Regulatory Newsletter January - March 2014

Transcription

1 Regulatory Newsletter January - March 2014

2 Introduction CROMSOURCE is committed to sharing our expertise with our clients and future clients. This reflects the first part of our Advise Agree Deliver motto! In this spirit we have pleasure in making available this issue of our Regulatory Newsletter. This newsletter is put together by our expert regulatory team and tracks the changes occurring in European and USA regulations relating to clinical research performed in both medicinal products and medical devices. The Newsletter is a quarterly publication distributed via and posted on the CROMSOURCE website. We hope you find this information useful, and welcome feedback, questions and suggestions. Contact us on cromsource@cromsource.com at any time.

3 European Union From the European Commission Medicinal Products Update on the proposed Clinical Trials Regulation With the aim of further harmonising the regulatory requirements for clinical trials between the EU Member States and of supporting the development of new and innovative medicines, the European Commission published on 17 July 2012 a proposal for a regulation ( Proposal for a Regulation on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC ). In accordance with European Union legislation procedure, the proposal was submitted at the end of 2012 to the European Parliament and the European Council for review and approval. In the course of 2013, the regulation proposal was extensively debated within the responsible European Parliament Committee, ENVI (Environmental, Public Health and Food Safety) who made several amendments. On 20 December 2013, the European Parliament and the European Council came to an informal agreement on the proposal. On 2 April 2014, the EU Parliament voted positively on the proposed text of the Clinical Trials Regulation. The text voted by the European Parliament can be found on: TA The final step for the adoption of the Clinical Trials Regulation is the approval by the European Council of Ministers, which is planned for 19 and 20 June Once published in the Official Journal of the European Union, the Clinical Trials Regulation will enter into force on the 20 th day following publication. Being a regulation, it will immediately become law within the whole EU as no transcription into the national legislation of an EU Member State is required. It shall however be highlighted that the application of the Regulation is linked to the full functionality of the EU portal and the EU database under development by the European Medicines Agency and to the confirmation of the full functionality, by the European Commission in the EU Official Journal. Therefore, it is expected that the provisions laid down in the Clinical Trials Regulation will not come into effect before mid-2016.

4 The regulation will introduce the following main changes in the European Union regulatory framework for clinical trials: o Streamline submission and communication process, using a single EU portal All clinical trial submissions will go through a unique EU portal. Regardless of the number of Member States involved, there will be a single submission. This will replace the current individual submissions to both Competent Authorities and Ethics Committees, in each Member State. All further information, communication and data on a given clinical trial will be performed through the single EU portal. o Simplified authorisation procedure, with single decision per Member State The application dossier will consist of 2 parts: - Part I, covering the scientifically related aspects (EU application form, protocol, investigator brochure, investigational medicinal product dossier, documentation on GMP compliance, documentation on auxiliary medicinal products, labelling of the investigational medicinal products, scientific advice, paediatric investigation plan decision) - Part II, covering the ethically and investigator/site facility qualificatication related aspects (recruitment arrangements, subject information and consent form, investigator qualification, facilities suitability, insurance, financial arrangements sponsor/site/investigator, data protection requirements). For each involved Member State, there will be one single decision, covering both parts and replacing the currently separate approvals by the Competent Authorities and the Ethics Committees. In the case of a multinational trial, the Member States will jointly assess the Part I of the application, the ethical review (Part II) remaining at national level and under the responsibility of the Ethic Committees. For the purpose of the Part I joint assessment, the sponsor shall propose one of the involved Member States as Reporting Member State. The Reporting Member State will coordinate the validation of the clinical trial application, assess the clinical trial application for the Part I aspects and issue the Part I assessment report. All concerned Member States must then adopt the conclusion of the Reporting Member State report, unless they opt out and provide their reasons through the EU Portal. o Low- intervention clinical trial concept Low-intervention clinical trials are defined as trials fulfilling all of the following conditions: trials with authorised medicinal products, used within the terms of their marketing authorisation or used with evidence-based on their safety and efficacy, and not posing more than minimal additional risk or burden to the subjects compared to normal clinical practice. For these trials, no additional insurance will be required to the sponsor, if any possible damage that could suffer a patient in the clinical trial is covered by the compensation system already in place, on the territory of the Member State.

5 o Possibility of co-sponsorship A clinical trial may have one or more sponsors. In the case of co-sponsorship, all sponsors are subject to sponsor s responsibilities, unless respective responsibilities are specified in a written contract. Additionally, one of the sponsors must be responsible for: - the compliance with the obligations related to the authorisation procedures - answering all questions from patients, investigators or Member States - implementing the measures required by any Member State o Increased requirements for transparency on clinical trial results Within one year from the end of the trial in all EU Member States, the sponsor will be required to submit in addition to the summary of clinical trial results, as currently required, a summary of the clinical trial results for laypersons. When the protocol provides for an intermediate data analysis, a summary of the results shall be submitted, within one year of the intermediate data analysis date. When a clinical study report has been submitted in the frame of a marketing authorisation request, this report will be required to be submitted within 30 days after regulatory decision on the marketing authorisation application. Medical Devices Update on the proposed Medical Devices and In-Vitro Diagnostic Medical Devices Regulations On 2 April 2014, the European Parliament voted on its first reading on the draft Medical Device and In-Vitro Diagnostic Regulations. This can be considered as a consolidation of the work done so far and as a handover to the next Parliament. Some aspects were particularly addressed by the European Parliament e.g. a stricter monitoring and certification procedures to ensure traceability for medical devices, patient implant card and stricter safety rules for In-Vitro Diagnostic Medical Devices. Furthermore for these types of devices, the Parliament called for an ethics committee to be set up and to introduce provisions requiring the informed consent of patients to testing protocols and genetic counselling. Nevertheless, the final Medical Devices Regulation and In-Vitro Diagnostic Medical Devices Regulations are to be awaited. It is expected that the documents will be reviewed after the election of the European Parliament members that will occur end May For more details see:

