Next event: Commission response to text adopted in plenary 2014/07/09 more...
- Final act published in Official Journal 2014/05/27
- Draft final act 2014/04/16
- Final act signed 2014/04/16
- End of procedure in Parliament 2014/04/16
- Act adopted by Council after Parliament's 1st reading 2014/04/14
- Council Meeting 2014/04/14
- Results of vote in Parliament 2014/04/02
- Debate in Parliament 2014/04/02
- Decision by Parliament, 1st reading/single reading 2014/04/02
- Committee report tabled for plenary, 1st reading/single reading 2013/06/10
- Vote in committee, 1st reading/single reading 2013/05/29
- Amendments tabled in committee 2013/05/27
- Committee opinion 2013/04/09
- Committee opinion 2013/03/26
- Committee opinion 2013/03/21
- Amendments tabled in committee 2013/03/06
- Amendments tabled in committee 2013/03/06
Progress: Procedure completed
Role | Committee | Rapporteur | Shadows |
---|---|---|---|
Lead | ENVI | WILLMOTT Dame Glenis ( S&D) | JUVIN Philippe ( PPE), PARVANOVA Antonyia ( ALDE), AUKEN Margrete ( Verts/ALE), CABRNOCH Milan ( ECR), SOUSA Alda ( GUE/NGL) |
Committee Opinion | IMCO | BUŞOI Cristian-Silviu ( ALDE) | Philippe JUVIN ( PPE), Emma McCLARKIN ( ECR), Matteo SALVINI ( ENF) |
Committee Opinion | LIBE | LÓPEZ AGUILAR Juan Fernando ( S&D) | |
Committee Opinion | ITRE | SARTORI Amalia ( PPE) | Françoise GROSSETÊTE ( PPE), Sajjad KARIM ( ECR) |
Lead committee dossier:
Legal Basis:
TFEU 114-p1, TFEU 168-p4
Legal Basis:
TFEU 114-p1, TFEU 168-p4Subjects
Events
PURPOSE: to promote public health and research throughout the European Union (EU) by establishing harmonised rules concerning the authorisation and the conduct of clinical trials.
LEGISLATIVE ACT: Regulation (EU) No 536/2014 of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC.
CONTENT: the new Regulation replaces Directive 2001/20/CE and applies to all clinical trials conducted in the Union . It relies on the general principle according to which a clinical trial may be conducted only: a) if the rights, safety, dignity and well-being of subjects are protected and prevail over all other interests; and b) if it is designed to generate reliable and robust data.
According to the Regulation, any clinical trial shall be subject to a scientific and ethical review and shall be subject to prior authorisation . The ethical review shall be performed by an ethics committee in accordance with the law of the Member State concerned.
Procedures for authorisation : the procedure to be used should be flexible and efficient , in order to avoid administrative delays for starting a clinical trial, without compromising patient safety or public health.
To obtain an authorisation, the sponsor must submit one application dossier to all the Member States concerned through a single EU portal . The Regulation sets the deadline for authorisation of clinical trials at 60 days . If no decision is taken within this period, the autorisation shall be deemed to have been given (tacit approval). Decisions on requests for substantial changes to clinical trials should be taken within 49 days . In the absence of a decision, the authorisation will be taken as given.
Application dossier for authorisation of a clinical trial : it should contain information on: a) the conduct of the clinical trial, including the scientific context and arrangements taken; b) the sponsor, investigators, potential subjects, subjects, and clinical trial sites; c) the investigational medicinal products and, where necessary, the auxiliary medicinal products, in particular their properties, labelling, manufacturing and control; d) measures to protect subjects; e) justification as to why the clinical trial is a low-intervention clinical trial, in cases where this is claimed by the sponsor.
V ulnerable people : clinical trials involving subjects in emergency situations, minors, incapacitated subjects, pregnant and breastfeeding women and, where appropriate, other identified specific population groups, such as elderly people or people suffering from rare and ultra rare diseases, will be strictly supervised and their evaluation subject to specific expertise .
Protection of participants : the Regulation stipulates that a clinical trial may be conducted only where certain conditions are met. In particular:
the anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this condition is constantly monitored; the subjects have been informed and given their informed consent; the rights of the subjects to physical and mental integrity, to privacy and to the protection of the data concerning them are safeguarded; the clinical trial has been designed to involve as little pain, discomfort, fear and any other foreseeable risk as possible for the subjects; the subject has been provided with the contact details of an entity where further information can be received in case of need; no undue influence, including that of a financial nature, is exerted on subjects to participate in the clinical trial.
Informed consent : informed consent must be written, dated and signed by the person conducting the interview and the participant, or if he is not able to give his consent, his legally designated representative .
Information given to the subject or his legally designated representative should allow them to understand: i) the nature, objectives, benefits, implications, risks and inconveniences of the clinical trial; ii) the subject's rights and guarantees regarding his or her protection; iii) the conditions under which the clinical trial is to be conducted, including the expected duration of the subject's participation in the clinical trial; iv) the possible treatment alternatives, including the follow-up measures if the participation of the subject in the clinical trial is discontinued.
In addition, the information should be: i) comprehensive and understandable to a layperson; ii) provided in a prior interview with a member of the investigating team who is appropriately qualified according to the law of the Member State concerned; iii) include information about the applicable damage compensation system.
Transparency : 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 the recruitment of subjects 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 within one year from the end of the trial.
The European Medicines Agency shall set up and maintain an electronic database for the reporting provided for in the clinical trial framework.
Supervision, Union inspections and controls : where a Member State concerned has justified grounds for considering that the requirements set out in this Regulation are no longer met, it may: a) revoke the authorisation of a clinical trial; b) suspend a clinical trial; c) require the sponsor to modify any aspect of the clinical trial. Qualifed inspectors shall be designated by the Membe States to supervise compliance with this Regulation.
The Commission should be able to control whether Member States correctly supervise compliance with this Regulation. Moreover, the Commission should be able to control whether regulatory systems of third countries ensure compliance with the specific provisions of this Regulation and Directive 2001/83/EC concerning clinical trials conducted in third countries .
Union database : in order to streamline and facilitate the flow of information between sponsors and Member States as well as between Member States, the Agency should, in collaboration with Member States and the Commission, set up and maintain an EU database, accessed through an EU portal. In order to ensure a sufficient level of transparency in the clinical trials, the EU database should contain all relevant information as regards the clinical trial submitted through the EU portal.
ENTRY INTO FORCE: 16.06.2014. The Regulation shall apply no earlier than 28.05.2016.
DELEGATED ACTS: the Commission may adopt delegated acts in order to supplement or amend non-essential aspects of the Regulation. The power to adopt such acts shall be conferred on the Commission for a period of five years from the date of the implementation of the Regulation. The European Parliament or the Council may object to a delegated act within a period of two months from the date of notification (this period can be extended for two months). If the European Parliament or the Council make objections, the delegated act will not enter into force.
The European Parliament adopted by 594 votes to 17, with 13 abstentions, a legislative resolution 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.
Parliament adopted its position at first reading following the ordinary legislative procedure. The amendments adopted in plenary are the result of an agreement negotiated between the European Parliament and the Council. They amend the proposal as follows:
General principle: a clinical trial may be conducted only if: (i) the rights, safety, dignity and well-being of subjects are protected and prevail over all other interests; and (ii) it is designed to generate reliable and robust data.
A clinical trial shall be subject to scientific and ethical review and shall be authorised in accordance with this Regulation. The ethical review shall be performed by an ethics committee in accordance with the law of the Member State concerned.
Simplified procedures: application dossiers for clinical trials should be submitted by means of a single submission portal. In order to avoid administrative delays for starting a clinical trial, the procedure to be used should be flexible and efficient , without compromising patient safety or public health.
According to the new text, Member States should efficiently assess all clinical trials applications within the given timelines . A rapid yet in-depth assessment is of particular importance for clinical trials concerning medical conditions which are severely debilitating and/or life threatening and for which therapeutic options are limited or non-existent, as in the case of rare and ultra-rare diseases.
Vulnerable persons: the assessment of applications for the authorisation of clinical trials should be conducted on the basis of appropriate expertise. Specific expertise should be considered when assessing clinical trials involving subjects in emergency situations, minors, incapacitated subjects, pregnant and breastfeeding women and, where appropriate, other identified specific population groups, such as elderly people or people suffering from rare and ultra rare diseases.
The text underlines that in order to improve treatments available for vulnerable groups such as frail or older people, people suffering from multiple chronic conditions, and people affected by mental health disorders, medicinal products which are likely to be of significant clinical value should be fully and appropriately studied for their effects in these specific groups.
Conditions for the conduct of a clinical trial: the following conditions should be met:
the anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this condition is constantly monitored; the subjects, or where a subject is not able to give informed consent, his or her legally designated representative, have been informed; the subjects, or where a subject is not able to give informed consent, his or her legally designated representative, have given informed consent; the rights of the subjects to physical and mental integrity, to privacy and to the protection of the data concerning them are safeguarded; the clinical trial has been designed to involve as little pain, discomfort, fear and any other foreseeable risk as possible for the subjects and both the risk threshold and the degree of distress are specifically defined in the protocol and constantly monitored; the medical care provided to the subjects is the responsibility of an appropriately qualified medical doctor or, where appropriate, a qualified dental practitioner; the subject or, where the subject is not able to give informed consent, his or her legally designated representative has been provided with the contact details of an entity where further information can be received in case of need; no undue influence, including that of a financial nature, is exerted on subjects to participate in the clinical trial.
Informed consent: information given to the subject or his or her legally designated representative shall enable an understanding of:
the nature, objectives, benefits, implications, risks and inconveniences of the clinical trial; the subject's rights and guarantees regarding his or her protection, in particular his or her right to refuse to participate and the right to withdraw from the clinical trial at any time without any resulting detriment and without having to provide any justification; the conditions under which the clinical trial is to be conducted, including the expected duration of the subject's participation in the clinical trial; and the possible treatment alternatives, including the follow-up measures if the participation of the subject in the clinical trial is discontinued.
Information should be: (i) be kept comprehensive, concise, clear, relevant, and understandable to a layperson; (ii) be provided in a prior interview with a member of the investigating team who is appropriately qualified according to the law of the Member State concerned; (iii) include information about the applicable damage compensation system .
The sponsor should provide within the time limits a summary of the results of the clinical trial and a summary presented in terms understandable to a layperson and, if appropriate, the clinical trial report.
Subject safety: in addition to serious adverse events and reactions, the new text stipulates that all unexpected events that might materially influence the benefit-risk assessment of the medicinal product or that would lead to changes in the administration of a medicinal product or in overall conduct of a clinical trial are notified to the Member States concerned.
Transparency: Members amended the legal text in order to increase transparency, requiring that detailed summaries of the trial be published on a European database that is accessible to the public .
Penalties may be imposed in the cases of non-compliance with the provisions laid down in the Regulation on submission of information intended to be made publicly available to the EU database and non-compliance with the provisions on subject safety.
The Committee on the Environment, Public Health and Food Safety adopted the report by Glenis WILLMOTT (S&D, UK) 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.
The committee recommends that the European Parliament’s position at first reading adopted under the ordinary legislative procedure should amend the Commission proposal as follows:
General principle : a clinical trial may be conducted only if : (i) the rights, safety, physical and mental integrity, dignity and well-being of subjects are protected , and the ethics
committee has provided assurances thereof; (ii) the data generated in the clinical trial can be expected to be reliable, robust and relevant for improving the prevention and treatment of diseases.
In a clinical trial the safety, rights, health and well-being of subjects should be protected and the data generated should be relevant, reliable and robust and reflect the diversity of the population in terms of age and gender balance. The interests of the participants should always take priority over other interests.
Members insist that it should be ensured that persons assessing the application do not have conflicts of interest , are independent of the sponsor, the trial site and the investigators involved, as well as free of any undue influence.
Ethics committee : a clinical trial should be subject to prior authorisation after having been examined by the ethics committee concerned in accordance with the World Medical Association’s Declaration of Helsinki.
The Ethics committee shall be an independent body in a Member State, consisting of health-care professionals and nonmedical members including at least one well-experienced, knowledgeable patient or patient representative. In cases of clinical trials involving minors, the ethics committee shall include at least one healthcare professional with paediatric expertise.
Vulnerable persons : where the subjects belong to vulnerable population groups including pregnant and breastfeeding women, persons deprived of liberty, persons with specific needs including the elderly, frail people and people with dementia, specific consideration shall be given to the assessment of the application for authorisation of a clinical trial.
Low-risk clinical trials : given that low-risk clinical trials have only a very limited and temporary adverse effect, they should be subject to less stringent rules, such as shorter deadlines for approval. Less stringent rules should not compromise scientific standards and should guarantee the safety of subjects at all times. Those low-risk trials should, however, be subject to the vigilance and traceability rules governing normal clinical practice.
For low-risk trials and when marketing authorisation 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.
Assessment report on clinical trials in the field of rare and ultra-rare diseases : in the specific case of clinical trials in the field of rare or ultra-rare diseases, Members propose that the reporting Member State shall seek the expert opinion of the Scientific Advice Working Party of the European Medicines Agency on the disease or group of diseases concerned by the clinical trial in order to help the reporting Member State and the Member States concerned to provide a well informed assessment of the application.
Transparency : Members propose that the assessment report shall be submitted through the EU portal, and stored in the EU database . It shall be made publicly available to foster public confidence in the authorisation process.
The subject shall be informed that within one year from the end of the clinical trial or its early termination, the summary of the results of the trial and a summary presented in terms understandable to a layperson will be made available in the EU database , irrespective of the trial outcome, or that he or she can obtain information from the investigator or its representative about the overall results of the trial.
The reasons for early termination of a clinical trial shall be published in the EU database.
Members also propose that Member States should impose fines on sponsors that do not meet their responsibilities in terms of transparency.
Informed consent : rules on informed consent are established in detail by the Members in order to ensure access to information and to damage compensation.
Informed consentment should be given freely and voluntarily . During the prior interview, the potential subject shall also be informed of the right to refuse to participate in the clinical trial without any resulting detriment. The prior interview with the investigator or a member of the investigating team in order to obtain the subject’s informed consent shall include a test of full understanding on the part of the subject and/or his or her de facto representative.
Within the original consent, an option of broad consent should be made available to the patient, whereby his/her data could be allowed to be used at the behest of the treating institution for future research.
Specific measures are also applied to clinical trials on pregnant or breastfeeding women, persons deprived of liberty or subjects with specific needs.
Reporting on efficacy defects of authorised investigational medicinal products : efficacy defect on an authorised medicinal product could represent a serious risk for patient safety and should therefore be added as a reporting obligation under this regulation.
Clinical trial master file : although the Commission proposed that the sponsor shall archive the content of the clinical trial master file for at least five years, Members are of the opinion that should a sponsor come under investigation for misconduct, the clinical trial master file would be vital. Therefore the master file should be archived indefinitely unless national legislation states otherwise. The master file can be stored in the EU database if necessary.
In order to follow a given clinical trial from initial ethical approval to final publication, Members proposal that a Universal Trial Registration Number (UTRN) should be assigned to each trial to be conducted in the Union.
Opinion of the European Data Protection Supervisor (EDPS)
The EDPS welcomes the fact that the Commission has made an effort to guarantee the correct application of EU rules concerning the protection of personal data in the proposed Regulation on clinical trials on medicinal products for human use.
The EDPS considers, however, that clarifications are necessary with regard to where sensitive data regarding health might be processed and stored, regarding the authorisation procedure in the EU Portal and database and the reporting of adverse effects in the European Medicines Agency (EMA) database.
