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Pharma Brexit Article Pack ARTICLE PACK
UK Unveils Go-It-Alone Drug Approval System
Accelerated Reviews Part Of MHRA’s Post-Brexit Plans
Executive Summary manufacturers to bring innovative products to the
Special approval procedures for new drugs UK.”
and biosimilars, more use of real-world data, a
streamlined drug safety monitoring system, and These are among a long list of proposals outlined
a ‘patient-first culture.’ The MHRA has plenty in the MHRA’s business plan for 2020-21, which
of ideas in store for its post-Brexit life as a fully was published on 10 June and lays out what the
independent regulator from January next year. agency calls “a program of substantial strategic
and cultural change.”
While the program responds to the need for a
The UK regulator, the MHRA, is to introduce a new “new and effective regulatory model now that the
accelerated licensing procedure for innovative UK has left the EU,” it also “reflects a new focus
medicines from the beginning of 2021, when it is on involving and engaging with patients, enabling
due to assume full responsibility for marketing patient access to new innovative medicines and
authorizations and related regulatory activities as devices, and speedier response to risks to patient
a result of the country’s departure from the EU. safety and public health,” the MHRA says.
The agency will have a closer focus on patient Clearly mindful of the need to strengthen the
access to highly innovative products, and post-Brexit attractiveness of the UK as a location
more use will be made of real-world data to for carrying out innovative pharmaceutical R&D, it
support both clinical trials and drug approvals. says it will develop a “new compelling innovation
It will use regulatory science to advance its offer.”
regulatory decision making, and new analytical
techniques and innovative methodologies will It will also support the government in preparing
be explored. The MHRA will also move towards for “its new relationships with the EU and the rest
more transparency in the disclosure of data and of the world” and ensuring that the regulatory
information. system works in “the best interests of patients,
industry and our partners across the health and
A new process will be introduced for approving care system.”
biosimilar medicines, with a “reduced burden”
in terms of clinical trial data requirements. Asked by the Pink Sheet for its views on the
Patients will be better served by more proactive proposals, the Association of the British
publication of data, information and knowledge. Pharmaceutical Industry said: “We want the UK to
be one of the best places in the world to research,
More generally, the MHRA will “focus engagement develop and use new medicines. That means
with key strategic partners to support innovation fostering an environment where industry and
and influence clinical practice to encourage regulators work together to get patients timely
2 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)access to safe, new medicines. It is good to see New Routes To Approval
this ambition in the MHRA’s plan.” It said it was A key priority, the MHRA says, is to be “ready for 1
“equally important that this is considered in the January with new routes to market for medicines
context of the UK’s future relationship with the and medical devices.” For innovative drugs, it will
EU and its place in the European life sciences hub, develop a “National Accelerated Licensing route”
and in the context of the COVID-19 pandemic.” that will come onstream from the beginning of
next year “so that innovative products submitted
The UK BioIndustry Association said it was to the UK can be authorised with a shorter
“reviewing the MHRA Business Plan 2020-2021 timeline.”
with its membership and will provide comments
and feedback to the MHRA in due course.” The agency does not go into detail about how
much shorter this procedure would be, but
The Post-Brexit Scenario if guidance issued in March 2019 (and now
The UK left the EU on 31 January this year, but it withdrawn) on regulatory processes in the
is still subject to EU legislation and regulations event of a no-deal Brexit is anything to go by,
for the duration of the Brexit transition period, an accelerated 150-day assessment for new
which is scheduled to expire on 31 December. active substances and biologics may be what the
This means, for example, that EU centralized agency has in mind. (Also see “New UK Drug
approvals – which are mainly for innovative drugs, Assessment Routes Among Latest Measures
biosimilars and sometimes generic medicines – For No-Deal Brexit” - Pink Sheet, 4 Jan, 2019.)
remain valid for the remainder of the year, as do
other related activities. The MHRA is also proposing a “new innovative
UK licensing procedure” for biosimilar medicines
However, the UK can no longer play an active role that will also operate from 1 January 2021 and
in any of the EU institutions or its bodies, including will “reduce the burden on clinical trial data
the European Medicines Agency, nor can it act as generation.” More details of these procedures,
rapporteur for any EU marketing authorization together with accompanying guidelines, are
procedures. expected in the third quarter of this year.
