eSignature Legality for Drug Testing Consent Agreement in European Union

How to eSign a document: eSignature legality for Drug Testing Consent Agreement in European Union

it is my pleasure to introduce your chair today martin o'kane manager clinical trials unit m m-a-a-m-h-r-a martin over to you thank you alex and hello everyone and a very warm welcome to this morning's webinar which is one of a series of eu exit and post-transition guidance webinars provided by mhra it was fantastic to see the level of interest in this webinar today and this morning we will cover clinical trials of investigational medicinal products before i begin um i'd just like to point out that in some cases uh in the presentation we've illustrated the transition guidance using charts or figures or used graphics to enhance the explanation of the guidance these will not be included as official enhancements in the guidance published so just a brief overview of how we'll run things this morning and again thank you for joining this webinar will last around 90 minutes we'll begin with a short presentation providing you plenty of time for questions and answers our presenters will update you on the guidance that has been published it is the approved guidance that is current as of today the webinar is being recorded and a link will be sent out to delegates the recording will not include the q a as both the guidance and the related questions and answers are subject to change thank you very much to those of you who pre-submitted questions as part of your registration we've tried to include as many of those up front in the presentation so they'll be answered we have grouped these and we'll answer them during the presentation and we'll work through questions that have been submitted to us today again trying to group as much as possible we're aware that there's a very large number of people registered on this webinar so apologies if we don't meet uh or we can't answer your question during the webinar and if you have a question that has not been answered we recommend that you get in touch with our customer service center or contact your trade association which is also working to answer questions so again as a general approach um this provides an overview of our approach from first of january 2021. when the uk left the eu on the 31st of january 2020 the withdrawal agreement created a transition period until the end of 2020 that provided certainty to business whilst the uk and eu negotiated its future trading relationship so from the first of january 2021 the medicines and healthcare products regulatory agency or mhra will be the uk standalone medicines and medical devices regulator as such the mhra has published detailed guidance on how medicines and medical devices will be regulated at the end of the transition period in both a negotiated and non-negotiated outcome with the eu great britain which consists of england wales and scotland will operate an initial legal framework that incorporates eu legislation into uk law however the uk regulator will be able to take sovereign regulatory decisions to help evolve the uk legal regime to meet future uk needs and to take regulatory decisions that will also apply directly in northern ireland as long as those decisions do not conflict with the eu decisions while the northern ireland protocol applies underpinning all these actions is the uk's government's commitment to ensure that there will be no impediment across the uk to securing access of vital medicines including vaccines following the end of the transition period and just to add from a specific clinical trials perspective the northern ireland protocol refers to article 13 of the eu clinical trials directive relating to manufacture and import of an investigational medicinal product authorization of a clinical trial um application to mhra will consist of a single submission and mhra will regulate and authorize for both northern ireland and great britain so before we move into the content of the presentation i'd like to introduce you to the the team that we have available for you this morning as alex mentioned my name is martin o'kee and i manage the clinical trials unit within the licensing division at mhra we also have louisa obilo who is our senior clinical safety scientist within the clinical trials unit graham mcnaughton who is a leading senior pharmaceutical assessor within clinical trials unit we also have colleagues from our inspectorate alan moon who is a senior good manufacturing practice inspector gil francis an expert good clinical practice inspector i'm also delighted to say that we have colleagues joining us from the health research authority clive cola and sue bourne who will be available to answer questions so today we'll run through the guidance of course and that will cover areas such as the sponsor and legal representative submitting an application to mhra registration and reporting results submitting safety reports and then manufacture and supply of the imp so the mhra guidance was published on the 1st of september 2020 there are 31 or 32 items of guidance relating to regulation of medicines and medical devices in great britain from the 1st of january 2021. six of these relate either directly or indirectly to clinical trials of investigational medicinal products these are registering to make submissions to the mhra from first of january a webinar associated with those submissions guidance on substantial amendments to a clinical trial from first of january and in terms of transparency registration of clinical trials of inps and publication of summary results there are there is also guidance on importing investigation medicinal products into great britain from approved countries and a list of those approved countries for the definition of marketing authorization so to start at the beginning