The EDPS recommends in particular, that the proposal:
explicitly refers to Article 8 of Directive 95/46/EC and Article 10 of Regulation (EC) No 45/2001 regarding the processing of personal data concerning health; clarifies whether personal data concerning health will be processed in the EU database, and if so, for what purpose; refers to the right of the data subjects to block their personal data; ensures, for the EMA database, a provision which more clearly defines in what situations and subject to what safeguards information containing patient data will be processed and stored; explicitly mentions that the annual reports should only be using anonymous data; replaces or complements the minimum retention period of 5 years by a maximum retention period.
PURPOSE: to promote public health and research in the EU by laying down harmonised rules on the authorisation and conduct of clinical trials.
PROPOSED ACT: Regulation of the European Parliament and of the Council.
BACKGROUND: clinical trials are an indispensable part of clinical research which, in turn, is essential to develop medicinal products and improve medical treatment. In the EU/EEA, approximately 4 400 clinical trials are applied for every year. Approximately 24 % of all clinical trials applied for in the EU are multinational clinical trials, i.e. clinical trials intended to be performed in at least two Member States. These 24% clinical trials involve approximately 67% of all subjects enrolled in a clinical trial.
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.
Directive 2001/20/EC has brought about important improvements in the safety and ethical soundness of clinical trials in the EU and in the reliability of clinical trials data. However, it is criticized by all stakeholders in the pharmaceutical sector for the following reasons: (i) the number of applications for clinical trials fell by 25 % from 2007 to 2011; (ii) the costs for conducting clinical trials have increased; (iii) the average delay for launching a clinical trial has increased by 90 % to 152 days.
It would be wrong to attribute the fall in clinical trial activity solely and exclusively to the Directive 2001/20/EC. However, the Directive has had many direct effects on the cost and feasibility of conducting clinical trials, which, in turn, have led to a decline in clinical trial activity in the EU. The Commission considers it necessary, therefore, to take new measures.
IMPACT ASSESSMENT: the Commission has carried out an impact assessment in accordance with its guidelines and published the results.
LEGAL BASIS: Articles 114 and 168(4)(c) of the Treaty on the Functioning of the European Union (TFEU.) The Regulation aims at achieving an internal market as regards clinical trials and medicinal products for human use, taking as a base a high level of protection of health. At the same time, the Regulation sets high standards of quality and safety for medicinal products to meet common safety concerns as regards these products.
CONTENT: the proposed legislation takes the form of a Regulation and replaces Directive 2001/20/EC. This legal form ensures that Member States base their assessment of an application for authorisation of a clinical trial on an identical text, rather than on diverging national transposition measures. This holds not only for the entire authorisation process, but also for all other issues addressed in the Regulation, such as safety reporting during clinical trials, and the requirements for labelling of the medicinal products used in the context of a clinical trial.
A Regulation also allows actors to plan and conduct clinical trials, including multi-national clinical trials, on the basis of one regulatory framework.
The main points of the proposal are as follows:
New authorisation procedure for clinical trials: this based on the following:
· a harmonised authorisation dossier;
· a ‘single portal’ to submit an application for conducting a clinical trial linked to an EU database;
· a flexible and swift assessment procedure;
· a clear mechanism to appoint a ‘reporting Member State’;
· clear timelines with a concept of tacit approval in order to ensure compliance;
· a coordination and advisory forum to address issues which may arise in the authorisation procedure;
· a clear distinction between aspects where Member States cooperate in the assessment and aspects of an intrinsic ethical or national/local nature where the assessment is made by each Member State individually;
· the option for a Member State to 'opt-out' of the conclusions of an assessment of an application for conducting a clinical trial ('qualified opt-out');
· a swift procedure to ‘extend’ a clinical trial to additional Member States;
· where a clinical trial is modified after it has been authorised, this modification is subject to authorisation if, and only if, the modification has a substantial impact on the safety or rights of the subjects or on the reliability and robustness of the data generated in the clinical trial.
Simplified safety reporting: compared to Directive 2001/20/EC, the rules have been streamlined, simplified and modernised as follows:
· the option to exclude reporting by the investigator to the sponsor of adverse events, if this is provided for in the protocol;
· direct reporting of suspected unexpected serious adverse reactions by the sponsor to the European database EudraVigilance;
· simplified submission of the annual safety report by the sponsor.
Protection of subjects and informed consent : Directive 2001/20/EC does not address the specific situation where, because of the urgency of the situation, it is impossible to obtain free and informed consent from the subject or the legal representative (‘clinical trials in emergency situations’). To address this, specific provisions on clinical trials in emergency situations have been added in line with existing international guidance documents on this issue.
Furthermore, as regards the protection of personal data, provisions of Directive 95/46/EC and Regulation (EC) No 45/200110 apply.
No personal data of data subjects participating in a trial will be collected in the EU database. Personal data of investigators, which may be collected in the EU database, are kept in accordance with the exception provided in the text.
Compensation for damage : where there is no additional risk, or where that additional risk is negligible, the Regulation does not provide a specific damage compensation (be it an insurance or an indemnification) for the clinical trial. However, in cases where a clinical trial does pose an additional risk, the proposed Regulation obliges the sponsor to ensure compensation – be it through insurance, or through an indemnification mechanism.
Sponsors, co-sponsorship, EU contact person: every clinical trial must have a ‘sponsor’, i.e. a legal or natural person responsible for initiating and managing the clinical trial. Clinical trials are increasingly initiated by loose networks of scientists or scientific institutions within one Member State or across several Member States. The proposed Regulation introduces the concept of ‘co-sponsorship’. At the outset, all co-sponsors are responsible for the entire clinical trial. However, the proposal allows co-sponsors to ‘split’ the responsibility for the clinical trials amongst themselves.
If the sponsor is established in a third country, an EU contact person must be provided in order to ensure an effective supervision of a clinical trial.
Inspections: the proposed Regulation provides the legal basis for Commission staff to perform controls in Member States and in third countries in the context of the EU acquis for medicinal products for human use and clinical trials.
BUDGETARY IMPLICATIONS: EUR 4 144 000 in commitment appropriations for the period 2014-2020.
The budgetary implications of this proposal are as follows:
· costs for databases (one-off costs and maintenance);
· Commission staff to manage the functioning of the Regulation;
· costs for meetings of Member States to ensure that the authorisation procedure set out in this Regulation functions properly;
· Commission staff and other costs to conduct Union controls and Union inspections.
The costs will be covered with the envelope of the Health for Growth Programme 2014-2020 2014-2020.
Documents
- Commission response to text adopted in plenary: SP(2014)471
- Final act published in Official Journal: Regulation 2014/536
- Final act published in Official Journal: OJ L 158 27.05.2014, p. 0001
- Final act published in Official Journal: Corrigendum to final act 32014R0536R(04)
- Final act published in Official Journal: OJ L 311 17.11.2016, p. 0025
- Draft final act: 00002/2014/LEX
- Results of vote in Parliament: Results of vote in Parliament
- Debate in Parliament: Debate in Parliament
- Decision by Parliament, 1st reading/single reading: T7-0273/2014
- Committee report tabled for plenary, 1st reading/single reading: A7-0208/2013
- Amendments tabled in committee: PE513.021
- Committee opinion: PE506.211
- Committee opinion: PE500.727
- Committee opinion: PE504.167
- Amendments tabled in committee: PE506.159
- Amendments tabled in committee: PE506.160
- Amendments tabled in committee: PE506.158
- Amendments tabled in committee: PE506.161
- Amendments tabled in committee: PE506.162
- Committee draft report: PE504.236
- Amendments tabled in committee: PE502.281
- Document attached to the procedure: OJ C 253 03.09.2013, p. 0010
- Document attached to the procedure: N7-0092/2013
- Economic and Social Committee: opinion, report: CES2059/2012
- Contribution: COM(2012)0369
- Contribution: COM(2012)0369
- Contribution: COM(2012)0369
- Contribution: COM(2012)0369
- Document attached to the procedure: EUR-Lex
- Document attached to the procedure: SWD(2012)0200
- Document attached to the procedure: EUR-Lex
- Document attached to the procedure: SWD(2012)0201
- Legislative proposal published: COM(2012)0369
- Legislative proposal published: EUR-Lex
- Document attached to the procedure: EUR-Lex SWD(2012)0200
- Document attached to the procedure: EUR-Lex SWD(2012)0201
- Economic and Social Committee: opinion, report: CES2059/2012
- Document attached to the procedure: OJ C 253 03.09.2013, p. 0010 N7-0092/2013
- Amendments tabled in committee: PE502.281
- Committee draft report: PE504.236
- Amendments tabled in committee: PE506.158
- Amendments tabled in committee: PE506.161
- Amendments tabled in committee: PE506.162
- Amendments tabled in committee: PE506.159
- Amendments tabled in committee: PE506.160
- Committee opinion: PE504.167
- Committee opinion: PE500.727
- Committee opinion: PE506.211
- Amendments tabled in committee: PE513.021
- Draft final act: 00002/2014/LEX
- Commission response to text adopted in plenary: SP(2014)471
- Contribution: COM(2012)0369
- Contribution: COM(2012)0369
- Contribution: COM(2012)0369
- Contribution: COM(2012)0369
Activities
- Milan CABRNOCH
Plenary Speeches (0)
- António Fernando CORREIA DE CAMPOS
Plenary Speeches (0)
- Viorica DĂNCILĂ
Plenary Speeches (0)
- Philippe JUVIN
Plenary Speeches (0)
- Christa KLASS
Plenary Speeches (0)
- Claudio MORGANTI
Plenary Speeches (0)
- Franz OBERMAYR
Plenary Speeches (0)
- Antonyia PARVANOVA
Plenary Speeches (0)
- Gilles PARGNEAUX
Plenary Speeches (0)
- Maria do Céu PATRÃO NEVES
Plenary Speeches (0)
- Gianni PITTELLA
Plenary Speeches (0)
- Bogusław SONIK
Plenary Speeches (0)
- Alda SOUSA
Plenary Speeches (0)
- Claudiu Ciprian TĂNĂSESCU
Plenary Speeches (0)
- Jarosław WAŁĘSA
Plenary Speeches (0)
- Dame Glenis WILLMOTT
Plenary Speeches (0)
Amendments | Dossier |
549 |
2012/0192(COD)
2013/02/01
IMCO
170 amendments...
Amendment 100 #
Proposal for a regulation 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
Amendment 101 #
Proposal for a regulation 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
Amendment 102 #
Proposal for a regulation 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
Amendment 103 #
Proposal for a regulation Article 6 – paragraph 1 – point a – point i – indent 3 – the reliability and robustness of the data generated in the clinical trial, reflecting the population groups to be treated. taking account of statistical approaches, design of the trial and methodology (including sample size and randomisation, comparator and endpoints);
Amendment 104 #
Proposal for a regulation Article 6 – paragraph 1 – point a – subparagraph 1 a (new) Amendment 105 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – introductory part For the purposes of this Chapter, the assessment date shall be the date on which the assessment report is submitted to the other Member States concerned and the reporting date shall be the date when the final assessment report is submitted to the sponsor and to the other Member States concerned. 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 within the following time periods
Amendment 106 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point a (a) within 10 days from the validation date for low-intervention clinical trials; the time for the joint assessment and for consolidation by Member States concerned and the reporting Member State shall not be shorter than 5 days;
Amendment 107 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point b (b) within 25 days from the validation date for clinical trials other than low- intervention clinical trials; the time for the joint assessment and for consolidation by Member States concerned and the reporting Member State shall not be shorter than 10 days;
Amendment 108 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point c (c) within 30 days from the validation date for any clinical trial with an advanced therapy investigational medicinal product; the time for the joint assessment and for consolidation by Member States concerned and reporting Member State shall not be shorter than 10 days.
Amendment 109 #
Proposal for a regulation Article 6 – paragraph 5 5. Until the assessment date
Amendment 110 #
Proposal for a regulation Article 6 – paragraph 5 a (new) 5a. The assessment report shall be submitted through the EU portal and be made publically available.
Amendment 111 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 1 Amendment 112 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 1 The reporting Member State, and only the reporting Member State, may, between the validation date and the
Amendment 113 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 2 For the purpose of obtaining those additional explanations, the reporting Member State may
Amendment 114 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 3 Amendment 115 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 5 a (new) The reporting Member State may also extend the time referred to in paragraphs 4 and 6a further 60 days for trials involving Advanced Therapy Medicinal Products or other novel therapies, for the purpose of consulting with expert committees.
Amendment 116 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 5 a (new) Member States shall ensure that the application and existence of the EU portal are sufficiently communicated to the public.
Amendment 117 #
Proposal for a regulation 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 118 #
Proposal for a regulation Article 7 a (new) Article 7a Assessment report on clinical trials in the field of rare diseases 1. In the specific case of clinical trials in rare diseases as defined in the Regulation (EC) No 141/2000 of the European Parliament and of the Council on orphan medicinal products1, the reporting Member State shall seek the expert opinion of the Scientific Advice Working Party of the European Medicines Agency on the disease or group of diseases concerned by the clinical trial, including on aspects covered by Part II of the assessment. 2. For the purposes of assessing the aspects referred to in Article 7, the reporting Member State shall notify the opinion of the Scientific Advice Working Party to the Member States concerned without undue delay. _____________ 1 OJ L 18, 22.1.2000, p. 1.
Amendment 119 #
Proposal for a regulation 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) 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) 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 Amendment 123 #
Proposal for a regulation 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 Article 8 – paragraph 2 – subparagraph 2 – point a (a) significant differences in normal clinical practice between the Member State concerned and the reporting Member State which would lead to a subject receiving an inferior
Amendment 125 #
Proposal for a regulation Article 8 – paragraph 2 – subparagraph 2 – point b a (new) (ba) Infringement of more comprehensive national provisions for clinical trial subjects' protection than the provisions of this Regulation, in particular as regards vulnerable populations;
Amendment 126 #
Proposal for a regulation Article 8 – paragraph 2 – subparagraph 2 – point b a (new) (ba) refusal of the Ethics Committee to approve the conduct of the clinical trial in the Member State concerned
Amendment 127 #
Proposal for a regulation Article 8 – paragraph 2 – subparagraph 2 – point b b (new) (bb) refusal of the Ethics Committee to approve the conduct of the clinical trial in the Member State concerned.
Amendment 128 #
Proposal for a regulation Article 8 – paragraph 2 – subparagraph 2 – point b b (new) (bb) infringement of more comprehensive national legislation for clinical trail subject protection, particularly regarding vulnerable persons
Amendment 129 #
Proposal for a regulation Article 8 – paragraph 2 – subparagraph 3 Where the Member State concerned disagrees with the conclusion 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. The reasons for the disagreement must be published through the EU portal.
Amendment 130 #
Proposal for a regulation 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 Article 8 – paragraph 2 – subparagraph 3 Where the Member State concerned disagrees with the conclusion o
Amendment 132 #
Proposal for a regulation 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
Amendment 133 #
Proposal for a regulation Article 9 – paragraph 2 2. Member States shall ensure that the assessment
Amendment 134 #
Proposal for a regulation Article 9 – paragraph 3 3. In the assessment, the view of at least one person whose primary area of interest is non-scientific shall be taken into account. The view of at least one patient shall be taken into account. An independent Ethics Committee as referred to in the Declaration of Helsinki and ICH-GCP shall be involved in the assessment of each clinical trial.
Amendment 135 #
Proposal for a regulation 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 136 #
Proposal for a regulation Article 12 – paragraph 1 The sponsor may withdraw the application at any time until the assessment date. In such a case, the application may only be withdrawn with respect to all Member States concerned. The reasons for the withdrawal must be communicated to all Member States concerned and published through the portal mentioned in this Regulation.
Amendment 137 #
Proposal for a regulation Article 12 – paragraph 1 The sponsor may withdraw the application at any time until the assessment date. In such a case, the application may only be withdrawn with respect to all Member States concerned. A record of withdrawn applications shall remain in the EU data based and reasons for each withdrawal shall be given.
