Article 43 Annual reporting by the sponsor to the Agency
1. Regarding investigational medicinal products other than placebo, the sponsor shall submit annually through the database referred to in Article 40(1) to the Agency a report on the safety of each investigational medicinal product used in a clinical trial for which it is the sponsor. 2. In the case of a clinical trial involving the use of more than one investigational medicinal product, the sponsor may, if provided for in the protocol, submit a single safety report on all investigational medicinal products used in that clinical trial. 3. The annual report referred to in paragraph 1 shall only contain aggregate and anonymised data. 4. The obligation referred to in paragraph 1 starts with the first authorisation of a clinical trial in accordance with this Regulation. It ends with the end of the last clinical trial conducted by the sponsor with the investigational medicinal product.
Article 44 Assessment by Member States
1. The Agency shall, by electronic means, forward to the Member States concerned the information reported in accordance with Article 42 and 43. 2. Member States shall cooperate in assessing the information reported in accordance with Articles 42and 43. The Commission may, by means of implementing acts, set up and modify the rules on such cooperation. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 88(2). 3. The responsible ethics committee shall be involved in the assessment of the information referred to in paragraphs 1 and 2, if it has been provided for in the law of the Member State concerned.
Article 45 Technical aspects
Technical aspects for safety reporting in accordance with Articles 41 to 44 are contained in Annex III. Where necessary in order to improve the level of protection of subjects, the Commission shall be empowered to adopt delegated acts in accordance with Article 89 in order to amend Annex III for any of the following purposes: (a) improving the information on the safety of medicinal products; (b) adapting technical requirements to technical progress; (c) taking account of international regulatory developments in the field of safety requirements in clinical trials, endorsed by bodies in which the Union or the Member States participate.
Article 46 Reporting with regard to auxiliary medicinal products
Safety reporting with regard to auxiliary medicinal products shall be made in accordance with Chapter 3 of Title IX of Directive 2001/83/EC.
Article 47 Compliance with the protocol and good clinical practice
The sponsor of a clinical trial and the investigator shall ensure that the clinical trial is conducted in accordance with the protocol and with the principles of good clinical practice. Without prejudice to any other provision of Union law or Commission guidelines, the sponsor and the investigator, when drawing up the protocol and when applying this Regulation and the protocol, shall also take appropriate account of the quality standards and the ICH guidelines on good clinical practice. The Commission shall make publicly available the detailed ICH guidelines on good clinical practice referred to in the second paragraph.
Article 48 Monitoring
In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical trial is in compliance with the requirements of this Regulation, the sponsor shall adequately monitor the conduct of a clinical trial. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical trial, including the following characteristics: (a) whether the clinical trial is a low-intervention clinical trial; (b) the objective and methodology of the clinical trial; and (c) the degree of deviation of the intervention from normal clinical practice.
Article 49 Suitability of individuals involved in conducting the clinical trial
The investigator shall be a medical doctor as defined in national law, or a person following a profession which is recognised in the Member State concerned as qualifying for an investigator because of the necessary scientific knowledge and experience in patient care. Other individuals involved in conducting a clinical trial shall be suitably qualified by education, training and experience to perform their tasks.
Article 50 Suitability of clinical trial sites
The facilities where the clinical trial is to be conducted shall be suitable for the conduct of the clinical trial in compliance with the requirements of this Regulation.
Article 51 Traceability, storage, return and destruction of investigational medicinal products
1. Investigational medicinal products shall be traceable. They shall be stored, returned and/or destroyed as appropriate and proportionate to ensure the safety of the subject and the reliability and robustness of the data generated in the clinical trial, in particular, taking into account whether the investigational medicinal product is an authorised investigational medicinal product, and whether the clinical trial is a low-intervention clinical trial. The first subparagraph shall also apply to unauthorised auxiliary medicinal products. 2. The relevant information regarding the traceability, storage, return and destruction of medicinal products referred to in paragraph 1 shall be contained in the application dossier.
Article 52 Reporting of serious breaches
1. The sponsor shall notify the Member States concerned about a serious breach of this Regulation or of the version of the protocol applicable at the time of the breach through the EU portal without undue delay but not later than seven days of becoming aware of that breach. 2. For the purposes of this Article, a ‘serious breach’ means a breach likely to affect to a significant degree the safety and rights of a subject or the reliability and robustness of the data generated in the clinical trial.
Article 53 Other reporting obligations relevant for subject safety
1. The sponsor shall notify the Member States concerned through the EU portal of all unexpected events which affect the benefit-risk balance of the clinical trial, but are not suspected unexpected serious adverse reactions as referred to in Article 42. That notification shall be made without undue delay but no later than 15 days from the date the sponsor became aware of this event. 2. The sponsor shall submit to the Member States concerned, through the EU portal, all inspection reports of third country authorities concerning the clinical trial. When requested by a Member State concerned, the sponsor shall submit a translation of the report or of its summary in an official language of the Union indicated in the request.
Article 54 Urgent safety measures
1. Where an unexpected event is likely to seriously affect the benefit-risk balance, the sponsor and the investigator shall take appropriate urgent safety measures to protect the subjects. 2. The sponsor shall notify the Member States concerned, through the EU portal, of the event and the measures taken. That notification shall be made without undue delay but no later than seven days from the date the measures have been taken. 3. This Article is without prejudice to Chapters III and VII.
Article 55 Investigator's brochure
1. The sponsor shall provide the investigator with the investigator's brochure. 2. The investigator's brochure shall be updated where new and relevant safety information becomes available, and shall be reviewed by the sponsor at least once per year.
Article 56 Recording, processing, handling and storage of information
1. All clinical trial information shall be recorded, processed, handled, and stored by the sponsor or investigator, as applicable, in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable law on personal data protection. 2. Appropriate technical and organisational measures shall be implemented to protect information and personal data processed against unauthorised or unlawful access, disclosure, dissemination, alteration, or destruction or accidental loss, in particular where the processing involves the transmission over a network.
Article 57 Clinical trial master file
The sponsor and the investigator shall keep a clinical trial master file. The clinical trial master file shall at all times contain the essential documents relating to that clinical trial which allow verification of the conduct of a clinical trial and the quality of the data generated, taking into account all characteristics of the clinical trial, including in particular whether the clinical trial is a low-intervention clinical trial. It shall be readily available, and directly accessible upon request, to the Member States. The clinical trial master file kept by the investigator and that kept by the sponsor may have a different content if this is justified by the different nature of the responsibilities of the investigator and the sponsor.
Article 58 Archiving of the clinical trial master file
Unless other Union law requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least 25 years after the end of the clinical trial. However, the medical files of subjects shall be archived in accordance with national law. The content of the clinical trial master file shall be archived in a way that ensures that it is readily available and accessible, upon request, to the competent authorities. Any transfer of ownership of the content of the clinical trial master file shall be documented. The new owner shall assume the responsibilities set out in this Article. The sponsor shall appoint individuals within its organisation to be responsible for archives. Access to archives shall be restricted to those individuals. The media used to archive the content of the clinical trial master file shall be such that the content remains complete and legible throughout the period referred to in the first paragraph. Any alteration to the content of the clinical trial master file shall be traceable.
Article 59 Auxiliary medicinal products
1. Only authorised auxiliary medicinal products may be used in a clinical trial. 2. Paragraph 1 shall not apply where no authorised auxiliary medicinal product is available in the Union or where the sponsor cannot reasonably be expected to use an authorised auxiliary medicinal product. A justification to this effect shall be included in the protocol. 3. Member States shall ensure that unauthorised auxiliary medicinal products may enter their territories for the purpose of their use in a clinical trial in accordance with paragraph 2.
Article 60 Scope of this Chapter
This Chapter shall apply to the manufacture and import of investigational medicinal products and auxiliary medicinal products.
Article 61 Authorisation of manufacturing and import
1. The manufacturing and import of investigational medicinal products in the Union shall be subject to the holding of an authorisation. However, the import of investigational medicinal products from other parts of the United Kingdom into Northern Ireland and, until 31 December 2024, into Cyprus, Ireland and Malta shall not be subject to the holding of such an authorisation provided that all of the following conditions are fulfilled: (a) the investigational medicinal products have undergone certification of batch release either in the Union or in parts of the United Kingdom other than Northern Ireland to verify compliance with the requirements set out in Article 63(1); (b) the investigational medicinal products are only made available to subjects in the Member State into which those investigational medicinal products are imported or, if imported into Northern Ireland, are only made available to subjects in Northern Ireland. In order to obtain the authorisation referred to in paragraph 1, the applicant shall meet the following requirements: (a) it shall have at its disposal, for manufacture or import, suitable and sufficient premises, technical equipment and control facilities complying with the requirements set out in this Regulation; it shall have permanently and continuously at its disposal the services of at least one qualified person who fulfils the conditions of qualification set out in Article 49(2) and (3) of Directive 2001/83/EC (‘qualified person’). 3. The applicant shall specify, in the application for authorisation, the types and pharmaceutical forms of the investigational medicinal product manufactured or imported, the manufacturing or import operations, the manufacturing process where relevant, the site where the investigational medicinal products are to be manufactured or the site in the Union to which they are to be imported, and detailed information concerning the qualified person. 4. Articles 42 to 45, and point (e) of Article 46 of Directive 2001/83/EC shall apply mutatis mutandis to the authorisation referred to in paragraph 1. 5. Paragraph 1 shall not apply to any of the following processes: (a) re-labelling or re-packaging, where those processes are carried out in hospitals, health centres or clinics, by pharmacists or other persons legally authorised in the Member State concerned to carry out such processes, and if the investigational medicinal products are intended to be used exclusively in hospitals, health centres or clinics taking part in the same clinical trial in the same Member State; (b) preparation of radiopharmaceuticals used as diagnostic investigational medicinal products where this process is carried out in hospitals, health centres or clinics, by pharmacists or other persons legally authorised in the Member State concerned to carry out such process, and if the investigational medicinal products are intended to be used exclusively in hospitals, health centres or clinics taking part in the same clinical trial in the same Member State; (c) the preparation of medicinal products referred to in points (1) and (2) of Article 3 of Directive 2001/83/EC for use as investigational medicinal products, where this process is carried out in hospitals, health centres or clinics legally authorised in the Member State concerned to carry out such process and if the investigational medicinal products are intended to be used exclusively in hospitals, health centres or clinics taking part in the same clinical trial in the same Member State. 6. Member States shall make the processes set out in paragraph 5 subject to appropriate and proportionate requirements to ensure subject safety and reliability and robustness of the data generated in the clinical trial. They shall subject the processes to regular inspections.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 61 Authorisation of manufacturing and import):
1. The manufacturing and import of investigational medicinal products in the Union shall be subject to the holding of an authorisation. However, the import of investigational medicinal products from other parts of the United Kingdom into Northern Ireland and, until 31 December 2024, into Cyprus, Ireland and Malta shall not be subject to the holding of such an authorisation provided that all of the following conditions are fulfilled: (a) the investigational medicinal products have undergone certification of batch release either in the Union or in parts of the United Kingdom other than Northern Ireland to verify compliance with the requirements set out in Article 63(1); (b) the investigational medicinal products are only made available to subjects in the Member State into which those investigational medicinal products are imported or, if imported into Northern Ireland, are only made available to subjects in Northern Ireland. 3. The applicant shall specify, in the application for authorisation, the types and pharmaceutical forms of the investigational medicinal product manufactured or imported, the manufacturing or import operations, the manufacturing process where relevant, the site where the investigational medicinal products are to be manufactured or the site in the Union to which they are to be imported, and detailed information concerning the qualified person. 4. Articles 42 to 45, and point (e) of Article 46 of Directive 2001/83/EC shall apply mutatis mutandis to the authorisation referred to in paragraph 1. 6. Member States shall make the processes set out in paragraph 5 subject to appropriate and proportionate requirements to ensure subject safety and reliability and robustness of the data generated in the clinical trial. They shall subject the processes to regular inspections.
