules
hps://www.ema.europa.eu/en/documents/other
/revised-cs-transparency-rules_en.pdf
Guidance document on how to approach the
protecon of personal data and commercially
confidenal informaon while using the Clinical
Trials Informaon System (CTIS)
hps://accelerang-clinical-
trials.europa.eu/document/download/6a0b836f-
4779-4bb9-9584-
1ce504a9ae38_en?filename=guidance-document-
how-approach-protecon-personal-data-
commercially-confidenal-informaon-while_.pdf
Annex I to the Guidance document
hps://accelerang-clinical-
trials.europa.eu/document/download/824905dd-
3033-41e6-a871-
67b20c4f4c94_en?filename=annex-i-guidance-
document-how-approach-protecon-personal-
data-commercially-confidenal_.pdf
Q&A on the protecon of Commercially
Confidenal Informaon and Personal Data while
using CTIS
hps://accelerang-clinical-
trials.europa.eu/document/download/33702a5d-
13be-4c4f-936d-
3627dd73085b_en?filename=ACT%20EU_Q%26A%
20on%20protecon%20of%20Commercially%20Co
nfidenal%20Informaon%20and%20Personal%20
Data%20while%20using%20CTIS_v1.3.pdf
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Quick user guide
hps://accelerang-clinical-
trials.europa.eu/document/download/a101771b-
0be7-492f-b8bd-
7f551b7a7_en?filename=Revised%20CTIS%20tr
ansparency%20rules%2C%20Interim%20period%20
%26%20Historical%20trials_quick%20guide%20for
%20users_1.pdf
CTIS structured data form - Applicaons (IN,
AMSC, SM, non-SM)
hps://www.ema.europa.eu/documents/template-
form/cs-structured-data-form-inial-applicaon-
addional-member-state-concerned-
substanal_en.xlsx
CTIS structured data form – Noficaons and
Results
hps://www.ema.europa.eu/documents/template-
form/cs-structured-data-form-
noficaons_en.xlsx
CTIS Training Material Module 12 ‘Data
protecon: e-learning course’
hps://www.ema.europa.eu/en/learning-
module/data-protecon-cs/story.html
9. Safety reporng obligaons
9.1. Suspected Unexpected Serious Adverse Reacons (SUSARs)
The reporng of SUSARs by the sponsor to the European Medicines Agency in the context of the CTR is
outlined in Arcle 42. The most relevant change for sponsors is the legal obligaon for the electronic
reporng of SUSARs to the clinical trial module of EudraVigilance for a CT performed in at least one
Member State (Art 42.1).
Where a sponsor, due to a lack of resources, does not have the possibility to report to EudraVigilance,
and the sponsor has the agreement of the MSC, it may report to the Member State where the SUSARs
occurred. That Member State shall then report the SUSARs to EudraVigilance (Art 42.3).
Since CTIS was launched, CT-3 final arrangement for SUSARs applies also to all trials approved
through the CTD, as announced by the Clinical Trials Expert Group (CTEG) in April 2021. This means
that from 31 January 2022, sponsors report SUSARs to EudraVigilance only and it is no longer
required to send them to member states, regardless of whether the trial has been approved
through the CTR or CTD. This brings the benefit of a single submission process and harmonised
procedures to the area of SUSAR reporting. Member states have the ability to set up SUSAR rerouting
rules in EudraVigilance if they wish to receive copies of SUSARs for their national systems. This applies
for all trials approved under the CTD or CTR.
For some member states, continued direct SUSAR reporting to ethics committees for clinical trials
under the CTD is still also required under their national law; thus, this may be considered on top of the
direct reporting to EudraVigilance. In case of doubt, liaise directly with the member state concerned
(for a link to the member states contact points, refer to Section 11 ‘Other references’).
Updated informaon regarding reporng safety informaon on clinical trials can be found on the EMA
webpage.
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Secon 7c (REPORTING OF ADVERSE EVENTS/REACTIONS) of the EudraLex Volume 10 Q&A published by
the Commission addresses some addional quesons in the context of SUSAR reporng.