Amendment 138 #
Proposal for a regulation Article 13 – paragraph 1 This Chapter is without prejudice to the possibility for the sponsor to submit, following the refusal to grant an authorisation or the withdrawal of an application, an application for authorisation to any intended Member State concerned. That application shall be considered as a new application for authorisation of another clinical trial. Explanations about previous applications, withdrawals and refusals must be included in the new application.
Amendment 139 #
Proposal for a regulation Article 13 – paragraph 1 Amendment 140 #
Proposal for a regulation Article 14 – paragraph 2 2.
Amendment 141 #
Proposal for a regulation Article 15 – paragraph 1 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 previously approved by an independent Ethics Committee.
Amendment 142 #
Proposal for a regulation 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
Amendment 143 #
Proposal for a regulation Article 25 – paragraph 5 5. Where the clinical trial has been conducted outside the Union, it shall comply with
Amendment 144 #
Proposal for a regulation Article 28 – paragraph 1 – point a Amendment 145 #
Proposal for a regulation Article 28 – paragraph 1 – point b (b)
Amendment 146 #
Proposal for a regulation Article 28 – paragraph 1 – point c Amendment 147 #
Proposal for a regulation 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
Amendment 148 #
Proposal for a regulation 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 149 #
Proposal for a regulation 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 possible, sufficient time shall be given to the subject to consider the decision. 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 150 #
Proposal for a regulation 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 (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 (f) such research relates directly to a
Amendment 153 #
Proposal for a regulation 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
Amendment 154 #
Proposal for a regulation 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 Article 31 – paragraph 1 – point a (a) the
Amendment 156 #
Proposal for a regulation Article 31 – paragraph 1 – point h (h) some direct benefit for the
Amendment 157 #
Proposal for a regulation 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
Amendment 158 #
Proposal for a regulation 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 or its legal representative (parent or guardian) and it is impossible to supply prior information to the subject or its legal representative (parent or guardian);
Amendment 159 #
Proposal for a regulation Article 32 – paragraph 1 – point a (a) due to the urgency of the situation,
Amendment 160 #
Proposal for a regulation Article 32 – paragraph 1 – point b (b)
Amendment 161 #
Proposal for a regulation Article 32 – paragraph 1 – point c (c) the subject or legal representative has not previously expressed objections known to the investigator;
Amendment 162 #
Proposal for a regulation Article 32 – paragraph 1 – point d Amendment 163 #
Proposal for a regulation Article 32 – paragraph 1 – point e (e) the clinical trial poses
Amendment 164 #
Proposal for a regulation Article 32 – paragraph 1 – point e (e) the
Amendment 165 #
Proposal for a regulation 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 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 That notification shall be made within
Amendment 168 #
Proposal for a regulation Article 33 – paragraph 2 a (new) 2a. Prior to the start, all clinical trials should be registered in the database mentioned in this Regulation. Information provided shall include the start and the end date of the recruitments of subjects.
Amendment 169 #
Proposal for a regulation Article 33 – paragraph 2 – subparagraph 2 That notification shall be made within
Amendment 170 #
Proposal for a regulation Article 34 – title End of the clinical trial, early termination of the clinical trial and submission of results
Amendment 171 #
Proposal for a regulation Article 34 – paragraph 2 – subparagraph 2 That notification shall be made within
Amendment 172 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 Within one year from the end of a clinical trial, the sponsor shall submit to the EU database a summary of the results of the clinical trial and a clinical study report.
Amendment 173 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 a (new) Where the clinical trial is intended, at the time of submission of the application for authorisation, to be used for obtaining a marketing authorisation for a medicinal product, the summary of the results referred to in paragraph 1 shall be submitted within 30 days after the marketing authorisation date or, where applicable, within one year from the decision to discontinue the development of a medicinal product.
Amendment 174 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 Amendment 175 #
Proposal for a regulation 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 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. After 12 months' of temporary halt, the clinical trial data shall be made publically accessible, even if incomplete.
Amendment 176 #
Proposal for a regulation 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 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. If a clinical trial is discontinued, the sponsor shall notify the reasons thereof to the Member State concerned through the EU portal within 15 days from the decision to discontinue the clinical trial.
Amendment 177 #
Proposal for a regulation Article 34 – paragraph 5 a (new) 5a. 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 178 #
Proposal for a regulation 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 and 39.
Amendment 179 #
Proposal for a regulation Article 38 – paragraph 1 1. The sponsor shall report electronically and with
Amendment 180 #
Proposal for a regulation Article 39 – paragraph 1 a (new) Amendment 181 #
Proposal for a regulation Article 39 – paragraph 2 2. The obligation for a particular sponsor, referred to in paragraph 1, starts with the first authorisation of a clinical trial in accordance with this Regulation for that sponsor. It ends with the end of the last clinical trial conducted by the sponsor with the investigational medicinal product. The annual reporting obligation does not apply when a sponsor is not currently conducting any clinical trials with the investigational medicinal product.
Amendment 182 #
Proposal for a regulation Article 43 – paragraph 1 Safety reporting with regard to auxiliary
Amendment 183 #
Proposal for a regulation Article 45 – paragraph 1 – point a (a) whether the clinical trial is a
Amendment 184 #
Proposal for a regulation 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
Amendment 185 #
Proposal for a regulation Article 49 – paragraph 2 2. For the purposes of this Article, a
Amendment 186 #
Proposal for a regulation Article 50 – paragraph 1 1. The sponsor shall notify the competent bodies of the Member States concerned through the EU portal and without undue delay, of all unexpected events which affect the benefit-risk balance
Amendment 187 #
Proposal for a regulation Article 55 – paragraph 1 Amendment 188 #
Proposal for a regulation Article 66 – paragraph 1 The language of the information on the label shall be determined by the Member State concerned and shall be one of the official languages of the Union. The medicinal product may be labelled in several languages.
Amendment 189 #
Proposal for a regulation Article 72 – paragraph 1 For clinical
Amendment 190 #
Proposal for a regulation Article 72 – paragraph 1 For clinical trials other than low- intervention clinical trials, the sponsor shall ensure that compensation in accordance with the applicable laws on liability of the sponsor and the investigator, including by means of insurance, is provided for any damage suffered by the subject. This damage compensation shall be provided independently of the financial capacity of the sponsor and the investigator. Where damage compensation is provided by means of insurance, a sponsor may use a single insurance policy to cover one or more clinical trials within the same Member State.
Amendment 191 #
Proposal for a regulation Article 73 – paragraph 1 1. For clinical trials which, for objective reasons, were not intended, at the time of submission of the application for authorisation, to be used for obtaining a marketing authorisation for a medicinal product, Member States shall provide for a national indemnification mechanism for compensating damage as referred to in Article 72. The use of the national indemnification system shall be free of charge or subject to a nominal fee.
Amendment 192 #
Proposal for a regulation Article 73 – paragraph 3 Amendment 193 #
Proposal for a regulation Article 74 – paragraph 2 2. The measures referred to in paragraph 1 shall be made publicly available on and communicated to all Member States concerned through the EU portal.
Amendment 194 #
Proposal for a regulation Article 76 – paragraph 1 – point a Amendment 195 #
Proposal for a regulation Article 78 – paragraph 3 – indent 2 –
Amendment 196 #
Proposal for a regulation 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 93 – paragraph 2 It shall apply
Amendment 198 #
Proposal for a regulation Annex I – part 2 – point 9 9. In the case of a resubmission, the cover letter shall highlight the
Amendment 199 #
Proposal for a regulation Annex I – part 4 – point 13 – point 3 · an evaluation of the anticipated benefits and risks, including for specific subpopulations, to allow assessment in accordance with Article 6;
Amendment 200 #
Proposal for a regulation Annex I – part 16 – point 61 Amendment 201 #
Proposal for a regulation Annex I – part 16 – point 61 61. Description of any agreement between the sponsor and the site shall be submitted and made publicly available.
Amendment 202 #
Proposal for a regulation Annex III a (new) Amendment 33 #
Proposal for a regulation Recital 1 (1) In a clinical trial the safety and rights of subjects should be protected and the data generated should be reliable
Amendment 34 #
Proposal for a regulation 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
Amendment 35 #
Proposal for a regulation 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 ‘
Amendment 36 #
Proposal for a regulation Recital 10 (10) The assessment of the application for a clinical trial should address in particular the anticipated therapeutic and public health benefits (
Amendment 37 #
Proposal for a regulation 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
Amendment 38 #
Proposal for a regulation Recital 12 a (new) Amendment 39 #
Proposal for a regulation Recital 14 (14) It should be left to the Member State concerned to determine the appropriate body or bodies to be involved in this assessment. This decision is a matter of internal organisation of each Member State.
Amendment 40 #
Proposal for a regulation Recital 14 a (new) (14a) The Commission shall issue guidelines in consultation with Member States, academia and civil society organisations to specify the content and format of the results of the clinical trial.
Amendment 41 #
Proposal for a regulation Recital 14 a (new) Amendment 42 #
Proposal for a regulation Recital 16 (16) The sponsor should be allowed to withdraw the application for authorisation of a clinical trial. To ensure the reliable functioning of the assessment procedure, however, an application for authorisation of a clinical trial should be withdrawn only for the entire clinical trial. It should be possible for the sponsor to submit a new application for authorisation of a clinical trial following the withdrawal of an application, provided that the new application contains explanations regarding any previous withdrawals.
Amendment 43 #
Proposal for a regulation Recital 20 (20) In order to increase transparency in the area of clinical trials, clinical trial data submitted in support of a clinical trial application should be based only on clinical trials recorded in a publicly a
Amendment 44 #
Proposal for a regulation 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.
Amendment 45 #
Proposal for a regulation 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 46 #
Proposal for a regulation 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.
Amendment 47 #
Proposal for a regulation Recital 25 a (new) (25a) The sponsor shall submit, in a timely manner, to the EU database a summary of the results of a clinical trial. This submission shall respect the level of development of the product and shall not include any personal data or commercially confidential information. The summary of the results of the clinical trial should be submitted either within one year of the end of the clinical trial or of the decision to discontinue the development of a medicinal product, or no later than 30 days after the marketing authorisation has been granted.
Amendment 48 #
Proposal for a regulation Recital 33 During a clinical trial, a sponsor may become aware of serious breaches of the rules for the conduct of the clinical trial. This should be reported to
Amendment 49 #
Proposal for a regulation Recital 34 (34) Apart from the reporting of suspected unexpected serious adverse reactions, there may be other events which are relevant in terms of benefit-risk balance and which should be reported in a timely manner to the
Amendment 50 #
Proposal for a regulation Recital 36 (36) In order to ensure compliance of the conduct of the clinical trial with the protocol, and in order for investigators to be informed about the investigational medicinal products they administer, the sponsor should supply the investigators with an investigator's brochure. This brochure should be updated whenever new safety information becomes available, including information about events other than suspected unexpected serious adverse reactions.
Amendment 51 #
Proposal for a regulation Recital 37 a (new) (37a) The Commission should within two years after the adoption of this Regulation submit the European Parliament with an evaluation of the management of raw data and the feasibility of introducing open access for independent scientists to raw data.
Amendment 52 #
Proposal for a regulation Recital 46 (46) In clinical trials
Amendment 53 #
Proposal for a regulation Recital 47 (47) At present, such damage compensation is provided by way of insurance. This insurance may cover damages to be paid to the subject by the sponsor and investigator in the case of established liability. It may also compensate the subject directly without prior establishment of the liability of the sponsor or investigator. Experience shows that the insurance market is small and costs for insurance coverage are
Amendment 54 #
Proposal for a regulation Recital 51 (51) In order to streamline and facilitate the flow of information between sponsors and Member States as well as between Member States, the Commission should set up and maintain a database, accessed through a portal. The Commission and Member States should raise awareness among the general public on the existence of the portal.
Amendment 55 #
Proposal for a regulation Recital 64 a (new) (64a) According to the Commission Communication on "An Integrated Industrial Policy for the Globalisation Era Putting Competitiveness and Sustainability at Centre Stage" systematic evaluations of legislation must become an integral part of smart regulation. In order to ensure this Regulation keeps pace with scientific and technological progress in the organization and conduct of clinical trials and interfaces with other legal provisions, the Commission should periodically report on the experience and functioning of the Regulation and present its conclusions thereof.
Amendment 56 #
Proposal for a regulation Article 2 – paragraph 2 – point 1 – introductory part (1) ‘Clinical
Amendment 57 #
Proposal for a regulation Article 2 – paragraph 2 – point 1 – point a (a) to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products; or
Amendment 58 #
Proposal for a regulation Article 2 – paragraph 2 – point 2 Amendment 59 #
Proposal for a regulation Article 2 – paragraph 2 – point 2 – point a a) the investigational medicinal products
Amendment 60 #
Proposal for a regulation Article 2 – paragraph 2 – point 2 – point c Amendment 61 #
Proposal for a regulation Article 2 – paragraph 2 – point 2 – point d d) the decision to prescribe the investigational medicinal product
Amendment 62 #
Proposal for a regulation Article 2 – paragraph 2 – point 3 – introductory part 3) ‘
Amendment 63 #
Proposal for a regulation Article 2 – paragraph 2 – point 3 – point a a) the investigational medicinal products
Amendment 64 #
Proposal for a regulation 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
Amendment 65 #
Proposal for a regulation 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
Amendment 66 #
Proposal for a regulation Article 2 – paragraph 2 – point 3 – point c a (new) (ca) the aim of the study is not that of identifying, characterising or quantifying a safety hazard, confirming the efficacy or safety profile of the medicinal product, or of measuring the effectiveness of risk management measures.
Amendment 67 #
Proposal for a regulation Article 2 – paragraph 2 – point 4 (4) ‘Non-interventional study’: a
Amendment 68 #
Proposal for a regulation Article 2 – paragraph 2 – point 4 – indent 1 (new) - No payment or other advantage or facilities can be made to healthcare professionals in order to encourage them to prescribe, dispense or use a given medicinal product.
Amendment 69 #
Proposal for a regulation Article 2 – paragraph 2 – point 6 (6)
Amendment 70 #
Proposal for a regulation Article 2 – paragraph 2 – point 6 Amendment 71 #
Proposal for a regulation 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
Amendment 72 #
Proposal for a regulation Article 2 – paragraph 2 – point 11 a (new) (11a) 'Reporting Member State': the Member State coordinating and documenting the assessment of an application for authorisation or of a substantial modification involving three or more Member States, which has been submitted under Chapters II and III of this Regulation.
Amendment 73 #
Proposal for a regulation Article 2 – paragraph 2 – point 12 (12)
Amendment 74 #
Proposal for a regulation Article 2 – paragraph 2 – point 12 (12)
Amendment 75 #
Proposal for a regulation Article 2 – paragraph 2 – point 13 (13)
Amendment 76 #
Proposal for a regulation Article 2 – paragraph 2 – point 13 (13)
Amendment 77 #
Proposal for a regulation 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) 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) 14b. ‘Coordinating investigator’: investigator responsible for coordinating a multicentre trial in one or more Member States;
Amendment 80 #
Proposal for a regulation Article 2 – paragraph 2 – point 17 17) ‘Incapacitated subject’: a subject who is,
Amendment 81 #
Proposal for a regulation Article 2 – paragraph 2 – point 19 19)
Amendment 82 #
Proposal for a regulation Article 2 – paragraph 2 – point 20 (20) ‘Protocol’: a document that describes the objectives, design, methodology, statistical considerations and organisation of a clinical trial. The term protocol refers to the protocol, successive versions of the protocol and protocol amendments;
Amendment 83 #
Proposal for a regulation Article 2 – paragraph 2 – point 30 a (new) (30a) 'Clinical study report' : a report containing the full protocol and its eventual subsequent modifications and dates thereof, a statistical analysis plan, summarised efficacy and safety data on all outcomes, and individual anonymised patient data in the format of tabulations or listings.
Amendment 84 #
Proposal for a regulation Article 2 – paragraph 2 – point 30 a (new) (30a) 'Clinical study report': a report containing the full protocol and its eventual subsequent modifications, a statistical analysis plan, summarised efficacy and safety data on all outcomes, and individual anonymised patient data in the format of tabulations or listings.
Amendment 85 #
Proposal for a regulation Article 3 – paragraph 1 – indent 2 – the data generated in the clinical trial are going to be relevant, reliable and robust.
Amendment 86 #
Proposal for a regulation Article 3 – paragraph 1 – indent 2 a (new) - it responds to therapeutic and public health needs;
Amendment 87 #
Proposal for a regulation Chapter 2 – title Amendment 88 #
Proposal for a regulation Article 4 a (new) Amendment 89 #
Proposal for a regulation Article 4 a (new) Article 4a An authorisation for a proposed clinical trial by a competent authority of a Member State must be taken after the approval by the concerned ethics committee.
Amendment 90 #
Proposal for a regulation Article 4 b (new) Article 4b Best current proven intervention The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances: (a) the use of placebo, or no treatment, is acceptable in studies where no current proven intervention exists; or (b) where for compelling and scientifically sound methodological reasons the use of placebo is necessary to determine the efficacy or safety of an intervention and the patients who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care must be taken to avoid abuse of the option set out in point (b) of the first subparagraph.
Amendment 91 #
Proposal for a regulation Article 4 c (new) Amendment 92 #
Proposal for a regulation Article 5 – paragraph 1 – subparagraph 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’).Within six days following submission of the application dossier, Member States shall collectively appoint a reporting Member State and a co- reporting Member State.
Amendment 93 #
Proposal for a regulation Article 5 – paragraph 1 – subparagraph 2 Amendment 94 #
Proposal for a regulation Article 5 – paragraph 1 – subparagraph 3 Amendment 95 #
Proposal for a regulation 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 96 #
Proposal for a regulation Article 5 – paragraph 2 – introductory part 2. Within six days following
Amendment 97 #
Proposal for a regulation Article 5 – paragraph 2 – point a (a)
Amendment 98 #
Proposal for a regulation Article 5 – paragraph 2 – point d a (new) (da) the clinical trial registration number in the EU portal.
Amendment 99 #
Proposal for a regulation 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
source: PE-504.308
2013/02/27
ITRE
127 amendments...
Amendment 100 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 1 The reporting Member State, and only the reporting Member State, may, between the validation date and the
Amendment 101 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 2 For the purpose of obtaining those additional explanations, the reporting Member State may
Amendment 102 #
Proposal for a regulation Article 6 – paragraph 6 – subparagraph 3 Amendment 103 #
Proposal for a regulation Article 6 – paragraph 7 7. The sponsor may at its own initiative change the content of the application only between the validation date and the
Amendment 104 #
Proposal for a regulation Article 7 – paragraph 1 – subparagraph 1 – point a (a) compliance with the requirements for the protection of subjects and informed consent as set out in Chapter V;
Amendment 105 #
Proposal for a regulation Article 7 – paragraph 1 – subparagraph 1 – point a a (new) (aa) compliance with national legislative provisions related to ethics.
Amendment 106 #
Proposal for a regulation Article 7 – paragraph 2 2. Each Member State concerned shall complete its assessment within twenty days from the validation date. It may request, with justified reasons, additional explanations from the sponsor regarding the aspects referred to in paragraph 1 only within that time period.
Amendment 107 #
Proposal for a regulation Article 8 – paragraph 1 – subparagraph 2 Notification shall be done by way of one single decision, already comprising the views of the concerned Ethics Committee, within ten days from the assessment date or the last day of the assessment referred to in Article 7, whichever is later.
Amendment 108 #
Proposal for a regulation Article 8 – paragraph 2 – subparagraph 3 Where the Member State concerned disagrees with the conclusion 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. The Member State concerned may not infer ethical concerns as a justification.
Amendment 109 #
Proposal for a regulation Article 8 – paragraph 4 4. Where the Member State concerned has not notified the sponsor of its decision within the time periods referred to in paragraph 1, the conclusion on Part I of the assessment report shall be considered as the decision of the Member State concerned on the application for authorisation of the clinical trial, provided that it was considered a low-intervention clinical trial in accordance with Article 5(2).
Amendment 110 #
Proposal for a regulation Article 8 – paragraph 5 5.
Amendment 111 #
Proposal for a regulation 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 experience. In addition, the views of the concerned Ethics Committee shall be taken into account.
Amendment 112 #
Proposal for a regulation Article 9 – paragraph 3 3. In the assessment, the view of a
Amendment 113 #
Proposal for a regulation Article 11 – paragraph 1 Where the sponsor so requests, the application for authorisation of a clinical trial
Amendment 114 #
Proposal for a regulation Article 11 – paragraph 2 After the notification of the decision on the aspects covered by Part I of the assessment report, the sponsor
Amendment 115 #
Proposal for a regulation Article 13 – paragraph 1 This Chapter is without prejudice to the possibility for the sponsor to submit, following the refusal to grant an authorisation or the withdrawal of an application, an application for authorisation to any intended Member State
Amendment 116 #
Proposal for a regulation Article 14 – paragraph 1 – subparagraph 2 The application may be submitted in any Member State only after the notification date of the initial
Amendment 117 #
Proposal for a regulation Article 14 – paragraph 3 – point a (a)
Amendment 118 #
Proposal for a regulation Article 14 – paragraph 3 – point b (b)
Amendment 119 #
Proposal for a regulation Article 14 – paragraph 3 – point c (c)
Amendment 120 #
Proposal for a regulation Article 14 – paragraph 4 – subparagraph 2 – point b a (new) (ba) refusal of the Ethics Committee to approve the conduct of the clinical trial.
Amendment 121 #
Proposal for a regulation Article 14 – paragraph 5 5.
Amendment 122 #
Proposal for a regulation Article 14 – paragraph 6 – subparagraph 1 The reporting Member State, and only the reporting Member State, may,
Amendment 123 #
Proposal for a regulation Article 17 – paragraph 2 – introductory part 2. Within
Amendment 124 #
Proposal for a regulation Article 19 – paragraph 1 – subparagraph 1 Each Member State concerned shall notify the sponsor through the EU portal as to whether the substantial modification is authorised, whether it is authorised subject to conditions, or whether authorisation is refused. Notification shall be done by way of one single decision, already comprising the views of the concerned Ethics Committee, within fifteen days from the assessment date.
Amendment 125 #
Proposal for a regulation Article 19 – paragraph 2 – subparagraph 2 – point b a (new) (ba) refusal of the Ethics Committee to approve the conduct of the clinical trial.
Amendment 126 #
Proposal for a regulation Article 20 – paragraph 5 – subparagraph 2 Notification shall be done by way of one single decision already comprising the views of the concerned Ethics Committee, within
Amendment 127 #
Proposal for a regulation Article 20 – paragraph 7 7. Where the Member State concerned has not notified the sponsor of its decision within the time periods set out in paragraphs 5 and 6, the substantial modification shall be considered as authorised, provided that it was considered a low-intervention clinical trial in accordance with Article 5(2).
Amendment 128 #
Proposal for a regulation Article 22 – paragraph 1 1. Each Member State concerned shall assess, for its territory, the aspects of the substantial modification which are covered by Part II of the assessment report within
Amendment 129 #
Proposal for a regulation Article 23 – paragraph 1 – subparagraph 2 Notification shall be done by way of one single decision, already comprising the views of the concerned Ethics Committee, within
Amendment 130 #
Proposal for a regulation Article 23 – paragraph 2 – subparagraph 2 – point b a (new) (ba) refusal of the Ethics Committee to approve the conduct of the clinical trial.
Amendment 131 #
Proposal for a regulation Article 23 – paragraph 4 4. Where the Member State concerned has not notified the sponsor of its decision within the time periods referred to in paragraph 1, the conclusion on the substantial modification of aspects covered by Part I of the assessment report shall be considered as the decision of the Member State concerned on the application for authorisation of the substantial modification provided that it remains a low-intervention clinical trial in accordance with Article 5(2).
Amendment 132 #
Proposal for a regulation Article 25 – paragraph 5 – subparagraph 1 (new) Amendment 133 #
Proposal for a regulation Article 27 – paragraph 1 The Commission shall be empowered to adopt delegated acts in accordance with Article 85 in order to
Amendment 134 #
Proposal for a regulation Article 27a (new) Amendment 135 #
Proposal for a regulation Article 28 – paragraph 2 a (new) 2a. When the subject is required to give his/her consent for a clinical trial, the option of broad consent should be available to the subject, to be given to the treating institution, for his data to be used after the end of the clinical trial for historical, statistical or scientific research purposes, and to withdraw consent at any time.
Amendment 136 #
Proposal for a regulation Article 28 – paragraph 2 a (new) Amendment 137 #
Proposal for a regulation Article 29 – paragraph 1 1. Informed consent for each trial 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
Amendment 138 #
Proposal for a regulation Article 29 – paragraph 2 2. Written information given to the subject and/or the legal representative for the
Amendment 139 #
Proposal for a regulation Article 30 – paragraph 1 – point h a (new) (ha) the research protocol has been endorsed by an Ethics Committee, with expertise in the relevant disease;
Amendment 140 #
Proposal for a regulation Article 31 – paragraph 1 – point h a (new) (ha) The research protocol has been endorsed by an Ethics Committee, with paediatric expertise or after taking advice in clinical, ethical and psychosocial problems in the field of paediatrics;
Amendment 141 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 Within one year from the end of a clinical trial or discontinuation of development of a medicinal product, the sponsor shall submit to the EU database a summary of the positive and/or negative results of the clinical trial, as laid down in Annex IIIa. Until the publication of the summary of the results in accordance with the provisions of this paragraph, it shall only be accessible to the competent authorities of the Member States concerned.
Amendment 142 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 Within one year from the end of a clinical trial or interruption of a trial, the sponsor shall submit to the EU database a
Amendment 143 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 Within one year 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 clinical study report (CSR) and the full dataset of clinical trial data. These elements shall be made publicly accessible through the EU database.
Amendment 144 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 Within one year from the end of a clinical trial, the sponsor shall submit to the EU database a summary of the results of the clinical trial, whether the results are positive or negative or inconclusive.
Amendment 145 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 Amendment 146 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 a (new) In order to protect personal data and commercially confidential information and subject to the provisions of Article 78(3), the summary of the results of a clinical trial intended to obtain a marketing authorisation shall be made public 30 days after the date of the marketing authorisation or 1 year after the end of the clinical trial in case of the discontinuation of the product development.
Amendment 147 #
Proposal for a regulation 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 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. After 12 months of temporary halt, the clinical trial's data shall be submitted to the EU database and made publicly accessible, even if incomplete.
Amendment 148 #
Proposal for a regulation Article 34 – paragraph 5 a (new) 5a. 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 149 #
Proposal for a regulation Article 37 – paragraph 2 2. The investigator shall immediately report serious adverse events to the sponsor, to the Agency and to the competent authority of the concerned Member States, 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 150 #
Proposal for a regulation Article 53 – paragraph 1 1. All clinical trial information shall be recorded, processed, handled, and stored in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable legislation on personal data protection, with easily searchable clinical study reports being publicly available online.
Amendment 151 #
Proposal for a regulation Article 55 – paragraph 1 Unless other Union legislation requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least
Amendment 152 #
Proposal for a regulation Article 55 – paragraph 1 Amendment 153 #
Proposal for a regulation Article 68 – paragraph 2 Any sponsor may delegate any or all of its logistic tasks to an individual, a company, an institution or an organisation. Such delegation shall be without prejudice to the scientific and ethical responsibility of the sponsor.
Amendment 154 #
Proposal for a regulation Article 73 – paragraph 1 1. Member States shall provide for a national indemnification mechanism for compensating damage as referred to in Article 72. It shall be funded for through fees, and no public money shall be used.
Amendment 155 #
Proposal for a regulation Article 73 – paragraph 3 – subparagraph 1 Amendment 156 #
Proposal for a regulation Article 73 – paragraph 3 – subparagraph 2 Amendment 157 #
Proposal for a regulation Article 78 – paragraph 1 – subparagraph 2 Public access to detailed and summary raw clinical data is particularly important to safeguard public health. The EU database shall contain the data and information submitted in accordance with this Regulation.
Amendment 158 #
Proposal for a regulation Article 78 – paragraph 2 2. The EU database shall be established to enable the co-operation between the competent authorities of the Member States to the extent that it is necessary for the application of this Regulation and to search for specific clinical trials. It shall also enable sponsors to refer to previous submissions of an application for authorisation of a clinical trial or a substantial modification. Publicly available information contained in the database shall contribute to protecting public health and fostering the innovation capacity of European medical research, while recognising the legitimate economic interests of sponsors.
Amendment 159 #
Proposal for a regulation Article 78 – paragraph 3 – introductory part 3. The EU database shall be publicly accessible in accordance with the provisions of Regulation (EC) 1049/2001 unless, f
Amendment 160 #
Proposal for a regulation Article 78 – paragraph 3 – indent 1 - protecting personal data in accordance with
Amendment 161 #
Proposal for a regulation Article 78 – paragraph 3 – indent 2 – protecting commercially confidential information; specifically when related to clinical trials intended for the support of any marketing authorisation application for indications which have not yet been approved;
Amendment 162 #
Proposal for a regulation Article 78 – paragraph 3 a (new) 3a. The definition of what is considered as commercial confidential shall be in accordance with EMA guidelines and shall not be allowed to override the interest of public health research.
Amendment 163 #
Proposal for a regulation Article 78 – paragraph 5 5. No personal data of subjects, commercially confidential information or information undermining intellectual property rights shall be publicly accessible.
Amendment 164 #
Proposal for a regulation Article 78 – paragraph 5 5. No personal data of subjects shall be publicly accessible and such data shall be protected in accordance with applicable Union legislation.
Amendment 165 #
Proposal for a regulation Annex 1 – part 2 – point 6 – point 6 a (new) whether the clinical trial significantly contributes to bringing a greater understanding of the physiology and pathology of a condition for which data is lacking, specifically for rare and ultra- rare diseases.
Amendment 166 #
Proposal for a regulation Annex 2 – part 4 – point 4 – indent 2 a (new) - the rationale for the modification proposed;
Amendment 167 #
Proposal for a regulation Annex 3 – part 1 – point 4 a (new) 4a. The sponsor shall keep detailed records of all adverse events reported to it by the investigator(s) and register them in the EU portal.
Amendment 168 #
Proposal for a regulation Annex 3 a (new) Amendment 42 #
Proposal for a regulation Recital 1 (1) In a clinical trial the safety
Amendment 43 #
Proposal for a regulation 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. The conduct of a clinical trial should be conditioned to prior approval by an Ethics Committee.
Amendment 44 #
Proposal for a regulation Recital 6 (6) The Member States concerned should cooperate in assessing a request for authorisation of a clinical trial.
Amendment 45 #
Proposal for a regulation Recital 8 a (new) (8a) The fact that clinical trials are conducted in both public and private centres makes it necessary to recognise them and adopt monitoring, authorisation and assessment measures that apply to both types of centre.
Amendment 46 #
Proposal for a regulation Recital 9 (9) The risk to subject safety in a clinical trial mainly stems from two sources: the
Amendment 47 #
Proposal for a regulation 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 48 #
Proposal for a regulation Recital 12 (12) Some aspects in a clinical trial application relate to issues of an intrinsic national nature or to ethical aspects of a clinical trial.
Amendment 49 #
Proposal for a regulation Recital 22 a (new) (22a) Whereas most clinical trials are implemented for the assessment of therapies consisting of large samples of patient populations, the present Regulation should not discriminate patients suffering from rare and ultra- rare diseases and should integrate the specificities of low-prevalence conditions when assessing a trial.
