MHRA regulatory centre and Research Ethics Service (RES) combined ways of working pilot Instructions to sponsors (version 2.1)

Transcription

1 MHRA regulatory centre and Research Ethics Service (RES) combined ways of working pilot Instructions to sponsors (version 2.1) Document purpose: The purpose of this document is to provide instructions to sponsors participating in the MHRA regulatory centre and RES Combined Ways of Working Pilot. Process: Step 1: Select your REC meeting Contact or (please title your combined ways of working pilot) to confirm that you have a trial to submit into the pilot. You will need to provide the following details (where possible): your contact details trial title IRAS ID phase of the trial which UK nation the trial is led from name and contact details of the sponsor expected submission date. If you are able to confirm an expected submission date then please also state if you have a preferred REC meeting. Committee meeting dates and submission periods are available here. If you do not have an expected submission date then this can be confirmed later. There will be a small number of RECs involved in this pilot during the early stage. This means that you may not be able to submit to the REC which you would usually submit to. The RECs involved will increase as the pilot develops so please always check the HRA website for the most up to date information. Once you have confirmed your submission and REC meeting you will be issued with a REC reference number.

2 Step 2: Submit application via Eudralink and IRAS* The IRAS form is currently required to be submitted but under the pilot, the full IRAS form is not provided to the REC for review. It is therefore important that the protocol is written in a way which means that the study is described clearly and comprehensively. Additional documents may be produced to describe the recruitment and informed consent procedure if not included in the protocol. We are working to simplify the submission process as much as possible but, by the nature of the current systems, this is a multi-step process: 1. Complete the integrated dataset in IRAS (in the same way as for all CTIMPs). 2. Do not upload supporting documentation to IRAS checklist (you will need to add CWOW Pilot into the Reason not supplied column for all documents listed as mandatory). 3. On the day that you are ready to submit your application and you have your document set ready you will need to generate the MHRA (EudraCT equivalent) form in a pdf and xml format, by: a. navigating to the MHRA submission tab in IRAS b. selecting the button to submit the MHRA form this will generate a pdf of the MHRA (EudraCT) form c. scrolling down to the bottom of the tab to save a copy of the XML of the MHRA (EudraCT) form d. note: this will be required for submission through Eudralink and should not be submitted through IRAS. 4. Contact or to enable e-submission of the IRAS form. 5. Submit the IRAS form via the E-submission tab in IRAS (do not upload supporting documents) and for trials with non NHS sites, also submit the SSI via IRAS. 6. Submit the application pack (see figure 1) via Eudralink ( to the MHRA clinical trial helpline (clintrialhelpline@mhra.gov.uk) with the subject line MHRA-RES PILOT INITIAL APPLICATION, checking the following: Page 2 of 7

3 a. the covering letter should include the completed checklist of documents outlined in Appendix 1 b. the folder should include the IRAS generated MHRA form in both pdf and xml format c. the folder structure should be organised as per Figure 1 below. 7. Steps 2-5 MUST be completed on the same day to ensure there is a single day 0. If you will not complete the above process by the date agreed in Step 1, contact to rearrange your REC review as soon as possible. Figure 1 - Application Pack (submitted via Eudralink) 1. Cover letter 2. EudraCT form PDF and XML file 3. Protocol 4. Investigator s Brochure (IB) 5. Documents relating to compliance with Good Manufacturing Practice (GMP) for the IMP 6. Investigational Medicinal Product Dossier (IMPD) 7. Auxiliary (I,e non-imp) Medicinal Product Dossier 8. Scientific Advice and Paediatric Investigation Plan 9. Content of the labelling of the Investigational Medicinal Product 10. Recruitment arrangements 11. Subject information, informed consent form and informed consent procedure 12. Suitability of the investigator 13. Suitability of the facilities (For non NHS sites the SSI form should continue to be submitted via IRAS until further notice) 14. Proof of insurance cover or indemnification 15. Financial and other arrangements 16. Proof that data will be processed in compliance with current data protection legislation. Step 3: Validation process Validation checks will be completed on your application within three days of receipt. This will involve checking that all required documents have been submitted and that the documents can be opened and are readable. If the application is not valid, you will be given the opportunity to correct this and will have until day Submission+5 to complete. For further information on which documents are required, please refer to the Application Dossier Guidance which can be found here. Not all documents in the proceeding table may be appropriate for all trials. Where a document listed in the table is not submitted because it is not relevant or because the information is contained Page 3 of 7