References
Locaon (area or document)
Regulaon (EU) No 536/2014 of the European
Parliament and of the Council of 16 April 2014 on
clinical trials on medicinal products for human
use, and repealing Direcve 2001/20/EC
hps://eur-lex.europa.eu/legal-
content/EN/TXT/?uri=celex%3A32014R0536
Link to EudraLex - Volume 10 - Clinical trials
guidelines - Set of documents applicable to
clinical trials authorised under Regulaon EU No
536/2014
8
hps://health.ec.europa.eu/medicinal-
products/eudralex/eudralex-volume-10_en#set-of-
documents-applicable-to-clinical-trials-authorised-
under-regulaon-eu-no-5362014
Detailed guidance on the collecon, verificaon
and presentaon of adverse events/reacons
arising from clinical trials on medicinal products
for human use (‘CT-3’)
hps://eur-lex.europa.eu/legal-
content/EN/TXT/?uri=CELEX:52011XC0611(01)
CTEG announcement that CT-3 final
arrangements for SUSAR reporng will apply
since CTIS launch
hps://ec.europa.eu/transparency/expert-groups-
register/core/api/front/document/56534/download
Reporng safety informaon on clinical trials
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/reporng-safety-informaon-clinical-trials
EudraVigilance: electronic reporng
hps://www.ema.europa.eu/en/human-
regulatory/research-
development/pharmacovigilance/eudravigilance/eudrav
igilance-electronic-reporng
9.2. Annual Safety Report (ASR)
The reporng of ASRs by the sponsor to the Agency in the context of the CTR is outlined in Arcle 43,
applicable to trials registered in CTIS and managed under the CTR. The sponsor shall submit annually
through CTIS a report on the safety of each invesgaonal medicinal product (IMP) used in a clinical trial,
other than placebo, for which it is the sponsor. This obligaon referred to in paragraph 1 starts with the
first authorisaon of a clinical trial in accordance with the CTR and it ends with the end of the last clinical
trial conducted by the sponsor with the IMP.
Secon 7d (ANNUAL SAFETY REPORTS) of the Q&A published by the Commission in EudraLex Volume 10
(see ‘References’ table above) may address some of the quesons in the context of ASR reporng.
8
The latest published European Commission Clinical Trials Regulaon No 536/2014 Q&A document can be found under the ‘Set of documents applicable
to clinical trials authorised under Regulaon EU No 536/2014’ secon.
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The documents referred to in this handbook’s Secon 9.2. apply also to this secon. In addion, you can
find the link to the ASR submission training module below:
References
Locaon (area or document)
CTIS Training Material Module 18 ‘How to
create and submit an annual safety report and
respond to related requests for informaon’
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-cs-online-
modular-training-programme#sponsor-workspace-
secon
CTIS Training Material Module 18 ‘How to
create and submit an annual safety report and
respond to related requests for informaon:
Step by Step Guide’
hps://www.ema.europa.eu/en/documents/other/st
ep-step-guide-how-create-submit-annual-safety-
report-respond-related-requests-informaon-
cs_en.pdf
10. Support
10.1. Release notes and known issues
EMA regularly performs technical updates to CTIS to improve its features and funconality. When
significant updates are made to CTIS, EMA publishes release notes that outline what has changed in the
system. Updates may include improvements to exisng features and funconality, the addion of new
features as well as funconality and technical improvements.
In addion, EMA publishes known issues that sponsor and authority users may encounter when using the
CTIS secure workspaces. Where possible, workarounds to apply are proposed.
All versions of the release notes and known issues documents can be found on the ‘Website outages and
system releases’ page of EU Clinical Trials. CTIS users are advised to make use of the latest version of the
lists of known issues published on this page.
References
Locaon (area or document)
EU Clinical Trials Website – Website outages and
system releases
hps://euclinicaltrials.eu/website-outages-and-
system-releases
10.2. CTIS Highlights Newsleers
To stay up to date with developments and plans, see EMA Clinical Trials Highlights Newsleers on EMA
corporate website: subscribe at hps://ec.europa.eu/newsroom/ema/user-subscripons/3201/create
References
Locaon (area or document)
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Clinical Trials Highlights Newsleer
hps://www.ema.europa.eu/en/news-
events/publicaons/newsleers#clinical-trials-
highlights-secon
10.3. CTIS informaon events
The events page on the EMA corporate website displays informaon events organised by EMA on CTIS
(search words e.g. CTIS; SME).