In January 2021, assuming there no extension Other plans include new guidance on the use of
to the transition period, the MHRA will become real-world evidence in supporting clinical trial data
a free-standing agency and among other things and regulatory approvals, and the establishment
will take over responsibility for products that of a “financially sustainable model to deliver
are currently regulated by the EMA. It will also regulatory science across the health care system
be looking to carry over some of the initiatives “to evolve regulatory decision making.”
already undertaken by the EMA, such as greater
patient involvement in its activities and more
transparency on data publication.
3 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)The table below shows some of the MHRA’s specific proposals in the regulatory science area for
2021-22:
Regulatory Science: MHRA proposals Target date
Test and be ready to launch for 1 January 2021 a dynamic and compelling market entry
End Q3
proposal
Develop the National Accelerated Licensing route to operate from 1 January 2021, and
publish relevant guidance, so that innovative products submitted to the UK can be End Q3
authorised with a shorter timeline
Develop and publish guidance on a new innovative UK licensing procedure for biosimilar
End Q3
products to operate from 1 January 2021
Develop practical proposals and publish guidance on the use of Real-World Evidence in
Q3
supporting clinical trial data and regulatory approvals to support innovation
Establish a network and financially sustainable model to deliver regulatory science across
Q3
the healthcare system to evolve regulatory decision-making
Review Agency pre-market activities and develop a new Science Strategy to underpin work
Q3
on innovation and life cycle management
Source: MHRA
Lifecycle And Safety Management assets” to strengthen the way it regulates
The MHRA says it will review its regulatory medicines and devices, and to use its analytical
processes with a view to creating a “streamlined” capabilities to “enhance risk evaluation and safety
approach to life cycle management that management.”
also involves seeking the views of health
care professionals and patients to inform A ‘Patient-First Culture’
decision0making. The MHRA also wants to increase patient
involvement in its activities – something that the
On the pharmacovigilance front it plans to put in EMA has put among its highest priorities. By the
place a single process for safety signal detection second quarter of 2021, the agency says, it will
by the end of the first quarter of next year, as part have ready “a new patient and public engagement
of a program for an “integrated vigilance system” plan,” to be followed by a similar plan for engaging
governing both medicines and medical devices. with health care professionals in Q3. This will
include the development and embedding of a
A “proportionate” benefit-risk decision-making “patient-first culture.”
process will be developed, taking into account
patient views, while new IT vigilance systems will The agency’s websites will be improved to
be delivered, making use of developments in AI. make them more accessible to all users, and
new notification platform will be developed,
In the area of data and analytics, the agency including for safety alerts to health care
commits to improving the way it uses its “unique professionals. Proposals will be put forward for
4 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)“more transparency on how we publish data and will include an “appropriately structured Agency
information.” Executive Committee and a refreshed unitary
Board,” all due by the end of Q1 2021. A new
Structural Changes model for setting industry fees will be developed,
Changes are also envisaged for the overall and an “efficiency program” will be devised and
structure and governance of the MHRA. These taken forward during next year.
5 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)European Medicines Agency Counts The Cost Of Brexit
Activities To Be Restarted With Fewer Staff
Executive Summary Now it will also begin ramping up those activities
As the EMA settles into its permanent that were put on hold as part of the Brexit
headquarters in Amsterdam, it hopes that new Business Continuity Plan (BCP) following the 2016
recruits will swell its depleted staff numbers. But Brexit referendum.
much will depend on the necessary expertise
being available, particularly following the loss of One of the activities impacted was the
access to experts working at the UK regulator, the production of several scientific guidelines, whose
MHRA. development was put on hold or their publication
delayed. In 2019, a total of 92 guidelines were
affected in various areas of human medicine.
