Standard Operating Procedure. Clinical Trial Authorisation

Transcription

1 Standard Operating Procedure for Clinical Trial Authorization Scope This SOP has been written to describe the procedure undertaken to apply for Clinical Trial Authorisation from Competent Authorities in countries wishing to participate in prospective clinical trials with an investigational medicinal product. Abbreviations CA: CTA: CTO: EBMT: EMEA: EU: IMP: MHRA: SOP: Competent Authority Clinical Trial Authorisation (EBMT) Clinical Trials Offices European Group for Blood and Marrow Transplantation European Medicines Evaluation Agency European Union Investigational Medicinal Product Medicines and Healthcare Regulatory Agency Standard Operating Procedure Introduction Any research that fulfils the definition of a clinical trial, as described by the EU Directive 2001/20/EC Article 2 (a), requires a CTA from the CA in the Member State in which research is being carried out. The CA will only issue a CTA if it has no objections to the proposed research. The EU Directive 2001/20/EC definition of a clinical trial is: Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy 1 of 9

2 It is the responsibility of the Sponsor to obtain a EudraCT number, complete the CTA form and submit all required documentation to the Competent Authorities. The following pages describe the process for applying for a CTA Responsible Personnel Applications to CA s must be made by the Sponsor or someone authorized to submit the request on the Sponsor s behalf. If the Sponsor is not established in the European Community then there must be a legal representative who is so established. For EBMT sponsored trials, staff from the three Clinical Trials Offices (London, Leiden, or Paris) prepare an application pack to submit to the CA in the respective country. For other countries aiming to participate in the trial, one nominated and contracted physician per country takes on the role of Country Lead Investigator and this lead investigator is authorised to submit the CTA on behalf of the EBMT. Procedure 1) Obtain a EudraCT number Before submitting an application to the CA, the Sponsor must obtain a unique EudraCT number from the EMEA EudraCT database. This number identifies the protocol for the trial whether conducted at a single site or at multiple sites in one or more member states. See SOP 3 on how to obtain a EudraCT number 2) The Clinical Trial Application The clinical trial application form contains the following sections: A. Trial Identification B. Sponsor Identification C. Applicant Identification If the applicant is not a member of staff from one of the CTO s, the applicant requires a letter authorizing him/her to make the application on behalf of the sponsor D. Information on the IMPs Repeat the section if more than one product (test and/or comparator) is used Complete Sections D1, D2 and D3 for all products 2 of 9

3 Complete Sections D4, D5 and D6 only if certain types of product are used: Section D4 is for biological/biotechnological products Section D5 is for somatic cell therapy Section D6 is for gene therapy D.7. Information on the Placebos Complete this section only if a placebo product is being used. Repeat Section D.7 if more than one placebo is being used. D.8. Site(s) where the qualified person certifies batch release E. General Information on the Trial F. Population of Trial Subjects G. Clinical Trial Sites/ Investigators in the Member State H. Ethics Committee/ MS Competent Authority I. Signature Enter the name of the person who will make the application on behalf of the Sponsor. The signature itself will be added to the (printed) paper copy. J. Check List Check all applicable boxes to indicate the information and documentation provided for the approval request. 2.a) Create an application form with general information applicable for all Member States To access the application form go to the website of the EMEA ( and enter the EudraCT Website section, then click on Access to EudraCT Application (direct link: Proceed to EudraCT Number Step 2: Click here to create a new Clinical Trial Application and enter the EudraCT number only (do not yet specify any Member State at this stage). To create a general application form valid for every applicable country, complete all non-member State and non-investigator related information in the different sections, then return to the Application Menu Page and save the entered information by selecting Save as XML onto your local drive. NOTE: The system will 'timeout' if there is a period of inactivity. To avoid accidental data loss you must 'Save as XML' to your local computer at regular intervals. The EudraCT system only stores data during the current session. 3 of 9

4 2.b) Create an application form for a specific Member State To complete the application form for a particular member state, re-enter the EMEA website (direct link: Select EudraCT Number Step 2: Click here to load saved Clinical Trial Application then click Browse to select the previously saved XML file. Click Upload to enter the XML file. When you are back in the Application Menu Page enter the remaining country specific information. When all required sections are completed, or regularly throughout the session, return to the Application Menu Page and Save as XML giving the file a new name to differentiate the form from the non-country-specific application form. Return to the Application Menu Page, then click on Validate Application and resolve the list of inconsistencies, if any. To finalize the process click on Get Printable Copy, followed by Continue to Pdf creation, then select the language (available options are English or Spanish only). Select Download Current Form for MS Competent Authority and save the Pdf file on your local computer. You now have a full XML file and PDF file of the same document. Repeat the process for every applicable country using the non-specific form generated at the beginning. The XML file should be copied onto a disc and sent along with the all the required paper documents as part of the application to the CA. The applicant should print the completed form, sign and date it, and send it as part of the application to the CA of each Member State where he/she intends to conduct the trial. The applicant's signature will confirm that the sponsor is satisfied that a) the information provided is complete, b) the attached documents contain an accurate account of the information available, c) in their opinion it is reasonable for the proposed clinical trial to be undertaken, and d) any information provided to both the CA and the ethics committee concerned is based on the same data. 3) Supporting data required for CTA The European Commission Guidance Document (specified below) includes further information on additional documents required for CTA in EU Member States and must be consulted when preparing the application pack. Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial (available from 4 of 9