Article 62 Responsibilities of the qualified person
1. The qualified person shall ensure that each batch of investigational medicinal products manufactured in or imported into the Union complies with the requirements set out in Article 63 and shall certify that those requirements are fulfilled. 2. The certification referred to in paragraph 1 shall be made available by the sponsor at the request of the Member State concerned.
Article 63 Manufacturing and import
1. Investigational medicinal products shall be manufactured by applying manufacturing practice which ensures the quality of such medicinal products in order to safeguard the safety of the subject and the reliability and robustness of clinical data generated in the clinical trial (‘good manufacturing practice’). The Commission shall be empowered to adopt delegated acts in accordance with Article 89 in order to specify the principles and guidelines of good manufacturing practice and the detailed arrangements for inspection for ensuring the quality of investigational medicinal products, taking account of subject safety or data reliability and robustness, technical progress and global regulatory developments in which the Union or the Member States are involved. In addition, the Commission shall also adopt and publish detailed guidelines in line with those principles of good manufacturing practice and revise them when necessary in order to take account of technical and scientific progress. 2. Paragraph 1 shall not apply to the processes referred to in Article 61(5). 3. Investigational medicinal products imported into the Union shall be manufactured by applying quality standards at least equivalent to those laid down pursuant to paragraph 1. 4. The Member States shall ensure compliance with the requirements of this Article by means of inspections.
Article 64 Modification of authorised investigational medicinal products
Articles 61, 62 and 63 shall apply to authorised investigational medicinal products only as regards any modification of such products not covered by a marketing authorisation.
Article 65 Manufacturing of auxiliary medicinal products
Where the auxiliary medicinal product is not authorised, or where an authorised auxiliary medicinal product is modified while such modification is not covered by a marketing authorisation, it shall be manufactured according to the good manufacturing practice referred to in Article 63(1) orto at least an equivalent standard, in order to ensure appropriate quality.
Article 66 Unauthorised investigational and unauthorised auxiliary medicinal products
The following information shall appear on the outer packaging and on the immediate packaging of unauthorised investigational medicinal products and unauthorised auxiliary medicinal products: (a) information to identify contact persons or persons involved in the clinical trial; (b) information to identify the clinical trial; (c) information to identify the medicinal product; (d) information related to the use of the medicinal product. 2. The information which is to appear on the outer packaging and immediate packaging shall ensure subject safety and reliability and robustness of the data generated in the clinical trial, while taking account of the design of the clinical trial, whether the products are investigational or auxiliary medicinal product, and whether they are products with particular characteristics. The information which is to appear on the outer packaging and immediate packaging shall be clearly legible. A list of information which is to appear on the outer packaging and immediate packaging is set out in Annex VI.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 66 Unauthorised investigational and unauthorised auxiliary medicinal products):
2. The information which is to appear on the outer packaging and immediate packaging shall ensure subject safety and reliability and robustness of the data generated in the clinical trial, while taking account of the design of the clinical trial, whether the products are investigational or auxiliary medicinal product, and whether they are products with particular characteristics. The information which is to appear on the outer packaging and immediate packaging shall be clearly legible. A list of information which is to appear on the outer packaging and immediate packaging is set out in Annex VI.
Article 67 Authorised investigational and authorised auxiliary medicinal products
1. Authorised investigational medicinal products and authorised auxiliary medicinal products shall be labelled: (a) in accordance with Article 66(1); or (b) in accordance with Title V of Directive 2001/83/EC. 2. Notwithstanding point (b) of paragraph 1, where the specific circumstances, provided for in the protocol, of a clinical trial so require in order to ensure the safety of the subject or the reliability and robustness of data generated in a clinical trial, additional particulars relating to the identification of the clinical trial and of the contact person shall appear on the outer packaging and the immediate packaging of authorised investigational medicinal products. A list of these additional particulars appearing on the outer packaging and immediate packaging is set out in section C of Annex VI.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 67 Authorised investigational and authorised auxiliary medicinal products):
2. Notwithstanding point (b) of paragraph 1, where the specific circumstances, provided for in the protocol, of a clinical trial so require in order to ensure the safety of the subject or the reliability and robustness of data generated in a clinical trial, additional particulars relating to the identification of the clinical trial and of the contact person shall appear on the outer packaging and the immediate packaging of authorised investigational medicinal products. A list of these additional particulars appearing on the outer packaging and immediate packaging is set out in section C of Annex VI.