The European Medicines Agency says it wants For the first time, the EMA says, there was
2020 to be the “final year of transition” following a delay in the processing of certificates and
the UK’s decision to leave the EU. It plans to parallel distribution annual updates, giving rise
relaunch a series of key activities that were cut to a backlog, and there were also hold-ups in
back or suspended during the “period of change” the validation of some variation procedures.
that was triggered by Brexit, but it will be doing “Crucial” workshops and training programs
so under pressure because of the fall in the staff for stakeholders were postponed, and the
numbers caused by its move out of the UK. development of the EMA’s project portfolio and
project management capabilities had to be put on
It has also set aside substantial financial reserves hold.
to cover Brexit-related expenses this year, but 2021
should be the last year in which Brexit costs figure The agency also saw a fall in its participation in
in its annual budget, according to the agency’s external stakeholder forums and a “consequent
“Final programming document” for 2020-22. reduced level of engagement with key stakeholder
groups.”
As for the future relationship between the UK and
the EMA in the area of medicines regulation, the As well as aiming to reinstate these activities
agency says that “this is part of the negotiations this year, the EMA says it will prepare Q&As and
between the EU and the UK.” guidance documents for the pharmaceutical
industry on the Brexit-related changes to
The EMA relocated to its permanent building marketing authorizations, and will be handling
in south Amsterdam last month, a move it additional Brexit-related post-authorization
says brought “additional challenges” such as applications. It also plans to identify ways to
transferring and maintaining operational IT address any supply shortages of centrally
systems, ensuring the necessary services are in authorized medicines caused by Brexit.
place, “as well as the logistics of the actual move
of the organisation and staff with minimum Staff Impacts
disruption to the agency’s day-to-day activities.” A major blow to the agency from Brexit will be the
6 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)loss of UK experts, who accounted for some 15% When staff on short-term contracts are included,
of its expert pool and conducted around 20% of EMA has lost “a total of 159 resources within 2019
the scientific work at the EMA when the Medicines which puts the agency’s continuity of operations
and Healthcare products Regulatory Agency was under significant pressure, including the EMA
part of the EU network. As of 31 January this capacity to deliver core activities”.
year, the UK can no longer play any role in EU
institutions, agencies or committees. It forecasts that staff numbers will increase in
2020, but staffing levels “will depend on the
“Loss of this expertise has had significant agency’s ability to maintain a high recruitment
consequences not just for the agency, but for rate and the required expertise being available.”
the EU regulatory network as a whole,” with a Although recruitment is ongoing to replace staff
“significant increase in workload for EU experts” who decide not to relocate to Amsterdam, the
and a potential loss of specific expertise. To agency “will not reach its previous headcount,
help manage this, the agency and the network which included a large number of staff on short-
have worked to ensure capacity building and re- term contracts.”
distribution of the workload among the member
states,” the programming document says. Considering the “exceptional transitional Brexit
challenges still facing the agency,” the EMA is also
The EMA still expects to lose 20-25% of the 901 seeking approval to continue to employ up to a
staff it had at the end of 2018, across all functions maximum of an additional 35 contract agents in
and profiles, including “critical” activities. 2020, falling to 25 in 2021, “to ensure a smooth
relocation and knowledge transfer transition.”
More than 70% of losses so far have been of staff
working on the core scientific activities considered The EMA recently announced a “future proofing”
the most critical “Category 1” priorities under the exercise involving a restructuring of its operations
BCP, such as initial evaluations, post-authorization to allow it to respond more effectively to a
activities, and support for various working groups. “permanently reduced headcount” as well
“In addition to this, staff loss is impacting key as to other challenges. (Also see “European
support/administrative areas, such as information Medicines Agency Restructures To Tackle New
management, HR, infrastructure and others,” it Challenges” - Pink Sheet, 23 Dec, 2019.)
says.