Amendment 50 #
Proposal for a regulation Recital 25 a (new) (25a) A data subject should always have the option to give broad consent, to be given to the treating institution, for his or her data to be used for historical, statistical or scientific research purposes, and to withdraw his or her consent at any time.
Amendment 51 #
Proposal for a regulation Recital 25 a (new) (25a) It should be possible for a data subject to give broad consent to the treating institutions so that data can be used for historical, statistical or scientific research purposes; and to withdraw this consent at any time.
Amendment 52 #
Proposal for a regulation Recital 26 (26) In order for the sponsor to assess all potentially relevant safety information, the investigator should re
Amendment 53 #
Proposal for a regulation Recital 52 (52) The database should contain all relevant information as regards the clinical trial
Amendment 54 #
Proposal for a regulation Recital 52 a (new) (52a) Commercially confidential information should be identified and protected in order to avoid harming the interests of patients and/or the competitive position of the sponsors.
Amendment 55 #
Proposal for a regulation Article 2 – paragraph 2 – point 3 – introductory part (3) ‘Low-intervention clinical trial’: a clinical
Amendment 56 #
Proposal for a regulation Article 2 – paragraph 2 – point 3 – point a (a) the investigational medicinal products
Amendment 57 #
Proposal for a regulation Article 2 – paragraph 2 – point 3 – point a a (new) (aa) the investigational medicinal products are not products subject to additional monitoring, indentified by a black symbol;
Amendment 58 #
Proposal for a regulation 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
Amendment 59 #
Proposal for a regulation 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
Amendment 60 #
Proposal for a regulation Article 2 – paragraph 2 – point 4 (4)
Amendment 61 #
Proposal for a regulation Article 2 – paragraph 2 – point 4 (4) ‘Non-interventional study’: a clinical study other than a clinical trial
Amendment 62 #
Proposal for a regulation Article 2 – paragraph 2 – point 6 (6) ‘
Amendment 63 #
Proposal for a regulation Article 2 – paragraph 2 – point 6 (6)
Amendment 64 #
Proposal for a regulation Article 2 – paragraph 2 – point 10 a (new) (10a) 'Ethics Committee': an independent body in a Member State, which includes healthcare professionals, laypersons and at least one well-experienced knowledgeable patient or patient representative, for the review of the scientific, medical and ethical aspects of a clinical trial and whose responsibility is to protect the rights, safety and well-being of subjects and to provide public assurance of that protection.
Amendment 65 #
Proposal for a regulation Article 2 – paragraph 2 – point 13 (13) ‘Sponsor’: an individual, company, institution or organisation which takes responsibility for the initiation
Amendment 66 #
Proposal for a regulation Article 2 – paragraph 2 – point 15 (15)
Amendment 67 #
Proposal for a regulation Article 2 – paragraph 2 – point 19 (19)
Amendment 68 #
Proposal for a regulation Article 2 – paragraph 2 – point 28 a (new) (28a) 'Adverse reaction': all untoward and unintended responses to an investigational medicinal product related to any dose administered;
Amendment 69 #
Proposal for a regulation Article 3 – paragraph 1 – indent 1 a (new) - the rights of the subject to physical and mental integrity, to privacy and to the protection of personal data in accordance with applicable Union legislation are safeguarded;
Amendment 70 #
Proposal for a regulation Article 3 – paragraph 1 – indent 1 a (new) - the evaluation of the ethical acceptability of the clinical trial is positive;
Amendment 71 #
Proposal for a regulation Article 3 – paragraph 1 – indent 2 – the data generated in the clinical trial are going to be relevant, reliable and robust.
Amendment 72 #
Proposal for a regulation Article 4 – paragraph 1 – subparagraph 1 (new) Comparative clinical trials of new drugs shall be required against the best current proven intervention.
Amendment 73 #
Proposal for a regulation Article 4 a (new) Article 4a Role of and guidelines for Ethics Committees 1. An authorisation for the conduct of a clinical trial by a competent authority of a Member States may be given after and only if the concerned Ethics Committee has given its approval. 2. The Commission shall, within one year, come forward with guidelines for Member States on Ethics Committees in order to streamline procedures and make it easier to conduct trials in several Member States, without compromising the safety of subjects.
Amendment 74 #
Proposal for a regulation Article 5 – paragraph 1 – subparagraph 2 Amendment 75 #
Proposal for a regulation Article 5 – paragraph 1 – subparagraph 3 Amendment 76 #
Proposal for a regulation Article 5 – paragraph 1 – subparagraph 3 Where the proposed reporting Member State does not wish to be the reporting Member State,
Amendment 77 #
Proposal for a regulation Article 5 – paragraph 2 – introductory part 2. Within
Amendment 78 #
Proposal for a regulation Article 5 – paragraph 2 – point a (a) wh
Amendment 79 #
Proposal for a regulation Article 5 – paragraph 3 Amendment 80 #
Proposal for a regulation 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, and the clinical trial shall be considered a low-intervention clinical trial if this is claimed by the sponsor
Amendment 81 #
Proposal for a regulation 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-intervention 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. The reporting Member State may not infer ethical concerns as a justification for considering the application not complete or not falling within the scope of this Regulation.
Amendment 82 #
Proposal for a regulation 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
Amendment 83 #
Proposal for a regulation Article 5 – paragraph 5 a (new) 5a. The assessment report shall be submitted through the EU portal and made publicly available.
Amendment 84 #
Proposal for a regulation Article 6 – paragraph 1 – point a – point i – indent 2 – the relevance and acceptability of the clinical trial, taking account of the current state of scientific
Amendment 85 #
Proposal for a regulation 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
Amendment 86 #
Proposal for a regulation Article 6 – paragraph 1 – point a – point ii – indent 2 – the characteristics of the intervention compared to
Amendment 87 #
Proposal for a regulation 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 88 #
Proposal for a regulation 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 within the following time periods, which shall include periods for initial assessment, for joint assessment and for consolidation of the final report:
Amendment 89 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – introductory part The reporting Member State shall submit Part I of the assessment report, including its conclusion, already comprising the views of the concerned Ethics Committee, to the sponsor and to the other Member States concerned within the following time periods:
Amendment 90 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point a (a) within 10 days from the validation date for low-intervention clinical trials; the time for the joint assessment and for consolidation by Member States concerned and reporting Member State shall not be shorter than 5 days.
Amendment 91 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point a (a) within
Amendment 92 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point b (b) within 25 days from the validation date for clinical trials other than low- intervention clinical trials; the time for the joint assessment and for consolidation by Member States concerned and reporting Member State shall not be shorter than 10 days.
Amendment 93 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point b (b) within
Amendment 94 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point c (c) within 30 days from the validation date for any clinical trial with an advanced therapy investigational medicinal product; the time for the joint assessment and for consolidation by Member States concerned and reporting Member State shall not be shorter than 10 days.
Amendment 95 #
Proposal for a regulation Article 6 – paragraph 4 – subparagraph 1 – point c (c) within
Amendment 96 #
Proposal for a regulation 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 other Member States concerned and the reporting date shall be the date when the final assessment report is submitted to the sponsor and to the other Member States concerned.
Amendment 97 #
Proposal for a regulation Article 6 – paragraph 5 5. Until the assessment date
Amendment 98 #
Proposal for a regulation 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
Amendment 99 #
Proposal for a regulation Article 6 – paragraph 6 a (new) 6a. The reporting Member State may also extend the time referred to in paragraphs 4 and 6 a further 60 days for trials involving Advanced Therapy Medicinal Products or other novel therapies, for the purpose of consulting with expert committees
source: PE-506.087
2013/03/01
ENVI
252 amendments...
Amendment 100 #
Proposal for a regulation 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-
Amendment 101 #
Proposal for a regulation 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 102 #
Proposal for a regulation Recital 9 b (9b) The concept of 'Normal Clinical Practice' is of vital importance in determining whether an application is authorised as a 'low intervention clinical trial'. The definition of 'Normal Clinical Practice' should be clarified by the Commission in guidelines.
Amendment 103 #
Proposal for a regulation Recital 9 c (9 c) Clinical studies supporting the registration of generic medicinal products (e.g. bioequivalence or therapeutic equivalence studies) pose minimal risks and inconveniences for the study subjects compared to the normal clinical practice, as defined in this Regulation, since the reference medicinal product, used as comparator, is a well-characterised authorised product for which the quality safety and efficacy have already been assessed.
Amendment 104 #
Proposal for a regulation 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 (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 (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 107 #
Proposal for a regulation Recital 10 (10) The assessment of the application for a clinical trial should address in particular the anticipated therapeutic and public health benefits (
Amendment 108 #
Proposal for a regulation Recital 10 (10) The assessment of the application for a clinical trial should address in particular the anticipated therapeutic and public
Amendment 109 #
Proposal for a regulation Recital 10 (10) The assessment of the application for a clinical trial should address in particular the anticipated therapeutic and public health benefits (‘relevance’) and the risk and inconveniences for the subject. Regarding the relevance, numerous aspects should be taken into account, which includes that the group of subjects is relevant to the aimed population to be treated and including whether the clinical trial has been recommended or imposed by regulatory authorities in charge of the assessment and authorisation of the placing on the market of medicinal products.
Amendment 110 #
Proposal for a regulation Recital 10 (10) The assessment of the application for a clinical trial should address in particular the anticipated therapeutic and public health benefits (
Amendment 111 #
Proposal for a regulation Recital 10 a (new) Amendment 112 #
Proposal for a regulation Recital 10 a (new) (10a) Experience with Directive 2001/20/EC has also shown that 60% of clinical trials are sponsored by the pharmaceutical industry and 40% by other stakeholders, such as academics. The value of academic contribution should be duly recognized by member states. Academic sponsors frequently rely on funding which partly or entirely comes from the public funds or charities. In order to maximize the use of this valuable contribution and to further stimulate academic research but without any discrimination towards the quality of trials, measures should be put in place by member states to make appropriate exemptions from fees (application fees, inspection fees etc...) for trials conducted by academic sponsors.
Amendment 113 #
Proposal for a regulation 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-
Amendment 114 #
Proposal for a regulation Recital 11 a (new) (11a) In order to follow a given trial from initial ethical approval to final publication, a Universal Trial Registration Number (UTRN) should be assigned to each trial to be conducted in the European Union or whose results are used as part of the Common technical document for a marketing authorisation of a medicinal product.
Amendment 115 #
Proposal for a regulation Recital 12 a (new) (12a) In the case of rare diseases as defined by EU legislation, the necessary data and expertise to perform a well- informed assessment of the application for authorisation of a clinical trial may be scarce at national level. Therefore, such expertise should be sought at European level. To this end, the reporting Member State should cooperate in the assessment process with the Scientific Advice Working Party of the European Medicines Agency which should provide an opinion on the disease or disease group concerned. Where relevant, this opinion may cover aspects related to Part II of the assessment, in which case the reporting Member State should notify it to the Member States concerned. This cooperation should be organised within the same deadlines foreseen in this Regulation for clinical trials conducted in the field of diseases other than rare diseases.
Amendment 116 #
Proposal for a regulation 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 Recital 13 (13) The authorisation of a clinical trial should address all aspects in relation to subject protection and data reliability and robustness. The permission to conduct a clinical trial should therefore be contained in one single
Amendment 118 #
Proposal for a regulation Recital 14 (14) It should be left to the Member State concerned to determine the appropriate body or bodies to be involved in this assessment. These bodies should be established according to the ICH Topic E 6 (R1) Guideline for Good Clinical Practice, which details the responsibilities, composition, functions, operations and procedures. This decision is a matter of internal organisation of each Member State. Member States, when determining the appropriate body or bodies, should ensure the involvement of lay persons and patients. They should also ensure that the necessary expertise is available. In any case, however, and in accordance with international guidelines, the assessment should be done jointly by a reasonable number of persons who collectively have the necessary qualifications and experience. The persons assessing the application should be independent from the sponsor, the institution of the trial site, and the investigators involved, as well as free of any other undue influence.
Amendment 119 #
Proposal for a regulation Recital 14 (14) It should be left to the Member State concerned to determine the appropriate body or bodies to be involved in this assessment. This decision is a matter of internal organisation of each Member State. Member States, when determining the appropriate body or bodies, should ensure the involvement of lay persons and patients. They should also ensure that the necessary expertise is available. In any case, however, and in accordance with international guidelines, the assessment should be done jointly by a reasonable number of persons who collectively have the necessary qualifications and experience. The persons assessing the application should be independent from the sponsor, the institution of the trial site, and the investigators involved, as well as free of any other undue influence. Names, qualifications and declarations of interest of the persons assessing the application should be made publicly available.
Amendment 120 #
Proposal for a regulation Recital 20 a (new) (20a) Before a marketing authorisation has been obtained, clinical trial data should be considered commercially confidential. Once a marketing authorisation is obtained, it should be presumed that data contained in the marketing authorisation dossier may contain some confidential and commercially sensitive information.
Amendment 121 #
Proposal for a regulation Recital 21 (21) It should be left to Member States to establish the language requirements for the application dossier. To ensure that the assessment of the application for authorisation of a clinical trial functions smoothly, Member States should
Amendment 122 #
Proposal for a regulation 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.
Amendment 123 #
Proposal for a regulation 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. Subjects from vulnerable population groups such as incapacitated subjects, minors, the elderly or other vulnerable people, require additional protection measures. Regarding the rules concerning the determination of the legal representative of incapacitated persons and minors, those rules diverge in Member States. It should therefore be left to Member States to determine the legal representative of incapacitated
Amendment 124 #
Proposal for a regulation 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
Amendment 125 #
Proposal for a regulation 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 and by the judgment in Case C-34/10 (Brüstle v. Greenpeace). 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 the rules concerning the determination of the legal representative of incapacitated persons and
Amendment 126 #
Proposal for a regulation 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
Amendment 127 #
Proposal for a regulation 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
Amendment 128 #
Proposal for a regulation Recital 24 (24) In accordance with international guidelines, the free and informed consent of the subject should be given in writing, save in exceptional situations. It should be based on information which is clear, relevant and understandable to the subject. Where possible, such information should be given orally, with the opportunity for the subject to ask questions, and the subject should be provided with comprehensive written information which he or she is allowed to keep. Adequate time should be provided for the subject to consider his or her decision.
Amendment 129 #
Proposal for a regulation Recital 24 (24) In accordance with international guidelines, the free and informed consent of the subject should be in writing, save in exceptional situations. It should be based on information which is clear, relevant and understandable to the subject, and should be in the subject's own language.
Amendment 130 #
Proposal for a regulation Recital 24 a (new) (24a) In accordance to the Ethical Recommendations (EC, 2008) and in addition to what is stated before, in paediatric clinical trials appropriate procedures on the informed assent should be applied. These procedures should take into account the age and maturity of children.
Amendment 131 #
Proposal for a regulation 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
Amendment 132 #
Proposal for a regulation Recital 26 (26) In order for the sponsor to assess all potentially relevant safety information, the investigator should report to him all serious adverse events
Amendment 133 #
Proposal for a regulation Recital 27 (27) The sponsor should assess the information received from the investigator, and immediately report safety information on serious adverse events which are suspected unexpected serious adverse reactions to the Agency via the electronic database referred to in Article 36.
Amendment 134 #
Proposal for a regulation Recital 28 (28) The Agency should as soon as possible forward this information to the Member States for them to assess this information.
Amendment 135 #
Proposal for a regulation Recital 29 (29) The members of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) have agreed on a detailed set of guidelines for good clinical practice which are now an internationally accepted standard for designing, conducting, recording and reporting clinical trials, consistent with principles that have their origin in the World Medical Association's Declaration of Helsinki. When designing, conducting, recording and reporting clinical trials,
Amendment 136 #
Proposal for a regulation Recital 30 Amendment 137 #
Proposal for a regulation 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.