Article 68 Radiopharmaceuticals used as investigational medicinal products or as auxiliary medicinal products for a medical diagnosis
Articles 66 and 67 shall not apply to radiopharmaceuticals used as diagnostic investigational medicinal products or as diagnostic auxiliary medicinal products. The products referred to in the first paragraph shall be labelled appropriately in order to ensure the safety of the subject and the reliability and robustness of data generated in the clinical trial.
Article 69 Language
The language of the information on the label shall be determined by the Member State concerned. The medicinal product may be labelled in several languages.
Article 70 Delegated act
The Commission shall be empowered to adopt delegated acts in accordance with Article 89 in respect of amending Annex VI in order to ensure subject safety and the reliability and robustness of data generated in a clinical trial or to take account of technical progress.
Article 71 Sponsor
A clinical trial may have one or several sponsors. Any sponsor may delegate, in a written contract, any or all of its tasks to an individual, a company, an institution or an organisation. Such delegation shall be without prejudice to the responsibility of the sponsor, in particular regarding the safety of subjects and the reliability and robustness of the data generated in the clinical trial. The investigator and the sponsor may be the same person.
Article 72 Co-sponsorship
1. Without prejudice to Article 74, where a clinical trial has more than one sponsor, all sponsors shall have the responsibilities of a sponsor set out in this Regulation, unless the sponsors decide otherwise in a written contract setting out their respective responsibilities. Where the contract does not specify to which sponsor a given responsibility is attributed, that responsibility shall lie with all sponsors. By way of derogation from paragraph 1, the sponsors shall be jointly responsible for establishing: (a) a sponsor responsible for compliance with the obligations of a sponsor in the authorisation procedures set out in Chapters II and III; (b) a sponsor responsible for being a contact point for receiving all questions from subjects, investigators or any Member State concerned regarding the clinical trial and providing answers to them; (c) a sponsor responsible for implementing the measures taken in accordance with Article 77.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 72 Co-sponsorship):
1. Without prejudice to Article 74, where a clinical trial has more than one sponsor, all sponsors shall have the responsibilities of a sponsor set out in this Regulation, unless the sponsors decide otherwise in a written contract setting out their respective responsibilities. Where the contract does not specify to which sponsor a given responsibility is attributed, that responsibility shall lie with all sponsors.
Article 73 Principal investigator
A principal investigator shall ensure compliance of a clinical trial at a clinical trial site with the requirements of this Regulation. The principal investigator shall assign tasks among the members of the team of investigators in a way which is not compromising the safety of subjects and the reliability and robustness of the data generated in the clinical trial at that clinical trial site.
Article 74 Legal representative of the sponsor in the Union
1. Where the sponsor of a clinical trial is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor's obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation. Any communication to that legal representative shall be deemed to be a communication to the sponsor. 2. Member States may choose not to apply paragraph 1 as regards clinical trials to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical trial who shall be the addressee for all communications with the sponsor provided for in this Regulation. 3. As regards clinical trials to be conducted in more than one Member State, all those Member States may choose not to apply paragraph 1 provided that they ensure that the sponsor establishes at least a contact person in the Union in respect of that clinical trial who shall be the addressee for all communications with the sponsor provided for in this Regulation.
Article 75 Liability
This Chapter shall not affect the civil and criminal liability of the sponsor, investigator, or persons to whom the sponsor has delegated tasks.
Article 76 Damage compensation
1. Member States shall ensure that systems for compensation for any damage suffered by a subject resulting from participation in a clinical trial conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk. 2. The sponsor and the investigator shall make use of the system referred to in paragraph 1 in the form appropriate for the Member State concerned where the clinical trial is conducted. 3. Member States shall not require any additional use of the system referred to in paragraph 1 from the sponsor for low-intervention clinical trials, if any possible damage that could be suffered by a subject resulting from the use of the investigational medicinal product in accordance with the protocol of that specific clinical trial on the territory of that Member State is covered by the applicable compensation system already in place.
Article 77 Corrective measures to be taken by Member States
1. Where a Member State concerned has justified grounds for considering that the requirements set out in this Regulation are no longer met, it may take the following measures on its territory: (a) revoke the authorisation of a clinical trial; (b) suspend a clinical trial; (c) require the sponsor to modify any aspect of the clinical trial. 2. Before the Member State concerned takes any of the measures referred to in paragraph 1 it shall, except where immediate action is required, ask the sponsor and/or the investigator for their opinion. That opinion shall be delivered within seven days. 3. The Member State concerned shall immediately after taking a measure referred to in paragraph 1 inform all Member States concerned through the EU portal. 4. Each Member State concerned may consult the other Member States concerned before taking any of the measures referred to in paragraph 1.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 77 Corrective measures to be taken by Member States):
2. Before the Member State concerned takes any of the measures referred to in paragraph 1 it shall, except where immediate action is required, ask the sponsor and/or the investigator for their opinion. That opinion shall be delivered within seven days. 3. The Member State concerned shall immediately after taking a measure referred to in paragraph 1 inform all Member States concerned through the EU portal. 4. Each Member State concerned may consult the other Member States concerned before taking any of the measures referred to in paragraph 1.
