Activities of Philippe JUVIN related to 2012/0192(COD)
Plenary speeches (1)
Clinical trials on medicinal products for human use (debate)
Shadow reports (1)
REPORT on the proposal for a regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC PDF (1 MB) DOC (2 MB)
Shadow opinions (1)
OPINION on the proposal for a regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC
Amendments (226)
Amendment 35 #
Proposal for a regulation
Recital 9
Recital 9
(9) The risk to subject safety in a clinical trial mainly stems from two sources: the investigational medicinal product and the intervention. Many clinical trials, however, pose only a minimal additional risk to subject safety compared to normal clinical practice. This is in particular the case where the investigational medicinal product is covered by a marketing authorisation (i.e. the quality, safety and efficacy has already been assessed in the course of the marketing authorisation procedure) and where the intervention poses only very limited additional risk to the subject compared to normal clinical practice. Those ‘low-interventionminimal-risk clinical trials’ are often of crucial importance to assess standard treatments and diagnoses, thereby optimising the use of medicinal products and thus contributing to a high level of public health. They should be subject to less stringent rules, such as shorter deadlines for approvalGiven that minimal- risk clinical trials have only a very limited and temporary adverse effect – if any – on the subject’s health, they should be subject to less stringent rules, such as shorter deadlines for approval. They should, however, be subject to the vigilance and traceability rules governing normal clinical practice.
Amendment 37 #
Proposal for a regulation
Recital 11
Recital 11
(11) The authorisation procedure should provide for the possibility to suspend the assessment in order to allow the sponsor to address questions or comments raised during the assessment of the application dossier. The maximum duration of the suspension should reflect whether the clinical trial is a low-intervention clinical trialposes only a low risk or not. Moreover, it should be ensured that, following the end of the suspension, there is always sufficient time for assessing the additional information submitted.
Amendment 44 #
Proposal for a regulation
Recital 22
Recital 22
(22) The human dignity and right to the integrity of the person are recognized in the Charter of Fundamental Rights of the European Union. In particular, the Charter requires that any intervention in the field of biology and medicine cannot be performed without free and informed consent of the person concerned. Directive 2001/20/EC contained an extensive set of rules for the protection of subjects. These rules should be upheld. Regarding tThe rules concerning the determination of the legal representative of incapacitated persons and minors, those rulee definition of incapacitated persons and vulnerable persons and the resulting provisions diverge in Member States. It should therefore be left to Member States to determine the legal representative of incapacitated persons and minors and, where applicable, to introduce more restrictive provisions at national level.
Amendment 45 #
Proposal for a regulation
Recital 23
Recital 23
(23) This Regulation should provide for clear rules concerning informed consent in emergency situations. Such situations relate to cases where for example a patient has suffered a sudden life-threatening medical condition due to multiple traumas, strokes or heart attacks, necessitating immediate medical intervention. For such cases, intervention within an ongoing clinical trial, which has already been approved, may be pertinent. However, in certain circumstances, due to the unconsciousness of the patient and the absence of an immediately available legal representative, it is not possible to obtain informed consent prior to the intervention. The Regulation should therefore set clear rules whereby such patients may be enrolled in the clinical trial under very strict conditions. For example, in cases where the research needs to start without delay and there is reason to expect that the potential benefit to the subject of taking part in the clinical trial outweighs the risks or the subject’s participation entails only a minimal risk, it should be possible for the clinical trial to begin without his or her prior consent. In addition, the said clinical trial should relate directly to the medical condition which causes the impossibility of the patient to give informed consent. Any previously expressed objection by the patient must be respected, and informed consent from the subject or the legal representative should be sought as soon as possible.
Amendment 59 #
Proposal for a regulation
Article 2 – paragraph 2 – point 2 – point a
Article 2 – paragraph 2 – point 2 – point a
a) the investigational medicinal products arhave not been granted a marketing authorisedation;
Amendment 60 #
Proposal for a regulation
Article 2 – paragraph 2 – point 2 – point c
Article 2 – paragraph 2 – point 2 – point c
Amendment 61 #
Proposal for a regulation
Article 2 – paragraph 2 – point 2 – point d
Article 2 – paragraph 2 – point 2 – point d
d) the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical studydetermined by the research protocol;
Amendment 62 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – introductory part
Article 2 – paragraph 2 – point 3 – introductory part
3) ‘Low-interventionMinimal-risk clinical trial’ : a clinical trial whichpresents a minimal risk if, given the nature and extent of the intervention, it can be expected to have only a very small and temporary impact - if any - on the subject’s health. A ‘minimal-risk clinical trial’ fulfils all of the following conditions:
Amendment 63 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – point a
Article 2 – paragraph 2 – point 3 – point a
a) the investigational medicinal products arehave been granted a marketing authorisedation;
Amendment 65 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – point b
Article 2 – paragraph 2 – point 3 – point b
b) according to the protocol of the clinical trial, the investigational medicinal products are used in accordance with the terms of the marketing authorisation or their use is a standard treatmentin line with normal clinical practice in any of the Member States concerned;
Amendment 70 #
Proposal for a regulation
Article 2 – paragraph 2 – point 6
Article 2 – paragraph 2 – point 6
Amendment 71 #
Proposal for a regulation
Article 2 – paragraph 2 – point 8
Article 2 – paragraph 2 – point 8
8) ‘Auxiliary medicinal product’: a medicinal product used in the context of a clinical trial, but not as an investigational medicinal product;. Auxiliary medicinal products include, in particular, medicinal products used for background treatment, pharmacological agents, rescue medication or medicinal products used to assess end-points in a clinical trial. Auxiliary medicinal products do not include medicaments which are unconnected with the clinical trial and are not pertinent to the trial design.
Amendment 77 #
Proposal for a regulation
Article 2 – paragraph 2 – point 14
Article 2 – paragraph 2 – point 14
14) ‘Investigator’: an individual whose training and experience meet the requirements laid down in Article 46 of this Regulation and who is responsible for the conduct of a clinical trial at a clinical trial site;
Amendment 78 #
Proposal for a regulation
Article 2 – paragraph 2 – point 14 a (new)
Article 2 – paragraph 2 – point 14 a (new)
14a. ‘Principal investigator’: an investigator responsible for a team of investigators tasked with the conduct of a clinical trial at the same clinical trial site;
Amendment 79 #
Proposal for a regulation
Article 2 – paragraph 2 – point 14 b (new)
Article 2 – paragraph 2 – point 14 b (new)
14b. ‘Coordinating investigator’: investigator responsible for coordinating a multicentre trial in one or more Member States;
Amendment 80 #
Proposal for a regulation
Recital 2
Recital 2
(2) In order to allow for independent control as to whether these principles are adhered to, a clinical trial should be subject to prior authorisation, and approval by an ethics committee prior to commencement.
Amendment 80 #
Proposal for a regulation
Article 2 – paragraph 2 – point 17
Article 2 – paragraph 2 – point 17
17) ‘Incapacitated subject’: a subject who is, for other reasons than the age of legal competence to give informed consent, legallylegally or de facto, incapable of giving informed consent according to the laws of the Member State concerned;
Amendment 81 #
Proposal for a regulation
Article 2 – paragraph 2 – point 19
Article 2 – paragraph 2 – point 19
19) '‘Informed consent'’: a process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been duly informed, according to the laws of the Member State concerned, of all aspects of the trial that are relevant to the subject'’s decision to participate;
Amendment 84 #
Proposal for a regulation
Recital 3 a (new)
Recital 3 a (new)
(3a) The scope of this Regulation is essentially identical to that of Directive 2001/20/EC. Although it is limited to clinical research on medicinal products for human use, it is very wide in that it only excludes clinical studies that do not involve an ‘intervention’ i.e. surveys by medical practitioners without additional intervention. ‘Non-interventional studies’ are post-authorisation safety studies initiated, managed or financed by the marketing authorisation holder. These enable data to be ‘mined’, and are covered by Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use.
Amendment 86 #
Proposal for a regulation
Recital 4
Recital 4
(4) Directive 2001/20/EC aimed to simplify and harmonise the administrative provisions governing clinical trials in the European Union. However, experience shows that a harmonised approach to the regulation of clinical trials has only been partly achieved. This makes it in particular difficult to perform a clinical trial in several Member States. Scientific development however, suggests that future clinical trials will target more specific patient populations, such as subgroups identified through genomic information. In order to include a sufficient number of patients for such trials it may be necessary to involve many, or all, Member States. The new procedures for the authorisation of clinical trials should stimulate the inclusion of as many member states as possible. Therefore, in order to simplify submission procedures, the multiple submission of largely identical information should be avoided and replaced by the submission of one application dossier through a single submission portal to all the Member States concerned. Given that clinical trials carried out in a single Member State are equally indispensable to European clinical research, the procedure under this regulation should also cover such trials. The application dossier for such clinical trials should also be sent via the single European portal.
Amendment 90 #
Proposal for a regulation
Recital 8
Recital 8
(8) The timelines for assessing an application dossier for clinical trials should be sufficiently long to assess the file, while ensuring quick access to new, innovative treatments and ensuring that the Union remains an attractive place for conducting clinical trials. Against this background, Directive 2001/20/EC introduced the concept of tacit authorisation. This concept should be maintained in order to ensure that timelines are adhered to. If a Member State concerned and a reporting Member State do not produce the assessment report, the assessment or the decision within the set deadlines, the concept of tacit authorisation should apply automatically. In the event of a public health crisis, Member States should have the possibility to assess and authorise a clinical trial application swiftly. No minimal timelines for approval should therefore be established.