In order to further support CTIS sponsor users aer CTIS go-live, EMA has launched series of virtual
events where sponsors can ask their quesons live to CTIS experts. CTIS walk-in clinics
provide an
opportunity for sponsors to receive praccal guidance about the Clinical Trials Informaon System by
asking quesons to CTIS experts in real-me.
CTIS bitesize talks are themed events offering users live
system demonstraons on a specific CTIS funconality on each session, and quesons are also received
and answered by CTIS experts in real-me. In addion, EMA introduced OMS troubleshoong sessions
for CTIS users, another series of virtual events aiming to address and clarify outstanding issues and
quesons related to registering organisaon and/or locaon data in OMS for use in CTIS CTAs.
All of these events are open to everyone. The recorded videos of past events become available for the
public on EMA’s YouTube channel and can be accessed also through the dedicated event pages.
For a complete list of the CTIS-related virtual events, sessions and webinars, visit the EMA’s webpage on
CTIS Training and informaon events.
References
Locaon (area or document)
EMA corporate website Events page
hps://www.ema.europa.eu/en/events/upcoming-
events
EMA CTIS Training and informaon events page
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-training-
support#training-and-informaon-events-secon
10.4. CTIS training
Training from EMA on how to use the Clinical Trials Informaon System (CTIS) is available. The EMA’s
training resources are tailored for clinical trial sponsors and staff of the European Union (EU) Member
States, European Commission and other organisaons who will use the system.
The EMA CTIS training programme is mainly composed of online training modules published on the CTIS
training programme page on the EMA corporate website. A wide selecon of materials in different
formats are available on introductory modules, common funconalies for all registered users, modules
on the authority (Member States, EMA and European Commission) workspace and on the sponsor
workspace. It also includes recordings from virtual training sessions organised by EMA as well as a secon
with informaon about the Master trainer programme.
When starng to use the training materials, it is advised that organisaons and users first make use of the
Guide to CTIS Training Material Catalogue.
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Reproducon and/or distribuon of the content of the published training materials is authorised for non-
commercial or commercial purposes, provided that the EMA is acknowledged as the source of the
materials.
EMA has developed the training materials to enhance public access to informaon on CTIS. The training
materials describe inially a preliminary version of CTIS and while the material will undergo revision it
may therefore, not enrely describe the system as it is at the me of use of the material. The Agency
does not warrant or accept any liability in relaon to the use (in part or in whole) or the interpretaon of
the informaon contained in this training material by third pares.
Limited end user training events are organised by EMA and announcements are made on the events page
(see ‘References’ table in 10.4) of the EMA corporate website (search e.g. with word ‘CTIS’ or ‘SME’).
References
Locaon (area or document)
Clinical Trials Informaon System (CTIS) online
training modules page (EMA corporate website)
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/training-support/clinical-trials-informaon-
system-cs-online-training-modules
Guide to CTIS Training Material Catalogue (EMA
corporate website)
hps://www.ema.europa.eu/en/documents/other
/guide-cs-training-material-catalogue_en.pdf
10.5. CTIS training environment for user training and organisaon preparedness
The Clinical Trial Information System training environment (CTIS Sandbox) is a copy of a recent
version of CTIS albeit not always identical to the latest version. The purpose of CTIS Sandbox is to
enable knowledge acquisition of the already implemented functionalities of CTIS, by the future CTIS
users and their organisations in a practical way and in a safe environment. CTIS Sandbox use is
directed by conditions, instructions and guidance, and is made available by EMA. EMA will maintain
support for the CTIS Sandbox users through a CTIS Training Environment Support Service (TESS).
Access to CTIS Sandbox is based on need and is therefore intended for, and limited to, those
individuals and organisations that are the already using or intending to use the secure workspaces of
CTIS (authority and sponsor workspace).
A phased rollout of the CTIS Training Environment is provided to defined user groups in sequence,
started with Member States and the European Commission and followed by Sponsors.