Article 78 Member State inspections
1. Member States shall appoint inspectors to perform inspections in order to supervise compliance with this Regulation. They shall ensure that those inspectors are adequately qualified and trained. 2. Inspections shall be conducted under the responsibility of the Member State where the inspection takes place. 3. Where a Member State concerned intends to carry out an inspection on its territory or in a third country with regard to one or several clinical trials which are conducted in more than one Member State concerned, it shall notify its intention to the other Member States concerned, the Commission and the Agency, through the EU portal, and shall inform them of its findings after the inspection. 4. Inspections fees, if any, may be waived for non-commercial sponsors. 5. In order to efficiently use the resources available and to avoid duplications, the Agency shall coordinate the cooperation between Member States concerned on inspections conducted in Member States, in third countries, and inspections conducted in the framework of an application for a marketing authorisation under Regulation (EC) No 726/2004. 6. Following an inspection, the Member State under whose responsibility the inspection has been conducted shall draw up an inspection report. That Member State shall make the inspection report available to the inspected entity and the sponsor of the relevant clinical trial and shall submit the inspection report through the EU portal. 7. The Commission shall specify, by means of implementing acts, the detailed arrangements for the inspection procedures including the qualification and training requirements for inspectors. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 88(2).
Article 79 Union controls
The Commission may conduct controls in order to verify: (a) whether Member States correctly supervise compliance with this Regulation; (b) whether the regulatory system applicable to clinical trials conducted outside the Union ensures that point 8 of the Introduction and general principles contained in Annex I to Directive 2001/83/EC is complied with; (c) whether the regulatory system applicable to clinical trials conducted outside the Union ensures that Article 25(5) of this Regulation is complied with. 2. The Union controls referred to in point (a) of paragraph 1 shall be organised in cooperation with the Member States concerned. The Commission shall prepare in cooperation with the Member States a programme for the Union controls referred to in points (b) and (c) of paragraph 1. The Commission shall report on the findings of each Union control carried out. Those reports shall, if appropriate, contain recommendations. The Commission shall submit those reports through the EU portal.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 79 Union controls):
2. The Union controls referred to in point (a) of paragraph 1 shall be organised in cooperation with the Member States concerned. The Commission shall prepare in cooperation with the Member States a programme for the Union controls referred to in points (b) and (c) of paragraph 1. The Commission shall report on the findings of each Union control carried out. Those reports shall, if appropriate, contain recommendations. The Commission shall submit those reports through the EU portal.
Article 80 EU portal
The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a portal at Union level as a single entry point for the submission of data and information relating to clinical trials in accordance with this Regulation. The EU portal shall be technically advanced and user-friendly so as to avoid unnecessary work. Data and information submitted through the EU portal shall be stored in the EU database.
Article 81 EU database
1. The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a EU database at Union level. The Agency shall be considered to be the controller of the EU database and shall be responsible for avoiding unnecessary duplication between the EU database and the EudraCT and Eudravigilance databases. The EU database shall contain the data and information submitted in accordance with this Regulation. The EU database shall identify each clinical trial by a unique EU trial number. The sponsor shall refer to this EU trial number in any subsequent submission relating or referring to that clinical trial. 2. The EU database shall be established to enable cooperation between the competent authorities of the Member States concerned to the extent that it is necessary for the application of this Regulation and to search for specific clinical trials. It shall also facilitate the communication between sponsors and Member States concerned and enable sponsors to refer to previous submissions of an application for authorisation of a clinical trial or a substantial modification. It shall also enable citizens of the Union to have access to clinical information about medicinal products. To this end all data held in the EU database shall be in an easily searchable format, all related data shall be grouped together by way of the EU trial number, and hyperlinks shall be provided to link together related data and documents held on the EU database and other databases managed by the Agency. 3. The EU database shall support the recording and submission to the Medicinal Product Dictionary, contained in the Eudravigilance database, of all the data on medicinal products without a marketing authorisation in the Union and substances not authorised as part of a medicinal product in the Union, that are necessary for the maintenance of that dictionary. To this effect and also with the purpose of enabling the sponsor to cross-refer to prior applications, an EU medicinal product number shall be issued for every medicinal product without a marketing authorisation and an EU active substances code shall be issued for each new active substance not previously authorised as part of a medicinal product in the Union. This shall be done before or during the application for authorisation of the first clinical trial with that product or active substance submitted in accordance with this Regulation. Those numbers shall be mentioned in all subsequent applications for clinical trials and for substantial modifications. The data submitted, in accordance with the first subparagraph, describing medicinal products and substances shall comply with Union and international standards for the identification of medicinal products and active substances. When an investigational medicinal product which already has a marketing authorisation in the Union and/or an active substance which is part of a medicinal product with a marketing authorisation in the Union, is to be used in a clinical trial, the relevant product and active substance numbers shall be referred to in the application for that clinical trial. The EU database shall be publicly accessible unless, for all or part of the data and information contained therein, confidentiality is justified on any of the following grounds: (a) protecting personal data in accordance with Regulation (EC) No 45/2001; (b) protecting commercially confidential information, in particular through taking into account the status of the marketing authorisation for the medicinal product, unless there is an overriding public interest in disclosure; (c) protecting confidential communication between Member States in relation to the preparation of the assessment report; (d) ensuring effective supervision of the conduct of a clinical trial by Member States. 5. Without prejudice to paragraph 4, unless there is an overriding public interest in disclosure, data contained in the application dossier shall not be publicly accessible before the decision on the clinical trial has been made. 6. The EU database shall contain personal data only insofar as this is necessary for the purposes of paragraph 2. 