Amendment 95 #
Proposal for a regulation
Article 5 – paragraph 2 – introductory part
Article 5 – paragraph 2 – introductory part
2. Within six calendar days following submission of the application dossier, the proposed reporting Member State shall notify the sponsor through the EU portal of the following:
Amendment 100 #
Proposal for a regulation
Recital 9
Recital 9
(9) The risk to subject safety in a clinical trial mainly stems from two sources: the investigational medicinal product and the intervention. Many clinical trials, however, pose only a minimal additional risk to subject safety compared to normal clinical practice. This is in particular the case where the investigational medicinal product is covered by a marketing authorisation (i.e. the quality, safety and efficacy has already been assessed in the course of the marketing authorisation procedure) and where the intervention poses only very limited additional risk to the subject compared to normal clinical practice. Those "low-interventionrisk clinical trials" are often of crucial importance to assess standard treatments and diagnoses, thereby optimising the use of medicinal products and thus contributing to a high level of public health. They should be subject to less stringent rules, such as shorter deadlines for approval.
Amendment 100 #
Proposal for a regulation
Article 5 – paragraph 3
Article 5 – paragraph 3
3. Where the proposed reporting Member State has not notified the sponsor within the time period referred to in paragraph 2, the clinical trial applied for shall be considered as falling within the scope of this Regulation, the application shall be considered complete, the clinical trial shall be considered a low-intervention clregarded as posing a minicmal trialsk if this is claimed by the sponsor, and the proposed reporting Member State shall be the reporting Member State.
Amendment 101 #
Proposal for a regulation
Recital 9 a (new)
Recital 9 a (new)
(9a) In case of an urgent situation as well as for rare and ultra-rare diseases which are life-threatening and for which therapeutic options and expertise are limited and geographically spread across the world, Member-States should have the possibility to assess and authorise clinical trial applications in priority.
Amendment 101 #
Proposal for a regulation
Article 5 – paragraph 4 – subparagraph 1
Article 5 – paragraph 4 – subparagraph 1
Where the proposed reporting Member State finds that the application is not complete, that the clinical trial applied for does not fall within the scope of this Regulation, or that the clinical trial is not a low-interventionminimal-risk clinical trial while this is claimed by the sponsor, it shall inform the sponsor thereof through the EU portal and shall set a maximum of six days for the sponsor to comment or to complete the application through the EU portal.
Amendment 102 #
Proposal for a regulation
Article 5 – paragraph 4 – subparagraph 3
Article 5 – paragraph 4 – subparagraph 3
Where the proposed reporting Member State has not notified the sponsor according to points (a) to (d) of paragraph 2 within three days following receipt of the comments or of the completed application, the application shall be considered complete, the clinical trial shall be considered as falling within the scope of this Regulation, the clinical trial shall be considered as a low-intervention clregarded as posing a minicmal trialsk if this is claimed by the sponsor, and the proposed reporting Member State shall be the reporting Member State.
Amendment 104 #
Proposal for a regulation
Recital 9 d
Recital 9 d
(9d) ‘Experimental medicinal product’ means any active ingredient in a pharmaceutical or placebo form tested or used as a reference in a clinical trial, including a medicinal product which is covered by a marketing authorisation but which is used off-label or in accordance with current clinical practice.
Amendment 105 #
Proposal for a regulation
Recital 9 e
Recital 9 e
(9e) ‘Auxiliary medicinal product’ means any medicinal product used in the context of a clinical trial but not as an experimental medicinal product. Auxiliary medicinal products include, in particular, medicinal products used for background treatment, pharmacological agents, rescue medication or medicinal products used to assess end-points in a clinical trial. Auxiliary medicinal products do not include medicaments which are unconnected with the clinical trial and are not pertinent to the trial design.
Amendment 106 #
Proposal for a regulation
Recital 9 f
Recital 9 f
(9f) All the deadlines set out in this regulation should be based on calendar days. Since the Member States of the European Union have different calendars of public holidays, a procedure based on working days could result in different deadlines for validation, assessment and decisions in one of the Member States concerned.
Amendment 111 #
Proposal for a regulation
Article 6 – paragraph 6 – subparagraph 1
Article 6 – paragraph 6 – subparagraph 1
Amendment 113 #
Proposal for a regulation
Recital 11
Recital 11
(11) The authorisation procedure should provide for the possibility to suspend the assessment in order to allow the sponsor to address questions or comments raised during the assessment of the application dossier. The maximum duration of the suspension should reflect whether the clinical trial is a low-intervention or medium-risk clinical trial or not. Moreover, it should be ensured that, following the end of the suspension, there is always sufficient time for assessing the additional information submitted.
Amendment 116 #
Proposal for a regulation
Recital 12 a (new)
Recital 12 a (new)
(12a) Whereas most clinical trials are conducted for the assessment of therapies, targeted at large patient populations, and involving a large sample of patient populations, the present regulation should not discriminate against patients suffering from rare and ultra-rare diseases, and should integrate the specificities of low- prevalence conditions into the assessment of a trial.
Amendment 117 #
Proposal for a regulation
Article 6 – paragraph 7 a (new)
Article 6 – paragraph 7 a (new)
7a. Where the reporting Member State does not submit the assessment report within the time periods stipulated in paragraphs 4, 6 and 7, Part I of the clinical trial shall be considered as accepted by the reporting Member State.
Amendment 119 #
Proposal for a regulation
Article 7 – paragraph 1 – subparagraph 1 – point h a (new)
Article 7 – paragraph 1 – subparagraph 1 – point h a (new)
(ha) compliance with more restrictive national provisions relating to clinical trials involving vulnerable individuals.
Amendment 120 #
Proposal for a regulation
Article 7 – paragraph 3 a (new)
Article 7 – paragraph 3 a (new)
3a. Where the Member State concerned does not submit the assessment report within the time periods stipulated in paragraphs 2 and 3, Part II shall be considered as accepted by the Member State concerned.
Amendment 121 #
Proposal for a regulation
Article 7 – paragraph 3 b (new)
Article 7 – paragraph 3 b (new)
3b. In the event of a Member State refusing authorisation on the basis of Part II, the sponsor may appeal, once only, to the Member State concerned through the European Union portal referred to in Article 77. The sponsor may send additional explanations within seven days. The Member State concerned shall assess for a second time, for its own territory, the aspects referred to in Article 7(1), and shall take account of the additional explanations provided by the sponsor. The Member State concerned shall complete its assessment within seven days from the date on which the additional explanations are received. Where the Member State concerned refuses authorisation or does not provide a conclusion as regards Part II within the seven-day time period, the application shall be considered as definitively refused and the clinical trial shall not take place in the Member State concerned.
Amendment 122 #
Proposal for a regulation
Article 7 – paragraph 3 – subparagraph 3
Article 7 – paragraph 3 – subparagraph 3
Amendment 123 #
Proposal for a regulation
Article 8 – paragraph 2 a (new)
Article 8 – paragraph 2 a (new)
2a. Where the Member State concerned disagrees with the conclusion of the reporting Member State on the basis of points (a) and (b) of the second subparagraph of paragraph 2, the clinical trial shall not take place in the Member State concerned.
Amendment 124 #
Proposal for a regulation
Recital 22
Recital 22
(22) The human dignity and right to the integrity of the person are recognized in the Charter of Fundamental rights of the European Union. In particular, the Charter requires that any intervention in the field of biology and medicine cannot be performed without free and informed consent of the person concerned. Directive 2001/20/EC contained an extensive set of rules for the protection of subjects. These rules should be upheld. Regarding tThe rules concerning the determination of the legal representative of incapacitated persons and minors, those rulese definition of incapacitated and vulnerable persons and the provisions resulting from that definition, diverge in Member States. It should therefore be left to Member States to determine the legal representative of incapacitated persons and minors and where necessary to enact rules affording greater protection at national level.
Amendment 126 #
Proposal for a regulation
Recital 23
Recital 23
(23) This Regulation should provide for clear rules concerning informed consent in emergency situations. Such situations relate to cases where for example a patient has suffered a sudden life-threatening medical condition due to multiple traumas, strokes or heart attacks, necessitating immediate medical intervention. For such cases, intervention within an ongoing clinical trial, which has already been approved, may be pertinent. However, in certain circumstances, due to the unconsciousness of the patient and the absence of an immediately available legal representative, it is not possible to obtain informed consent prior to the intervention. The Regulation should therefore set clear rules whereby such patients may be enrolled in the clinical trial under very strict conditions. For example, in cases where the research needs to start without delay and there is reason to expect that the potential benefit to the subject of taking part in the clinical trial outweighs the risks of the subject’s participation or entails only a minimal risk, it should be possible for the clinical trial to begin without his or her prior consent. In addition, the said clinical trial should relate directly to the medical condition which causes the impossibility of the patient to give informed consent. Any previously expressed objection by the patient must be respected, and informed consent from the subject or the legal representative should be sought as soon as possible.
Amendment 130 #
Proposal for a regulation
Article 8 – paragraph 2 – subparagraph 3
Article 8 – paragraph 2 – subparagraph 3
Where the Member State concerned disagrees with the conclusion of the reporting Member State on the basis of point (a) of the second subparagraph, it shall communicate its disagreement, together with a detailed justification based on scientific and socio-economic arguments, and a summary thereof, through the EU portal to the Commission, to all Member States, and to the sponsor.
Amendment 131 #
Proposal for a regulation
Recital 25
Recital 25
(25) In order to allow patients to assess possibilities to participate in a clinical trial, and to allow for effective supervision of a clinical trial by the Member State concerned, the start of the clinical trial, the end of recruitment for the clinical trial and the end of the clinical trial should be notified. In accordance with international standards, the results of the clinical trial should be reported to the competent authorities within onetwo years of the end of the clinical trial.
Amendment 132 #
Proposal for a regulation
Article 9 – paragraph 1
Article 9 – paragraph 1
1. Member States shall ensure that the persons validating and assessing Parts I and II of the application do not have conflicts of interest, are independent of the sponsor, the institution of the trial site and the investigators involved, as well as free of any other undue influence.