Amendment 138 #
Proposal for a regulation Recital 31 Amendment 139 #
Proposal for a regulation Recital 31 (31) The individuals involved in conducting the clinical trial, in particular investigators and other healthcare
Amendment 140 #
Proposal for a regulation Recital 32 Amendment 141 #
Proposal for a regulation Recital 33 Amendment 142 #
Proposal for a regulation Recital 33 (33) During a clinical trial, a sponsor may become aware of serious breaches of the rules for the conduct of the clinical trial. This should be reported to the Member States concerned, as well as to the Agency, in order for action to be taken by those Member States, where necessary.
Amendment 143 #
Proposal for a regulation Recital 34 Amendment 144 #
Proposal for a regulation Recital 35 Amendment 145 #
Proposal for a regulation Recital 36 Amendment 146 #
Proposal for a regulation Recital 36 (36) In order to ensure compliance of the conduct of the clinical trial with the protocol, and in order for investigators to be informed about the investigational medicinal products they administer, the sponsor should supply the investigators with an investigator's brochure. This brochure should be updated whenever new safety information becomes available, including information about events other than suspected unexpected serious adverse reactions.
Amendment 147 #
Proposal for a regulation Recital 37 Amendment 148 #
Proposal for a regulation Recital 37 (37) The information generated in the clinical trial should be recorded, handled and stored adequately for the purpose of ensuring subject rights
Amendment 149 #
Proposal for a regulation Recital 37 (37) The information generated in the clinical trial should be recorded, handled and stored adequately for the purpose of ensuring subject rights
Amendment 150 #
Proposal for a regulation Recital 37 a (new) (37a) Within two years after the adoption of this Regulation, the Commission should submit the European Parliament an evaluation of the management of raw data, and the feasibility of introducing an open access for independent scientists to raw data from all clinical trials.
Amendment 151 #
Proposal for a regulation Recital 38 Amendment 152 #
Proposal for a regulation Recital 39 Amendment 153 #
Proposal for a regulation Recital 40 Amendment 154 #
Proposal for a regulation Recital 41 Amendment 155 #
Proposal for a regulation 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.
Amendment 156 #
Proposal for a regulation Recital 44 (44) The sponsor of a clinical trial may be located in a third country. In order to facilitate supervision and control, a sponsor located in a third country should establish a
Amendment 157 #
Proposal for a regulation Recital 46 (46) In clinical trials with non-authorised investigational medicinal products, or where the intervention poses more than an insignificant risk to subject safety, compensation should be ensured for damages successfully claimed in accordance with the applicable laws. The legal certainty of the subject should, however, always be guaranteed and the change under the regulation in the requirement to provide damage compensation must not lead to a reduction in legal certainty.
Amendment 158 #
Proposal for a regulation Recital 46 (46) In clinical trials with non-authorised investigational medicinal products, or w
Amendment 159 #
Proposal for a regulation Recital 47 (47) At present, such damage
Amendment 160 #
Proposal for a regulation Recital 47 (47) At present, such damage compensation is provided by way of insurance. This insurance may cover damages to be paid to the subject by the sponsor and investigator in the case of established liability. It may also compensate the subject directly without
Amendment 161 #
Proposal for a regulation Recital 47 (47) At present, such damage compensation is provided by way of insurance. This insurance may cover damages to be paid to the subject by the sponsor and investigator in the case of established liability. It may also compensate the subject directly without prior establishment of the liability of the sponsor or investigator. Compensation may also cover medical care for long or medium term physical injuries, pain and suffering. Experience shows that the insurance market is small and costs for insurance coverage are disproportionately high. Moreover, as liability regimes differ widely between Member States, it is difficult and burdensome for the sponsor of a multinational trial to obtain insurance in accordance with those national laws.
Amendment 162 #
Proposal for a regulation Recital 47 (47) At present, such damage compensation is provided by way of insurance. This insurance may cover damages to be paid to the subject by the sponsor and investigator in the case of established liability. It may also compensate the subject directly without prior establishment of the liability of the sponsor or investigator. Experience shows that the insurance market is small and costs for insurance coverage are disproportionately high. Moreover, as liability regimes differ widely between Member States, it is difficult and burdensome for the sponsor of a multinational trial to obtain insurance in
Amendment 163 #
Proposal for a regulation Recital 47 (47)
Amendment 164 #
Proposal for a regulation Recital 51 (51) In order to streamline and facilitate the flow of information between sponsors and Member States as well as between Member States, the Commission should set up and maintain a database, accessed through a portal. The Commission and the Member States should raise awareness among the general public about the existence of this portal.
Amendment 165 #
Proposal for a regulation Recital 51 (51) In order to streamline and facilitate the flow of information between sponsors and Member States as well as between Member States, the European Medicines Agency, on behalf of the Commission, should set up and maintain a database, accessed through a portal.
Amendment 166 #
Proposal for a regulation Recital 52 (52) The database should contain all relevant information as regards the clinical trial
Amendment 167 #
Proposal for a regulation Recital 52 (52) The database should contain all relevant information as regards the clinical trial. All clinical trials should be registered in the database prior to being started. The start and end dates of the recruitment of subjects should also be published in the database. It should be possible for sponsors to enter this information directly into the database without the need to further notify Member States. No personal data of data subjects participating in a clinical trial should be recorded in the database. 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.
Amendment 168 #
Proposal for a regulation Recital 52 (52) The database should contain all relevant information as regards the clinical trial and should be publicly accessible. No personal data of data subjects participating in a clinical trial should be recorded in the database. 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.
Amendment 169 #
Proposal for a regulation Recital 52 a (new) Amendment 170 #
Proposal for a regulation Recital 52 b (new) (52b) Results of clinical trials, as well as clinical trial data, represent a relevant and valuable source of information for the continuation of biomedical or public health research on a medicinal product or active principle, and should be made available in order to support and foster the development of independent research related to a medicinal product and its clinical, pharmacological or other pharmacodynamic effects, or to its relative efficacy and effectiveness. The authorisation status of a medicinal product should however be duly considered before releasing data from clinical trial, in order not to disrupt the marketing authorisation process or the competition dynamics operating on the EU market while fostering attractiveness and long term viability of the EU based clinical research.
Amendment 171 #
Proposal for a regulation Recital 52 c (new) (52c) Access to, release and processing of clinical trial data for medicines once the decision-making process on an application for a marketing authorisation is complete should be without prejudice to the protection of personal data, and should respond to specific guidelines in order to define and guarantee good analysis practice, clinical trial data formats, rules of engagement as well as other legal aspects. Such guidelines should promote an optimal level of transparency and public information, while ensuring the development of reliable scientific research and avoiding bias or misuse of information.
Amendment 172 #
Proposal for a regulation Recital 55 (55) In order to carry out the activities provided for in this Regulation, Member States should be allowed to levy fees
Amendment 173 #
Proposal for a regulation Recital 59 a (new) (59a) The right of access to documents is recognised by the Charter of Fundamental Rights of the European Union. In particular, Article 42 states the right of access to documents of the institutions, bodies, offices and agencies of the Union, regardless of the medium of the document. Those rules should be upheld.
Amendment 174 #
Proposal for a regulation 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 175 #
Proposal for a regulation Recital 62 a (new) (62a) According to the Commission Communication on "An Integrated Industrial Policy for the Globalisation Era-Putting Competitiveness and Sustainability at Centre Stage", systematic evaluation of legislation should become an integral part of smart regulation. To ensure that this Regulation keeps pace with scientific, technological and medical progress with regard to the organization and conduct of clinical trials and that it interfaces with other legal provisions, the Commission should periodically report on the experience with and functioning of the Regulation, and present its conclusions to the Parliament and Council.
Amendment 176 #
Proposal for a regulation Recital 64 a (new) (64a) As stated in the Commission Communication on "An Integrated Industrial Policy for the Globalisation Era-Putting Competitiveness and Sustainability at Centre Stage", systematic evaluations of legislation should become an integral part of smart regulation. To ensure that this Regulation keeps pace with scientific and technological progress with regard to the organization and conduct of clinical trials and that it interfaces with other legal provisions, the Commission should periodically report on the experience with and functioning of the Regulation, and present its conclusions thereof.
Amendment 177 #
Proposal for a regulation Recital 63 (63) This Regulation is in accordance with the Convention on Human Rights and Biomedecine (1997) and its Additional Protocol on biomedical research (2005) of the Council of Europe and the International Convention on the rights of the Child (UN-1989). It is line with the major international guidance documents on clinical trials, such as the most recent (2008) version of the World Medical Association's Declaration of Helsinki and ICH-GCP good clinical practice, which has its origins in the Declaration of Helsinki.
Amendment 178 #
Proposal for a regulation Recital 66 (66) Since the objective of this Regulation, namely to ensure that, throughout the Union, clinical trial data are reliable and robust while ensuring the safety and rights and well-being of subjects, cannot sufficiently be achieved by the Member States and can, by reason of the scale of the measure, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve that objective,
Amendment 179 #
Proposal for a regulation Recital 66 (66) Since the objective of this Regulation, namely to ensure that, throughout the Union, clinical trial data are reliable and robust while ensuring the safety, well- being and rights of subjects, cannot sufficiently be achieved by the Member States and can, by reason of the scale of the measure, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve that objective,
Amendment 180 #
Proposal for a regulation Recital 66 a (new) (66 a) The regulation should be assessed and where necessary revised at five-year intervals in order to ensure its flexibility. A continuing assessment process is essential so that innovations can continue to be made in future in the context of constantly developing medical science. The administrative burden of the current directive is regarded as a constraint on science and on the right of patients to obtain the best possible care. The regulation’s impact in terms of red tape should therefore be monitored regularly and the assessment process should guarantee its effectiveness as legislation supporting clinical research. Particular attention should be paid to the position of academic research, and to ensuring that red tape does not divert resources from innovation in academic research and that the new tasks required by the regulation do not have a negative impact on the attractiveness of a research career. The importance of public access to information in making Europe attractive as a research environment and its effect on the balance between individual data protection, intellectual property, and contract, patent and intangible rights, should also be assessed. The assessment process should also look at the impact of the regulation on whether, in place of clinical trials, more experimental treatment is being carried out which has unpredictable effects on patient safety and the reliability of experimental results.
Amendment 461 #
Proposal for a regulation 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
Amendment 462 #
Proposal for a regulation Article 29 – paragraph 1 1.
Amendment 463 #
Proposal for a regulation 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
Amendment 464 #
Proposal for a regulation 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
Amendment 465 #
Proposal for a regulation 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) 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 467 #
Proposal for a regulation Article 29 – paragraph 2 2. Written information shall be given to the subject and/or the legal representative
Amendment 468 #
Proposal for a regulation Article 29 – paragraph 2 2. Written information given to the subject and/or the legal representative for the purposes of obtaining his or her informed consent shall be presented in the mother tongue of the subject and/or representative and be kept concise, clear, relevant, and understandable to a lay person. It shall include both medical and legal information, as well as any controversial ethical issues, as necessary. It shall inform the subject about his or her right to revoke his or her informed consent.
Amendment 469 #
Proposal for a regulation 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 470 #
Proposal for a regulation Article 29 – paragraph 3 3. The subject shall be
Amendment 471 #
Proposal for a regulation Article 29 – paragraph 3 3. The subject shall be provided with
Amendment 472 #
Proposal for a regulation Article 29 – paragraph 3 a (new) 3a. If requested by the subject, he or she shall be provided with information on the results of the clinical trial that he or she has participated in, once the results are available.
Amendment 473 #
Proposal for a regulation Article 29 – paragraph 3 a (new) Amendment 474 #
Proposal for a regulation Article 30 – paragraph 1 – point a (a) the informed consent of the legal representative has been obtained
Amendment 475 #
Proposal for a regulation 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 476 #
Proposal for a regulation Article 30 – paragraph 1 – point c (c) the explicit wish of an incapacitated subject who is capable of forming an opinion and assessing this information to refuse participation in, or to be withdrawn from, the clinical trial at any time
Amendment 477 #
Proposal for a regulation Article 30 – paragraph 1 – point c (c) the investigator considers the explicit wish of an incapacitated subject who is capable of forming an opinion and assessing this information to refuse participation in, or to be withdrawn from, the clinical trial at any time
Amendment 478 #
Proposal for a regulation Article 30 – paragraph 1 – point c (c) the explicit wish of an incapacitated subject who is capable of forming an opinion and assessing this information to refuse participation in, or to be withdrawn from, the clinical trial at any time is
Amendment 479 #
Proposal for a regulation Article 30 – paragraph 1 – point f (f) such research relates directly to a
Amendment 480 #
Proposal for a regulation Article 30 – paragraph 1 – point h (h) there are grounds for expecting that
Amendment 481 #
Proposal for a regulation 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 482 #
Proposal for a regulation Article 30 – paragraph 1 – point h a (new) (h a) a capacitated subject is not available to perform a clinical trial.
Amendment 483 #
Proposal for a regulation Article 30 – paragraph 2 a (new) 2a. Both the incapacitated subject and their legal representative may revoke their consent at any time without giving a reason and with no liability or prejudice whatsoever being incurred by the subject or their legal representative as a result.
Amendment 484 #
Proposal for a regulation Article 31 – paragraph 1 – point a (a) the informed consent of the legal representative or representatives has been obtained, whereby
Amendment 485 #
Proposal for a regulation Article 31 – paragraph 1 – point a (a) the written informed consent of the legal representative has been obtained
Amendment 486 #
Proposal for a regulation Article 31 – paragraph 1 – point a a (new) (aa) the informed and express consent of the minor has been obtained, where they are 12 years old and over,
Amendment 487 #
Proposal for a regulation 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
Amendment 488 #
Proposal for a regulation Article 31 – paragraph 1 – point c (c) the investigator duly takes into consideration, in accordance with the age and maturity of the minor concerned, the explicit wish of a minor who is capable of forming an opinion and assessing this information to refuse participation in, or to be withdrawn from, the clinical trial at any time,
Amendment 489 #
Proposal for a regulation Article 31 – paragraph 1 – point c (c) the
Amendment 490 #
Proposal for a regulation Article 31 – paragraph 1 – point c (c) the explicit wish of a
Amendment 491 #
Proposal for a regulation Article 31 – paragraph 1 – point c (c) the explicit wish of a minor who is capable of forming an opinion and assessing this information to refuse participation in, or to be withdrawn from, the clinical trial at any time, is duly taken into consideration by the investigator
Amendment 492 #
Proposal for a regulation Article 31 – paragraph 1 – point e Amendment 493 #
Proposal for a regulation Article 31 – paragraph 1 – point h (h) some direct benefit for the
Amendment 494 #
Proposal for a regulation Article 31 – paragraph 1 – point h (h)
Amendment 495 #
Proposal for a regulation Article 31 – paragraph 1 – point h a (new) (ha) the indemnification/insurance system include specific provisions related to long- term effects on the development of the child;
Amendment 496 #
Proposal for a regulation Article 31 – paragraph 1 – point h b (new) (hb) the corresponding scientific guidelines of the Agency have been followed;
Amendment 497 #
Proposal for a regulation Article 31 – paragraph 1 – point h c (new) (h c) the trial does not replicate other trials based on the same hyphothesis and age-appropriate formulations are used;
Amendment 498 #
Proposal for a regulation 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 499 #
Proposal for a regulation Article 31 – paragraph 1 – point h e (new) (he) a restrictive use of placebo is adopted and, if relevant, a Specific Data Safety Monitoring Board (DSMB) is set up;
Amendment 500 #
Proposal for a regulation 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 501 #
Proposal for a regulation Article 31 – paragraph 2 2. The minor shall take part in the consent procedure in a manner adapted to his or her age and maturity. Minors who are 12 years old and over must also give their informed and express consent to participate in the trial.
Amendment 502 #
Proposal for a regulation 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 503 #
Proposal for a regulation Article 31 – paragraph 2 a (new) 2a. Both the minor and their legal representative may revoke their consent at any time without giving a reason and with no liability or prejudice whatsoever being incurred by the minor or their legal representative as a result.