5 For applications to non-eu countries liaise with the Country Lead Investigator as to the specific requirements in the relevant country. 4) Where to apply Consult the MHRA website for the correct delivery address < The contact addresses of Competent Authorities in other Member States can be found on the EMEA website at: The postal addresses and links to the websites of Competent Authorities in other Member States can be found on the EUROPA website at: Alternatively confirm the contact details with the respective Country Lead Investigator. 5) What to send A request for a clinical trial authorisation consists of: Cover letter Application form (signed paper copy and xml file of complete data set on disc) The specified particulars and documents as indicated in the EU Commission Guideline (see section 3 of this SOP) Summary of supporting data (Form J of the CTA application form) Where required application fee, or proof that payment has been made Ensure you have all the required documents in the correct format before sending off the application package. It is advisaable to consult the CA s website for specifics. 6) How to pay the fees The MHRA charges fees for a CTA. Their website lists a table with the different fees, which can be viewed at the following link: ue&ssdocname=con See the country specific CA websites for information on whether fees are charged and how to make the payments. The EudraCT number should be included with the payment or cheque. Proof of payment should be included in the application sent to the CA s. 7) The approval process The application is validated on receipt and an acknowledgement letter will be sent to the person submitting the application (person named in Section C of the application form). 5 of 9

6 If the application is valid then the assessment period will begin. This starts from the date of receipt of a valid application. If the application is not valid then the person making the application will be told of the deficiencies. Nothing will happen to the application until the missing components are provided. The MHRA website mentions that the initial assessment will be performed within 30 days. For the purposes of this calculation, the day of receipt of the application by the Clinical Trials Unit is day 0. There are two possible outcomes of the approval proces: Acceptance (with or without conditions) Grounds for non-acceptance If there are grounds for non-acceptance, the sponsor has at least 14 days (at least 30 days for gene therapy, somatic cell therapy or products containing genetically modified organisms) to submit an amended request for authorisation. These periods may be extended in certain circumstances. The amended request is assessed within a total of 60 days from receipt of the initial application (90 days for gene therapy products) and there are two possible outcomes: Acceptance (with or without conditions) Grounds for non-acceptance 6 of 9

7 References 1) Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial Revision 2, Version October 2005 see < for the current version 2) EMEA Website: 3) MHRA Website: 4) European Commission Website: 5) EU Directive 2001/20/EC Appendix 1 Outline of protocol summary Suggested headers for the translations of protocols in countries where a summary of the protocol in the national language is a required document for CTA. 1. Administrative information Name of sponsor Name of investigational medicinal product EudraCT number 2. Clinical use Medical condition or disease under investigation Any other medical condition or disease under investigation with this product 3. Date of protocol overview submission 4. Title of clinical trial 5. Purpose of clinical trial 6. Design of clinical trial 7. Patient population in clinical trial 8. Maximum number of patients to be included in clinical trial 9. Main inclusion criteria 10. Main exclusion criteria 11. Procedures for safety monitoring during trial 12. Criteria for withdrawal of patients on safety grounds 13. Route(s) of administration 14. Maximum dosage allowed (specify daily or total) 15. Maximum duration of treatment of a patient 16. Active comparator product(s) 7 of 9

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9 Appendix 2 Clinical Trials Office Outline of all active trials with an investigational medicinal product. Complete the following table for every ongoing EBMT sponsored trial with the same IMP For official use: Date received Date approved CTA no. 1. ADMINISTRATIVE INFORMATION Name of sponsor Name of the investigational medicinal product Eudract number for proposed trial Eudract number for first trial undertaken Eudract number(s) for subsequent trial(s) 2. CLINICAL USE Medical condition or disease under investigation Any other medical condition or disease under investigation with this product 3. DATE OF PROTOCOL OVERVIEW SUBMISSION 4. TITLE OF ON-GOING CLINICAL TRIAL(S) 5. PURPOSE OF ON-GOING CLINICAL TRIAL(S) 6. DESIGN OF ON-GOING TRIAL(S) 7. PATIENT POPULATION IN ON-GOING TRIAL(S) 8. MAXIMUM NUMBER OF PATIENTS TO BE INCLUDED IN ON-GOING TRIAL(S) 9. MAIN INCLUSION CRITERIA IN ONGOING TRIAL(S) 10. MAIN EXCLUSION CRITERIA IN ONGOING TRIAL(S) 11. CRITERIA FOR WITHDRAWAL OF PATIENTS ON SAFETY GROUNDS IN ONGOING TRIAL(S) 12. ROUTE(S) OF ADMINISTRATION (USE STANDARD TERMS) 13. MAXIMUM DOSAGE ALLOWED IN ONGOING TRIAL(S) (specify daily or total) 14. MAXIMUM DURATION OF TREATMENT OF A SUBJECT 15. ACTIVE COMPARATOR PRODUCT(S) Form available from MHRA website at: < ON of 9