Currently, access to the CTIS Training Environment is provided to representatives of sponsor
organisations based on the need to create an initial clinical trial application. Organisations have been
offered the opportunity to access the CTIS Training Environment in several phases before and after
CTIS go-live.
Access to the CTIS Training Environment can be requested by completing a self-assessment through a
survey (Survey) that collects information on contact details of individuals, the organisations that they
represent, and their plans/need for the use of CTIS. The data collected allows EMA to understand the
need for access to CTIS Training Environment and to consider when access will be granted to ensure
that the Agency is able to support the CTIS Training Environment users effectively. Organisations
wishing to express interest for access to the CTIS Training Environment after the closure of the Survey,
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can stay tuned for latest updates on the Survey by subscribing to the Clinical Trials Highlights
Newsletters (see Section 10.2).
Before accessing the CTIS Training Environment, users need to be thoroughly trained on CTIS to get
the best out of their access. The EMA’s published online modular training program can be used for such
preparation purposes.
Version deployments and planned downtimes of the CTIS Training Environment are communicated to
users as required.
References
Locaon (area or document)
CTIS Training Environment Survey
hps://ec.europa.eu/eusurvey/runner/2abb5ba8-
0ec4-9979-b692-0c63f4508b9b
CTIS Training Environment Support Service (TESS)
hps://support.ema.europa.eu/
10.6. Quesons and answers on CTR, CTIS and other EMA IT systems
Quesons and answers on the Clinical Trials Regulaon are available in EudraLex Volume 10 Q&A.
Frequently Asked Quesons on CTIS funconalies are available as part of the published online training
material modules.
If answers cannot be found, sponsors with an EMA account can direct their queries to the EMA’s Service
Desk on CTIS. For sponsors that have not yet created an EMA account, general quesons on CTIS
funconalies can be directed through AskEMA by use of the general form.
For technical support with other EMA IT systems (e.g. EudraVigilance, IRIS, EudraCT), use the EMA
ServiceNow portal (see table below for links).
References
Locaon (area or document)
Quesons & Answers on CTR - EudraLex
Volume 10 - Clinical trials guidelines
9
hps://health.ec.europa.eu/medicinal-
products/eudralex/eudralex-volume-10_en#set-of-
documents-applicable-to-clinical-trials-authorised-under-
regulaon-eu-no-5362014
Frequently Asked Quesons (FAQs) on CTIS
funconalies
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-trials/clinical-
trials-informaon-system-cs-online-modular-training-
programme
FAQs are available within each respecve training module
9
The latest published European Commission Clinical Trials Regulaon No 536/2014 Q&A document can be found under the ‘Set of documents applicable
to clinical trials authorised under Regulaon EU No 536/2014’ secon.
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EMA Service Desk for CTIS: Quesons on
CTIS funconalies - for EMA account
holders
hps://support.ema.europa.eu/esc?id=emp_taxonomy_t
opic&topic_id=2111dcb6c39d9d10e68bf1f4e40131ee
AskEMA: Quesons on CTIS funconalies
- for non-EMA account holders
hps://www.ema.europa.eu/en/about-us/contact/send-
queson-european-medicines-agency
EMA ServiceNow: Assistance with
informaon technology (IT) systems
hps://support.ema.europa.eu/esc
Q&A on the protecon of Commercially
Confidenal Informaon and Personal Data
while using CTIS
hps://accelerang-clinical-
trials.europa.eu/document/download/33702a5d-13be-
4c4f-936d-
3627dd73085b_en?filename=ACT%20EU_Q%26A%20on
%20protecon%20of%20Commercially%20Confidenal%
20Informaon%20and%20Personal%20Data%20while%2
0using%20CTIS_v1.3.pdf
Quesons and answers – Clinical Trials
Informaon System (CTIS) and Clinical Trials
Regulaon (CTR)
hps://www.ema.europa.eu/en/documents/other/ques
ons-answers-query-management-working-group-cs-
ctr_en.pdf
CTCG Q&A on submission Complex Clinical
Trials in CTIS, vs 1.0, dd 14 March 2023
hps://www.hma.eu/fileadmin/dateien/HMA_joint/00-
_About_HMA/03-
Working_Groups/CTCG/2023_03_CTCG_QA_complex_cli
nical_trials_and_CTIS_v1.0.pdf
Complex clinical trials – Quesons and
answers
hps://health.ec.europa.eu/system/files/2022-
06/medicinal_qa_complex_clinical-trials_en.pdf
10.7. Support for SME and academia sponsors
Specific events and dedicated training materials are organised for SME and academia sponsors. For more
informaon on future events and past recordings, users can visit ‘CTIS Training and informaon events’
webpage.