Amendment 504 #
Proposal for a regulation Article 31 a (new) Article 31a Clinical trials on subjects from other vulnerable population groups 1. A clinical trial on subjects from other vulnerable population groups may be conducted only where, in addition to the conditions set out in Article 28, all of the following conditions are met: (a) the subject concerned has received all relevant information from professionals trained or experienced in working with that group regarding the trial, the risks and the benefits; (b) the investigator considers the explicit wish of the subject concerned to refuse participation in, or to be withdrawn from, the clinical trial at any time, without giving a reason and with no liability or prejudice whatsoever being incurred by the subject as a result; (c) no incentives or financial inducements are given except compensation for participation in the clinical trial; (d) such research either relates directly to a medical condition from which the subject concerned suffers or it is relevant to the vulnerable population group to which the subject belongs; (e) the clinical trial has been designed to minimise pain, discomfort, fear and any other foreseeable risk in relation to the disease and developmental stage and both the risk threshold and the degree of distress are specially defined and constantly observed; (f) some direct benefit for the group of patients to which the subject concerned belongs (e.g. improved quality of life) is obtained from the clinical trial. 2. The subject shall take part in the consent procedure at all times. 3. The subject may revoke their consent at any time, without giving a reason and with no liability or prejudice whatsoever being incurred by the subject as a result.
Amendment 505 #
Proposal for a regulation 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
Amendment 506 #
Proposal for a regulation Article 32 – paragraph 1 – point a (a) due to the urgency of the situation,
Amendment 507 #
Proposal for a regulation 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 or its legal representative (parent or guardian) and it is impossible to supply prior information to the subject or its legal representative (parent or guardian);
Amendment 508 #
Proposal for a regulation Article 32 – paragraph 1 – point b (b)
Amendment 509 #
Proposal for a regulation Article 32 – paragraph 1 – point c (c) the subject or legal representative has not previously expressed objections known to the investigator;
Amendment 510 #
Proposal for a regulation Article 32 – paragraph 1 – point d Amendment 511 #
Proposal for a regulation Article 32 – paragraph 1 – point e (e) the
Amendment 512 #
Proposal for a regulation Article 32 – paragraph 1 – point e (e) the clinical trial poses a minimal risk to, and imposes a minimal burden on, the subject, although this should be judged in proportion to the underlying medical condition.
Amendment 513 #
Proposal for a regulation Article 32 – paragraph 1 – point e (e) the Ethics committee positively assesses that a direct benefit of the clinicial trial for the patient is to be expected, as well as the fact that the clinical trial poses a minimal risk to, and imposes a minimal burden on, the subject.
Amendment 514 #
Proposal for a regulation 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) 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) 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 517 #
Proposal for a regulation Article 33 – title Notification of the start of the clinical trial
Amendment 518 #
Proposal for a regulation Article 33 – paragraph 1 – subparagraph 2 That notification shall be made within
Amendment 519 #
Proposal for a regulation Article 33 – paragraph 2 – subparagraph 1 Amendment 520 #
Proposal for a regulation Article 33 – paragraph 2 – subparagraph 2 Amendment 521 #
Proposal for a regulation Article 33 – paragraph 2 – subparagraph 2 That notification shall be made within
Amendment 522 #
Proposal for a regulation Article 33 – paragraph 2 a (new) 2a. Prior to the start, all clinical trials shall be registered in the database mentioned in this Regulation. Information provided shall include the start date and the end date of the recruitments of subjects.
Amendment 523 #
Proposal for a regulation Article 34 – title End of the clinical trial, early termination of the clinical trial and submission of results
Amendment 524 #
Proposal for a regulation Article 34 – paragraph 1 – subparagraph 2 That notification shall be made within
Amendment 525 #
Proposal for a regulation Article 34 – paragraph 2 – subparagraph 2 That notification shall be made within
Amendment 526 #
Proposal for a regulation Article 34 – paragraph 1 – subparagraph 2 That notification shall be made within
Amendment 527 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 Within
Amendment 528 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 3. Within one year from the end of a clinical trial, the sponsor shall submit to the EU database a summary of the results of the clinical trial, whether the results are positive or negative and inconclusive.
Amendment 529 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 3. Within one year from the end of a clinical trial or discontinuation of the development of a medicinal product, the sponsor shall submit to the EU database a summary of the positive and/or negative results of the clinical trial, as laid down in Annex IIIa. Until the publication of the summary of the results in accordance with the provisions of this paragraph, it shall only be accessible to the competent authorities of the Member States concerned.
Amendment 530 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 3. Within one year 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 clinical study report (CSR) and the full dataset of clinical trial data. These elements shall be made publicly accessible through the EU database.
Amendment 531 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 3. Within one year from the end of a clinical trial, the sponsor shall submit to the EU database a
Amendment 532 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 3. Within one year from the end of a clinical trial, the sponsor shall submit to the EU database and to the public EudraPharm database a summary of the results of the clinical trial.
Amendment 533 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 1 3. Within one year from the end of a clinical trial, the sponsor shall submit to the EU database a
Amendment 534 #
Proposal for a regulation 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 However, where, for scientific reasons, it is not possible to submit a summary of the results within
Amendment 536 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 However, where, for justified scientific reasons, it is not possible to submit
Amendment 537 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 a (new) Amendment 538 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 a (new) In the event of non-compliance by the sponsor with the obligation referred to in paragraph 3, financial penalties shall be imposed by the Member State concerned. The Commission shall produce guidelines for Member States on the consistent application of such financial penalties.
Amendment 539 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 a (new) In order to protect personal data and commercially confidential information, and subject to the provisions of Article 78(3), the summary of the results of a clinical trial intended to obtain a marketing authorisation shall be made public 30 days after the date of the marketing authorisation, or one year after the end of the clinical trial in case of the discontinuation of the product development.
Amendment 540 #
Proposal for a regulation Article 34 – paragraph 3 – subparagraph 2 a and 2 b (new) For medicinal products which have been granted a marketing authorisation or for which the decision-making process on an application for a marketing authorisation is complete, the sponsor shall submit to the EU database the clinical study report of the clinical trial. The Commission, in cooperation with the Agency, shall be empowered to adopt delegated acts in accordance with Article 85, with regards to the public access to the clinical study report and other related clinical trial data, in order to define rules of engagement, clinical data formats and good analysis practice.
Amendment 541 #
Proposal for a regulation Article 34 – paragraph 3 a (new) 3a. In the event of non-compliance by the sponsor with the obligation referred to in paragraph 3, and in the absence of prospective and appropriate justification provided to the Member States concerned through the portal , financial penalties shall be imposed by the Member States concerned.
Amendment 542 #
Proposal for a regulation Article 34 – paragraph 3 a (new) 3a. In case of non-compliance by the sponsor with the obligation referred to in paragraph 3, harmonised penalties shall be enforced by the concerned Member States. The amount shall be up to 7 000 EUR for the 30 first day of non- compliance and up to 7 000 EUR per each additional delay day until compliance.
Amendment 543 #
Proposal for a regulation 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 544 #
Proposal for a regulation 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 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. After 12 months of temporary halt, and in the absence of appropriate prospective justification provided to the Member States concerned, the data from the clinical trial shall be submitted to the EU database, even if incomplete. The reasons for early termination of a clinical trial shall be published in the EU database.
Amendment 545 #
Proposal for a regulation 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 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
Amendment 547 #
Proposal for a regulation 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 and 39. That electronic database shall be a module of the database referred to in Article 25 of Regulation (EC) No 726/2004.
Amendment 548 #
Proposal for a regulation 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 and 39, which shall be publicly accessible.
Amendment 549 #
Proposal for a regulation Article 37 – paragraph 2 2.
Amendment 550 #
Proposal for a regulation Article 37 – paragraph 2 2. The investigator shall immediately report serious adverse events to the sponsor
Amendment 551 #
Proposal for a regulation Article 37 – paragraph 2 2. The investigator shall
Amendment 552 #
Proposal for a regulation 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 553 #
Proposal for a regulation Article 38 – paragraph 1 1. The sponsor shall report electronically and with
Amendment 554 #
Proposal for a regulation 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 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, in accordance with time limits set out in Annex III, points 2.4 and 2.5.
Amendment 555 #
Proposal for a regulation Article 38 – paragraph 1 1. The sponsor shall report electronically and with
Amendment 556 #
Proposal for a regulation 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 557 #
Proposal for a regulation Article 38 – paragraph 2 2. The time period for reporting shall take account of the se
Amendment 558 #
Proposal for a regulation Article 38 – paragraph 2 2. The time period for reporting shall take account of the se
Amendment 559 #
Proposal for a regulation Article 38 – paragraph 3 Amendment 560 #
Proposal for a regulation Article 38 – paragraph 3 3. Where a sponsor, due to a lack of resources because of the non-profit nature of the trial, does not have the possibility to report to the electronic database referred to in Article 36, it may report to the Member State where the suspected unexpected serious adverse reaction occurred. That Member State shall report the suspected unexpected serious adverse reaction in accordance with paragraph 1.
Amendment 561 #
Proposal for a regulation Article 39 – paragraph 1 1.
Amendment 562 #
Proposal for a regulation Article 39 – paragraph 1 1.
Amendment 563 #
Proposal for a regulation 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 authorisation, unless the trial has been designated a low-intervention trial, 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 564 #
Proposal for a regulation Article 39 – paragraph 1 a (new) 1a. Where the sponsor does not have access to certain information and, therefore, is not able to submit a complete report, this shall be stated in the report. In the case of a clinical trial involving the use of more than one investigational medicinal product, the sponsor may submit a single safety report on all investigational medicinal products used in the trial. The sponsor shall provide the reasons for this decision in the report.
Amendment 565 #
Proposal for a regulation Article 39 – paragraph 2 2. The obligation for a particular sponsor referred to in paragraph 1 starts with the first authorisation of a clinical trial in accordance with this Regulation for that sponsor. It ends with the end of the last clinical trial conducted by the sponsor with the investigational medicinal product. The annual reporting obligation shall not apply when a sponsor is not currently conducting any clinical trials with the investigational medicinal product.
Amendment 566 #
Proposal for a regulation Article 39 a (new) Article 39a Reporting of efficacy defect on authorised medicinal products Regarding authorised medicinal product which, according to the protocol, are used in accordance with the terms of the marketing authorisation, the investigator should inform the sponsor and the Agency of any observed efficacy defect related to the investigational medicinal product.
Amendment 567 #
Proposal for a regulation 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 39a.
Amendment 568 #
Proposal for a regulation 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
Amendment 569 #
Proposal for a regulation Article 40 – paragraph 2 2. Member States shall cooperate in assessing the information reported in accordance with Articles 38, 39 and
Amendment 570 #
Proposal for a regulation Article 40 – paragraph 2 a (new) 2 a. The responsible Ethics Committee shall be involved in the assessment of this information.
Amendment 571 #
Proposal for a regulation Article 41 – title Article 39 Annual reporting by the sponsor to the
Amendment 572 #
Proposal for a regulation 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
Amendment 573 #
Proposal for a regulation 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 at least annually the marketing authorisation holder of all suspected serious adverse reactions, in addition to safety reporting obligations for authorised medicinal products as per Directive 2001/83/EC and Regulation (EC) No 726/2004.
Amendment 574 #
Proposal for a regulation Article 43 Safety reporting with regard to auxiliary medicinal products shall be made by the investigator in accordance with
Amendment 575 #
Proposal for a regulation 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 576 #
Proposal for a regulation Article 44 – paragraph 2 Without prejudice to Union legislation and specific guidelines of the Commission the sponsor and the investigator, when drawing up the protocol and when
Amendment 577 #
Proposal for a regulation Article 44 – paragraph 3 The Commission shall make the detailed international guidelines on good clinical practice referred to in the second paragraph
Amendment 578 #
Proposal for a regulation Article 45 – title Amendment 579 #
Proposal for a regulation 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 a
Amendment 580 #
Proposal for a regulation 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
Amendment 581 #
Proposal for a regulation Article 45 – paragraph 1 – point a (a) whether the clinical trial is a
Amendment 582 #
Proposal for a regulation Article 45 – paragraph 1 – point c (c) the degree of deviation of the
Amendment 583 #
Proposal for a regulation 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 584 #
Proposal for a regulation Article 46 a (new) Amendment 585 #
Proposal for a regulation Article 48 – title Amendment 586 #
Proposal for a regulation Article 48 – paragraph 1 – subparagraph 1 Investigational medicinal products shall be traceable, stored, destroyed and returned as
Amendment 587 #
Proposal for a regulation 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) 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 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 590 #
Proposal for a regulation Article 49 – paragraph 2 2. For the purposes of this Article, a ‘serious breach’ means a breach likely to affect to a significant degree the safety
Amendment 591 #
Proposal for a regulation Article 50 – paragraph 1 1. The sponsor shall notify the Member States concerned through the EU portal and without undue delay, of all unexpected events which affect the benefit-risk balance of the clinical trial
Amendment 592 #
Proposal for a regulation Article 52 – paragraph 3 3. The investigator’s brochure shall be updated whenever
Amendment 593 #
Proposal for a regulation Article 52 – paragraph 3 3. The investigator's brochure shall be updated whenever
Amendment 594 #
Proposal for a regulation Article 52 – paragraph 3 3. The investigator’s brochure shall be updated whe
Amendment 595 #
Proposal for a regulation 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) 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 597 #
Proposal for a regulation Article 53 – paragraph 1 1. All clinical trial information shall be recorded, processed, handled, and stored in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable legislation on personal data protection with easily searchable clinical study reports being publicly available online.
Amendment 598 #
Proposal for a regulation Article 53 – paragraph 2 – subparagraph 1a (new) A supervision system covering the entire clinical trial process shall be established to determine liability on the part of the institutions, agencies and centres involved in the event of information on clinical trials or patients’ personal data being leaked.
Amendment 599 #
Proposal for a regulation Article 54 – paragraph 1 The sponsor
Amendment 600 #
Proposal for a regulation 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
Amendment 601 #
Proposal for a regulation Article 55 – paragraph 1 Amendment 602 #
Proposal for a regulation Article 55 – paragraph 1 Unless other Union legislation requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least
Amendment 603 #
Proposal for a regulation Article 55 – paragraph 1 Unless other Union legislation requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least
Amendment 604 #
Proposal for a regulation Article 55 – paragraph 1 Unless other Union legislation requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least twenty five years after the end of the clinical trial and, where a marketing authorisation has been granted for the investigational medicinal product tested, based on the clinical trial results, throughout the marketing authorisation life of any of the active principles having been investigated. However, the medical files of subjects shall be archived in accordance with national legislation.
Amendment 605 #
Proposal for a regulation Article 58 – paragraph 5 – point a (a) labelling, re-labelling, packaging, re- packaging or reconstitution prior to use or packaging, where those processes are carried out in hospitals, health centres or clinics, by pharmacists or other persons legally authorised in the Member State to carry out such processes, and if the investigational medicinal products are intended to be used exclusively by those institutions;
Amendment 606 #
Proposal for a regulation Article 58 – paragraph 5 – point c (c) the preparation of medicinal products referred to in Article 3(1) and (2) of Directive 2001/83/EC or in accordance with the study plan provided by the sponsor.
Amendment 75 #
Proposal for a regulation Recital 1 (1) In a clinical trial the safety
Amendment 76 #
Proposal for a regulation Recital 1 (1) In a clinical trial the safety
Amendment 77 #
Proposal for a regulation Recital 1 (1) In a clinical trial the safety and rights of subjects should be protected and the data generated should be reliable
Amendment 78 #
Proposal for a regulation Recital 1 (1) In a clinical trial the safety and rights of subjects should be protected and the data generated should be reliable and robust. The interests of the participants should always take priority over other interests.