7. No personal data of subjects shall be publicly accessible. 8. The user interface of the EU database shall be available in all official languages of the Union. 9. The sponsor shall permanently update in the EU database information on any changes to the clinical trials which are not substantial modifications but are relevant for the supervision of the clinical trial by the Member States concerned. 10. The Agency, the Commission and Member States shall ensure that the data subject may effectively exercise his or her rights to information, to access, to rectify and to object in accordance with Regulation (EC) No 45/2001 and national data protection legislation implementing Directive 95/46/EC, respectively. They shall ensure that the data subject may effectively exercise the right of access to data relating to him or her, and the right to have inaccurate or incomplete data corrected or erased. Within their respective responsibilities, the Agency, the Commission and Member States shall ensure that inaccurate and unlawfully processed data are deleted, in accordance with the applicable law. Corrections and deletions shall be carried out as soon as possible, but no later than 60 days of a request being made by a data subject.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 81 EU database):
1. The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a EU database at Union level. The Agency shall be considered to be the controller of the EU database and shall be responsible for avoiding unnecessary duplication between the EU database and the EudraCT and Eudravigilance databases. The EU database shall contain the data and information submitted in accordance with this Regulation. The EU database shall identify each clinical trial by a unique EU trial number. The sponsor shall refer to this EU trial number in any subsequent submission relating or referring to that clinical trial. 2. The EU database shall be established to enable cooperation between the competent authorities of the Member States concerned to the extent that it is necessary for the application of this Regulation and to search for specific clinical trials. It shall also facilitate the communication between sponsors and Member States concerned and enable sponsors to refer to previous submissions of an application for authorisation of a clinical trial or a substantial modification. It shall also enable citizens of the Union to have access to clinical information about medicinal products. To this end all data held in the EU database shall be in an easily searchable format, all related data shall be grouped together by way of the EU trial number, and hyperlinks shall be provided to link together related data and documents held on the EU database and other databases managed by the Agency. 3. The EU database shall support the recording and submission to the Medicinal Product Dictionary, contained in the Eudravigilance database, of all the data on medicinal products without a marketing authorisation in the Union and substances not authorised as part of a medicinal product in the Union, that are necessary for the maintenance of that dictionary. To this effect and also with the purpose of enabling the sponsor to cross-refer to prior applications, an EU medicinal product number shall be issued for every medicinal product without a marketing authorisation and an EU active substances code shall be issued for each new active substance not previously authorised as part of a medicinal product in the Union. This shall be done before or during the application for authorisation of the first clinical trial with that product or active substance submitted in accordance with this Regulation. Those numbers shall be mentioned in all subsequent applications for clinical trials and for substantial modifications. The data submitted, in accordance with the first subparagraph, describing medicinal products and substances shall comply with Union and international standards for the identification of medicinal products and active substances. When an investigational medicinal product which already has a marketing authorisation in the Union and/or an active substance which is part of a medicinal product with a marketing authorisation in the Union, is to be used in a clinical trial, the relevant product and active substance numbers shall be referred to in the application for that clinical trial. 5. Without prejudice to paragraph 4, unless there is an overriding public interest in disclosure, data contained in the application dossier shall not be publicly accessible before the decision on the clinical trial has been made. 6. The EU database shall contain personal data only insofar as this is necessary for the purposes of paragraph 2. 7. No personal data of subjects shall be publicly accessible. 8. The user interface of the EU database shall be available in all official languages of the Union. 9. The sponsor shall permanently update in the EU database information on any changes to the clinical trials which are not substantial modifications but are relevant for the supervision of the clinical trial by the Member States concerned. 10. The Agency, the Commission and Member States shall ensure that the data subject may effectively exercise his or her rights to information, to access, to rectify and to object in accordance with Regulation (EC) No 45/2001 and national data protection legislation implementing Directive 95/46/EC, respectively. They shall ensure that the data subject may effectively exercise the right of access to data relating to him or her, and the right to have inaccurate or incomplete data corrected or erased. Within their respective responsibilities, the Agency, the Commission and Member States shall ensure that inaccurate and unlawfully processed data are deleted, in accordance with the applicable law. Corrections and deletions shall be carried out as soon as possible, but no later than 60 days of a request being made by a data subject.
Article 82 Functionality of the EU portal and the EU database
1. The Agency shall, in collaboration with the Member States and the Commission, draw up the functional specifications for the EU portal and the EU database, together with the time frame for their implementation. 2. The Management Board of the Agency shall, on the basis of an independent audit report, inform the Commission when it has verified that the EU portal and the EU database have achieved full functionality and the systems meet the functional specifications drawn up pursuant to paragraph 1. 3. The Commission shall, when it is satisfied that the conditions referred to in paragraph 2 have been fulfilled, publish a notice to that effect in the Official Journal of the European Union .
Article 83 National contact points
1. Each Member State shall designate one national contact point in order to facilitate the functioning of the procedures set out in Chapters II and III. 2. Each Member State shall communicate the contact point referred to in paragraph 1 to the Commission. The Commission shall publish a list of the national contact points.
Article 84 Support by the Agency and the Commission
The Agency shall support the functioning of the cooperation of the Member States in the framework of the authorisation procedures set out in Chapters II and III of this Regulation by maintaining and updating the EU portal and the EU database in accordance with the experience acquired during the implementation of this Regulation. The Commission shall support the functioning of the cooperation of the Member States referred to in Article 44(2).