References
Locaon (area or document)
CTIS Training Module 19 ‘CTIS for SMEs and
academia’
hps://www.ema.europa.eu/en/documents/other/q
uick-guide-introducon-cs-smes-academia-cs-
training-programme-module-19_en.pdf
CTIS Training and informaon events
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-training-
support#training-and-informaon-events-secon
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11. Other references
References
Locaon (area or document)
Clinical Trials Informaon System – EMA
webpages
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system
hps://www.ema.europa.eu/en/human-
regulatory/research-development/clinical-
trials/clinical-trials-informaon-system-training-
support
Clinical Trials in the European Union
hps://euclinicaltrials.eu/home
Regulaon (EU) No 536/2014 of the European
Parliament and of the Council of 16 April 2014 on
clinical trials on medicinal products for human
use
hps://eur-lex.europa.eu/legal-
content/EN/TXT/?uri=celex%3A32014R0536
Link to Commission website containing
informaon on clinical trials in the context of
Regulaon EU No 536/2014
hps://ec.europa.eu/health/human-use/clinical-
trials/regulaon_en
Link to EudraLex - Volume 10 - Clinical trials
guidelines
hps://ec.europa.eu/health/documents/eudralex/vo
l-10_en#fragment1
List of naonal contact points
(frequently updated)
Last document in Chapter V of Eudralex vol.10 CTR
(see above)
EudraCT (European Union Drug Regulang
Authories Clinical Trials Database)
10
hps://eudract.ema.europa.eu/
CTIS website outages and system releases
hps://.eu/website-outages-and-system-releases
Conclusion of VHP Procedure - Deadline for
submissions to VHP in the context of the
Christmas Break 2021/2022 and transion to
CTIS/CTR starng with the CTR applicaon
hps://www.hma.eu/fileadmin/dateien/Human_Me
dicines/01-
About_HMA/Working_Groups/CTFG/2021_07_CTFG
_Conclusion_VHP_Deadlines_for_VHP_Submissions.
pdf
ACT EU website: Implementaon of the Clinical
Trials Regulaon
hps://accelerang-clinical-trials.europa.eu/priority-
acon-areas/implementaon-clinical-trials-
regulaon_en
10
EudraCT is the European database for intervenonal clinical trials on medicinal products authorized in the European Union (EEA) and outside the
EU/EEA if they are part of a Paediatric Invesgaon Plan (PIP) from 1 May 2004 onwards; established in accordance with Direcve 2001/20/EC.
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12. Acronyms and Glossaries
References
Locaon (area or document)
CTIS Training: List of Acronyms
hps://www.ema.europa.eu/en/documents/other/c
s-training-list-acronyms_en.pdf
EMA General Glossary of regulatory terms
hps://www.ema.europa.eu/en/about-us/about-
website/glossary
EMA Medical Terms Simplifier
hps://www.ema.europa.eu/en/documents/other/e
ma-medical-terms-simplifier_en.pdf
Acronym
Term
Definion
CAT
Commiee for Advanced
Therapies
The commiee that is responsible for assessing the quality,
safety and efficacy of advanced therapy medicines,
including medicines classified as gene therapy, somac cell
therapy or ssue-engineered products.
CCI
Commercially confidenal
informaon
Informaon whose publicaon might prejudice the
commercial interests of individuals or companies to an
unreasonable degree. The Agency cannot disclose
commercially confidenal informaon unless there is an
overriding public interest in disclosure.