Amendment 79 #
Proposal for a regulation 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 it should be ensured that those granting the authorisation do not have conflicts of interest and are independent of the sponsor, the institution of the trial site and the investigators involved.
Amendment 80 #
Proposal for a regulation 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 81 #
Proposal for a regulation 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 which should include review by an Ethics Committee.
Amendment 82 #
Proposal for a regulation 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. This authorisation should include scientific, ethical and administrative aspects.
Amendment 83 #
Proposal for a regulation Recital 3 (3) The existing definition of a clinical trial as contained in Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member
Amendment 84 #
Proposal for a regulation 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 85 #
Proposal for a regulation 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. The portal should reduce unnecessary red tape so that not only sponsors and academic researchers carrying out multinational research but also public authorities may benefit from its use.
Amendment 86 #
Proposal for a regulation 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 87 #
Proposal for a regulation Recital 5 (5) Experience with Directive 2001/20/EC has also shown that the aim of simplifying and harmonising the
Amendment 88 #
Proposal for a regulation Recital 6 (6) The Member States concerned should cooperate in assessing a request for authorisation of a clinical trial.
Amendment 89 #
Proposal for a regulation Recital 6 (6) The Member States concerned should cooperate in assessing a request for authorisation of a clinical trial. This cooperation should not include aspects of an intrinsically national nature
Amendment 90 #
Proposal for a regulation Recital 8 (8) The timelines for assessing an application dossier for clinical trials should be sufficiently long to assess the file, while
Amendment 91 #
Proposal for a regulation 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, unless Member States indicate that exceptional circumstances apply which justify minimal delays. 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
Amendment 92 #
Proposal for a regulation 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
Amendment 93 #
Proposal for a regulation 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, ensuring first and foremost the safety and wellbeing of all participants. 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. 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 94 #
Proposal for a regulation 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 as well as, existing (e.g. generic medicinal products) 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. 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 Recital 8 a (new) (8a) The Member States must guarantee that clinical trials can be conducted in both public and private centres under equal conditions, subject to any statutory requirements.
Amendment 96 #
Proposal for a regulation Recital 8 a (new) (8a) The modernisation of IT infrastructure, facilitating the Member States' adaptation to the authorisation timelines, could be cofinanced by the structural funds.
Amendment 97 #
Proposal for a regulation 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
Amendment 98 #
Proposal for a regulation 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-intervention 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 administrative rules, such as
Amendment 99 #
Proposal for a regulation 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-intervention 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
source: PE-506.158
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CELEX:52012PC0369:EN
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activities/0/docs/0/celexid |
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PreLexNew
EUR-Lex |
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EP
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CELEX:52012PC0369:EN |
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CELEX:52012DC0369:EN |
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Rules of Procedure of the European Parliament EP 138
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CELEX:52012PC0369:EN
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COM(2012)0369 |
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http://www.europarl.europa.eu/sides/getDoc.do?type=COMPARL&mode=XML&language=EN&reference=PE506.160New
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Rules of Procedure of the European Parliament EP 138
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Rules of Procedure of the European Parliament EP 138
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Rules of Procedure of the European Parliament EP 138
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http://www.europarl.europa.eu/sides/getDoc.do?type=REPORT&mode=XML&reference=A7-2013-208&language=EN
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Rules of Procedure of the European Parliament EP 138
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Old
PURPOSE: to promote public health and research in the EU by laying down harmonised rules on the authorisation and conduct of clinical trials. PROPOSED ACT: Regulation of the European Parliament and of the Council. BACKGROUND: clinical trials are an indispensable part of clinical research which, in turn, is essential to develop medicinal products and improve medical treatment. In the EU/EEA, approximately 4 400 clinical trials are applied for every year. Approximately 24 % of all clinical trials applied for in the EU are multinational clinical trials, i.e. clinical trials intended to be performed in at least two Member States. These 24% clinical trials involve approximately 67% of all subjects enrolled in a clinical trial. 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. Directive 2001/20/EC has brought about important improvements in the safety and ethical soundness of clinical trials in the EU and in the reliability of clinical trials data. However, it is criticized by all stakeholders in the pharmaceutical sector for the following reasons: (i) the number of applications for clinical trials fell by 25 % from 2007 to 2011; (ii) the costs for conducting clinical trials have increased; (iii) the average delay for launching a clinical trial has increased by 90 % to 152 days. It would be wrong to attribute the fall in clinical trial activity solely and exclusively to the Directive 2001/20/EC. However, the Directive has had many direct effects on the cost and feasibility of conducting clinical trials, which, in turn, have led to a decline in clinical trial activity in the EU. The Commission considers it necessary, therefore, to take new measures. IMPACT ASSESSMENT: the Commission has carried out an impact assessment in accordance with its guidelines and published the results. LEGAL BASIS: Articles 114 and 168(4)(c) of the Treaty on the Functioning of the European Union (TFEU.) The Regulation aims at achieving an internal market as regards clinical trials and medicinal products for human use, taking as a base a high level of protection of health. At the same time, the Regulation sets high standards of quality and safety for medicinal products to meet common safety concerns as regards these products. CONTENT: the proposed legislation takes the form of a Regulation and replaces Directive 2001/20/EC. This legal form ensures that Member States base their assessment of an application for authorisation of a clinical trial on an identical text, rather than on diverging national transposition measures. This holds not only for the entire authorisation process, but also for all other issues addressed in the Regulation, such as safety reporting during clinical trials, and the requirements for labelling of the medicinal products used in the context of a clinical trial. A Regulation also allows actors to plan and conduct clinical trials, including multi-national clinical trials, on the basis of one regulatory framework. The main points of the proposal are as follows: New authorisation procedure for clinical trials: this based on the following: · a harmonised authorisation dossier; · a single portal to submit an application for conducting a clinical trial linked to an EU database; · a flexible and swift assessment procedure; · a clear mechanism to appoint a reporting Member State; · clear timelines with a concept of tacit approval in order to ensure compliance; · a coordination and advisory forum to address issues which may arise in the authorisation procedure; · a clear distinction between aspects where Member States cooperate in the assessment and aspects of an intrinsic ethical or national/local nature where the assessment is made by each Member State individually; · the option for a Member State to 'opt-out' of the conclusions of an assessment of an application for conducting a clinical trial ('qualified opt-out'); · a swift procedure to extend a clinical trial to additional Member States; · where a clinical trial is modified after it has been authorised, this modification is subject to authorisation if, and only if, the modification has a substantial impact on the safety or rights of the subjects or on the reliability and robustness of the data generated in the clinical trial. Simplified safety reporting: compared to Directive 2001/20/EC, the rules have been streamlined, simplified and modernised as follows: · the option to exclude reporting by the investigator to the sponsor of adverse events, if this is provided for in the protocol; · direct reporting of suspected unexpected serious adverse reactions by the sponsor to the European database EudraVigilance; · simplified submission of the annual safety report by the sponsor. Protection of subjects and informed consent: Directive 2001/20/EC does not address the specific situation where, because of the urgency of the situation, it is impossible to obtain free and informed consent from the subject or the legal representative (clinical trials in emergency situations). To address this, specific provisions on clinical trials in emergency situations have been added in line with existing international guidance documents on this issue. Furthermore, as regards the protection of personal data, provisions of Directive 95/46/EC and Regulation (EC) No 45/200110 apply. No personal data of data subjects participating in a trial will be collected in the EU database. Personal data of investigators, which may be collected in the EU database, are kept in accordance with the exception provided in the text. Compensation for damage: where there is no additional risk, or where that additional risk is negligible, the Regulation does not provide a specific damage compensation (be it an insurance or an indemnification) for the clinical trial. However, in cases where a clinical trial does pose an additional risk, the proposed Regulation obliges the sponsor to ensure compensation be it through insurance, or through an indemnification mechanism. Sponsors, co-sponsorship, EU contact person: every clinical trial must have a sponsor, i.e. a legal or natural person responsible for initiating and managing the clinical trial. Clinical trials are increasingly initiated by loose networks of scientists or scientific institutions within one Member State or across several Member States. The proposed Regulation introduces the concept of co-sponsorship. At the outset, all co-sponsors are responsible for the entire clinical trial. However, the proposal allows co-sponsors to split the responsibility for the clinical trials amongst themselves. If the sponsor is established in a third country, an EU contact person must be provided in order to ensure an effective supervision of a clinical trial. Inspections: the proposed Regulation provides the legal basis for Commission staff to perform controls in Member States and in third countries in the context of the EU acquis for medicinal products for human use and clinical trials. BUDGETARY IMPLICATIONS: EUR 4 144 000 in commitment appropriations for the period 2014-2020. The budgetary implications of this proposal are as follows: · costs for databases (one-off costs and maintenance); · Commission staff to manage the functioning of the Regulation; · costs for meetings of Member States to ensure that the authorisation procedure set out in this Regulation functions properly; · Commission staff and other costs to conduct Union controls and Union inspections. The costs will be covered with the envelope of the Health for Growth Programme 2014-2020 2014-2020. New
PURPOSE: to promote public health and research in the EU by laying down harmonised rules on the authorisation and conduct of clinical trials. PROPOSED ACT: Regulation of the European Parliament and of the Council. BACKGROUND: clinical trials are an indispensable part of clinical research which, in turn, is essential to develop medicinal products and improve medical treatment. In the EU/EEA, approximately 4 400 clinical trials are applied for every year. Approximately 24 % of all clinical trials applied for in the EU are multinational clinical trials, i.e. clinical trials intended to be performed in at least two Member States. These 24% clinical trials involve approximately 67% of all subjects enrolled in a clinical trial. 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. Directive 2001/20/EC has brought about important improvements in the safety and ethical soundness of clinical trials in the EU and in the reliability of clinical trials data. However, it is criticized by all stakeholders in the pharmaceutical sector for the following reasons: (i) the number of applications for clinical trials fell by 25 % from 2007 to 2011; (ii) the costs for conducting clinical trials have increased; (iii) the average delay for launching a clinical trial has increased by 90 % to 152 days. It would be wrong to attribute the fall in clinical trial activity solely and exclusively to the Directive 2001/20/EC. However, the Directive has had many direct effects on the cost and feasibility of conducting clinical trials, which, in turn, have led to a decline in clinical trial activity in the EU. The Commission considers it necessary, therefore, to take new measures. IMPACT ASSESSMENT: the Commission has carried out an impact assessment in accordance with its guidelines and published the results. LEGAL BASIS: Articles 114 and 168(4)(c) of the Treaty on the Functioning of the European Union (TFEU.) The Regulation aims at achieving an internal market as regards clinical trials and medicinal products for human use, taking as a base a high level of protection of health. At the same time, the Regulation sets high standards of quality and safety for medicinal products to meet common safety concerns as regards these products. CONTENT: the proposed legislation takes the form of a Regulation and replaces Directive 2001/20/EC. This legal form ensures that Member States base their assessment of an application for authorisation of a clinical trial on an identical text, rather than on diverging national transposition measures. This holds not only for the entire authorisation process, but also for all other issues addressed in the Regulation, such as safety reporting during clinical trials, and the requirements for labelling of the medicinal products used in the context of a clinical trial. A Regulation also allows actors to plan and conduct clinical trials, including multi-national clinical trials, on the basis of one regulatory framework. The main points of the proposal are as follows: New authorisation procedure for clinical trials: this based on the following: · a harmonised authorisation dossier; · a single portal to submit an application for conducting a clinical trial linked to an EU database; · a flexible and swift assessment procedure; · a clear mechanism to appoint a reporting Member State; · clear timelines with a concept of tacit approval in order to ensure compliance; · a coordination and advisory forum to address issues which may arise in the authorisation procedure; · a clear distinction between aspects where Member States cooperate in the assessment and aspects of an intrinsic ethical or national/local nature where the assessment is made by each Member State individually; · the option for a Member State to 'opt-out' of the conclusions of an assessment of an application for conducting a clinical trial ('qualified opt-out'); · a swift procedure to extend a clinical trial to additional Member States; · where a clinical trial is modified after it has been authorised, this modification is subject to authorisation if, and only if, the modification has a substantial impact on the safety or rights of the subjects or on the reliability and robustness of the data generated in the clinical trial. Simplified safety reporting: compared to Directive 2001/20/EC, the rules have been streamlined, simplified and modernised as follows: · the option to exclude reporting by the investigator to the sponsor of adverse events, if this is provided for in the protocol; · direct reporting of suspected unexpected serious adverse reactions by the sponsor to the European database EudraVigilance; · simplified submission of the annual safety report by the sponsor. Protection of subjects and informed consent: Directive 2001/20/EC does not address the specific situation where, because of the urgency of the situation, it is impossible to obtain free and informed consent from the subject or the legal representative (clinical trials in emergency situations). To address this, specific provisions on clinical trials in emergency situations have been added in line with existing international guidance documents on this issue. Furthermore, as regards the protection of personal data, provisions of Directive 95/46/EC and Regulation (EC) No 45/200110 apply. No personal data of data subjects participating in a trial will be collected in the EU database. Personal data of investigators, which may be collected in the EU database, are kept in accordance with the exception provided in the text. Compensation for damage: where there is no additional risk, or where that additional risk is negligible, the Regulation does not provide a specific damage compensation (be it an insurance or an indemnification) for the clinical trial. However, in cases where a clinical trial does pose an additional risk, the proposed Regulation obliges the sponsor to ensure compensation be it through insurance, or through an indemnification mechanism. Sponsors, co-sponsorship, EU contact person: every clinical trial must have a sponsor, i.e. a legal or natural person responsible for initiating and managing the clinical trial. Clinical trials are increasingly initiated by loose networks of scientists or scientific institutions within one Member State or across several Member States. The proposed Regulation introduces the concept of co-sponsorship. At the outset, all co-sponsors are responsible for the entire clinical trial. However, the proposal allows co-sponsors to split the responsibility for the clinical trials amongst themselves. If the sponsor is established in a third country, an EU contact person must be provided in order to ensure an effective supervision of a clinical trial. Inspections: the proposed Regulation provides the legal basis for Commission staff to perform controls in Member States and in third countries in the context of the EU acquis for medicinal products for human use and clinical trials. BUDGETARY IMPLICATIONS: EUR 4 144 000 in commitment appropriations for the period 2014-2020. The budgetary implications of this proposal are as follows: · costs for databases (one-off costs and maintenance); · Commission staff to manage the functioning of the Regulation; · costs for meetings of Member States to ensure that the authorisation procedure set out in this Regulation functions properly; · Commission staff and other costs to conduct Union controls and Union inspections. The costs will be covered with the envelope of the Health for Growth Programme 2014-2020 2014-2020. |
activities/2/docs/0/celexid |
CELEX:52012AE2059:EN
|
procedure/Mandatory consultation of other institutions |
Economic and Social Committee Committee of the Regions
|
activities/3/docs/0/url |
http://www.europarl.europa.eu/sides/getDoc.do?type=COMPARL&mode=XML&language=EN&reference=PE504.236
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BORG Tonio |
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DALLI JohnNew
BORG Tonio |
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Old
http://eur-lex.europa.eu/smartapi/cgi/sga_doc?smartapi!celexplus!prod!DocNumber&lg=EN&type_doc=COMfinal&an_doc=2012&nu_doc=369New
http://www.europarl.europa.eu/registre/docs_autres_institutions/commission_europeenne/com/2012/0369/COM_COM(2012)0369_EN.pdf |
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2012-09-18T00:00:00
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activities/2/committees/1/rapporteur |
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committees/1/date |
2012-09-18T00:00:00
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committees/1/rapporteur |
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activities/2 |
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procedure/dossier_of_the_committee |
ENVI/7/10164
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procedure/stage_reached |
Old
Preparatory phase in ParliamentNew
Awaiting Parliament 1st reading / single reading / budget 1st stage |
activities/1/docs/0/text |
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activities |
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committees |
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links |
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other |
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procedure |
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