Amendment 133 #
Proposal for a regulation
Article 9 – paragraph 2
Article 9 – paragraph 2
2. Member States shall ensure that the assessment is done jointly by a reasonable number of persons who collectively have the necessary qualifications and experienceof Part II is done by a group of people at least half of whom meet the conditions laid down in Article 46 of this Regulation.
Amendment 135 #
Proposal for a regulation
Article 10 – paragraph 2 a (new)
Article 10 – paragraph 2 a (new)
2a. Where the clinical trial concerns other categories of subjects who are considered vulnerable under national law, the application to conduct the clinical trial shall be assessed on the basis of the national law of the Member States concerned.
Amendment 137 #
Proposal for a regulation
Recital 30
Recital 30
(30) The conduct of a clinical trial should be adequately monitored by the sponsor in order to ensure the reliability and robustness of the results. Monitoring may also contribute to subject safety, taking into account the characteristics of the clinical trial and respect for fundamental rights of subjects. When establishing the extent of monitoring, the characteristics of the clinical trial should be taken into accountMonitoring should be adapted to the nature of the trial and focus on mitigating the key risks.
Amendment 139 #
Proposal for a regulation
Article 13 – paragraph 1
Article 13 – paragraph 1
Amendment 142 #
Proposal for a regulation
Article 17 – paragraph 4 – subparagraph 3
Article 17 – paragraph 4 – subparagraph 3
Where the reporting Member State has not notified the sponsor according to points (a) to (c) of paragraph 2 within three days following receipt of the comments or of the completed application, the application shall be considered complete and, where the clinical trial is a low-intervention clinicposes a minimal trialsk, that it will remain a low-interventionminimal-risk clinical trial after its substantial modification.
Amendment 144 #
Proposal for a regulation
Article 28 – paragraph 1 – point a
Article 28 – paragraph 1 – point a
Amendment 145 #
Proposal for a regulation
Article 28 – paragraph 1 – point b
Article 28 – paragraph 1 – point b
(b) compliance with point (a) is permanently observedthe principles referred to in point (a) are observed throughout the study;
Amendment 146 #
Proposal for a regulation
Article 28 – paragraph 1 – point c
Article 28 – paragraph 1 – point c
Amendment 147 #
Proposal for a regulation
Article 28 – paragraph 1 – point d
Article 28 – paragraph 1 – point d
(d) the subject or, where the subject is not able to give informed consent, his or her legal representative has had the opportunity, in a prior interview with the investigator or a member of the investigating teamhis/her representative, to understand the objectives, risks and inconveniences of the clinical trial, and the conditions under which it is to be conducted and has also been informed of the right to withdraw from the clinical trial at any time without any resulting detriment;
Amendment 148 #
Proposal for a regulation
Article 28 – paragraph 1 – point d a (new)
Article 28 – paragraph 1 – point d a (new)
(da) the subject or, where the subject is not able to give informed consent, his or her legal representative has given informed consent;
Amendment 150 #
Proposal for a regulation
Article 29 – paragraph 1 a (new)
Article 29 – paragraph 1 a (new)
(1a) Without prejudice to Article 28, where the clinical trial poses a minimal risk, informed consent may be given orally, provided that it is duly documented, in accordance with the legislation of the Member State concerned;
Amendment 151 #
Proposal for a regulation
Article 30 – paragraph 1 – point b
Article 30 – paragraph 1 – point b
(b) the incapacitated subject has received adequate information in relation to his or her capacity for understanding regarding the trial, the risks and the benefits from the investigator or his/her representative, in accordance with the legislation of the Member State concerned;
Amendment 152 #
Proposal for a regulation
Article 30 – paragraph 1 – point f
Article 30 – paragraph 1 – point f
(f) such research relates directly to a life- threatening or debilitating medical condition from which the subjectperson concerned suffers;
Amendment 153 #
Proposal for a regulation
Article 30 – paragraph 1 – point h
Article 30 – paragraph 1 – point h
(h) there are grounds for expecting that participation in the clinical trial will produce a benefit to the incapacitated subject outweighing the risks or will produce no risk at allonly a minimal risk.
Amendment 154 #
Proposal for a regulation
Article 31 – paragraph 1 a (new)
Article 31 – paragraph 1 a (new)
(1a) Without prejudice to Article 31(1), where the clinical trial poses a minimal risk and the consent of the second person with parental authority cannot be given within a period consistent with the methodological requirements of the research, and provided that a favourable ethical opinion has been issued, the clinical trial on the minor may proceed on the basis of the consent of the only person present with parental authority.
Amendment 155 #
Proposal for a regulation
Recital 41
Recital 41
(41) Investigational and auxiliary medicinal products should be appropriately labelled in order to ensure subject safety and the reliability and robustness of data generated in a clinical trial, and in order to allow for the distribution of those products to clinical trial sites throughout the Union. The rules for labelling should be adapted to the risks to subject safety and the reliability and robustness of data generated in a clinical trial. WIn medium- or low-risk trials, where the investigational or auxiliary medicinal product have already been placed on the market as an authorised medicinal product in accordance with Directive 2001/83/EC, as a general rule no additional labelling should be required for open-label trials. Instead of a useless and inappropriate product labelling, and in line with GMP 2009 (Annex 13, Article 27), the participants to such researches could be given a leaflet or card which provides useful information on the trial and be instructed to keep this in their possession at all times. Moreover, there are specific products, such as radiopharmaceuticals used as diagnostic investigational medicinal product, where the general rules on labelling are inappropriate in view of the very controlled setting of the use of radiopharmaceuticals in clinical trials.
Amendment 155 #
Proposal for a regulation
Article 31 – paragraph 1 – point a
Article 31 – paragraph 1 – point a
(a) the informed consent of thetwo legal representatives has been obtainedve given their consent, whereby consent shall represent the minor’s presumed will;
Amendment 156 #
Proposal for a regulation
Article 31 – paragraph 1 – point h
Article 31 – paragraph 1 – point h
(h) some direct benefit for the groupcategory of patients isconcerned by the trial may be obtained from the clinical trial.
Amendment 157 #
Proposal for a regulation
Article 32 – paragraph 1 – introductory part
Article 32 – paragraph 1 – introductory part
1. By way of derogation from points (c) and (d) of Article 28(1), from points (a) and (b) of Article 30(1) and from points (a) and (b) of Article 31(1), informed consent may be obtained after the start of the clinical trial to continue, referred to in Article 29(1), shall be obtained as soon as possible after the start of the clinical trial and information on the clinical trial mayshall be given after the start of the clinical trial provided that all of the following conditions are fulfilled:
Amendment 158 #
Proposal for a regulation
Recital 46
Recital 46
(46) In clinical trials with non-authorised investigational medicinal products, or where the interventionith authorised investigational medicinal products used outside the terms of the marketing authorisation in a treatment regimen distinct from the standard of care, or where the diagnostic procedure poses more than an insignificant risk to subject safety, compensation should be ensured for damages successfully claimed in accordance with the applicable laws.
Amendment 159 #
Proposal for a regulation
Article 32 – paragraph 1 – point a
Article 32 – paragraph 1 – point a
(a) due to the urgency of the situation, caused by a sudden life-threatening or other sudden serious medical condition, it is impossible to obtain prior informed consent from the subject and it is impossible to supply prior information to the subject;
Amendment 160 #
Proposal for a regulation
Article 32 – paragraph 1 – point b
Article 32 – paragraph 1 – point b
(b) nothe consent of the legal representative is availablecannot be given within a period consistent with the methodological requirements of the research;
Amendment 162 #
Proposal for a regulation
Article 32 – paragraph 1 – point d
Article 32 – paragraph 1 – point d
Amendment 164 #
Proposal for a regulation
Article 32 – paragraph 1 – point e
Article 32 – paragraph 1 – point e
(e) the clinical trial poses a minimal risk to, and imposes a minimal burden on, the subjectre are grounds for expecting that participation in the clinical trial will produce a benefit to the subject outweighing the risks or will produce only a minimal risk.
Amendment 165 #
Proposal for a regulation
Article 32 – paragraph 2 a (new)
Article 32 – paragraph 2 a (new)
2a. If the subject or, where applicable, his/her legal representative does not give his/her consent for the research to continue, he/she shall be informed that he/she may object to the use of data obtained prior to the denial of consent.
Amendment 166 #
Proposal for a regulation
Recital 52
Recital 52
(52) The database should contain all relevant information as regards the clinical trial. No personal data of data subjects participating in a clinical trial should be recorded in the database and allow public dissemination of objective information in order to support European research and to increase knowledge in the field of public health. It should not undermine innovation or competitiveness of European industries. No personal data of data subjects participating in a clinical trial should be recorded in the database, and it should not hamper the protection of commercial interests, including intellectual property, as provided for by Article 4 of Regulation 1049/2001. The information in the database should be public, unless specific reasons require that a piece of information should not be published, in order to protect the right of the individual to private life and the right to the protection of personal data, recognised by Articles 7 and 8 of the Charter of Fundamental Rights of the European Union, or commercially confidential information, as foreseen by Article 4 of Regulation 1049/2001.
Amendment 166 #
Proposal for a regulation
Article 32 – paragraph 2 – subparagraph 1 – point a
Article 32 – paragraph 2 – subparagraph 1 – point a
(a) regarding incapacitated subjects and minors, the informed consent referred to in paragraph 1 shall be obtained as soon as possible from the legal representative and the information referred to in paragraph 1 shall be given as soon as possible to the subject by the investigator or his/her representative;
Amendment 167 #
Proposal for a regulation
Article 33 – paragraph 1 – subparagraph 2
Article 33 – paragraph 1 – subparagraph 2
That notification shall be made within 1530 days from the start of the clinical trial in relation to that Member State.