6 From European Medicines Agency (EMA) Guideline on good pharmacovigilance practices (GVP) Annex I - Definitions (rev 2), entering into force on 8 January 2014 This revised annex provides all current definitions applicable in the frame of performing pharmacovigilance activities. Compared to previous version, the revised annex adds in particular definitions relating to vaccine pharmacovigilance and explanatory notes for offlabel use. The document entered into force on 8 January The guideline can be downloaded from the following link: pdf From Individual Countries Belgium Loi portant des dispositions diverses en matière de santé, in preparation A Health Law amending both the law of 7 May 2004 concerning experiments on the human persons and the law of 19 December 2008 on human biological material is in preparation and expected to be published in the Belgian Official Journal, end April With respect to the law of 7 May 2004, the new Health Law will introduce the following changes: o o o o The request for approval to start a clinical with a medicinal product must compulsorily be submitted on the same day, to the Belgian Competent Authorities, the Lead Ethic Committee and all involved local Ethic Committees. This measure is introduced in order to prepare the Belgian regulatory framework for the future implementation of the EU Clinical Trials Regulation. The request to the Ethics Committees can be delegated by the coordinating investigator to the sponsor or an organisation acting on behalf of the sponsor. The written power of attorney from the coordinating investigator must be included in the submission package for all involved Ethic Committees. No amendment to add new sites can be introduced for 3 months, after initial clinical trial approval. In the case of critical clinical trials (first administration to humans, trials with children or pregnant women, trials in therapeutic indications for which there is no alternative treatment), the Lead Ethic Committee may require the opinion of the Belgian

7 Committee for Medicinal Products for Human Use, to assess the aspects of the proposed clinical trial related to the risk-benefit ratio, the patient safety or the application of Good Clinical Practice. The opinion provided by this committee will be communicated to the Belgian Competent Authorities, the Lead Ethics Committee and the sponsor. With respect to the law of 19 December 2008, the new Health Law will introduce a simplified notification procedure for a biobank, using human biological material exclusively collected and used in the frame of a clinical trial. In Belgian legislation, a biobank is defined as a structure that receives, processes, stores and provides human body material, exclusively for the purpose of scientific research, except for research with human medical applications. For a biobank set up in the frame of a clinical trial, the clinical trial authorisation will cover the notification of the biobank, provided that the human biological material is exclusively harvested and used, according to the objectives and purposes defined in the clinical trial protocol and that the objectives and activities of the biobank are approved by the Lead Ethic Committee. A specific biobank notification form will be required to be submitted in the clinical trial approval request to the Lead Ethic Committee and the Belgian Competent Authorities. The biobank notification form will be available on the website of the Belgian Competent Authorities. The following information will be required to be provided to notify the biobank: storage location of human biological material, name of the company operating the biobank, type of human biological material stored and provided, name and diploma of the physician managing the biobank. The validity of the biobank notification will expire at the end of the clinical trial. A royal decree specifying the implementing rules for biobanks operating in Belgium and the dates for entry into force is expected to be issued for summer Circular N 609 on accredited Ethic Committees (EC) allowed to provide EC approval, published on 4 April 2014 Belgian Competent Authorities (FAMHP) published circular n 609 on 4 April 2014, with the new list of accredited Ethics Committees (EC s) with full agreement. In Belgium, only Ethics Committees with full agreement are allowed to provide the Ethics Committee approval, in order to perform either a clinical study with a medicinal product or with a medical device. Compared to the previous list, only 22 EC s are authorised from 1 April 2014 to provide Ethics Committee approval, in the frame of either a single- or multi-centre study. The full agreement status of these EC s will be valid for a period of 4 years, i.e. until 1 April The circular n 609 also provides additional explanations on how the selection of the Ethics Committee allowed to give EC approval must be performed, for any new study to be initiated in Begium, from 1 April 2014.