CTD
Clinical Trial Direcve
2001/20/EC
Introduced to simplify and harmonise the administrave
provisions governing clinical trials in Europe. It was
repealed by the Clinical Trial Regulaon applicaon.
CTEG
Clinical Trials Experts Group
CTFG &
CTFG
Clinical Trials Facilitaon
Group
Acts as a forum for discussion to agree on common
principles and processes to be applied throughout the
European medicines regulatory network (EMRN). It also
promotes harmonisaon of clinical trial assessment
decisions and administrave processes across the naonal
competent authories (NCAs).
CTR
Clinical Trial Regulaon
European Union (EU) pharmaceucal legislaon known as
the Clinical Trials Regulaon entered into applicaon on 31
January 2022. It aims to ensure the EU offers an aracve
and favourable environment for carrying out clinical
research on a large scale, with high standards of public
transparency and safety for clinical trial parcipants.
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DMP
Development Medicinal
Product
A medicinal product under invesgaon in a clinical trial in
the EEA which does not have a markeng authorisaon in
the EEA and to which special confidenality arrangements
need to be applied.
DSMB
Clinical Trial Data Safety
Monitoring Board
A group of independent individuals, external to the trial,
who are experts in relevant areas. They review the
accumulated data from one or more ongoing clinical trials
on a regular basis and advise the sponsor about the
connued safety of the trial parcipants, the connued
validity of the trial, and the connued scienfic merit of
the trial.
EMA
European Medicines
Agency
Agency of the European Union in charge of the evaluaon
and supervision of pharmaceucal products.
EU
European Union
Supranaonal polical and economic union of 27 member
states that are located primarily in Europe.
EU MP
number
EU Medicinal Product
number
Idenfier issued by the European Medicines Agency for
treatments approved in the European Union.
EUDRACT
European Union Drug
Regulaon Authories
Clinical Trials Database
EudraCT (European Union Drug Regulang Authories
Clinical Trials) is the European Clinical Trials Database of all
intervenonal clinical trials of medicinal products
commencing in the European Union from 1 May 2004
onwards. The EudraCT database has been established in
accordance with Direcve 2001/20/EC.
EV code
EudraVigilance code
EudraVigilance Code
EVWEB
EudraVigilance web-based
tool
EVWEB allows the sending and receiving of safety and
acknowledgement messages in compliance with the latest
ICH M2 standards.
FAQ
Frequently Asked Quesons
A queson in a list of quesons and answers intended to
help people understand a parcular subject.
IB
Invesgator Brochure
A mulfunconal regulatory document essenal for the
conduct of clinical trials that summarises the physical,
chemical, pharmaceucal, pharmacological, and
toxicological characteriscs of an invesgaonal medicinal
product (IMP) as well as any clinical experience.
MAA
Markeng Authorisaon
Applicaon
An applicaon made to a European regulatory authority
for approval to market a medicine within the European
Union.
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PI
Principal Invesgator
The person(s) in charge of a clinical trial or a scienfic
research grant. The PI prepares and carries out the clinical
trial protocol (plan for the study) or research paid for by
the grant. The PI also analyses the data and reports the
results of the trial or grant research.
PIP
Paediatric invesgaon plan
A development plan aimed at ensuring that the necessary
data are obtained to support the authorisaon of a
medicine for children, through studies in children. All
applicaons for markeng authorisaon for new medicines
have to include the results of studies as described in an
agreed paediatric invesgaon plan, unless the medicine is
exempt because of a deferral or waiver.
SME
Micro, Small to Medium-
size Enterprise
SmPC
Summary of Product
Characteriscs
This is the product informaon document which is made
available to all prescribing physicians in the EU for
marketed products.
SUSAR
Suspected Unexpected
Serious Adverse Reacons
Suspected Unexpected Serious Adverse Reacon is the
term used to refer to an adverse event that occurs in a
clinical trial subject, which is assessed by the sponsor and
or study invesgator as being unexpected, serious and as
having a reasonable possibility of a causal relaonship with
the study drug.
TESS
CTIS Training Environment
Support Service
VHP
Voluntary Harmonisaon
Procedure
XEVPRM
eXtended EudraVigilance
Medicinal Product
Report Message