Amendment 169 #
Proposal for a regulation
Recital 52 a (new)
Recital 52 a (new)
Amendment 169 #
Proposal for a regulation
Article 33 – paragraph 2 – subparagraph 2
Article 33 – paragraph 2 – subparagraph 2
That notification shall be made within 1530 days from the end of the recruitment of subjects. In case of re-start of recruitment, paragraph 1 shall apply.
Amendment 171 #
Proposal for a regulation
Article 34 – paragraph 2 – subparagraph 2
Article 34 – paragraph 2 – subparagraph 2
That notification shall be made within 1530 days from the end of the clinical trial.
Amendment 174 #
Proposal for a regulation
Recital 60
Recital 60
(60) Without prejudice to the national systems for the cost and reimbursement of medical treatments, subjects should not have to pay for investigational medicinal products. For the low-risk trial, and the medium-risk trials (when the treatment regimen represents the standard of care), and when registration is not the initial objective of the investigator-initiated trial, the cost of the investigational medicinal product should be borne by the national healthcare system.
Amendment 181 #
Proposal for a regulation
Article 1 – paragraph 1
Article 1 – paragraph 1
This Regulation shall apply to all clinical trials conducted in the Union.
Amendment 182 #
Proposal for a regulation
Article 43 – paragraph 1
Article 43 – paragraph 1
Safety reporting with regard to auxiliary medicinal products shall be made in accordance with Chapter 3 of Directive 20010/834/ECU.
Amendment 183 #
Proposal for a regulation
Article 2 – paragraph 2 – point 1 – point a
Article 2 – paragraph 2 – point 1 – point a
(a) to discover or verify the clinical, pharmacological or othekinetic or pharmacodynamic effects of one or more medicinal products;
Amendment 183 #
Proposal for a regulation
Article 45 – paragraph 1 – point a
Article 45 – paragraph 1 – point a
(a) whether the clinical trial is a low- interventionminimal- risk clinical trial;
Amendment 184 #
Proposal for a regulation
Article 2 – paragraph 2 – point 1 – point c
Article 2 – paragraph 2 – point 1 – point c
(c) to study the abresorption, distribution, metabolism and excretion of one or more medicinal products;
Amendment 184 #
Proposal for a regulation
Article 48 – paragraph 1 – subparagraph 1
Article 48 – paragraph 1 – subparagraph 1
Investigational medicinal products shall be traceable, stored, destroyed and returned as appropriate and proportionate to ensure subject safety and the reliability and robustness of the data generated in the clinical trial, taking into account whether the investigational medicinal product is authorised, and whether the clinical trial is a low-interventionminimal-risk clinical trial.
Amendment 188 #
Proposal for a regulation
Article 2 – paragraph 2 – point 2 – point a
Article 2 – paragraph 2 – point 2 – point a
(a) there is no marketing authorisation for the investigational medicinal products are not authorised;
Amendment 192 #
Proposal for a regulation
Article 2 – paragraph 2 – point 2 – point c
Article 2 – paragraph 2 – point 2 – point c
Amendment 193 #
Proposal for a regulation
Article 2 – paragraph 2 – point 2 – point d
Article 2 – paragraph 2 – point 2 – point d
(d) the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical studydetermined by the research protocol;
Amendment 196 #
Proposal for a regulation
Article 90 a (new)
Article 90 a (new)
Article 90a Review of the Regulation As from the entry into force of this Regulation, every five years the Commission shall submit to the European Parliament and to the Council a report on the implementation of the Regulation. The report shall include an assessment of the impact that the Regulation has had on scientific and technological progress, and the measures required in order to maintain the competitiveness of European clinical research.
Amendment 197 #
Proposal for a regulation
Article 2 – paragraph 2 – point 2 a (new)
Article 2 – paragraph 2 – point 2 a (new)
(2a) Medium-risk trial : a clinical trial on investigational medicinal products, which are authorised and fall outside the terms of the marketing authorisation according to the protocol. Their use is either: a) supported by sufficient published evidence and/or standard treatment guidelines; b) not supported by sufficient published evidence and/or standard treatment guidelines; The additional diagnostic or monitoring procedures do not pose more than minimal additional risk or burden to the safety of the subjects compared to normal clinical practice in any Member State concerned.
Amendment 198 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – introductory part
Article 2 – paragraph 2 – point 3 – introductory part
(3) ‘Low-intervention clinical trial’: arisk clinical trial’: a clinical trial presents a low risk if, given the nature and extent of the intervention, it can be expected to have only a very small and temporary impact – if any – on the subject’s health. A low-risk clinical trial whichshall fulfils all of the following conditions: (The amendment whereby the term ‘low- intervention clinical trial’ is replaced by ‘low-risk clinical trial’ applies to the entire text. If it is adopted, the change will have to be made throughout the text.)
Amendment 198 #
Proposal for a regulation
Annex I – part 2 – point 9
Annex I – part 2 – point 9
9. In the case of a resubmission, the cover letter shall highlight the changes as compared to the previous submissiongrounds on which the original application was rejected and the changes as compared to the original version of the protocol.
Amendment 200 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – introductory part
Article 2 – paragraph 2 – point 3 – introductory part
(3) ‘Low-interventionrisk clinical trial’: a clinical trial which fulfils all of the following conditions: (Horizontal amendment applying throughout the text. Adopting it will necessitate corresponding changes.)
Amendment 200 #
Proposal for a regulation
Annex I – part 16 – point 61
Annex I – part 16 – point 61
Amendment 201 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – point a
Article 2 – paragraph 2 – point 3 – point a
(a) the investigational medicinal products are authorised; and tested in accordance with their marketing authorisation.
Amendment 202 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – point a
Article 2 – paragraph 2 – point 3 – point a
(a) there is marketing authorisation for the investigational medicinal products are authorised;
Amendment 206 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – point b
Article 2 – paragraph 2 – point 3 – point b
Amendment 208 #
Proposal for a regulation
Article 2 – paragraph 2 – point 3 – point b
Article 2 – paragraph 2 – point 3 – point b
(b) according to the protocol of the clinical trial, the investigational medicinal products are used in accordance with the terms of the marketing authorisation or their use is a standard treatmentin line with usual clinical practice in any of the Member States concerned;
Amendment 213 #
Proposal for a regulation
Article 2 – paragraph 2 – point 4
Article 2 – paragraph 2 – point 4
(4) ‘Non-interventional study’: a clinical study other than a clinical trial, in which the medicinal product or products are prescribed in the usual way in accordance with the terms of the marketing authorisation. The assignment of the subject to a particular therapeutic strategy is not decided in advance by a research protocol, it falls within usual practice, and the decision to prescribe the medicinal product is clearly dissociated from the decision to include the patient in the study. The patients must not be subject to any additional diagnostic or monitoring procedures, and epidemiological methods are used to analyse the data gathered;
Amendment 217 #
Proposal for a regulation
Article 2 – paragraph 2 – point 6
Article 2 – paragraph 2 – point 6
(6) 'Norm‘Usual clinical practice'’: the treatment regime typically followed to treat, prevent, or diagnose a disease or a disorder; (The amendment whereby the term ‘normal clinical practice’ is replaced by ‘usual clinical practice’ applies to the entire text. If it is adopted, the change will have to be made throughout the text.)
Amendment 227 #
Proposal for a regulation
Article 2 – paragraph 2 – point 14
Article 2 – paragraph 2 – point 14
(14) ‘Investigator’: an individual physical person who is trained or has experience to a level equivalent to the stipulations of Article 46 of this Regulation and who is responsible for the conduct of a clinical trial at a clinical trial site;
Amendment 228 #
Proposal for a regulation
Article 2 – paragraph 2 – point 14 a (new)
Article 2 – paragraph 2 – point 14 a (new)
(14a) ‘Principal investigator’: the investigator responsible for a team of investigators conducting a clinical trial at a single site;
Amendment 229 #
Proposal for a regulation
Article 2 – paragraph 2 – point 14 b (new)
Article 2 – paragraph 2 – point 14 b (new)
(14b) ‘Coordinating investigator’: an investigator responsible for the coordination of a clinical trial conducted at several centres in one or more of the Member States concerned;
Amendment 232 #
Proposal for a regulation
Article 2 – paragraph 2 – point 17
Article 2 – paragraph 2 – point 17
(17) ‘Incapacitated subject’: a subject who is, for other reasons than the age of legal competence to give informed consent, legally legally or de facto incapable of giving informed consent according to the laws of the Member State concerned;
Amendment 234 #
Proposal for a regulation
Article 2 – paragraph 2 – point 19
Article 2 – paragraph 2 – point 19
(19) '‘Informed consent'’: a process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been duly informed, in accordance with the law of the Member State in question, of all aspects of the trial that are relevant to the subject'’s decision to participate;
Amendment 238 #
Proposal for a regulation
Article 2 – paragraph 2 – point 22
Article 2 – paragraph 2 – point 22
(22) ‘Start of the clinical trial’: the first act of recruitment of a potential subject, unless defined differently in the protocol;Does not affect English version.)
Amendment 239 #
Proposal for a regulation
Article 2 – paragraph 2 – point 29
Article 2 – paragraph 2 – point 29
(29) ‘Serious adverse event’: any untoward medical occurrence, or other event deemed serious by the investigator in the context of the trial, that at any dose requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect, is life-threatening or results in death;
Amendment 246 #
Proposal for a regulation
Article 3 – paragraph 1 – indent 2
Article 3 – paragraph 1 – indent 2
– the data generated in the clinical trial are goingcan be expected to be reliable and robust.
Amendment 257 #
Proposal for a regulation
Article 5 – paragraph 1 – subparagraph 1
Article 5 – paragraph 1 – subparagraph 1
1. In order to obtain an authorisation, the sponsor shall submit an application dossier to the intended Member States concerned through the portal referred to in Article 77 (hereinafter '‘EU portal'’). At this stage the application dossier shall not be accessible to the public on the EU portal. It shall be made public only on completion of the Part I assessment referred to in Article 6 of this Regulation.