7 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)Industry Laments UK Change To SPC Waiver Approach
Manufacturing Of Products Under SPC Only Allowed For Non-EU Markets
Executive Summary However, under the latest draft of the Intellectual
Changes to how the UK plans to implement Property (Amendment etc.) (EU Exit) Regulations
the supplementary protection certificate 2020, the government has amended its proposal
manufacturing waiver after it separates itself fully to allow manufacturing in the UK for export to
from the EU following the current Brexit transition countries outside both the UK and the EU, or – for
period have been criticized by the generics the last six months of the SPC term – to stockpile
industry, while originators have welcomed the for ‘day one’ sale in the UK and the EU upon SPC
move. expiry.
While the UK brand industry has lauded the
changes, the off-patent industry has not been so
Draft legislation drawn up by the UK that alters welcoming.
the country’s planned approach to integrating the
EU’s supplementary protection certificate (SPC) BGMA Warns Decision May Undermine Local
manufacturing waiver into UK law has been met Generics Manufacturing
with dismay by the off-patent industry. Originator body the UK BioIndustry Association
called the new secondary legislation “a
As the UK prepares for the end of its transition welcome U-turn by the government on the SPC
period with the EU at the close of 2020 – following manufacturing waiver.” Pointing out that “the law
the country’s formal departure from the EU at will now only permit the making of SPC-protected
the end of January this year – the government drugs in the UK for export to countries outside the
has been working on integrating into UK law EU,” the BIA insisted that the previous proposed
provisions of the EU’s SPC manufacturing waiver, approach allowing export to EU member states
which came into effect just over a year ago at “could have reduced our members’ intellectual
the start of July 2019, after years of successful property rights in some of those countries.”
lobbying by the off-patent industry. (Also see “EU
SPC Waiver: Originators May Need To Act Soon” - “The BIA’s IP advisory committee made the case
Pink Sheet, 17 Jun, 2019.) for this change directly to government officials,
so it is great to see their efforts pay off,” the
The UK government had initially proposed to originator body said. “With a no-deal end to the
allow manufacturing in the UK during the SPC transition period looking ever more likely, we
term either for export to countries outside the continue to work to ensure the best possible
UK, or – for the last six months of the SPC term outcome for our sector,” it concluded.
– to stockpile for ‘day one’ sale in the UK upon
SPC expiry. This raised the prospect of potential However, the British Generic Manufacturers
exports to the EU. Association criticized the move.
8 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)BGMA director general Warwick Smith said that “After the transition period,” Smith pointed out,
“the decision not to apply the manufacturing “the UK will compete with EU member states
waiver to EU member states after the end of the as well as other countries as a base for the
transition period is disappointing and may well manufacturing of generic medicines.”
undermine the government’s desire to see more
generic medicines manufacturing in the UK.” “Along with other factors,” he concluded, “an
intellectual property regime which supports
“However,” Smith said, “we welcome the British competitiveness outside of the UK,
continuation of the date that an SPC in the including in comparison with the EU, will be
UK would expire based on first launch in the critical if the government’s objective of increasing
European Economic Area, which is likely to create the manufacture of generics in the UK is to be
an earlier launch date in the UK for generic delivered.”
medicines than if this decision had not been
taken.” Meanwhile, Adrian van den Hoven, director
general of European off-patent industry
“The EU adopted the SPC manufacturing waiver association Medicines for Europe, told said
to incentivize generic manufacturing in Europe that “as you might expect, we support the
without upsetting the balance in intellectual maintenance of the SPC manufacturing waiver in
property rights between originator and generic the UK.”
manufacturers,” Smith explained. “It does this by
allowing companies to manufacture generics in However, van den Hoven said, “limiting the scope
Europe during the period of the SPC for export to of the waiver will undermine the development and
markets where the products do not have patent manufacture of generic and biosimilar medicines
protection. This allows European manufacturers in the UK with no added benefit for originators.
to compete in those markets with companies This is regrettable at a time when European
from elsewhere in the world and thus also governments – including the UK – are looking for
makes Europe a more attractive base for the ways to incentivize manufacturing for security of
manufacture of generic medicines.” supply.”
9 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)UK MHRA Looks Beyond Brexit Transition
Executive Summary safety and the rest will follow,” Raine said.