of the process who can run a clinical trial in the uk so in terms of the location of the sponsor or legal representative we received a large number of questions about this prior to the webinar so hopefully this will provide some clarity and confidence for sponsors running international trials involving the uk so to confirm the sponsor or a legal representative of a uk clinical trial must be in the uk or a country on an approved country list and this list would initially include all eu and eea countries proposal is that this approved country list would be approved every three years and legislation would be developed to determine considerations for adding or removing countries from that list just to note that this flexibility isn't reciprocated so that if a uk sponsor is running a trial in the eu that uk sponsor must ensure that a sponsor or legal representative is established in the eu however an amendment to mhra will not be needed if a uk sponsor is adding an eu legal representative to cover eu eea sites as this will not affect the uk authorization if we move on then to submitting a clinical trial authority authorization application to mhra until the end of this year users will be able to submit applications for ctas which would include initial applications substantial amendments end of trial notifications and developmental safety update reports or annual safety reports or dsurs via cessp as you can today however from january 2021 users will need to submit their applications via the new mhra submissions all users requiring access to this system will need to register for access via mhra submissions and also to clarify a number of questions that we received we will still be asking applicants to use a udrac number as the trial reference number at least in the short term so i hope this chart illustrates that the submission process should not be challenging or significantly different from what happens today note again there won't be separate submissions needed for great britain and northern ireland mhra will authorize for all of the uk the left-hand system shows the current process so currently you would obtain your udract number complete your application form in either uder ct system or the iras system then download the application form in xml and submit viacesp when it's received by mhra mhra will validate the application and conduct the assessment and communicate directly with the applicant the process from the 1st of january 2021 is very similar so again we're asking for our udrac number as a reference number however complete the application form only in iras i will highlight again that this is entirely possible today that either you doctor irs can be used to complete the application form from january only iras should be used to complete the application form as today you will then download the application form and xml file however now you'll submit via mhra submissions rather than cesp when it's received by mhra the process is exactly the same as today for those who are aware of the combined ways of working project or pilot i'll mention that in a minute so as i've mentioned all sponsors wishing to make clinical trial submissions will have to register with the mhra submissions to gain access so our first poll this morning is have you registered for mhra submissions and the poll will be open for one minute to give you time to uh answer the question so i'll pause here whilst um you can vote thank you alex so we have the results in from about 75 of those on the call um and we can see that 28 have registered for the mhra submissions whereas 72 percent have not and it's very clear therefore that if you have a role in submitting applications to mhra you should as soon as possible and consult the guidance published on registering for mhra submissions and go ahead and register as soon as you can and definitely prior to the end of december this year just a word on the combined ways of working pilot project this is not part of the transition guidance but we've received some questions on this so i'll take the opportunity to clarify the mhra and hitch i just go back mhra and hra have been testing a more integrated process for researchers and sponsors involving single submission coordinated review combined communications to request any further information and a single communication to confirm the final decision on a clinical trial a cohort of pilot participants from industry cros and nhs organizations have been taking part in this pilot and we've received about 200 applications to date over the course of the next year we'll further develop and scale up this process to make available to all so for those of you who are aware or are a part of this pilot you'll continue with the same processes now that is using iras for preparation and submission of your joint application to mhra and hra if you're not aware of the pilot or aren't part of the pilot simply watch this space and we'll develop and scale up over the next year and provide further information so now that we've looked at who can run a trial how to submit we'll now look at registration of your trial on a public database and results reporting so as is the current situation any favorable opinion by a uk research ethics committee is subject to the clinical trial being registered on a publicly accessible database the hra recently published its make it public research transparency strategy and in the long term has made a commitment to register clinical trials on behalf of sponsors and researchers until that system is in place from first of january 2021 sponsors should register uk clinical trials on an established international register such as the isr ctn registry or clintontrials.gov to ensure the public is aware of your trial again as is the current expectation registration should occur before the first participant is recruited