Amendment 260 #
Proposal for a regulation
Article 5 – paragraph 1 – subparagraph 2
Article 5 – paragraph 1 – subparagraph 2
The sponsor shall propose one of the Member States concerned as reporting Member StateMember States concerned shall determine which state shall be the reporting Member State according to an established procedure based on objective criteria which are set by the Commission.
Amendment 262 #
Proposal for a regulation
Article 5 – paragraph 1 – subparagraph 2
Article 5 – paragraph 1 – subparagraph 2
The sponsor shall propose one of the Member States concerned as reporting Member State. The Member States concerned shall be free to choose one of their number as the reporting Member State.
Amendment 266 #
Proposal for a regulation
Article 5 – paragraph 1 – subparagraph 3 a (new)
Article 5 – paragraph 1 – subparagraph 3 a (new)
If the sponsor submits an application dossier to just one of the Member States concerned, that Member State shall automatically be designated as the reporting Member State.
Amendment 267 #
Proposal for a regulation
Article 5 – paragraph 2 – introductory part
Article 5 – paragraph 2 – introductory part
2. Within six calendar days following submission of the application dossier, the proposed reporting Member State shall notify the sponsor through the EU portal of the following:
Amendment 271 #
Proposal for a regulation
Article 5 – paragraph 2 – point d
Article 5 – paragraph 2 – point d
(d) whether the clinical trial is a low- interventionmedium- risk or low-risk clinical trial, where claimed by the sponsor.
Amendment 273 #
Proposal for a regulation
Article 5 – paragraph 3
Article 5 – paragraph 3
3. Where the proposed reporting Member State has not notified the sponsor within the time period referred to in paragraph 2, the clinical trial applied for shall be considered as falling within the scope of this Regulation, the application shall be considered complete, the clinical trial shall be considered a low-interventionmedium-risk or low-risk clinical trial if this is claimed by the sponsor, and the proposed reporting Member State shall be the reporting Member State.
Amendment 277 #
Proposal for a regulation
Article 5 – paragraph 4 – subparagraph 1
Article 5 – paragraph 4 – subparagraph 1
4. Where the proposed reporting Member State finds that the application is not complete, that the clinical trial applied for does not fall within the scope of this Regulation, or that the clinical trial is not a low-interventionmedium-risk or low-risk clinical trial while this is claimed by the sponsor, it shall inform the sponsor thereof through the EU portal and shall set a maximum of six days for the sponsor to comment or to complete the application through the EU portal.
Amendment 282 #
Proposal for a regulation
Article 5 – paragraph 4 – subparagraph 3
Article 5 – paragraph 4 – subparagraph 3
Where the proposed reporting Member State has not notified the sponsor according to points (a) to (d) of paragraph 2 within three days following receipt of the comments or of the completed application, the application shall be considered complete, the clinical trial shall be considered as falling within the scope of this Regulation, the clinical trial shall be considered as a low-interventionmedium-risk or low-risk clinical trial if this is claimed by the sponsor, and the proposed reporting Member State shall be the reporting Member State.
Amendment 283 #
Proposal for a regulation
Article 5 – paragraph 5
Article 5 – paragraph 5
5. For the purposes of this Chapter, the date on which the sponsor is notified in accordance with paragraph 2 shall be the validationadmissibility date of the application. Where the sponsor is not notified, the validationadmissibility date shall be the last day of the time periods referred to in paragraphs 2 and 4. (The amendment substituting ‘admissibility date’ for ‘validation date’ applies to the entire text. If it is adopted, the change will have to be made throughout the text.)
Amendment 287 #
Proposal for a regulation
Article 5 – paragraph 5 b (new)
Article 5 – paragraph 5 b (new)
5b. Any of the Member States concerned shall be free to select those aspects of Parts I and II to be assessed by an ethics committee.
Amendment 293 #
Proposal for a regulation
Article 6 – paragraph 1 – point a – point i – indent 3
Article 6 – paragraph 1 – point a – point i – indent 3
– the reliability and robustness of the data generated in the clinical trial, taking account of statistical approaches, design of the trial and, methodology (including sample size and randomisation, comparator and endpoints); and the prevalence of the condition, especially for rare diseases (which affect no more than five persons per 10 000), and ultra-rare diseases (which meet a prevalence threshold of no more than one affected person per 50 000).
Amendment 297 #
Proposal for a regulation
Article 6 – paragraph 1 – point a – point i – indent 3
Article 6 – paragraph 1 – point a – point i – indent 3
– the reliability and robustness of the data generated inexpected from the clinical trial, taking account of statistical approaches, design of the trial and methodology (including sample size and randomisation, comparator and endpoints);
Amendment 300 #
Proposal for a regulation
Article 6 – paragraph 1 – point a – point ii – indent 4 a (new)
Article 6 – paragraph 1 – point a – point ii – indent 4 a (new)
- the life-threatening and debilitating effects of certain diseases, such as some rare and ultra-rare diseases for which there are limited existing treatment options;
Amendment 306 #
Proposal for a regulation
Article 6 – paragraph 4 – subparagraph 1 – introductory part
Article 6 – paragraph 4 – subparagraph 1 – introductory part
The reporting Member State shall submit Part I of the assessment report, including its conclusion, to the sponsor and to the other Member States concerned, via the EU portal referred to in Article 77 of this Regulation, within the following time periods:
Amendment 312 #
Proposal for a regulation
Article 6 – paragraph 4 – subparagraph 1 – point a
Article 6 – paragraph 4 – subparagraph 1 – point a
(a) within 10 days from the validation date for low-intervention clinical trialrisk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines;
Amendment 315 #
Proposal for a regulation
Article 6 – paragraph 4 – subparagraph 1 – point b
Article 6 – paragraph 4 – subparagraph 1 – point b
(b) within 25 days from the validation date for clinical trials other than low- intervention clinical trialsrisk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines ;
Amendment 319 #
Proposal for a regulation
Article 6 – paragraph 4 – subparagraph 2
Article 6 – paragraph 4 – subparagraph 2
For the purposes of this Chapter, the assessment date shall be the date on which the assessment report is submitted to the sponsor and to the other Member States concerned. As of that date, the assessment report shall be accessible on the EU portal.
Amendment 321 #
Proposal for a regulation
Article 6 – paragraph 5
Article 6 – paragraph 5
5. Until the assessment date, any Member State concerned may communicate to the reporting Member State any considerations relevant to the application. The reporting Member State shall take those considerations duly into account and shall document them in the assessment report. If the assessment report of the reporting Member State deviates from the considerations of the Member States concerned, it shall state the reasons for this deviation in the assessment report.
Amendment 323 #
Proposal for a regulation
Article 6 – paragraph 6 – subparagraph 1
Article 6 – paragraph 6 – subparagraph 1
6. The reporting Member State, and only the reporting Member State, may, between the validation date and the assessment date, request additional explanations from the sponsor, taking into account the considerations that it identifies, as well as considerations raised by the other Member States concerned, as referred to in paragraph 5.
Amendment 325 #
Proposal for a regulation
Article 6 – paragraph 6 – subparagraph 2
Article 6 – paragraph 6 – subparagraph 2
For the purpose of obtaining those additional explanations, the reporting Member State may suspend the time period referred to in paragraph 4 for a maximum of 10 days for low-intervention clinical trials and for a maximum of 20 days for trials other than low-intervention clinical trialrisk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or or standard treatment guidelines and for a maximum of 20 days for trials other than low-risk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines.
Amendment 326 #
Proposal for a regulation
Article 6 – paragraph 6 – subparagraph 2
Article 6 – paragraph 6 – subparagraph 2
For the purpose of obtaining those additional explanations, the reporting Member State may suspend the relevant time period referred to in paragraph 4 for a maximum of 10 days for low-intervention clinical trials and for a maximum of 20 days for trials other than low-intervention clinical trials. The reporting Member State shall inform the sponsor, via the EU portal, of the suspension of the time period.
Amendment 329 #
Proposal for a regulation
Article 6 – paragraph 7 a (new)
Article 6 – paragraph 7 a (new)
7a. Where the reporting Member State does not submit the assessment report within the time periods stipulated in paragraphs 4, 6 and 7, Part I of the clinical trial shall be considered as accepted by the reporting Member State.
Amendment 331 #
Proposal for a regulation
Article 7 – paragraph 1 – subparagraph 1 – introductory part
Article 7 – paragraph 1 – subparagraph 1 – introductory part
The assessments of Parts I and II shall be conducted simultaneously. Each Member State concerned shall assess, for its own territory, the application with respect to the following aspects:
Amendment 338 #
Proposal for a regulation
Article 7 – paragraph 1 – subparagraph 1 – point h a (new)
Article 7 – paragraph 1 – subparagraph 1 – point h a (new)
(ha) compliance with more restrictive national provisions relating to clinical trials involving vulnerable individuals.
Amendment 342 #
Proposal for a regulation
Article 7 – paragraph 3 – subparagraph 1 a (new)
Article 7 – paragraph 3 – subparagraph 1 a (new)
The Member State concerned shall inform the sponsor of the suspension of the deadline via the EU portal.
Amendment 343 #
Proposal for a regulation
Article 7 – paragraph 3 – subparagraph 3
Article 7 – paragraph 3 – subparagraph 3
Where, in response to a request from the Member State concerned, the sponsor does not provide additional explanations within the time period set by the Member State in accordance with the first subparagraph, the application for a clinical trial which is being assessed shall be considered as withdrawn. The withdrawal shall apply only with respect to the Member State concerned.
Amendment 345 #
Proposal for a regulation
Article 7 – paragraph 3 a (new)
Article 7 – paragraph 3 a (new)
3a. Where the Member State concerned does not submit the assessment report within the time periods stipulated in paragraphs 2 and 3, Part II shall be deemed to have been accepted by the Member State concerned.
Amendment 347 #
Proposal for a regulation
Article 8 – title
Article 8 – title
Amendment 348 #
Proposal for a regulation
Article 8 – paragraph 1 – subparagraph 1
Article 8 – paragraph 1 – subparagraph 1
1. Each Member State concerned shall notify the sponsor through the EU Portal as to whetherof its final decision to authorise the clinical trial is, to authorised, whether it is authorised it subject to conditions, or whetherto refuse authorisation is refused.
Amendment 357 #
Proposal for a regulation
Article 8 – paragraph 2 – subparagraph 3
Article 8 – paragraph 2 – subparagraph 3
Where the Member State concerned disagrees with the conclusion of the reporting Member State on the basis of point (a) of the second subparagraph, it shall communicate its disagreement, together with a detailed justification based on scientific and socio-economic arguments, and a summary thereof, through the EU portal to the Commission, to all Member States, and to the sponsor.
Amendment 360 #
Proposal for a regulation
Article 8 – paragraph 2 a (new)
Article 8 – paragraph 2 a (new)
2a. Where the Member State concerned disagrees with the conclusion of the reporting Member State on the basis of points (a) and (b) of the second subparagraph of paragraph 2, the clinical trial shall not take place in the Member State concerned.
Amendment 362 #
Proposal for a regulation
Article 8 – paragraph 3 a (new)
Article 8 – paragraph 3 a (new)
3a. In the event of a Member State refusing authorisation on the basis of Part II, the sponsor may appeal, once only, to the Member State concerned through the EU portal referred to in Article 77. The sponsor may send additional explanations within seven days. The Member State concerned shall assess for a second time, for its own territory, the aspects referred to in Article 7(1), and shall take account of the additional explanations provided by the sponsor. The Member State concerned shall complete its assessment within seven days from the date on which the additional explanations are received. Where the Member State concerned refuses authorisation or fails to provide a conclusion as regards Part II within the seven-day time period, the application shall be deemed to have been definitively refused and the clinical trial shall not take place in the Member State concerned.
Amendment 367 #
Proposal for a regulation
Article 9 – title
Article 9 – title
Persons assessing Parts I and II of the application file
Amendment 368 #
Proposal for a regulation
Article 9 – paragraph 1
Article 9 – paragraph 1
1. Member States shall ensure that the persons validating and assessing Parts I and II of the application do not have conflicts of interest, are independent of the sponsor, the institution of the trial site and the investigators involved, as well as free of any other undue influence.
Amendment 373 #
Proposal for a regulation
Article 9 – paragraph 2
Article 9 – paragraph 2
2. Member States shall ensure that the assessment is done jointly by a reasonable number of persons who collectively have the necessary qualifications and experienceof Part II is done by a group of people at least half of whom meet the conditions laid down in Article 46 of this Regulation.
Amendment 383 #
Proposal for a regulation
Article 10 – paragraph 2 a (new)
Article 10 – paragraph 2 a (new)
2a. Where the clinical trial concerns other categories of subjects who are considered vulnerable under national law, the application to conduct the clinical trial shall be assessed on the basis of the national law of the Member States concerned.
Amendment 388 #
Proposal for a regulation
Article 11 – paragraph -1 (new)
Article 11 – paragraph -1 (new)
The assessments of Parts I and II shall be conducted simultaneously.
Amendment 391 #
Proposal for a regulation
Article 11 a (new)
Article 11 a (new)
Article 11a Clinical trial applications shall be prioritized by Member States to improve, where possible, the defined timelines when the clinical trial is related to a condition that is a rare or ultra-rare disease and, as such, is subject to significant administrative burden due to the extremely small patient populations. Rare and ultra-rare disease are defined as severe, debilitating and often life- threatening diseases which affect fewer than 5 persons per 10 000 or fewer than one person 50 000 in the Union respectively.
Amendment 393 #
Proposal for a regulation
Article 13
Article 13
Amendment 395 #
Proposal for a regulation
Article 14 – paragraph 1 – subparagraph 2
Article 14 – paragraph 1 – subparagraph 2
The application may be submitted only after the notification date of the initial authorisation decision in any Member State.
Amendment 397 #
Proposal for a regulation
Article 14 – paragraph 3 – point a
Article 14 – paragraph 3 – point a
(a) 25 days from the date of submission of the application referred to in paragraph 1 for low-intervention clinical trialsrisk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines ;
Amendment 398 #
Proposal for a regulation
Article 14 – paragraph 3 – point b
Article 14 – paragraph 3 – point b
(b) 35 days from the date of submission of the application referred to in paragraph 1 for clinical trials other than low- intervention clinical trials; risk clinical trials and medium-risk clinical trials using treatment regimens supported by published and/or standard treatment guidelines;
Amendment 402 #
Proposal for a regulation
Article 14 – paragraph 6 – subparagraph 2
Article 14 – paragraph 6 – subparagraph 2
For the purpose of obtaining those additional explanations, the reporting Member State may suspend the relevant time period referred to in paragraph 3 for a maximum of 10 days for low-intervention clinical trials and for a maximum of 20 days for trials other than low-intervention clinical trialsrisk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines, and for a maximum of 20 days for trials other than low-risk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines guidance .
Amendment 403 #
Proposal for a regulation
Article 14 – paragraph 6 – subparagraph 3
Article 14 – paragraph 6 – subparagraph 3
Where, upon receipt of the additional explanations, the remaining time period for notifying the decision referred to in paragraph 4 is less than three days in the case of low-intervention clinical trials, and less than five days for other than low- intervention clinical trialrisk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines, and less than five days for other than low-risk clinical trials and medium-risk clinical trials using treatment regimens supported by published evidence and/or standard treatment guidelines, it shall be extended to three and five days respectively.
Amendment 408 #
Proposal for a regulation
Article 14 – paragraph 11
Article 14 – paragraph 11
11. A sponsor shall not submit an application in accordance with this Article where a procedure referred to in Chapter III as regards that clinical trial, and relating to an aspect covered by Part I of the assessment report, is pending.
Amendment 409 #
Proposal for a regulation
Article 15
Article 15
A substantial modification may only be implemented if it has been approved in accordance with the procedure set out in this Chapter, and if it has been approved by an independent ethics committee before its implementation.
Amendment 413 #
Proposal for a regulation
Article 17 – paragraph 2 – point c
Article 17 – paragraph 2 – point c
(c) where the clinical trial is a low- interventionmedium-risk or low-risk clinical trial, whether it will remain a low-interventionmedium-risk or low-risk clinical trial after its substantial modification.
Amendment 415 #
Proposal for a regulation
Article 17 – paragraph 3
Article 17 – paragraph 3
3. Where the reporting Member State has not notified the sponsor within the time period referred to in paragraph 2, the substantial modification applied for shall be considered as concerning an aspect covered by Part I of the assessment report, the application shall be considered as complete and, where the clinical trial is a low-interventionmedium-risk or low-risk clinical trial, it shall be considered as remaining a low-interventionmedium-risk or low-risk clinical trial after its substantial modification.
Amendment 417 #
Proposal for a regulation
Article 17 – paragraph 4 – subparagraph 1
Article 17 – paragraph 4 – subparagraph 1
4. Where the reporting Member State finds that the application does not concern an aspect covered by Part I of the assessment report, that the application is not complete, or that the clinical trial will no longer be a low-interventionmedium-risk or low-risk clinical trial after the substantial modification, contrary to what the sponsor claims, it shall inform the sponsor thereof through the EU portal and shall set a maximum of six days for the sponsor to comment or to complete the application through the EU portal.
Amendment 444 #
Proposal for a regulation
Article 26 – subparagraph 1 a (new)
Article 26 – subparagraph 1 a (new)
As regards clinical trials conducted in a single Member State, the application file may be drawn up in one of official languages of the Member State concerned.
Amendment 445 #
Proposal for a regulation
Article 26 – subparagraph 1 b (new)
Article 26 – subparagraph 1 b (new)
In the event of the enlargement of the Union to include another Member State, subparagraph 3 of this article shall apply.
Amendment 448 #
Proposal for a regulation
Article 28 – paragraph 1 – point a
Article 28 – paragraph 1 – point a
Amendment 449 #
Proposal for a regulation
Article 28 – paragraph 1 – point b
Article 28 – paragraph 1 – point b
(b) compliance with point (a) is permanently observedthe principles referred to in point (a) are observed throughout the study;
Amendment 450 #
Proposal for a regulation
Article 28 – paragraph 1 – point c
Article 28 – paragraph 1 – point c
Amendment 453 #
Proposal for a regulation
Article 28 – paragraph 1 – point d
Article 28 – paragraph 1 – point d
(d) the subject or, where the subject is not able to give informed consent, his or her legal representative has had the opportunity, in a prior interview with the investigator or a member of the investigating teamhis/her representative, to understand the objectives, risks and inconveniences of the clinical trial, and the conditions under which it is to be conducted and has also been informed of the right to withdraw from the clinical trial at any time without any resulting detriment;
Amendment 455 #
Proposal for a regulation
Article 28 – paragraph 1 – point d a (new)
Article 28 – paragraph 1 – point d a (new)
(da) the subject or, where the subject is not able to give informed consent, his or her legal representative has given informed consent;
Amendment 458 #
Proposal for a regulation
Article 28 – paragraph 3
Article 28 – paragraph 3
3. Any subject may, without any resulting liability or detriment, withdraw from the clinical trial at any time by revoking without any justification his or her informed consent. The withdrawal of consent shall not affect the activities carried out based on consent before its withdrawal.