8 The circular n 609 can be accessed, via the following link : Set-up of an interactive and secure website by the Belgian Competent Authorities, update As foreseen by the last amendment of the law on experiments on human persons, published on 29 March 2013,, the Belgian Ethics Committees (EC) should communicate with the Belgian Competent Authorities (CA) through an interactive and secure website, in the frame of clinical trials with medicinal products. Accordingly, in order to enhance the communication with the Belgian EC and track their activities in the frame of clinical trials approval, the Belgian CA have started working on this interactive website, in the course of the fourth quarter of Initial test results showed that additional testing and training of the EC is needed. This occurred in March A follow-up meeting between the Belgian CA and the Belgian EC is foreseen in April 2014, to discuss and review the test results. Depending on the results of these additional tests, it is currently expected that this interactive website will be launched in May When the interactive website will be launched, it will allow sponsor/applicant of clinical trials application to track the status of a clinical trial request. Tutorials to use the secure website will also been developed by the Belgian CA and posted on Belgian CA website. Additionally, a Questions & Answers document on the interactive website will be published by the Belgian CA. France New method of reporting adverse reactions in clinical trials with medicinal products, since 17 March 2014 Since 17 March 2014, French Competent Authorities (ANSM) have implemented new methods of reporting adverse reactions in clinical trials with medicinal products. Previously the declaration to ANSM of Suspected Unexpected Serious Adverse Reactions (SUSAR) occurring during a clinical trial with a medicinal product was required to be performed by post or by fax. From 17 March 2014, SUSAR declaration to ANSM is required to be performed only by e- mail to the following address: declarationsusars@ansm.sante.fr. Each SUSAR must be reported in an individual .

9 The must contain the following attachments: o the CIOMS form in pdf format o the new accompanying SUSAR form available on ANSM website and that must be completed and submitted on-line. In order to explain the new modalities for SUSAR declaration, the ANSM has published a user manual. Additionally, the subject of the , the name of the CIOMS report and the name of the accompanying SUSAR form must be made according to the rules defined in the user manual. Detailed information on the new SUSAR form and the user manual can be accessed, via the following link: Spain New instructions for the notification of participating sites in a clinical trial with a medicinal product to the Spanish Competent Authority, published on 17 January 2014 The Spanish Competent Authority released on 17 January 2014, new instructions for the mandatory notification of the Conformidad de la Direccíon del Centro (CDC), in the case of clinical trials with medicinal products. The CDC is a document signed by the Hospital Director confirming that he/she agrees that the clinical trial is carried out at the site. In order to obtain the approval from the Spanish Competent Authority to perform a clinical trial, the CDC of a least one of the sites authorised by the Comité ético de investigacíon clínica de referencia (Lead Ethics Committee) must be submitted to the Spanish Competent Authority (CA), within a timeframe of 60 days after confirmation of valid submission from CA. The revised instructions for the CDC notification introduce a simplication in the notification procedure. Indeed, the remaining CDC s from the authorised sites by the Lead Ethics Committee are now allowed to be submitted as a group to CA. In order to take into account the new instructions for CDC notification, the instruction manuals to submit clinical trial requests in Spain have been updated. In particular, a volume 5 manual Manual de centros participantes en ensayo clínico has been added to explain in detail the CDC submission requirements to CA. The revised manuals with the instructions for submission of clinical trial requests in Spain can be consulted, using the following link:

10 New electronic platform for the submission of clinical studies to regional EC in Andalusia, applicable since 1 March 2014 Since September 2010, any documentation needed in the frame of an application to the national Competent Authorities (AEMPS) and Ethics Committees in Spain for an interventional clinical trial with medicinal products must be submitted through the AEMPS web portal, ECM (Ensayos Clínicos con Medicamentos). Additionally shall the trial involve a site in Andalusia, documentation required for the Regional EC of Andalusia must be submitted electronically, through the web portal PANAKEIA. For other types of clinical studies (clinical investigations with medical devices, noninterventional studies, etc.), submission to the regional EC of Andalusia was up to now performed on paper or CD-ROM. Since 1 March 2014, for all clinical studies (except interventional clinical trial with medicinal products), the initial submission of the documentation requiring evaluation by the Regional EC of Andalusia must be performed through the web portal, PEIBA (Portal de Ética de Investigación Biomédica de Andalucía). It shall be highlighted that the web portal is only accessible to Spanish citizens having a digital electronic certificate. This digital electronic certificate allows access to PEIBA, PANAKEIA and the ECM portals. For studies approved before 1 March 2014, sponsor can choose to submit additional application (amendments, annual progress reports, end of study notifications) either via PEIBA or by paper/cd-rom. The PEIBA platform can be accessed, via the following link: At this moment, both the Panakeia and PEIBA platforms are working. However, in the future, the Panakeia platform will disappear and only submission through PEIBA will be feasible. The PEIBA platform will also be used to provide the approval of the regional EC of Andalusia. An electronic EC approval will be delivered, downloadable from the PEIBA platform. In the coming future, a user manual will be published to explain the functionalities of the PEIBA platform.

11 United Kingdom MHRA- Revised Guidance for the Notification of Serious Breaches of GCP or the Trial Protocol, published on 6 January 2014 The MHRA published a new version (version 5) of the guidance document Guidance for the Notification of Serious Breaches of GCP or the Trial Protocol. The updated guidance includes a recommendation that the sponsor notifies the chief or principal investigator of breaches reported to MHRA. This recommendation is intended to facilitate the implementation of corrective and preventive action. The revised document can be downloaded via the following link : European Headquarters Verona - Italy Phone: North American Headquarters Cambridge - USA Phone: