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.
The International Council for Harmonisation (ICH) has proposed modernising the E8 Guideline in
order to incorporate the most current concepts, achieving fit-for-purpose data quality as one of the
essential considerations for all clinical trials.
The modernisation of the ICH E8 Guideline is the first step towards GCP renovation. The final
Concept Paper on the revision of the guideline (E8(R1)) was endorsed by the ICH Management
Committee on 14 November 2017. It notes that the E8 Guideline (‘General Considerations for
Clinical Trials’), which sets out general principles on the conduct of clinical trials, was adopted
in 1997 and has not previously undergone revision. Since 1997, clinical trial design and conduct have become more complex, and a wide range of trial designs and data sources that now routinely contribute to drug development are not adequately addressed in the original E8 Guideline.
Approaches for optimising trial quality, which promote the reliability, efficiency and patient focus of clinical trials, are needed. This involves identifying factors that are critical to the quality of a clinical trial at the design stage, and planning the trial conduct proportionate to the risks to these quality factors, thereby protecting human subjects and ensuring the reliability of trial results.
Specifically, the E8 Guideline has high-level descriptions of trial objectives and design but does not address how design or planning considerations can optimise trial and data quality. Moreover, the set of trial designs described in the E8 Guideline is limited and does not reflect today’s best practice.
To resolve these issues, E8(R1) will
• identify a basic set of critical-to-quality factors (eg. eligibility criteria, masking, types of controls,
outcome ascertainment, site feasibility, safety monitoring, statistical analysis, and investigational
product handling and administration) that can be adapted to different types of trials to support the
meaningfulness and reliability of trial results and protect human subjects
• address a broader range of trial designs and data sources
• provide an updated comprehensive guide to, or cross-referencing of, all other relevant ICH
guidelines that inform the design, planning and conduct of clinical research, without reproducing
the detailed material found in those guidelines.
The plan for E8(R1) is an outcome of the ICH Reflection Paper ‘“GCP Renovation”:
Modernization of ICH E8 and Subsequent Renovation of ICH E6’, which outlined an
approach to renovating and modernising the ICH guidelines related to clinical trial design, planning, management, conduct and reporting.
The proposed revision will include a review of the issues and questions that are most critical to clinical
trial quality and the ability of a trial to achieve meaningful and reliable results. Additionally, E8(R1) will incorporate the most current guidelines for achieving fit-for-purpose data quality as one of the essential considerations for all clinical trials, including the broad range of trial designs and data sources currently in use.
The revision of the ICH E8 Guideline is expected to enhance the reliability of trial results through
attention to trial quality. It will also
• better integrate the overall design and planning with subject protection and data reliability
considerations that are the focus of the ICH E6 Guideline, statistical considerations that are the focus of the ICH E9 Guideline, and other considerations addressed in other ICH efficacy guidelines
• enhance the utility of the ICH efficacy guidelines by including critical-to-quality factors as a key
consideration in trial planning and design
• promote the quality of trial design and conduct for a broad range of trial types and data sources
with critical-to-quality factors aligned to the objectives of the trial.
Following E8(R1), the ICH Reflection Paper proposes the updating of the ICH E6(R2) Guideline on Good Clinical Practice, to address the increasing diversity of trial designs and data sources.
The project, which began in September 2017, is expected to be completed by 2021. With the final Concept Paper now approved, it is anticipated that the Step 2b Guideline will be completed by Q1 2019, following further face-to-face meetings of the Expert Working Group in June and November 2018.
A meeting with stakeholders will be held to discuss the Step 2b document, possibly at the end of the public consultation period.
BIA reacts to announcement from European Commission President Jean-Claude Juncker and Prime Minister Theresa May this morning [8 December] that ‘sufficient progress’ has been agreed on phase one of the Brexit negotiations.
CEO, Steve Bates, said: “We welcome today’s agreement. It is now crucial that the UK and EU agree a transition period to ensure that the supply of medicines to patients in the UK and across Europe is not affected. Public health and health security should be the first priority for the second phase of talks and we stand ready as a unified life science sector to provide expert input on such a process.
"On the detail, greater certainty in key areas proposed is welcome. I hope the citizens rights proposals enable people to better plan their life science careers with their families. My initial reading of the ‘goods on the market’ proposals is that it should enable medicinal products that have been tested and released prior to the Brexit date (which may well now be later than March 2019) to be freely available in the EU, even if that testing and release is carried out in the UK and the goods are shipped to other EU countries after the UK withdraws. This is important detail for global companies deciding how, and crucially when, to progress existing Brexit contingency plans."
BIA CEO Steve Bates responds to the announcement of the Life Sciences Sector Deal
Responding to today’s announcement of the Life Sciences Sector Deal, BIA CEO, Steve Bates, said: “It is fantastic that the life sciences are the first sector to have a deal published and this document showcases a range of investment in to the industry and partnerships working across this exciting and entrepreneurial industry. BIA members are particularly prominent in advanced therapies manufacturing and genomics.
“The sector deal shows government commitment to the agenda we have long led on access to finance, support for start-up and scale-up businesses, Innovate UK funding and medicines manufacturing. The BIA will be involved in the implementation of the deal as a clear voice for small businesses and I look forward to engaging in the planned funding and review next year.”
Many BIA members are also highlighted directly in the sector deal, showing the increasing strength and importance of the UK bioscience sector:
• Oxford BioMedica’s lentiviral vector platform technology has been endorsed by the FDA through approval of Novartis’s CAR-T cell therapy product, Kymriah™. Continued growth is assured through recent regulatory filings by Novartis in both Europe and in the United States, and with additional OXB strategic partnerships with other organisations, including Orchard Therapeutics.
• Touchlight Genetics is expanding operations at Hampton, London, with a Good Manufacturing Practice (GMP) facility to synthetically manufacture commercial-scale DNA (for gene therapy/gene editing/DNA vaccines) in two weeks, disrupting decades old fermentation approaches.
• Adaptimmune, with its pipeline of T-cell therapies to treat cancer, has to date raised over £300m and invested in new facilities for its growth and has over 200 UK employees. In 2017 alone it raised $100m
BIA members will recognise many of the announcements from meetings and discussions at BIA events and forums throughout 2017:
• The Medicines Manufacturing Industry Partnership (MMIP) has led on the key initiatives and catalysing major investments in new facilities
• The Finance and Tax Advisory Committee has shaped the BIA’s input into the Patient Capital Review, which forms the business environment finance commitments in the deal
• £86m investment to support SMEs through the Accelerated Access Review was announced at the BIA’s joint conference with the MHRA in July
• BIA members have shaped the BIA’s policy calls for the industrial strategy through surveys, interviews and a dedicated workshop in March 2017
You can read the full sector deal document here: https://www.gov.uk/government/publications/life-sciences-sector-deal
About the UK BioIndustry Association (BIA)
Established over 25 years ago at the infancy of biotechnology, the BioIndustry Association (BIA) is the trade association for innovative enterprises involved in UK bioscience. Members include emerging and more established bioscience companies; pharmaceutical companies; academic, research and philanthropic organisations; and service providers to the bioscience sector. The BIA represents the interests of its members to a broad section of stakeholders, from government and regulators to patient groups and the media. Our goal is to secure the UK's position as a global hub and as the best location for innovative research and commercialisation, enabling our world-leading research base to deliver healthcare solutions that can truly make a difference to people's lives.
For further information, please go to www.bioindustry.org and twitter.com/BIA_UK
A Guide to GCP for Clinical Data Management
A brand new book for data management teams. Written by experienced head of data management, Mark Elsley, in conjunction with Professor David Hutchinson.
This book covers the key ICH GCP E6(R2) requirements relevant to members of the data management team. It also provides valuable practical advice gained from the author’s extensive experience in this field.
Content is based on a GCP checklist providing more detail on the following general requirements
• Ensure that staff are suitably qualified and trained
• Create, maintain and follow sops describing the clinical data management processes
• Validate and control all computerized systems used to collect and handle clinical data
• Ensure that the flow of data from the source to the database is well documented
• Ensure that source data meet ALCOA+ standards
• Create a user-friendly CRF and database
• Check CRF data for accuracy, consistency and completeness
• Produce, maintain and archive high-quality documentation
• Ensure that CROs are suitably qualified and experienced
• Use a risk register at functional and study level
• Have input into risk-based approaches to trial management
The book includes a GCP checklist for clinical data management and supports an online training course on the same subject.
UK government unveils pharma research HQ coup
The UK government’s Autumn Budget struck a gloomy note for the economy, with figures pointing towards low productivity and the likelihood of slowing growth in the years to come.
With Brexit negotiations progressing at a snail’s pace, the government needed a boost to show that its economic plans were proving fruitful and they have released news that will allow them to claim some success.
This comes in the form of MSD’s investment in a research hub in the UK, with the company (known as Merck in North America) pumping up to £1 billion into the facility and creating 950 roles to staff the facility. The “Discovery Centre” will be based in London and the company hopes to have the facility ready by 2020.
Greg Clark, UK Business Secretary, heralded the move as a mark of the UK’s ability to draw investment: “Our life sciences sector is one of the UK’s fastest developing industries, with a turnover in excess of £64 billion, employing 233,000 across the UK. MSD’s commitment today, and the wider Sector Deal investment we have secured, proves the process outlined in the Industrial Strategy can give companies the confidence and direction they need to invest in the UK. It will ensure Britain continues to be at the forefront of innovation and represents a huge vote of confidence in our Industrial Strategy.”
The UK government has touted the life sciences industry as one that can drive growth, regardless of the outcome of negotiations. Admittedly, this angle sustained a blow almost immediately after the Brexit decision – when it became clear that the EMA headquarters would be leaving London, settling on Amsterdam as its preferred location.
However, it seems that the UK government has scored several successes in encouraging life sciences companies to invest in the UK – with further announcements expected over the next few weeks signposting the country’s competitiveness in the field. One is expected from GSK, one of the big two pharma companies that calls the country its home – the other being AstraZeneca.
“We believe London to be a unique bioscience centre of excellence and a key component of the established golden triangle for academic science of London-Oxford-Cambridge,” said Louise Houson, Managing Director of MSD in the UK and Ireland. “This investment presents a major opportunity for us to work in collaboration with the UK Government to build on the forward thinking and ambitious Industrial Strategy White Paper published by the Government today.”
Alongside the announcement of MSD’s facility, there was also the announcement that Qiagen, a provider of sample and assay technologies for molecular diagnostics, would also build a facility in Manchester. This would also provide a boost of 800 roles, through the development of a genomics campus
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 firstname.lastname@example.org 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.
MHRA releases latest annual pharmacovigilance inspection metrics
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has summarised the findings of
inspections performed by the Good Pharmacovigilance Practice (GPvP) Inspectorate in the 12 months to
FDA issues draft best practice guidance
New draft guidance describes best practices for communication between the FDA and sponsors of investigational new drug applications (INDs). Published in the Federal Register on 9 December 2015, the new guidance aims to facilitate the earlier availability of safe and effective drugs to the US public. It recommends procedures for timely, transparent and effective communication between IND sponsors and the FDA at critical junctures in the drug development process.
The document details
• FDA philosophy on timely interactive communication with IND sponsors
• the scope of appropriate interactions between the review team and the sponsor
• the types of advice appropriate for sponsors to seek from the FDA in pursuing their drug development programme
• general expectations for the timing of FDA responses to sponsor enquiries
• best practices and communication methods to facilitate interactions between the FDA review team and the IND sponsor
• the expectations for appropriate methods for such communication, including their frequency.
The draft guidance is available for a 60-day consultation period until 8 February 2016.
Latest Clinical Trials Regulation timeline
At a meeting on 16–17 December 2015, the European Medicines Agency’s (EMA’s) Management Board formally adopted the agency’s multi-annual programme and work plan for 2016.
Details of the EMA’s work programme for 2016 will be published in the first quarter of 2016, but a few highlights are already available. The agency has also made the following forecasts on key medicines development activities:
• the level of pre-authorisation activities for human medicines is expected to be stable, with
around 546 requests for scientific advice in 2016 compared with 510 in 2015
• approximately 33 requests for parallel advice with heath technology assessment bodies are expected
• the number of applications for initial marketing authorisation is expected to remain constant, with
110 applications in 2016 compared with 112 in 2015
• the number of applications for medicines containing a new active substance should also remain stable.
EU clinical trial portal and database
The agency’s multi-annual programme makes reference to the EU clinical trial portal and database,
the single portal for the submission and maintenance of clinical trial applications and authorisations that will underpin the new European Clinical Trials Regulation. The portal and database will also serve as the source of public information on the full lifecycle of all clinical trials conducted in the EU.
It is critically important that the EU system provides the required functionalities for all stakeholders in the most efficient and stable way possible from the outset, so as to ensure the delivery of the broad-reaching benefits foreseen by the Clinical Trials Regulation.
The following timeframe for the implementation of the portal and database was endorsed at the
Management Board meeting, and outlined in an EMA notification on 17 December 2015:
• independent audit: August – November 2017
• audit endorsed by EMA Management Board: December 2017
• European Commission notice published in the Official Journal of the European Union: March 2018
• Production Version completed: July 2018
• Production Version available: September 2018
• Clinical Trials Regulation (EU) No. 536/2014 becomes applicable: October 2018.
The new Clinical Trials Regulation entered into force on 16 June 2014. At that time it was stated
that the Regulation will apply no earlier than 28 May 2016, so for many the new October 2018 date may seem surprisingly far away. The agency is keen to stress that the current timeframe includes
provision for the resolution of unforeseen difficulties and potential issues (ie. it is considered to be a
maximum), and that all possible efforts will be made to bring the Regulation into operation earlier.
Revision to CIOMS Ethical Guidelines for Biomedical Research
The Council for International Organizations of Medical Sciences (CIOMS) has published online the revised draft of its Ethical Guidelines for Biomedical Research, with a deadline for comments of 1 March 2016.
A CIOMS Working Group has been working on a revision of the 2002 CIOMS Ethical Guidelines for Biomedical Research since 2012, looking at recent developments in the fields of biomedical research and research ethics, most notably the revised Declaration of Helsinki of 2013. Most of the original guidelines have been substantially revised, and several guidelines have been added to address new issues that require ethical guidance (eg. disaster research). In addition, the ‘Green Book’ (CIOMS Guidelines for Biomedical Research, 2002) and the ‘Blue Book’ (CIOMS Guidelines for Epidemiological Research, 2009) have been merged as they overlap substantially. The scope of the guidelines has also been broadened from biomedical research to health-related research with humans. Thus there are now 25 individual guidelines covering a broad range of topics, including the following:
• research in low-resource settings
• the equitable distribution of benefits and burdens in the selection of research participants
• the potential benefits and risks of research
• the choice of control in clinical trials
• caring for participants’ health needs
• community engagement, and collaborative partnership and capacity building for research and review
• individual informed consent, modifications and waivers of informed consent
• the use of stored biological materials and related data, and health-related data
• reimbursement and compensation for participants
• treatment and compensation for research-related harm
• research involving vulnerable persons, individuals who are not capable of giving informed consent, children and adolescents
• women, pregnant women and lactating women as research participants
• research in disaster situations
• implementation research
• research ethics committees and review
• public accountability
• conflicts of interest.
[original source www.cioms.ch/index.php/guidelines-test]
EMA position paper aims to reinforce compliance with GCP
The European Medicines Agency (EMA) has issued a Position Paper explaining that it will permit the replacement of a pivotal clinical trial that has been found to be non-compliant with GCP by another study, in the context of a marketing authorisation application. This position aims to reinforce the application of GCP during the conduct of clinical trials.
In the EU all clinical trials submitted to a regulatory authority to support a marketing authorisation application must be compliant with GCP, in order to ensure that the rights, safety and well-being of trial subjects and the integrity of trial data are protected.
In the event that a clinical trial is found to be non-compliant with GCP during an inspection relating to a marketing authorisation application, the applicant may respond to the inspection findings, provide a re-analysis of the data or provide a justification of why it believes the data are reliable. The EMA’s Committee for Medicinal Products for Human Use will take these representations into account during its assessment of the benefits and risks of the medicine. However, the new Position Paper makes it clear that the EMA will not allow a non-GCP compliant pivotal study to be replaced by another study during the assessment of the application.
Applicants may still submit a new application for marketing authorisation for the same medicine supported by appropriate GCP-compliant data from a pivotal study.
New EU trade and investment strategy to boost access to medicines
The European Federation of Pharmaceutical Industries and Associations (EFPIA) has welcomed the European Commission’s new trade and investment strategy for the EU as “a comprehensive means of addressing existing barriers to trade in a constructive and inclusive manner”.
In its statement on 15 October 2015, the EFPIA explained that it believes the new strategy – ‘Trade for all: towards a more responsible trade and investment policy’ – will enable the pharmaceutical industry to operate in a more transparent and predictable environment, by removing trade barriers and eliminating regulatory hurdles in third countries while increasing market access. In addition, it should reduce production costs and generate cost savings, which may then be re-invested into research and development and improving the regulatory environment. Such changes have the potential to boost medicines innovation and accelerate patient access to new treatments.
EFPIA Director General Richard Bergström said, “We welcome the new trade strategy of the Commission and the renewed impetus for dialogue and negotiations with key strategic partners such as US, China and Turkey as well as the resumed focus on the ASEAN [Association of Southeast Asian Nations] region. This will not only create a level-playing field for our companies, but will also offer opportunities for medicines innovation and faster access to treatments for patients worldwide.”
New global approach to tackle medicines counterfeiting
A unique international instrument that criminalises the trade in counterfeit (falsified) medicines – the Medicrime Convention – will enter into force on 1 January 2016. The Medicrime Convention was originally launched by the Council of Europe in an effort to curb counterfeit medicines (ie. those medicines whose identity and/or source have been falsely represented). In October 2015 it was announced that the Convention had been ratified by five countries, paving the way for it to be enforced in order to
• ensure international cooperation between the competent health, police and customs authorities in fighting counterfeit medicines worldwide
• mark the beginning of a new era in collective efforts to criminalise the production and distribution of counterfeit medicines, and to highlight how counterfeiting puts patients at risk.
Several pharmaceutical associations – including those in the USA and Europe, and representing both the innovative and generic/biosimilar pharmaceutical industries – have issued a statement welcoming the development. They encourage countries worldwide to sign and ratify the agreement, and share the view that there is a global shared responsibility to deal with the issue effectively and promptly in order to protect patients. This can be tackled by improving product security (eg. through the European Medicines Verification System) and by raising awareness of the dangers of counterfeit medicines.
As Chair of the International Generic Pharmaceutical Alliance, Jim Keon noted, "Counterfeit medicines are a serious public health threat. This international tool can help strengthen the global pharmaceutical supply chain to stop the spread of counterfeit medicines and ultimately protect patients."
ICH announces Organisational Changes
The International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation (ICH) held the inaugural meetings of its new Assembly [and Management Committee] on 23 October 2015.
The reforms build on a 25-year track record of successful delivery of harmonised guidelines for global pharmaceutical development, and their regulation. The changes announced today build on that success and will reinforce the foundations of ICH to make it better-equipped to face the challenges of global pharmaceutical development and regulation.
The reforms will mean that ICH is a truly global initiative, expanding beyond the current ICH members. More involvement from regulators around the world is welcomed and expected, as they will be invited to join counterparts from Europe, Japan, USA, Canada and Switzerland as ICH regulatory members. This is matched by the possibility of wider inclusion of global industry sectors affected by ICH harmonisation. The reforms strengthen ICH as the leading platform for global pharmaceutical regulatory harmonisation, and one that brings together in a transparent manner all key regulatory authorities and industry stakeholders.
The changes give ICH a more stable operating structure through the establishment of an ICH association, a legal entity under Swiss law. The association establishes the new Assembly as the over-arching governing body that will be instrumental in facilitating future growth through the participation of new members.
At the end of the inaugural meeting, ICH Assembly members declared “The fundamentals of what the ICH parties are trying to achieve are not changed, but the reforms to the process and organisation were needed to adapt to changes in how medicines are developed and regulated. These changes mark an exciting moment for us to help harmonise and streamline the global drug development process for the benefit of patients around the world.”
This press release, together with more information on the work of ICH, can be found on its website: www.ich.org
EC, EMA and WHO enhance cooperation to better protect global public health
The European Commission (EC) and the European Medicines Agency (EMA) have agreed with the World Health Organization (WHO) to share certain non-public information on the safety, quality and efficacy of medicines already authorised or under review in the EU, or pre-qualified or under review by WHO.
The new working arrangement, which began on 1 September 2015, will strengthen the communication between the organisations, making it easier and quicker to take action to protect public health. The arrangement is expected to accelerate patient access to new and innovative medicines in the EU, to avoid the duplication of assessments, and to improve the authorisation and safety of medicines by involving the best expertise from both sides. It also further strengthens the existing collaboration between WHO, the EC and the EMA.
Under the confidentiality arrangement, the organisations involved may share information such as
EMA issues new guidance to speed up development of antibiotics
The European Medicines Agency (EMA) is seeking comments on a new draft guideline on the use of pharmacokinetic and pharmacodynamic analyses in the development of antibiotics. Comments should be submitted by 31 March 2016.
The emergence of bacteria that are resistant to a wide range of antibiotics is a major and global public health issue. As well as encouraging the prudent use of antibiotics to minimise antimicrobial resistance, new antibiotics are urgently needed for the treatment of serious infectious diseases, particularly when patients have very limited or no remaining treatment options. An environment that stimulates and facilitates the development of innovative antibiotics is therefore needed.
Pharmacokinetic and pharmacodynamic analyses play an increasing role during the development of a new antibiotic. They provide evidence on the appropriateness of the dose and the frequency of administration needed in order to achieve the optimal benefit-risk balance and minimise the development of resistance. They are also crucial in the development of new antibiotics that address unmet medical needs or that target multi-drug resistant bacteria; they help to streamline and accelerate development via the use of innovative data-gathering strategies, consistent with the EMA’s new regulatory approach for the evaluation of medicines for the treatment of bacterial infections.
The draft guideline reflects both recent scientific advances and regulatory experience. It provides guidance on the conduct of robust pharmacokinetic and pharmacodynamic analyses, and outlines the regulatory requirements on the type of data that need to be collected, and their analyses and interpretation. The guideline replaces the Points to Consider document on pharmacokinetics and pharmacodynamics in the development of antibacterial medicinal products (CHMP/EWP/2655/99).