Now that the UK has left the EU, the UK’s
medicines regulator says it will use the rest of this Irrespective of the way forward adopted for drug
year to work out how best to ensure continuity of regulation, Raine said that the MHRA was ready
drug regulation after the Brexit transition period to meet the challenges brought about by the UK’s
ends on 31 December. exit from the EU. “There will be no interruption to
our supervision and the regulatory obligations of
oversight of medicines,” she maintained.
The UK Medicines and Healthcare products The MHRA chief also said that “if, and when,
Regulatory Agency is gearing up for possible changes do need to happen” to the UK’s approach
changes to its approach to medicines regulation to drug regulation, there will be consultation,
when the Brexit transition period concludes at the information and guidance for stakeholders. She
end of this year. referred to the “intense” effort put in by the MHRA
to prepare for a possible no-deal Brexit situation
The government will use the Brexit transition and said that one should “expect the same level
period to forge “new partnerships and new of intense preparation and collaboration” if a new
relationships with the EU and the rest of approach is decided.
the world, which will potentially lead to new
arrangements for businesses and trade,” said June The pharmaceutical industry supports alignment,
Raine, the agency’s interim chief executive. cooperation and mutual recognition between
the UK and the EU regarding the authorization,
Raine was speaking at the MHRA’s 2020 Good testing and surveillance of medicines. Following
Pharmacovigilance Practice Symposium in London Brexit, however, Sajid Javid, who resigned as UK
on 11 February. She told the Pink Sheet that the chancellor on 13 February, had stated that there
MHRA would like to continue participating in the would not be any alignment with EU regulations.
European Medicines Agency’s procedures. On He had later clarified that “where it is in the UK’s
the agency’s potential collaboration with other interests to align, it will align,” raising hope for
regulators and developing UK-specific pathways, the pharmaceutical industry. (Also see “BIA Sees
she said: “It’s all to play for.” Some Hope For Regulatory Alignment After
Brexit” - Pink Sheet, 31 Jan, 2020.)
On the drug safety front, she said that UK
pharmacovigilance inspectors in particular were During the Brexit transition period, which ends
“very engaged at an international level,” especially on 31 December 2020, the UK will remain aligned
with their counterparts in the US, and that with EU regulations and it will be “business as
they participate in global inspections. “I believe usual,” Raine said at the symposium.
whether it is Washington or Wolverhampton – the
patients should get the same level of protection If the UK and the EU do not agree to a deal by the
everywhere… Pharmacovigilance knows no end of this year and no extension is made to the
boundaries… The focus should be on patient Brexit transition period, then EU regulations will
10 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)stop applying in the UK as of 1 January 2021 and Regarding the possible impact of a no deal-like
the no-deal arrangements will come into force by situation on pharmacovigilance inspections by
default. The MHRA’s senior pharmacovigilance the MHRA, Trevet said that under existing UK
inspector, Kiernan Trevet, said the agency legislation (The Human Medicines Regulations
would update its own no-deal guidance for the 2012), the MHRA has the authority to inspect a
life sciences industry as and when information company’s full pharmacovigilance system.
becomes available.
Over the past few years, the MHRA has changed
Trevet, who was also speaking at the symposium its approach to pharmacovigilance inspections.
in London, clarified that companies would The agency now undertakes more targeted
still have another 21 months after the Brexit or detailed inspections focusing on specific
transition period ends to comply with any UK- pharmacovigilance processes or products, rather
specific requirements, if necessary, such as the than assessing the whole pharmacovigilance
need to appoint a UK-based qualified person system in one go, Trevet noted. (Also see “UK
for pharmacovigilance (QPPV) or locating the MHRA To Boost Pharmacovigilance With More
pharmacovigilance system master file (PSMF) in Focus On Office-Based Inspections” - Pink Sheet,
the UK. 22 May, 2018.)