Amendment 460 #
Proposal for a regulation
Article 28 – paragraph 3
Article 28 – paragraph 3
3. Any subject or his legal representative may, without any resulting detriment, withdraw from the clinical trial at any time by revoking his or her informed consent. The withdrawal of consent shall not affect the activities carried out based on consent before its withdrawal.
Amendment 463 #
Proposal for a regulation
Article 29 – paragraph 1
Article 29 – paragraph 1
1. Informed consent shall be written, dated and signed and given freely by the subject or his or her legal representative after having been ducomprehensively and comprehensibly informed of the nature, significance, implications and risks of the clinical trial, and after having received the corresponding information in writing. It shall be appropriately documented. Where the subject is unable to write, oral consent in the presence of at least one impartial witness may be given in exceptional cases. The subject or his or her legal representative shall be provided with a copy of the document by which informed consent has been given.
Amendment 465 #
Proposal for a regulation
Article 29 – paragraph 1
Article 29 – paragraph 1
1. Informed consent shall be written, dated and signed and given freely by the subject or his or her legal representative after having been duly informed of the nature, significance, implications and risks of the clinical trial. It shall be appropriately documented. Where the subject is unable to write, oral consent in the presence of at least one impartial witness, who is independent of the investigator, may be given in exceptional cases. The subject or his or her legal representative shall be provided with a copy of the document by which informed consent has been given.
Amendment 466 #
Proposal for a regulation
Article 29 – paragraph 1 a (new)
Article 29 – paragraph 1 a (new)
1a. Without prejudice to Article 28, where the clinical trial poses a minimal risk, informed consent may be given orally, provided that it is duly documented, in accordance with the legislation of the Member State concerned;
Amendment 469 #
Proposal for a regulation
Article 29 – paragraph 2 a (new)
Article 29 – paragraph 2 a (new)
2a. When the subject gives his/her consent, he/she shall also be informed that a summary of the results of the clinical trial, as referred to in Article 34(3)(2a), will be published on the EU database.
Amendment 473 #
Proposal for a regulation
Article 29 – paragraph 3 a (new)
Article 29 – paragraph 3 a (new)
Amendment 475 #
Proposal for a regulation
Article 30 – paragraph 1 – point b
Article 30 – paragraph 1 – point b
(b) the incapacitated subject has received adequate information in relation to his or her capacity for understanding regarding the trial, the risks and the benefits from the investigator or his/her representative, in accordance with the legislation of the Member State concerned; ;
Amendment 479 #
Proposal for a regulation
Article 30 – paragraph 1 – point f
Article 30 – paragraph 1 – point f
(f) such research relates directly to a life- threatening or debilitating medical condition from which the subjectperson concerned suffers;
Amendment 480 #
Proposal for a regulation
Article 30 – paragraph 1 – point h
Article 30 – paragraph 1 – point h
(h) there are grounds for expecting that participation in the clinical trial will produce a benefit to the incapacitated subject outweighing the risks or will produce no risk at allonly a minimal risk.
Amendment 481 #
Proposal for a regulation
Article 30 – paragraph 1 – point h a (new)
Article 30 – paragraph 1 – point h a (new)
(ha) the Ethics Committee, with expertise in the relevant disease and the patient population concerned, or after taking advice in clinical, ethical and psychosocial questions in the field of the relevant disease and patient population concerned, has endorsed the protocol;
Amendment 484 #
Proposal for a regulation
Article 31 – paragraph 1 – point a
Article 31 – paragraph 1 – point a
(a) the informed consent of the legal representative or representatives has been obtained, whereby consent shall represent the minor’s presumed will;
Amendment 487 #
Proposal for a regulation
Article 31 – paragraph 1 – point b
Article 31 – paragraph 1 – point b
(b) the minor has received all relevant information in a way adapted to his or her age and maturity, from professionalsa medical doctor (either the investigator or member of the trial team) trained or experienced in working with children, regarding the trial, the risks and the benefits;
Amendment 492 #
Proposal for a regulation
Article 31 – paragraph 1 – point e
Article 31 – paragraph 1 – point e
Amendment 493 #
Proposal for a regulation
Article 31 – paragraph 1 – point h
Article 31 – paragraph 1 – point h
(h) some direct benefit for the groupcategory of patients isconcerned by the trial may be obtained from the clinical trial.
Amendment 496 #
Proposal for a regulation
Article 31 – paragraph 1 – point h b (new)
Article 31 – paragraph 1 – point h b (new)
(hb) the corresponding scientific guidelines of the Agency have been followed;
Amendment 498 #
Proposal for a regulation
Article 31 – paragraph 1 – point h d (new)
Article 31 – paragraph 1 – point h d (new)
(hd) the Ethics Committee, with paediatric expertise or after taking advice in clinical, ethical and psychosocial problems in the field of paediatrics, has endorsed the protocol;
Amendment 500 #
Proposal for a regulation
Article 31 – paragraph 1 a (new)
Article 31 – paragraph 1 a (new)
1a. Without prejudice to Article 31(1), where the clinical trial poses a minimal risk and the consent of the second person with parental authority cannot be given within a period consistent with the methodological requirements of the research, and provided that a favourable ethical opinion has been issued, the clinical trial on the minor may proceed on the basis of the consent of the only person present with parental authority.
Amendment 502 #
Proposal for a regulation
Article 31 – paragraph 2 a (new)
Article 31 – paragraph 2 a (new)
2a. If during a clinical trial the minor reaches the age of majority as defined in the legislation of the Member State concerned, his/her express informed consent shall be obtained before the trial may continue.
Amendment 505 #
Proposal for a regulation
Article 32 – paragraph 1 – introductory part
Article 32 – paragraph 1 – introductory part
1. By way of derogation from points (c) and (d) of Article 28(1), from points (a) and (b) of Article 30(1) and from points (a) and (b) of Article 31(1), informed consent may be obtained after the start of the clinical trial to continue, referred to in Article 29(1), shall be obtained as soon as possible after the start of the clinical trial and information on the clinical trial mayshall be given after the start of the clinical trial provided that all of the following conditions are fulfilled:
Amendment 506 #
Proposal for a regulation
Article 32 – paragraph 1 – point a
Article 32 – paragraph 1 – point a
(a) due to the urgency of the situation, caused by a sudden life-threatening or other sudden serious medical condition, it is impossible to obtain prior informed consent from the subject and it is impossible to supply prior information to the subject;
Amendment 508 #
Proposal for a regulation
Article 32 – paragraph 1 – point b
Article 32 – paragraph 1 – point b
(b) nothe consent of the legal representative is availablecannot be given within a period consistent with the methodological requirements of the research;
Amendment 510 #
Proposal for a regulation
Article 32 – paragraph 1 – point d
Article 32 – paragraph 1 – point d
Amendment 511 #
Proposal for a regulation
Article 32 – paragraph 1 – point e
Article 32 – paragraph 1 – point e
(e) the clinical trial poses a minimal risk to, and imposes a minimal burden on, the subjectre are grounds for expecting that participation in the clinical trial will produce a benefit to the subject outweighing the risks or will produce only a minimal risk.
Amendment 514 #
Proposal for a regulation
Article 32 – paragraph 2 – subparagraph 1 – point a
Article 32 – paragraph 2 – subparagraph 1 – point a
(a) regarding incapacitated subjects and minors, the informed consent referred to in paragraph 1 shall be obtained as soon as possible from the legal representative and the information referred to in paragraph 1 shall be given as soon as possible to the subject by the investigator or his/her representative;
Amendment 515 #
Proposal for a regulation
Article 32 – paragraph 2 a (new)
Article 32 – paragraph 2 a (new)
2a. Without prejudice to paragraphs 1 and 2 of this article, national law relating to incapacitated and/or vulnerable persons, and measures taken thereunder, shall be complied with.
Amendment 516 #
Proposal for a regulation
Article 32 – paragraph 2 b (new)
Article 32 – paragraph 2 b (new)
2b. If the subject or, where applicable, his or her legal representative does not give his or her consent for the research to continue, he or she shall be informed that he or she may object to the use of data obtained prior to the denial of consent.
Amendment 518 #
Proposal for a regulation
Article 33 – paragraph 1 – subparagraph 2
Article 33 – paragraph 1 – subparagraph 2
That notification shall be made within 1530 days from the start of the clinical trial in relation to that Member State.
Amendment 521 #
Proposal for a regulation
Article 33 – paragraph 2 – subparagraph 2
Article 33 – paragraph 2 – subparagraph 2
That notification shall be made within 15 30 days from the end of the recruitment of subjects. In case of re-start of recruitment, paragraph 1 shall apply.
Amendment 523 #
Proposal for a regulation
Article 34 – title
Article 34 – title
End of the clinical trial, early termination of the clinical trial and submission of results
Amendment 526 #
Proposal for a regulation
Article 34 – paragraph 1 – subparagraph 2
Article 34 – paragraph 1 – subparagraph 2
That notification shall be made within 1530 days from the end of the clinical trial in relation to that Member State.
Amendment 527 #
Proposal for a regulation
Article 34 – paragraph 3 – subparagraph 1
Article 34 – paragraph 3 – subparagraph 1
Within onetwo years from the end of a clinical trial, the sponsor shall submit to the EU database a summary of the results of the clinical trial. The end of the clinical trial shall be considered to be the end of the period during which the last subject included in the clinical trial is subject to monitoring.
Amendment 534 #
Proposal for a regulation
Article 34 – paragraph 3 – subparagraph 1 a (new)
Article 34 – paragraph 3 – subparagraph 1 a (new)
The summary of the results of the clinical trial referred to in the first subparagraph of this paragraph shall be published by the Commission on the EU database and shall be accessible to the public. The summary shall cover all the points referred to in Annex III of this Regulation. The Commission shall be empowered to adopt delegated acts in accordance with Article 85 for the purpose of modifying the component elements of the summary.