Article 85 Clinical Trials Coordination and Advisory Group
1. A Clinical Trials Coordination and Advisory Group (CTAG), composed of the national contact points referred to in Article 83 is hereby established. The CTAG shall have the following tasks: (a) to support the exchange of information between the Member States and the Commission on the experience acquired with regard to the implementation of this Regulation; (b) to assist the Commission in providing the support referred to in the second paragraph of Article 84; (c) to prepare recommendations on criteria regarding the selection of a reporting Member State. 3. The CTAG shall be chaired by a representative of the Commission. 4. The CTAG shall meet at regular intervals and whenever the situation requires, on a request from the Commission or a Member State. Any item of the agenda of the meeting shall be placed at the request of the Commission or a Member State. 5. The secretariat shall be provided by the Commission. 6. The CTAG shall draw up its rules of procedure. The rules of procedure shall be made public.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 85 Clinical Trials Coordination and Advisory Group):
1. A Clinical Trials Coordination and Advisory Group (CTAG), composed of the national contact points referred to in Article 83 is hereby established. 3. The CTAG shall be chaired by a representative of the Commission. 4. The CTAG shall meet at regular intervals and whenever the situation requires, on a request from the Commission or a Member State. Any item of the agenda of the meeting shall be placed at the request of the Commission or a Member State. 5. The secretariat shall be provided by the Commission. 6. The CTAG shall draw up its rules of procedure. The rules of procedure shall be made public.
Article 86 General principle
This Regulation shall be without prejudice to the possibility for Member States to levy a fee for the activities set out in this Regulation, provided that the level of the fee is set in a transparent manner and on the basis of cost recovery principles. Member States may establish reduced fees for non-commercial clinical trials.
Article 87 One payment per activity per Member State
A Member State shall not require, for an assessment as referred to in Chapters II and III, multiple payments to different bodies involved in this assessment.
Article 88 Committee procedure
1. The Commission shall be assisted by the Standing Committee on Medicinal Products for Human Use established by Directive 2001/83/EC. That committee shall be a committee within the meaning of Regulation (EU) No 182/2011. 2. Where reference is made to this paragraph, Article 5 of Regulation (EU) No 182/2011 shall apply. Where the committee delivers no opinion, the Commission shall not adopt the draft implementing act and the third subparagraph of Article 5(4) of Regulation (EU) No 182/2011 shall apply.
Article 89 Exercise of the delegation
1. The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in this Article. 2. The power to adopt delegated acts referred to in Articles 27, 39, 45, 63(1) and 70 shall be conferred on the Commission for a period of five years from the date referred to in the second paragraph of Article 99. The Commission shall draw up a report in respect of the delegated powers not later than six months before the end of the five year period. The delegation of powers shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period. 3. The delegation of power referred to in Articles 27, 39, 45, 63(1) and 70 may be revoked at any time by the European Parliament or by the Council. A decision of revocation shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force. 4. As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council. 5. A delegated act adopted pursuant to Articles 27, 39, 45, 63(1) and 70 shall enter into force only if no objection has been expressed either by the European Parliament or the Council within a period of two months from notification of that act to the European Parliament and the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by two months at the initiative of the European Parliament or the Council.
Article 90 Specific requirements for special groups of medicinal products
This Regulation shall not affect the application of national law prohibiting or restricting the use of any specific type of human or animal cells, or the sale, supply or use of medicinal products containing, consisting of or derived from those cells, or of medicinal products used as abortifacients or of medicinal products containing narcotic substances within the meaning of the relevant international conventions in force such as the Single Convention on Narcotic Drugs of 1961 of the United Nations. The Member States shall communicate that national law to the Commission. No gene therapy clinical trials may be carried out which result in modifications to the subject's germ line genetic identity.
Article 91 Relation with other Union legislation
This Regulation shall be without prejudice to Council Directive 97/43/Euratom ( 3 ), Council Directive 96/29/Euratom ( 4 ), Directive 2001/18/EC of the European Parliament and of the Council ( 5 ), Directive 2004/23/EC of the European Parliament and of the Council ( 6 ), Directive 2002/98/EC of the European Parliament and of the Council ( 7 ), Directive 2010/53/EC of the European Parliament and of the Council ( 8 ), and Directive 2009/41/EC of the European Parliament and of the Council. ( 9 )
Article 92 Investigational medicinal products, other products and procedures, free of charge for the subject
Without prejudice to the Member States' competence for the definition of their health policy and for the organisation and delivery of health services and medical care, the costs for investigational medicinal products, auxiliary medicinal products, medical devices used for their administration and procedures specifically required by the protocol shall not be borne by the subject, unless the law of the Member State concerned provides otherwise.
Article 93 Data protection
1. Member States shall apply Directive 95/46/EC to the processing of personal data carried out in the Member States pursuant to this Regulation. 2. Regulation (EC) No 45/2001 shall apply to the processing of personal data carried out by the Commission and the Agency pursuant to this Regulation.
Article 94 Penalties
1. Member States shall lay down rules on penalties applicable to infringements of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate and dissuasive. 2. The rules referred to in paragraph 1 shall address, inter alia, the following: (a) non-compliance with the provisions laid down in this Regulation on submission of information intended to be made publicly available to the EU database; (b) non-compliance with the provisions laid down in this Regulation on subject safety. The rules referred to in paragraph 1 shall address, inter alia, the following: (a) non-compliance with the provisions laid down in this Regulation on submission of information intended to be made publicly available to the EU database; (b) non-compliance with the provisions laid down in this Regulation on subject safety.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 94 Penalties):
1. Member States shall lay down rules on penalties applicable to infringements of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate and dissuasive. 2. The rules referred to in paragraph 1 shall address, inter alia, the following: (a) non-compliance with the provisions laid down in this Regulation on submission of information intended to be made publicly available to the EU database; (b) non-compliance with the provisions laid down in this Regulation on subject safety.