“The transitional periods which are outlined in the Beyond the Brexit transition period, Trevet said
EU exit regulations will come into effect from the that the MHRA was keen to retain its ability to
1st January 2021, so you would have 21 months exchange information with the EU on supervisory
from that date to introduce a UK QPPV and UK authority inspection outcomes and schedules so
PSMF if that is required as part of the future that “we can take that information into account
framework. So hopefully that gives assurance that when we do our own risk-based inspection
there will still be plenty of time [for industry] to planning... That is our hope for the future,” she
transition to any new feature requirements,” she said.
said*.
11 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)UK Pulls Out Of Unified Patent Court Agreement
Lawyers Uncertain Whether The Move Will Stymie The Whole Project
Executive Summary “Participating in a court that applies EU law and is
The UK has formally withdrawn its ratification of bound by the CJEU would be inconsistent with the
the Unified Patent Court Agreement, adding to the Government’s aims of becoming an independent
uncertainty over its future. self-governing nation,” she said.
The statement notes that although the agreement
has not yet come into force, the withdrawal of the
The UK has formally withdrawn its ratification UK’s ratification will help facilitate the entry into
of Europe’s proposed Unified Patent Court force of the agreement for other countries. Also
Agreement (UPCA). It believes the move will take according to the statement, withdrawal will take
immediate effect, but legal experts claim that immediate effect and “it will be for the remaining
withdrawal could in fact take up to 12 months, participating states to decide the future of the
which could impact whether Germany ratifies the Unified Patent Court system.”
agreement – and determine the whole future of
the project. The UPC issued a statement confirming that a
deposit of the withdrawal notification had been
“Our view is that the UK’s withdrawal generates received. It described the news as “disappointing”
new, and potentially insurmountable, legal and said the preparatory committee would now
hurdles to the entry into force of the current UPC meet to “discuss the consequences of the UK
Agreement and/or of the Protocols (on Provisional withdrawal and agree a way forward.”
Application and Privileges and Immunities) that
also form an essential part of the Unitary Patent Uncertainties In Germany
Package ” said Mike Snodin from the patent Whether or not the agreement is viable remains
attorney firm, Park Grove IP. uncertain. Recent developments mean “a delay
(of between about 1 and 5 years) before a Unified
On 20 July, the UK withdrew its ratification of Patent Court becomes operational; or scrapping
the UPCA and of protocols associated with the of the entire Unitary Patent Package,” said Snodin.
agreement, by means of a “Note Verbale.” On the
same day, Amanda Solloway, the parliamentary One issue is whether Germany will ratify the
under secretary of state, minister for science, UPCA. Earlier this year German ratification was
research and innovation, tabled a written declared void because there were not enough
statement in the House of Commons. members of the lower house of parliament
present when the legislation was passed in 2017.
“In view of the United Kingdom’s withdrawal (Also see “German Ruling Spells More Trouble
from the European Union, the United Kingdom For Europe’s New Patent System” - Pink Sheet,
no longer wishes to be a party to the Unified 23 Mar, 2020.)
Patent Court system,” said the written statement.
12 / August 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.)There are now plans in Germany to proceed with is covered by the Vienna Convention on the Law of
ratification, but as Snodin points out they have Treaties (VCLT), said Snodin.
been met with a mixed response.
But it is unclear which VCLT mechanism the UK
One issue is that Germany as an EU member state has invoked to execute its withdrawal. “This could
cannot ratify an agreement that has been ratified be an important point, as a withdrawal under
by a non-EU state, according to Gregory Bacon, a the most likely provision (Article 56 VCLT) does
lawyer at Bristows. not take effect until 12 months after notification.
In this regard, it is uncertain whether the UK
Therefore, “ensuring the UK’s withdrawal is legally government is justified in considering that its
effective is important because this would remove withdrawals have immediate effect.”
one ground of a [threatened] constitutional
complaint,” said Bacon. Further complicating matters, the UK was also one
of the three member states – together with France
However, there is uncertainty over the nature of and Germany – that had to ratify the agreement
the UK’s withdrawal. The UPC agreement does in order for it to go ahead. Another member state
not include a formal withdrawal or exit clause, will now have to be selected to take the place of
which means that withdrawal from the agreement the UK.
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