Amendment 535 #
Proposal for a regulation
Article 34 – paragraph 3 – subparagraph 2
Article 34 – paragraph 3 – subparagraph 2
However, where, for scientific reasons, it is not possible to submit a summary of the results within onetwo years, the summary of results shall be submitted as soon as it is available. In this case, the protocol shall specify when the results are going to be submitted, together with an explanation.
Amendment 537 #
Proposal for a regulation
Article 34 – paragraph 3 – subparagraph 2 a (new)
Article 34 – paragraph 3 – subparagraph 2 a (new)
Amendment 543 #
Proposal for a regulation
Article 34 – paragraph 4
Article 34 – paragraph 4
4. For the purpose of this Regulation, if a suspended or temporarily halted clinical trial is not restarted, the date of the decision of the sponsor not to restart the clinical trial, extended to include the period during which the trial subjects are subject to monitoring under the terms of the protocol, shall be considered as the end of the clinical trial. In the case of early termination, the date of the early termination shall be considered as the date of the end of the clinical trial.
Amendment 545 #
Proposal for a regulation
Article 34 – paragraph 5 a (new)
Article 34 – paragraph 5 a (new)
5 a. The Commission shall be empowered to adopt delegated acts in accordance with Article 85 in order to amend Annex IIIa with the objective to adapt them to scientific or global regulatory developments.
Amendment 546 #
Proposal for a regulation
Article 36 – paragraph 1
Article 36 – paragraph 1
The European Medicines Agency established by Regulation (EC) No 726/2004 (hereinafter, the "Agency") shall set up and maintain an electronic database for the reporting provided for in Articles 38, 39 and 3941.
Amendment 549 #
Proposal for a regulation
Article 37 – paragraph 2
Article 37 – paragraph 2
2. The investigator shall immediately report serious adverse events to the sponsor unless the protocol provides, for certain adverse events, that no reporting is required. The investigator shall record all serious adverse events. Where necessary, the investigator shall send a follow-up report to the sponsor.(Does not affect English version.)
Amendment 551 #
Proposal for a regulation
Article 37 – paragraph 2
Article 37 – paragraph 2
2. The investigator shall immediately report serious adverse events to the sponsor as soon as possible and without unnecessary delay unless the protocol provides, for certain adverse events, that no reporting is required. The investigator shall record all serious adverse events. Where necessary, the investigator shall send a follow-up report to the sponsor.
Amendment 552 #
Proposal for a regulation
Article 37 – paragraph 2 a (new)
Article 37 – paragraph 2 a (new)
2a. In the case of low-risk clinical trials and clinical trials involving a moderate level of risk which use treatment strategies supported by published data or based on customary recommended practice, the protocol may stipulate that the normal rules on vigilance should apply.
Amendment 555 #
Proposal for a regulation
Article 38 – paragraph 1
Article 38 – paragraph 1
1. The sponsor shall report electronically and without delayin the time limits specified in points 2.4 and 2.5 of Annex III to the electronic database referred to in Article 36 all relevant information about suspected unexpected serious adverse reactions to investigational medicinal products insofar as the suspected unexpected serious adverse reaction occurred in a clinical trial conducted by the sponsor, or occurred in a clinical trial related to the sponsor.
Amendment 556 #
Proposal for a regulation
Article 38 – paragraph 1
Article 38 – paragraph 1
1. The sponsor shall report electronically and without delay to the electronic database referred to in Article 36 all relevant information about suspected unexpected serious adverse reactions to investigational and auxiliary medicinal products insofar as the suspected unexpected serious adverse reaction occurred in a clinical trial conducted by the sponsor, or occurred in a clinical trial related to the sponsor.
Amendment 561 #
Proposal for a regulation
Article 39 – paragraph 1
Article 39 – paragraph 1
1. Regarding non-authorised investigational medicinal products other than placebo, and authorised investigational medicinal products which, according to the protocol, are not used in accordance withThe sponsor shall submit annually by electronic means to the Agency a report on the safety of each investigational medicinal product - or of all the investigational medicinal products – used in a clinical trial for which it is the sponsor if the clinical trial involves authorised medicinal products being tested in accordance with treatment strategies which were not envisaged under the terms of their marketing authorisation, the sponsor shall submit annually by electronic means to the Agency a report on the safety of each investigational medicinal product used in a and which are not supported by data or recommendations and if the clinical trial for winvolves a hicgh it is the sponsorlevel of risk.
Amendment 562 #
Proposal for a regulation
Article 39 – paragraph 1
Article 39 – paragraph 1
1. Regarding non-authorised investigational medicinal products other than placebo, and authorised investigational medicinal products which, according to the protocol, are not used in accordance with the terms of the marketing authorisationFor clinical trials other than low-risk and medium-risk trials using treatment regimens supported by published evidence and/or standard treatment guidelines, the sponsor shall submit annually by electronic means to the Agency a report on the safety of each investigational medicinal product used in a clinical trial for which it is the sponsor.
Amendment 568 #
Proposal for a regulation
Article 40 – paragraph 1
Article 40 – paragraph 1
1. The Agency shall, by electronic means, forward to the relevant Member States the information reported in accordance with Article 38, 39 and 3941.
Amendment 569 #
Proposal for a regulation
Article 40 – paragraph 2
Article 40 – paragraph 2
2. Member States shall cooperate in assessing the information reported in accordance with Articles 38, 39 and 3941.
Amendment 571 #
Proposal for a regulation
Article 41 – title
Article 41 – title
Article 39 Annual reporting by the sponsor to the marketing authorisation holderAgency
Amendment 572 #
Proposal for a regulation
Article 41 – paragraph 1
Article 41 – paragraph 1
1. Regarding authorised medicinal products which, according to the protocol, are used in accordance with the terms of the marketing authorisation, the sponsor shall inform annually the marketing authorisation holderAgency of all suspected serious adverse reactions.
Amendment 575 #
Proposal for a regulation
Article 43
Article 43
Safety reporting with regard to auxiliary medicinal products shall be made in accordance with Chapter 3 of Directive 2001/83/EC as amended by Directive 2012/ 84/EU).
Amendment 578 #
Proposal for a regulation
Article 45 – title
Article 45 – title
Amendment 579 #
Proposal for a regulation
Article 45 – paragraph 1 – introductory part
Article 45 – paragraph 1 – introductory part
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 all characteristics of the clinical trial, including risk assessment covering all the risk determinants of the clinical trial (risk to subject rights, risk to subject safety and integrity, risk to data quality and robustness of results). The risk assessment shall determine the quality management and trial monitoring, taking into account the following characteristics:
Amendment 581 #
Proposal for a regulation
Article 45 – paragraph 1 – point a
Article 45 – paragraph 1 – point a
(a) whether the clinical trial is a low- interventionmedium- risk or low- risk clinical trial;
Amendment 582 #
Proposal for a regulation
Article 45 – paragraph 1 – point c
Article 45 – paragraph 1 – point c
(c) the degree of deviation of the interventiondiagnostic procedures from normal clinical practice.
Amendment 583 #
Proposal for a regulation
Article 46 – paragraph 2
Article 46 – paragraph 2
Other individuals involved in conducting and monitoring a clinical trial shall be suitably qualified by education, training and experience to perform their tasks.
Amendment 585 #
Proposal for a regulation
Article 48 – title
Article 48 – title
Amendment 586 #
Proposal for a regulation
Article 48 – paragraph 1 – subparagraph 1
Article 48 – paragraph 1 – subparagraph 1
Investigational medicinal products shall be traceable, stored, destroyed and returned as appropriate and proportionate to ensure subject safety and the reliability and robustness of the data generated in the clinical trial, taking into account whether the investigational medicinal product is authorised, and whether the clinical trial is a low-interventionclinical trial is a medium-risk or low- risk clinical trial.
Amendment 587 #
Proposal for a regulation
Article 48 – paragraph 1 – subparagraph 1
Article 48 – paragraph 1 – subparagraph 1
Investigational medicinal products shall be received, traceable, stored, administered, destroyed and returned as appropriate and proportionate to ensure subject safety and the reliability and robustness of the data generated in the clinical trial, taking into account whether the investigational medicinal product is authorised, and whether the clinical trial is a low- intervention clinical trial.
Amendment 588 #
Proposal for a regulation
Article 48 – paragraph 1 – subparagraph 2 a (new)
Article 48 – paragraph 1 – subparagraph 2 a (new)
These operations shall be carried out by persons legally authorised in the Member State to carry out the operations in question and, particularly where they are carried out in hospitals, medical centres or clinics, by pharmacists or other persons legally authorised in the Member State concerned to carry out the operations in question.
Amendment 589 #
Proposal for a regulation
Article 48 – paragraph 2
Article 48 – paragraph 2
2. The relevant information regarding the traceability, storage, administration, destruction and return of medicinal products referred to in paragraph 1 shall be contained in the application dossier.
Amendment 595 #
Proposal for a regulation
Article 52 – paragraph 3 a (new)
Article 52 – paragraph 3 a (new)
3a. The content of the investigator brochure shall be adapted for low risk and for medium-risk trials (see Annex I, part 5, point 20).
Amendment 596 #
Proposal for a regulation
Article 52 – paragraph 3 b (new)
Article 52 – paragraph 3 b (new)
3b. For authorised medicinal products which, according to the protocol, are used in accordance with the terms of the marketing authorisation, the approved summary of product characteristics may be the reference document.
Amendment 599 #
Proposal for a regulation
Article 54 – paragraph 1
Article 54 – paragraph 1
The sponsor andor the investigator shall keep a clinical trial master file.
Amendment 600 #
Proposal for a regulation
Article 54 – paragraph 2
Article 54 – paragraph 2
The content of the clinical trial master file shall allow verification of the conduct of a clinical trial, taking account of all characteristics of the clinical trial, including whether the clinical trial is a low- interventionmedium-risk or low-risk clinical trial.