Article 95 Civil and criminal liability
This Regulation is without prejudice to national and Union law on the civil and criminal liability of a sponsor or an investigator.
Article 96 Repeal
1. Directive 2001/20/EC is repealed as from the date referred to in the second paragraph of Article 99. 2. References to Directive 2001/20/EC shall be construed as references to this Regulation and shall be read in accordance with the correlation table laid down in Annex VII.
Article 97 Review
Five years after the date referred to in the second paragraph of Article 99, and every five years thereafter, the Commission shall present a report to the European Parliament and to the Council on the application of this Regulation. That report shall include an assessment of the impact that the Regulation has had on scientific and technological progress, comprehensive information on the different types of clinical trials authorised pursuant to this Regulation, and the measures required in order to maintain the competitiveness of European clinical research. The Commission shall, if appropriate, present a legislative proposal based on that report in order to update the provisions set out in this Regulation.
Article 98 Transitional provision
1. By way of derogation from Article 96(1) of this Regulation, where the request for authorisation of a clinical trial has been submitted before the date referred to in the second paragraph of Article 99 of this Regulation pursuant to Directive 2001/20/EC, that clinical trial shall continue to be governed by that Directive until three years from that date. 2. By way of derogation from Article 96(1) of this Regulation, where the request for authorisation of a clinical trial is submitted between six months after the date of publication of the notice referred to in Article 82(3) of this Regulation and 18 months after the date of publication of that notice, or, if the publication of that notice occurs earlier than 28 November 2015, where that request is submitted between 28 May 2016 and 28 May 2017, that clinical trial may be started in accordance with Articles 6, 7 and 9 of Directive 2001/20/EC. That clinical trial shall continue to be governed by that Directive until 42 months after the date of publication of the notice referred to in Article 82(3) of this Regulation, or, if that publication occurs earlier than 28 November 2015, until 28 May 2019.
Article 99 Entry into force
This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union . It shall apply as from six months after the publication of the notice referred to in Article 82(3), but in any event no earlier than 28 May 2016. This Regulation shall be binding in its entirety and directly applicable in all Member States.
Amendment rationale: CONTEXT OF THE PROPOSAL Reasons for and objectives of the proposal Pursuant to the Protocol on Ireland/Northern Ireland (“the Protocol”) of the Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community 1 (the ‘Withdrawal Agreement’) , the importation of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the possession of a manufacturing and import authorisation. These shall be in compliance with the obligations of the EU acquis for clinical trials . During these last years, the United Kingdom in respect of Northern Ireland as well as the small markets of the European Union (i.e. Malta, Ireland and Cyprus) that are dependent on supply of medicinal products from the United Kingdom, have raised issues with respect to the ability of economic operators to comply with all provisions of the acquis for medicines after the end of the transition period provided for in the Withdrawal Agreement, including medicines used in clinical trials, having regard in particular to the importation requirements . The Commission Notice of 25 January 2021 2 provides for a grace period of one year (until end-December 2021) , including for the importation requirements for investigational medicines , t o ensure undisrupte d supply of medicines to Northern Ireland, Cyprus, Ireland and Malta . Despite the transition period, it still proves very difficult for certain operators currently based in parts of the United Kingdom other than Northern Ireland to adapt as required by the Protocol. The main reasons are the too high adjustment costs relative to the small size of the Northern Irish market and the complex logistics involved, for which no viable alternative logistical hubs in Northern Ireland have been identified. For the markets of Cyprus, Malta and Ireland, the same issues arose, and in addition, difficulties were seen with to ensure that clinical trial participants have access to certain medicinal products due to supply chains reliance on other parts of the United Kingdom than Northern Ireland. Disruption in supply of investigational medicinal products would pose potential risk to the safety and well-being of participants in ongoing clinical trials as well as hinder the setting up of new clinical trials in these Member States and in Northern Ireland. The objectives of this proposal are to address the issues related to investigational medicinal products, to prevent an adverse impact on the ir supply and , as a result, on the execution of clinical trials authorised under Regulation (EU) 536/2014 3 in Northern Ireland, Cyprus, Ireland and Malta . This proposal allows exceptionally that the manufacturing and import authorisation is not required for investigational medicinal products imported into Cyprus, Ireland, Malta and Northern Ireland from parts of the United Kingdom other than Northern Ireland, provided that certain conditions are fulfilled. For Cyprus, Ireland and Malta, this derogation is of a temporary nature as it is expected that these markets will gradually be supplied through Member States. A transition period of 3 years seems sufficient. Although Regulation (EU) 536/2014 entered into force in 2014, its applicability was made dependent on the full functionality of the European Portal and Database. The Commission published th e notice of full functionality on 31 July 2021 , triggering a 6-month period before applicability on 31 January 2022. 4 As a transit i o nal measure, during the first year (until 31 January 2023), spon sors can chose to submit a clinical trial application in line with the rules of Regulation (EU) 536/2014 or through the rules of Directive 2001/20 /EC 5 . Trials authorised under that Directive can continue until 31 January 2025. Therefore, this proposal should be read in conjunction with the conceptually identical changes to Directive 2001/20 proposed in COM(2021)997 of 17 December 2021 as both legal acts can apply to different clinical trials in the EU until 31 January 2025. For this reason, this separate proposal was given an exemption from an additional fiche for the agenda planning. Considering the urgency needed to address the issues, the roadmap for this initiative will not be provided. 
Revised version (Article 99 Entry into force):
This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union . It shall apply as from six months after the publication of the notice referred to in Article 82(3), but in any event no earlier than 28 May 2016.