and no later than six weeks after recruitment of the first participant again as is the current situation hra run a deferrals process as per current guidelines so for example adult phase 1 studies may have an exemption or a deferral if you wish to do that please contact hra at the address shown moving on to results sponsors of ongoing trials conducted in the uk will be able to submit results to uder ct after the end of the transition period so those are trials that are in flight and already registered in uder ct and the eu clinical trials register you will be able to upload your summary results in that system however note that as mhra will not have access to uder ct we cannot update the trial status for you from ongoing to completed for new trials you should publish in the public register where your study is registered again as today and as for current expectations you should inform mhra when this has been done and provide hra with the final study report for those trials that are exempt from publication for example adult phase 1 studies please do provide that summary results to mhra i'll know i'll now pass over to my colleague louisa who will take you through the safety reporting requirements hello so i will be talking you through the safety aspects of clinical trials in particular the reference safety information and the submission of safety reports so with this slide this clarifies the implementation date and the type of rsi used based on the inps marketing authorization status so currently we're an imp that has a marketing authorization and is used within its license indication summary of product characteristics can be used as the rsi instead of the ib from january 2021 this will apply to inps with a marketing authorization in a listed country which will initially be eu and eea countries just to note that this list is subject to change in trials where there are both european and uk trial sites the rsi implementation date is the date when the rsi has been approved in all member states and the uk facilitate multinational trials it is advisable that substantial amendments including changes to the rsi are submitted to both europe and the uk at the same time in order to harmonize the implementation date with the last point the rsi used for expectedness until has been given approval by the mhra i'm just going to move on to the next slide so currently there are three possible routes for submitting souzas to the mhra and these are the huge revisions gateway ev web and our own east souza web website reporting tool from january 2021 we will be losing access to our european iot platforms and as a result you will no longer be able to submit souzas to the mhra using either evie web or the individuals gateway these will instead be replaced by our own contingency reporting routes and these are the icsr submissions portal and the mhra gateway these have been designed to mimic the exact same reporting processes for ev web and the u2 vigilance gateway so we will have a web reporting tool which allows you to submit the report using the online form and there will also be the functionality for you to upload your r2 in r3 files xml files that you submitted through the youtube admin system and just with the eugeo vigilance gateway the mhra gateway will enable a database of database transmission of souzas into the mhra with regards to our esusa website this will remain available from january with the exception that we will no longer be forwarding susan's to the ema's youtube vigilance clinical trial module or evc tm as a result you will need to ensure that you have alternative means to ensure that the evctm is populated with your isuzus just going back to the mhra gateway for all existing youtube vigilance gateway users intending on using the mhra gateway to submit suicides please note that you must be registered first with the mhra submissions portal as this is where the first steps of registering to the gateway are performed touching upon the last point on dhar reports currently they are submitted via their cesp portal however from january this will change and you will need to submit dhr's via the mhra submissions portal where you go to the human medicines tile and select the issue bars from the regulatory activity and then original submission as the subtype okay just moving on to the next slide it's going back to suzar reporting our guidance on reporting susan's fire their two new routes was updated last month and they could be found on the two links that i've included on this slide these links provide a wealth of information such as webinars short video demos and supporting documents which will give an in-depth step-by-step guide on the registration and submission of susan's wire ich r ichr submissions portal and the mhra gateway just a short note on the first link there is a statement that says that when you're submitting icsrs or susan via the two new routes that you should be receiving non-serious and serious uk reports just to clarify that this is applicable only to post marketing reporting of adrs so when you start to submit suicides through these two new routes you should only be expecting acknowledgements of receipt and finally on to the last point registration has been open since march of last year we are still receiving a request for registration so i would recommend that you haven't done so already to register as soon as possible additionally if you do have a souza by the deadline date force on the 31st of december you have up until 11 pm on that day to submit reports i'm aware that it could take up to 48 hours for acknowledgements to be received however we will be publishing a reconciliation list of all these souzas that we received on that day up until 11 pm so you could always look at that reconciliation list to confirm the seat of the souzas i will now hand you