4 elsewhere in the application dossier, such as in the protocol, then you just need to detail this in the comments column for the purposes of validation. When naming documents to be submitted, the full title may be listed in the cover letter but the naming of the document when saving it should be a short but clear version (Eudralink cannot accept documents with names which exceed 250 characters). If valid, we will notify you and supply a pilot reference number (in addition to the standard reference numbers - EudraCT, REC and IRAS) for the application. Day 0 will be the date of receipt of a valid application. Step 4: consolidated assessment; to be completed by day 30 MHRA and RES will work jointly to undertake the assessment which will result in two assessment outputs. Assessment one will include the full MHRA review and also a review by the REC of the risks, benefits, burdens and inconveniences (CMC-related information will be assessed by the MHRA only). Assessment two will be the REC review (other than the areas covered in assessment one) and an administrative assessment, which is largely in relation to compliance with legislation (e.g. data and tissue legislation). The output at this stage of the process will either be an overall authorisation of the trial (CTA from MHRA and favourable opinion from the ethics committee) or a request for further information. Step 5: Request for further information If we require further information, we will you to outline the further information required or the questions to be answered. This may include both assessment one and two or may involve just one of the assessments. Step 6: Request for further information response You will have 14 days to provide a full response. The response should be sent via Eudralink to the MHRA clinical trial helpline clintrialhelpline@mhra.gov.uk with the subject line MHRA-RES PILOT RFI RESPONSE and should include the pilot reference number which was provided to you in the validation letter. We anticipate there may be instances where you cannot respond in full to the requests for information. The UK clinical trials Regulation 2004 No SI1031 allows a fixed period of time, usually 14 days, to respond to a request for further information in relation to the CTA whereas the Regulation allows for the clock to be paused while awaiting a response to the REC. Page 4 of 7

5 Therefore, if you are unable to respond in full to the request for further information (including assessments one and two) within 14 days, then the application will not be able to continue in the pilot and will default into standard MHRA and REC processes. This is because we recognise that rejecting an application from the system at this stage would require a new REC submission and review. The preference would be that one REC review is undertaken and therefore we will continue with the application for REC purposes but a resubmission to the MHRA for a CTA may be required. The following scenarios would apply: Respond to assessment 1 and 2 within 14 days Respond to neither assessment 1 or 2 within 14 days Application proceeds in the pilot Application removed from the pilot A new CTA application would be required No new REC application required Continue to respond to assessment 2 as this will apply for REC purposes Respond to assessment 1 but unable to respond to assessment 2 Application removed from the pilot No new submissions required Assessment 1 will apply for CTA purposes Respond to assessment 2 but unable to respond to assessment 1 Application removed from the pilot A new CTA application would be required Assessment 2 would apply for REC purposes Step 7: Joint decision by day 60 After the review of a full response to all points raised (assessment one and two), an outcome will be confirmed (authorised or not authorised) and two letters will be issued via . An authorisation will be issued where the CTA is authorised and also the REC has issued a favourable opinion and will include both the CTA authorisation letter and the REC favourable opinion letter. A non-authorisation will occur because either the CTA has been rejected or the REC has issued an unfavourable opinion. The CTA and REC letters will both be provided and the reason for the non-authorisation will be made clear. Page 5 of 7

6 Fortnightly support and feedback call The purpose of the trial is to test a joint MHRA/RES process; this includes understanding the experience of applicants. As such, we want to ensure continued engagement with you throughout, to help you with any areas of need but also to ensure we re capturing your experience and feedback in a consistent and usable way. To support this, we will host a fortnightly call where we ll be on hand to help you with any areas and to ask you questions about your progress. While our preference is for matters to be raised during this weekly call, we will of course be on hand should you have needs that don t fit the scheduled call timeline. The meeting will run Mondays at 2pm (the next meeting will be 13 August 2018 and the alternate Mondays thereafter). Details on how to join will be sent out ahead of the meeting. Trials excluded from this stage of the pilot: first in UK first in human advanced Therapy Medicinal Product (ATMP) trials trials requiring review by the REC constituted by Scottish Ministers under Section 51(6) of the Adults with Incapacity Act Further information Further information and guidance will be issued via the combined ways of working pilot page on the HRA website which can be found here. Page 6 of 7

7 Appendix Checklist to be submitted via EudraLink Information 1. COVER LETTER 2. IRAS EudraCT form : PDF and XML file 3. PROTOCOL 4. INVESTIGATOR'S BROCHURE (IB) 5. DOCUMENTATION RELATING TO COMPLIANCE WITH GOOD MANUFACTURING PRACTICE (GMP) FOR THE INVESTIGATIONAL MEDICINAL PRODUCT 6. INVESTIGATIONAL MEDICINAL PRODUCT DOSSIER (IMPD) 7. AUXILIARY (ie non-imp) MEDICINAL PRODUCT DOSSIER 8. SCIENTIFIC ADVICE AND PAEDIATRIC INVESTIGATION PLAN (PIP) 9. CONTENT OF THE LABELLING OF THE INVESTIGATIONAL MEDICINAL PRODUCTS 10. RECRUITMENT ARRANGEMENTS 11. SUBJECT INFORMATION, INFORMED CONSENT FORM AND INFORMED CONSENT PROCEDURE 12. SUITABILITY OF THE INVESTIGATOR 13. SUITABILITY OF THE FACILITIES (For non NHS sites the SSI form should be submitted via IRAS until further notice) 14. PROOF OF INSURANCE COVER OR INDEMNIFICATION 15. FINANCIAL AND OTHER ARRANGEMENTS 16. PROOF THAT DATA WILL BE PROCESSED IN COMPLIANCE WITH UNION LAW ON DATA PROTECTION Present (Y/N/NA) Comment