How to Manage Clinical trials in a Pandemic Period Webinar
Please find attached a link for you to download relevant course notes and also copies of the regulatory guidance we referred to in order to develop our course
These are downloadable but also nice to view online as an e-book.
Webinar notes: https://brookwood-global.com/Books/Pandemic-webinar-notes
Regulatory documents (as of 12:00 25 March 2020): https://brookwood-global.com/Books/Regulatory-Docs-Pandemic-Webinar
You can view the presentation only by visiting …
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Advice for Management of Clinical trials in relation to Coronavirus
MHRA are aware that there are challenges arising in relation to Coronavirus and the effect this is having on the conduct of clinical trials. Patients may be advised to stay away from hospitals and GP sites due to existing health problems that may put them at risk of infection, or they may be reluctant to travel to sites where there are high densities of people. They may also have been advised to self-isolate as a precaution or as a result of confirmed infection so are unable to undertake required clinical trial activities. Organisations managing and sponsoring clinical trials are also experiencing a higher proportion of staff working from home during this period.
This has led to reports of protocol and standard operating procedure deviations due to missed visits, or changes in processes, for example posting out drug to patients. Wet-ink signatures have also been difficult to obtain in a timely manner if staff are not in the office, and this can delay some clinical trial processes.
We recognise the difficulties this creates for managing trials and would like to offer some advice.
There will be an increase in protocol deviations; please ensure they are well documented, to enable appropriate evaluation for the trial.
An increase in protocol deviations in relation to Coronavirus will not constitute a serious breach, therefore there is no need to report this to us (unless of course patients are being put at risk).
Resources may need to be assessed in hospital settings, with staff working primarily in research being required to assist in other areas. This may mean certain oversight duties, such as monitoring and quality assurance activities might need to be reassessed and alternative proportionate mechanisms of oversight introduced (such as phone calls, video calls etc) to ensure ongoing subject safety and well-being. We would advise a brief risk assessment and documentation of the impact of this, with consideration of prioritisation of critical activities such as safety reporting. Remote monitoring can be considered; however, this should not place an extra burden on trial sites, and subjects must consent to any sharing of their personal information outside the trial site.
Prospective protocol waivers remain unacceptable, we would not expect you to bypass the eligibility process due to difficulties in assessing subjects and carrying out tests. Safety of patients of course remains a priority and they should not be included into a trial unless you can confirm they meet the inclusion and exclusion criteria. Similarly, if the safety of a trial subject is at risk because they cannot complete key evaluations or adhere to critical mitigation steps, then consideration to discontinuing that subject must be discussed. This may also extend to the whole trial in some cases, and a Sponsor and Investigator should not forget they are able to use Urgent Safety Measures, or even temporarily halt a trial, or halt recruitment, if this is the best way forward. Do note that we are requesting that any temporary halt, including for logistical reasons such as trial team unavailability, should be submitted as a substantial amendment (which will be fast-tracked). This is to ensure MHRA has complete oversight of status and safety for these trials.
Subject safety is of course our highest priority, Sponsors should consider the risk/benefit of conducting trials in medicines that act as immunosuppressants, for example in early phase healthy volunteer trials, where there is no therapeutic benefit to the volunteer, but taking part in the trials does pose a risk of infection.
If your processes require wet-ink signatures, consider alternative methods of demonstrating approvals, such as email confirmation. Inspectors will take a pragmatic approach to this, but you may want to consider an SOP deviation to cover this in the interim.
NIH clinical trial of investigational vaccine for COVID-19 begins
16th March 2020
A Phase 1 clinical trial evaluating an investigational vaccine designed to protect against coronavirus disease 2019 (COVID-19) has begun at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is funding the trial. KPWHRI is part of NIAID’s Infectious Diseases Clinical Research Consortium. The open-label trial will enroll 45 healthy adult volunteers ages 18 to 55 years over approximately 6 weeks. The first participant received the investigational vaccine today.
The study is evaluating different doses of the experimental vaccine for safety and its ability to induce an immune response in participants. This is the first of multiple steps in the clinical trial process for evaluating the potential benefit of the vaccine.
The vaccine is called mRNA-1273 and was developed by NIAID scientists and their collaborators at the biotechnology company Moderna, Inc., based in Cambridge, Massachusetts. The Coalition for Epidemic Preparedness Innovations (CEPI) supported the manufacturing of the vaccine candidate for the Phase 1 clinical trial.
“Finding a safe and effective vaccine to prevent infection with SARS-CoV-2 is an urgent public health priority,” said NIAID Director Anthony S. Fauci, M.D. “This Phase 1 study, launched in record speed, is an important first step toward achieving that goal.”
Infection with SARS-CoV-2, the virus that causes COVID-19, can cause a mild to severe respiratory illness and include symptoms of fever, cough and shortness of breath. COVID-19 cases were first identified in December 2019 in Wuhan, Hubei Province, China. As of March 15, 2020, the World Health Organization (WHO) has reported 153,517 cases of COVID-19 and 5,735 deaths worldwide. More than 2,800 confirmed COVID-19 cases and 58 deaths have been reported in the United States as of March 15, according to the Centers for Disease Control and Prevention (CDC).
Currently, no approved vaccines exist to prevent infection with SARS-CoV-2.
The investigational vaccine was developed using a genetic platform called mRNA (messenger RNA). The investigational vaccine directs the body’s cells to express a virus protein that it is hoped will elicit a robust immune response. The mRNA-1273 vaccine has shown promise in animal models, and this is the first trial to examine it in humans.
Scientists at NIAID’s Vaccine Research Center (VRC) and Moderna were able to quickly develop mRNA-1273 because of prior studies of related coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Coronaviruses are spherical and have spikes protruding from their surface, giving the particles a crown-like appearance. The spike binds to human cells, allowing the virus to gain entry. VRC and Moderna scientists already were working on an investigational MERS vaccine targeting the spike, which provided a head start for developing a vaccine candidate to protect against COVID-19. Once the genetic information of SARS-CoV-2 became available, the scientists quickly selected a sequence to express the stabilized spike protein of the virus in the existing mRNA platform.
The Phase 1 trial is led by Lisa A. Jackson, M.D., senior investigator at KPWHRI. Study participants will receive two doses of the vaccine via intramuscular injection in the upper arm approximately 28 days apart. Each participant will be assigned to receive a 25 microgram (mcg), 100 mcg or 250 mcg dose at both vaccinations, with 15 people in each dose cohort. The first four participants will receive one injection with the low dose, and the next four participants will receive the 100 mcg dose. Investigators will review safety data before vaccinating the remaining participants in the 25 and 100 mcg dose groups and before participants receive their second vaccinations. Another safety review will be done before participants are enrolled in the 250 mcg cohort.
Participants will be asked to return to the clinic for follow-up visits between vaccinations and for additional visits across the span of a year after the second shot. Clinicians will monitor participants for common vaccination symptoms, such as soreness at the injection site or fever as well as any other medical issues. A protocol team will meet regularly to review safety data, and a safety monitoring committee will also periodically review trial data and advise NIAID. Participants also will be asked to provide blood samples at specified time points, which investigators will test in the laboratory to detect and measure the immune response to the experimental vaccine.
“This work is critical to national efforts to respond to the threat of this emerging virus,” Dr. Jackson said. “We are prepared to conduct this important trial because of our experience as an NIH clinical trials center since 2007.”
Adults in the Seattle area who are interested in joining this study should visit https://corona.kpwashingtonresearch.org. For more information about the study, visit ClinicalTrials.gov and search identifier NCT04283461.
NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
We are watching the situation carefully and should the Coronavirus situation risks remain significant we will cancel our June courses in Denmark, approx 2 weeks beforehand. If we cancel, course fees will be refunded in full. We will not however be able to refund travel or accommodation bookings and we suggest you ensure that you have a flexible reservation so that you do not incur any penalties should it be necessary to cancel. If we run the course but you decide to cancel our usual cancellation terms will apply.
We sincerely hope that the virus threat has passed by then and that we are able to run our planned events.
REAL WORLD STUDIES ONLINE TRAINING FOR SPONSORS AND INVESTIGATORS
Three new courses by Brookwood …
• Non-interventional studies: General Principles
• Non-interventional studies: Practical Aspects
• Guide for investigators performing non-interventional studies
Be the first to evaluate these new online, on demand courses – contact us by email firstname.lastname@example.org
UK Government launches plan to control AMR
The British government has announced a plan through which it will incentivise pharmaceutical companies to develop drugs aimed at tackling antimicrobial resistance (AMR).
Speaking at the World Economic Forum in Davos, Matt Hancock stated his intentions to “contain and control” AMR by 2040.
In addressing the global elite, Hancock warned that: “Antimicrobial resistance is as big a danger to humanity as climate change or warfare,” as he suggested “That's why we need an urgent global response.”
The Tory MP noted that even “a simple graze could be deadly” in a future in which AMR is ignored.
“Each and every one of us benefits from antibiotics but we all too easily take them for granted and I shudder at the thought of a world in which their power is diminished.” Hancock said.
Since 2015 the British government ahs cut antibiotic use by 7%. The Department of Health and Social Care’s plan aims to reduce the use of antibiotics by a further 15%, as new payment models would be introduced through which companies would be paid on the basis of the value they bring, rather than the quantity of antibiotics sold.
The government department pointed to a ‘global market failure’ as contributing to the AMR crisis. The government body noted that currently “companies have an incentive to sell as many antibiotics as possible at the same time as government is trying to reduce antibiotic use.”
“Low returns on investment in development means industry does not innovate enough and as a result, very few of the new drugs that are currently in the pipeline are targeted towards priority infections.”
As such, Britain’s cost effectiveness body NICE will explore new payment models which will “incentivise companies to invest in the development of drugs that will treat high-priority resistant infections.”
Mike Thompson, chief executive of the Association of the British Pharmaceutical Industry (ABPI) commented: "The UK has shown international leadership in raising the profile of this global health threat and today reinforces its commitment to finding solutions to the issues which have hampered the development of new medicines for so long."
Former Goldman Sachs chief economist Jim O’Neill commented in stating that he was “pleased to see the government’s ambition, particularly on trialling a new model for antibiotics, and I’d love to see pharmaceutical companies rise to the challenge. I also would be eager to observe some step change in the use of diagnostics to reduce unnecessary use.”
The endorsement comes after the financier wrote last year that he was“shocked at the endless words that come from the pharma industry about their collective belief in the need to fight AMR, but the lack of concrete initiatives, and more importantly money, they are prepared to underwrite.”
Clinical trial data transparency: should other regulators copy the EMA?
Under the banner ‘Strengthening Research for Health in the Americas’, the BMJ has published an article describing what is needed to ensure the reliability of health research in the region. The article (by members of the Faculty of Law at the University of Toronto, Canada) notes the key role of transparency in ensuring reliable health research. It also highlights how various stakeholders have mandated clinical trial registration and access to data submitted to regulatory agencies, in order to support fully informed decision making by clinicians, regulators and others.
Despite such support, the transparency of data submitted to the regulatory agencies has been hampered to varying degrees by issues relating to commercially confidential information and by inconsistencies across multiple regulators. To date, no national regulatory authority in the Americas has followed the example of the European Medicines Agency (EMA), which was the first regulatory authority to facilitate data access and to implement a policy that provides for clinical trials data submitted for regulatory approval to be made public.
The BMJ article discusses
• key developments related to registering pharmaceutical clinical trials and sharing data submitted to the regulatory agencies in the Americas
• how three countries have implemented key transparency measures (Canada, a mature market; Brazil, an emerging market; and Argentina, a second-tier emerging market) and the challenges that remain
• how ethical review could play a role in advancing data transparency.
After a thorough review, the authors conclude that if countries in the Americas were to streamline how they govern clinical trials data and follow the EMA’s lead, “they would take an important step towards the implementation of comprehensive data transparency”.
Source: BMJ 2018;362:k2493, <https://tinyurl.com/yb4thet3>
Regeneron Pharma and Bluebird bio announce immune cell collaboration
Regeneron Pharmaceuticals have announced that they will collaborate with the Massachusetts-based gene therapy specialist Bluebird bio in an effort to develop and commercialise novel immune cell therapies for cancer.
The collaborators aim to leverage Regeneron’s VelociSuite technologies as they push towards the development of human antibodies and T-cell receptors which will directed against tumour-specific proteins and peptides. Bluebird bio will contribute its expertise in gene transfer and cell therapy.
While bluebird bio’s technologies use a customised lentiviral vector to modify T-cells so that they can recognize tumor-specific proteins expressed by cancer cells and kill them upon engagement, Regeneron's VelociSuite technologies enable the creation of fully-human antibodies and T cell receptors. As such the complementary technologies may allow professionals to target a broader set of tumours.
Dr George D. Yancopoulos, President and Chief Scientific Officer of Regeneron commented: “Like Regeneron, bluebird is a science-focused company looking to push the limits of what novel technologies can do in drug discovery and development. We believe that the tremendous synergies between Regeneron's proven technologies and bluebird's toolbox of advanced cell and gene therapy technologies create a promising opportunity to help people with cancer by developing innovative new treatments. This collaboration adds yet another dimension to our rapidly advancing portfolio of immuno-oncology candidates and combination approaches.”
The collaborators will jointly share the cost of research and development up to the point of submitting an Investigational New Drug (IND) application. Regeneron is also set to make a $100 million investment in Bluebird bio common stock at a price of $238.10 per share, which represents a premium of 59 percent over the $150 closing price on August 3, 2018.
US government proposes renaming the FDA
The US government has outlined a proposal under which the FDA would be renamed the Federal Drug Administration, with the agency losing its responsibility for regulating food safety. The proposal aims to address “the current fragmented” oversight of food safety; if it goes ahead, the FDA’s remit will be limited to the regulation of drugs, devices, biological products, tobacco, dietary supplements and cosmetics. The plans are part of a wide-ranging initiative that includes renaming the Department of Health and Human Services as the Department of Health and Public Welfare.
Brookwood are pleased to be the principle sponsor for the 16th Pharmacovigilance 2018 conference in Massachusetts, USA 2nd – 4th October 2018
The Global Pharmacovigilance Market expected to Reach US$6.1 bn by 2020 expanding at a CAGR of 14.2% from 2015 to 2020 and also expected to reach a market size of $8.23 billion by 2022. By 2020, the size of the global pharmaceutical market is anticipated to grow to USD 1.3 trillion, with the E7 countries -- Brazil, China, India, Indonesia, Mexico, Russia and Turkey.
16th Pharmacovigilance 2018 will bring together top pharmaceutical, biotechnology and regulatory representatives under one roof that will address the key issues of the industry. The entire program will cover the detection, analysis and prevention of adverse drug reactions. It will be studied with the help of case studies and industry experiences.
This conference will help the drug safety representatives from the pharmaceutical industry and academic and quality research organizations who wish to understand how to avoid common deficiencies in inspections by learning from the experiences of others; to gain a greater understanding of new and existing Pv requirements, and to improve their organizations’ compliance with Pv requirements. Also it can help you control your product’s lifecycle, your patient’s trust, and your revenue. Hence, this conference will provide an important platform for pharmacovigilance stakeholders to discuss and share best practices in expediting Pv development. What does the future hold for Pv? Find out at our conference on opportunities and activities shaping Pv to 2020 with respect to regulations, technologies and services. Learn and know on what are drug producers and service providers doing? What regulations and technologies influence the current PV field? You can also discover at 16th Pharmacovigilance 2018 on spending forecasts for PV (US, the EU and Asia).
It gives me great pleasure in welcoming all of you to the Virtue Insight’s 16th Pharmacovigilance 2018. I wish and pray that all our efforts will be beneficial to our industries and to our country at large.
Key themes discussed at this conference
• Pharmacovigilance in the US: What comes next for the industry?
• Recent developments - legislation, policies, systems, technology, communication strategies and best practice in PV
• Optimising the overall PV ecosystem - Challenges and Opportunities
• Why does pharmacovigilance sometimes fail and where could the fault lie?
• Pharmacovigilance and healthcare system
• Technology Impact - Cloud – Big data – Analytics – AI – Machine learning
• Updates to PSUR, PBRERs, DSUR, PASS
• Good Clinical Practices and Good Pharmacovigilance practices
• Future of outsourced phase I, II and III trials and post-marketing studies,
• Data quality management and analysis – analyzing the new guidelines
• Strategies to improve clinical trials and PV
• Maintaining proper balance in relationships: Sponsor – Site – CRO & Patients
• Patient centric approach to help improve patient safety
• Outsourcing activities - Choosing your right vendor and setting the path right
• PV Audit & inspections - preparation, implementation and lessons to be learnt
• Discover approaches for collecting, integrating and analyzing all of the safety
data generated from preclinical models
• Current regulations and guidelines - USA, EU and RoW
• The developing regulatory framework in advanced and developing markets
• Be part of a major networking opportunity
For more conference details visit www.brookwoodacademy.org/documents/16th-Pharmacovigilance-2018.pdf
General Data Protection Regulation (GDPR)
The new EU General Data Protection Regulation (GDPR) is expected to apply in the UK from 25 May 2018. The detail of its application in the UK will be set out in a new Data Protection Act, which Parliament has yet to agree. Applicants should therefore not submit GDPR-related amendments at this time.
For health and social care research, the new Regulation is not very different from the current Act and the Health Research Authority will not be adding to the existing effective safeguards. In particular, Research Ethics Committee (REC) approval and the legal gateway for processing confidential patient information on the advice of the Confidentiality Advisory Group (CAG) will continue, as will the other common law provisions. A summary of the key changes for all data processing (not just research) is available from the Information Governance Alliance.
The Information Commissioner’s Office has published resources for GDPR preparation, but they are not specific to research. Preparation guidance for research community is available from the Medical Research Council.
The HRA has published detailed guidance about operational arrangements that researchers and organisations may need to put in place.
We've also developed technical guidance intended for Data Protection Officers (DPO), research managers or information governance leads / security architecture leads, or equivalent. It may also be relevant for researchers. Some prior knowledge of terminology is assumed.
All guidance will be kept up to date in light of relevant national and European guidelines and the Data Protection Act 2018. As guidance becomes available, we will publicise it and link to it from this page.
Canary have two books available covering this subject which can be found at https://www.canarybooks.com/Data-Protection
An online training module is also available which can be found at https://www.brookwoodtraining-online.net/Data-Protection
GCP lessons: US investigator fails to take responsibility for inadequate subject protection
FDA inspectors uncovered several violations of the federal regulations at a site in Washington, DC, including the enrolment of five subjects after the institutional review board (IRB) approval had expired. In his written response, the investigator blamed other members of his study team, rather than accepting responsibility for failure to adhere to the federal regulations.
The investigator explained that the protocol and revised informed consent document had been submitted to the IRB for continuing review approval, and that the IRB had required several actions to be undertaken before it could approve continuation of the study. These included the need for sub-investigators to complete updated GCP training and to sign a conflict of interest statement. The investigator added that the study coordinator was delegated with ensuring that the IRB’s stipulations were met and that IRB approval was obtained. He then claimed that failure to obtain IRB approval was the result of the actions of the study coordinator, and that he was not aware that IRB approval had expired until after the five subjects had been enrolled.
In a related finding, the FDA determined that the investigator had not maintained adequate and accurate case histories, because informed consent forms for the five subjects who were enrolled after the expiry of IRB approval had been stamped to indicate that they had been approved by the IRB. In an affidavit, the investigator stated that he was not aware that IRB approval had expired until almost 3 months after the expiry. He also claimed that a month later he was informed by his site manager that the study coordinator had bought a custom-made stamp and employed it to stamp the informed consent documents used to enrol subjects after the expiry date of IRB approval.
Furthermore, in response to the Form FDA 483 received at the end of the inspection, the investigator indicated that this finding was the “egregious actof one rogue employee”.
Following the inspection, the investigator submitted a corrective action plan to address the above findings. It included
• placing the IRB expiry/renewal dates for studies on his personal calendar
• seeing the actual IRB approval letter and approved informed consent
• using a clinical research associate (CRA) meeting form to enquire whether CRAs have any concerns about
documents or processes
• conducting a clinical study with two coordinators.
However, this response did not include the documentation of procedures to ensure that IRB review and approval are obtained, or for the regulatory oversight of studies that the investigator conducts. Without this information, the FDA was unable to conduct an informed evaluation of whether the corrective actions will prevent the recurrence of such violations in the future.
Furthermore, the FDA made a clear statement that the investigator was responsible for the proper conduct of the study and for adhering to applicable regulations, regardless of whether -- as he claimed -- his employer also closely monitors protocols nearing the expiry of their IRB approval and has internal processes to help ensure that updated informed consent documents are used.
The purpose of IRB review is to provide assurance – in advance and by periodic review – that appropriate steps are taken to protect the rights and welfare of subjects in clinical research. FDA regulations provide IRBs with the authority to approve, require modifications to (in order to secure approval) or disapprove research. In this case, the IRB
required certain activities to be completed before providing continued approval of the protocol in question.
The investigator should have ensured that all the conditions of approval were met and documented, and that this was then communicated appropriately to the IRB; the IRB should then have provided documentation of continuing approval.
If these actions could not be completed prior to the expiry of the previous IRB approval, then enrolment of new subjects in the study should have been temporarily halted until the approval was in place.
If this approach had been followed, the second violation -- that the investigator did not prepare and maintain adequate and accurate case histories -- could not have occurred.
Instead, the five subjects would have received up-to-date information about the approval status of the study and wouldhave only been allowed to enter the study when the relevant approval was in place.
The Clinical Trials Facilitation Group (CTFG) has updated the guidance for the reference safety information (RSI) for a clinical trial. The update, in the form of a Q&A document, follows detailed discussions between national competent authorities and sponsors, which arose from Clinical Trial application and substantial amendment procedures as well as GCP inspections. The full guidance can be found on the HMA website. As per the CTFG cover note, MHRA recommends full compliance with the Q&A from 1st January 2019.
EMA shares progress on Brexit preparations
At the EMA Management Board meeting in December 2017, the agency shared details of preparations for its move to The Netherlands and the operational arrangements for the UK’s withdrawal from the EU. This was the first meeting of the Board since the General Affairs Council of 20 November and the decision on the EMA’s relocation to Amsterdam. The agency now has just over a year to prepare, with a deadline of 30 March 2019 for taking up its new residence.
The agency reported that collaboration with The Netherlands commenced promptly and that agreement has been reached on the joint governance structure, with plans to progress activities within five workstreams:
• temporary premises
• permanent premises
• staff relocation
• financial and legal aspects
• external communication.
A delegation from the Dutch government attended the Management Board meeting and explained
how the Dutch authorities plan to meet the EMA’s requirements. While the Dutch authorities are committed to ensuring a seamless transition of the agency’s operations to its new location in Amsterdam, it is notable that the agency’s permanent new headquarters – the tailormade Vivaldi building – is not due for completion until November 2019.
The Dutch government will offer temporary premises to the EMA from 1 January 2019 (or earlier if requested) until the new building is ready.
The EMA and the Dutch authorities are working on a Memorandum of Understanding, and a
permanent Netherlands helpdesk has been set up within the EMA to offer guidance to staff on practical aspects to facilitate their relocation.
The Board was also informed that the EMA’s Brexit preparedness business continuity plan will enter Phase 2 in January 2018, in order to free up further resources that are needed to prepare for the UK’s withdrawal from the EU. Further details will be published within the EMA’s 2018 work programme.
The EU27 (ie. all current Member States except the UK) and the EMA have developed a methodology
for the redistribution of work currently performed by the UK’s regulatory agency. The joint redistribution
plan reflects the strengthened capacity of the European medicines regulatory network, and the risk-based methodology takes into account the diverse expertise in the network and the workload associated with the medicines. More details will be communicated soon.
Guidance for companies
The EMA website now has dedicated pages on the agency’s relocation and the agency has published
a 9-page procedural guidance document to help pharmaceutical companies prepare for the UK’s withdrawal from the EU. The document outlines the practical and simplified requirements that
companies should follow when they apply for changes to marketing authorisations to allow for the continued marketing of their medicinesin the European Economic Area post-Brexit.
The guidance assumes that the UK will become a third country on 30 March 2019. It should be read in conjunction with the questions and answers published in May 2017 on the UK’s withdrawal from the EU within the framework of the centralised procedure. Key questions relating to medicinal products include the following:
• how can I submit an application for the transfer of a marketing authorisation for my products and
what would the applicable fees be?
• how will planned or ongoing regulatory procedures be handled during the transfer of a marketing
• is it possible to submit a transfer of the orphan designation in parallel with a transfer of the
• is it possible to simplify transfer applications when these are Brexit-related?
• how can I submit a transfer or change in the name/ address of an orphan drug designation sponsor?
• how do I submit changes to the Qualified Person for Pharmacovigilance and/or changes in the
Pharmacovigilance Master File location?
• how do I submit changes to the person responsible for scientific services and to the person responsible
for batch recall and quality defects?
Marketing authorisation holders, applicants and sponsors of centrally authorised medicines should consider how Brexit will impact their medicines and which changes need to be addressed before the UK leaves the EU. They also need to ensure that the necessary changes are made by that date.
The EMA is preparing a series of additional Brexit-related guidances that will be published on its website. Companies are advised to regularly check the website for new information.
Amsterdam wins bid to host EU medicines agency post-Brexit
Amsterdam has won a vote to host the European Medicines Agency (EMA) which will relocate from London after the UK leaves the European Union.
The UK is losing both the EMA and the European Banking Authority (EBA) which employ around 1,000 people.
Ministers from the 27 EU countries remaining in the bloc after the UK departs in 2019 have taken part in the secret ballot.
They will now vote later on the new home for the EBA.
Some 16 cities bid for the EMA, while eight want to host the EBA - Brussels, Dublin, Frankfurt, Paris, Prague, Luxembourg City, Vienna and Warsaw.
The EMA is the more alluring of the two bodies, as it promises to make its new host into a hub for Europe's medical industry.
Update in Clinical research & GCP – Copenhagen 23rd October 2017
Refreshments & Registration from 8.30am
• EU Clinical Trial Regulation 2014 No. 536
A brief overview of the finalised Regulation awaiting implementation
• Risk proportionate approaches in clinical trials
Summary of the latest EMA Recommendations
• Pharmacovigilance update
Inspectors want to see that all staff have some basic PV knowledge. This session will
provide an update on what’s new as well as to provide some PV basics.
• Inspection expectations for the Trial Master File
Highlights of the EMA’s Trial Master File draft Reflection Paper
• Q&A using keypads on the draft EMA Serious breaches guideline
• EMA First-in-Human Guidance
A summary of EMA’s 2017 guideline on first-in-human studies
• Latest news on what’s coming and new
Including: AxMPs, modernization of ICH E8 and its knock on impact on ICH GCP E6,
Delegated Regulation on GMP affecting
Check out the website at www.brookwoodacademy.org to book a place
EU Clinical Trials Regulation: an update
Despite early promise that the EU Clinical Trials Regulation (No. 536/2014) might have been implemented in May 2016, it is now clear that it will not come into operation until 2018.
The Regulation aims to create an environment that is favourable for conducting clinical trials in the EU, with the highest standards of safety for participants and increased transparency of trial information.
The Regulation will harmonise the assessment and supervision processes for clinical trials via an EU
portal and database, set up and maintained by the European Medicines Agency (EMA) in collaboration with Member States and the European Commission.
Consequently, the rate-limiting step for implementing the Regulation has always been confirmation of the full functionality of the portal and database through an independent audit.
The EMA’s current delivery timeframe indicates that the EU portal and database should be available for independent audit by August 2017. If the systems pass the audit, the Regulation will come into effect by October 2018.
Lengthy transitional period
Assuming that the Regulation does come into effect in October 2018 – and the EMA states that it is doing everything possible to bring this date forward – there will be a 3-year transition period until October 2021, during which there will be an overlap of the new Clinical Trials Regulation with the Clinical Trials Directive 2001/20/EC:
• from October 2018 to October 2019, applications for clinical trials may be submitted under either the new Regulation using the EU portal and database or under the current Directive using the EudraCT database
• from October 2019 to October 2021, only clinical trials authorised under the Directive will continue to be governed by that Directive
• from October 2021, any ongoing trials that were originally authorised under the Directive will
fall under the new Regulation and will be governed accordingly.
ICH GCP E6 (R2) is born
The new ICH GCP guidelines including the Integrated Addendum E6 (R2) have finally been published and are now available to view in the ICH website at:
Here at Canary we have been busy rewriting our own version of the guidelines with a copyrighted index which allows users to search for the appropriate sections using subject index and key words.
It is ideal for investigators, monitors, auditors, regulatory authority inspectors, members of ethics committees and others who need regular access to the GCP guidelines. Prices start from as low as £3 per copy. For more details see our website at www.canarybooks.com. Our publication is available as a handy pocketbook or larger format A5 desk version.
Need a short course to update your staff on the new ICH GCP Guidelines Addendum E6 R2 ?
November 2016 marks a milestone in GCP history when the proposed changes to the ICH GCP guidelines in addendum R2 are signed off as a Step 4 document.
This course will cover the changes the addendum brings and its impact for sponsors and investigators.
The short course will include:
Online .......... On Demand .......... Global ..........
Take the course at a time to suit you.
ONLY £30 per participant
To Book online visit:
Hot news from 2nd European QA Conference in Nice
FDA has acceptance of e Consent and published guidance. Concept not so acceptable in EU. See next issue of Advisor
eTMF guidance from EMA IWG is due out for consultation in 5-6 weeks. Gabrielle Schwartz - Head of GCP inspection Germany
Poor publication and reporting rates for trials at US academic medical centres
Researchers in the USA have assessed the rates of publication and reporting of clinical trial results by leading academic centres. The primary outcome measure was the proportion of trials that disseminated results – defined as publication or reporting on <ClinicalTrials.gov> – both overall and within 24 months of study completion. The assessment focused only on academic medical centres that had 40 or more completed interventional trials registered on <ClinicalTrials.gov>, and on clinical trials with a primary completion date between October 2007 and September 2010. In addition, the lead investigator had to be affiliated with an academic medical centre.
The study findings were reported in <I>BMJ</I> and can be summarised as follows:
l among 4347 interventional clinical trials from across 51 academic medical centres, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double-blind and 2169 (50%) were Phases II to IV
l academic medical centres disseminated results for 2892 (66%) trials, with 1560 (36%) achieving this within 24 months of study completion
l the proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16% (6/37) to 55% (57/103) across the centres
l the proportion of clinical trials published within 24 months of study completion ranged from 11% (4/37) to 40% (31/77) across the centres, whereas results reporting on <ClinicalTrials.gov> ranged from 2% (2/122) to 41% (72/177).
The authors concluded that, despite best intentions, over the period of evaluation there was poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centres in the USA.
Source: </I>BMJ<I> 2016;352:i637, <http://bit.ly/1OhXlaf>
[original source www.bmj.com/content/352/bmj.i637]
EGA becomes Medicines for Europe
The European Generic and Biosimilar Medicines Association (EGA) has become Medicines for Europe. The new body has highlighted the importance of both generic and biosimilar medicines to European healthcare. The generic and biosimilar industries currently supply the majority of Europe’s prescription medicines, and this contribution is estimated to reach 75% in volume over the next 5 years. The repositioning of the EGA as Medicines for Europe aims to drive greater healthcare efficiency through better health outcomes, while providing solutions for the sustainability of European healthcare systems facing increased demographic demands on healthcare services.
Adrian van den Hoven, Medicines for Europe Director General, stated, “Medicines for Europe is a great opportunity to build on the EGA’s established reputation for partnership with stakeholders and authorities to deliver access to high quality medicines for patients, its commitment to the highest levels of quality, and to bringing even more value to pharmaceuticals while bridging the sustainability of healthcare with a competitive pharmaceutical manufacturing industry.”
[original source www.medicinesforeurope.com/news/ega-becomes-medicines-for-europe/]
Update Seminar in Clinical Research & GCP
As part of the pre-conference training at the European QA conference Brookwood Academy are pleased to offer:
An Update Seminar in Clinical Research & GCP
Tuesday 26th April 2016 Nice Acropolis, Nice, France
Ideal update and refresher consisting of executive summaries of the latest developments and discussion of clinical research topics to satisfy ongoing training needs.
Course Content Includes:
• Impact of the revision to the ICH GCP guidelines E6 R2
• Overview of the new EU Clinical Trial Regulation No.2014/536
• GCP update and refresher – an interactive Q&A on GCP questions and problems
• Consent in clinical trials – GCP requirements, individualising consent and testing knowledge
• Serious breaches – understanding the new reporting requirement with case studies
This seminar is suitable for those who need to update their general knowledge and to demonstrate recent and up-to-date training: those overseeing or actively managing clinical trials as sponsors, monitors, auditors, investigators, supervisors and administrators; academics; those responsible for research governance, members of ethics committees and site personnel involved in both commercial and non-commercial trials covered by European legislation
Price: €350 per person for bookings made until 31st March 2016 €450 per person thereafter. Discounts for groups can be negotiated. Book early to avoid disappointment as places are limited
Bookings can be made online at https://brookwoodacademy.org/Update-and-Refresher-Course-in-Clinical-Research-and-GCP
Bookings for the seminar may also be made by email at email@example.com or by calling (from UK) 01483 811383; from elsewhere +44 1483 811383
An invoice will be issued. Your place will be confirmed once payment has been received. Cancellations not permitted but the named participant may be replaced at any time.