over to martin he'll be able to take you onto the rest of the presentation thank you louisa so we have our next poll asking again about registration for new systems to provide information to mhra and this question which we'll keep open for again about one minute uh have you registered for mhra gateway and icsr submissions okay i see about two-thirds of our attendees have voted so perhaps we'll close the vote there and again it's very striking uh 86 of those who responded uh have not registered for mhra gateway or icsr submissions so once again if your role includes submission of safety reports to mhra strongly encouraged to look at that guidance and register as soon as possible so if we move back to the presentation thank you and i think now we'll just have a quick before we move on to the importation uh manufacture and supply of imps we'll just give a quick overview of where we've got to so far and maybe there we go um so to confirm the mhra clinical trials unit will assess and authorize clinical trial authorization applications for the uk the sponsor or a legal representative of a clinical trial can be in the uk or a country on an approved country list and this list would initially include eu eea countries preparation of a clinical trial authorization application post transition will be in iris that's preparation of the application form as is currently possible submission of the application package post transition will be via the new mhra submission system and you should continue to use existing and establish international registers so the public is aware of your trial and the trial results i'll now pass over to alan moon our inspector colleague who will discuss manufacture and supply of imps okay thanks martin um so as part of the guidance that uh that was published early september the information relating to the manufacturing supply of imps was included in in that so firstly in terms of authorization requirements for manufacture packaging and release of certification and release of imps within the uk no changes are there um for that we still require a uk mia inp for all of those manufacturing activities including the named personnel the production manager qcqp etc in terms of the supply from other countries into uk and gb and northern ireland the requirement for supplying in a number of cases directly to clinical trial sites rather than through licensed premises um may continue however the oversight mechanism for this needs to be implemented um so this is described in the the published guidance and to summarize um there's no requirement for uk qps to recertify product if it is received from a listed country an approved country list and as martin said initially that includes all of the eu and eea member states that oversight process does need to be managed and implemented by a uk mia inp holder um however all sites don't need to necessarily apply for that license it can be from an existing imp license holder um to to provide that as a as a service the qp for the oversight process actually may be resident within the uk or in the eea but the if it's not in if the up is not resident in the uk they are only able to perform those duties in terms of providing the oversight process not actual certification within the uk arrangements for supply of medicines including imps to northern ireland at this point remain under discussion with the eu commission so we're not able to provide further details on that part of the moment but we'll publish guidance as soon as possible in terms of importing qp certified nymphs or unmodified comparators from listed countries um that would be through the licensed medicinal product supply chain um using a wholesale dealer license and the rpi process which was discussed at yesterday's webinar for supply chain in in general for all medicines for existing wholesale dealer authorized holder authorization holders there's going to be a six month period for notifying mhra and a two-year period to name it to notify the intent and two-year period to name that rpi but for any new wholesale distribution authorization applicants after the 1st of january that rpi will need to be named on that application at the time of the application just going back to the supply and the oversight mechanism supply of imps i should have mentioned there will be a 12-month period from the first of january to uh to implement that okay so in terms of just for completeness i've included the things that are not changing um so the import of imps uh to the uk from non-listed countries so import from a third country as it stands today um that will remain as currently and um we'll need a uk mia imp holder and um a qp declaration from that uk mia imp holder submitted as part of the cta um for the from the site that's responsible for that important certification for non-investigational products that are imported from non-listed countries again remains as currently and are considered as unlicensed medicines and need to be imported under an ms license manufacturer's specials license and the advanced notification of 28 days is described in guidance note 14. okay um so just to hand back to you martin to summarize i i would like to say thank you very much to everyone who signed up for this webinar um thank you for your amazing engagement during the webinar in terms of questions and and indeed feedback in the chat box that that's really appreciated um special thanks to those panelists and particularly those from our colleagues at the hra for attending this morning and answering the questions so comprehensively and you'll see that the slide on the screen and another reminder to register for submissions and if you need further information there's also guidance from our customer service center and online so we will sign off there and say thank you very much and enjoy the rest of your day