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>>  Anabela Marcal:
Hello everyone.

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My name is
Anabela Marcal,

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and I'm the European
Medicines Agency

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liaison official to the Food
and Drug Administration.

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I've been at European
Medicines Agency for 24 years,

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and I've had different roles,
including in clinical trials,

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pharmacovigilance,
and inspections.

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In this lecture,
I'll give you

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an overview of the
authorization of medicines

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in the European Union,
in particular,

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an overview of the
centralized procedure.

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My lecture will cover,
amongst others,

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the following topics:

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which products are eligible
for the centralized procedure;

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timelines for assessment
of a marketing authorization

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application submitted through
the centralized procedure;

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the assessment procedure itself;
who is responsible for what;

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early access tools available
in the European Union;

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eye level overview on how
we monitor medicines

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once they are
on the market;

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and to finalize, an
overview on transparency,

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meaning what do we publish
for products we assess?

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How are medicines
approved in the E.U.?

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In the E.U., we have different
authorization routes,

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but in all cases, the
same set of rules apply.

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Medicines in the E.U.
can be authorized through

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the centralized procedure or
through national procedures

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at the level of the
E.U. member states.

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Let's start by the
centralized procedure.

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So, in the centralized
procedure,

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companies submit
their application

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to the European
Medicines Agency,

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and there will be one
assessment at the end.

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There will be one
marketing authorization

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that will be valid in all
E.U. 27-member states.

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There will be one marketing
authorization order

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for all E.U. member states,
one single product name,

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one set of product
information.

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So, the labeling
will be the same

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for all the E.U.
member states.

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And this is the procedure that
applies for the vast majority

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of all new medicines
in the E.U.

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When it comes to the
national procedures,

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applicants submit the marking
authorization application

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to the national competent
authorities of the member states

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where they want to place
the medicinal product.

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So, they can choose if they
are going to apply in two,

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three, 20-member states.

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For these national procedures,
we have two distinct procedures.

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The so-called mutual
recognition procedure,

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which applies where marking
authorization applicants

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have a product

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already authorized in
one E.U. member state.

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And then they apply in
another E.U. member state

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and ask for the initial
authorization to be recognized.

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So, in this process,
it allows member states

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to rely in each other
scientific assessment.

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The other route, it's the
decentralized procedure

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which applies
where applicants

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apply for the simultaneous
authorization of a medicine

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in more than
one-member state

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if it has not yet
been authorized

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in any E.U. member state.

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As I mentioned at the beginning,
the focus of this lecture

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will be the
centralized procedure.

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The centralized procedure
requires the applicant to submit

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a single application to the
European Medicines Agency.

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The centralized procedure

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is dedicated to
innovative products,

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and it is mandatory for
specific categories of products.

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Once a company submits a
marketing authorization

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application through the
centralized procedure,

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the European Medicines Agency
Scientific Committee

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for Human Medicines,

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the CHMP must,
within 210 active days,

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deliver a scientific opinion
recommending the granting

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or the refusal of the
marketing authorization.

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The scientific opinion is then
sent to the European Commission

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who is going to issue a
legally binding decision,

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meaning, for instance,

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the granting of a marketing
authorization valid

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throughout the E.U.
27-member states.

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Which medicines
are then approved

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through the
centralized procedure?

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The centralized
procedure is mandatory

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for certain categories
of products,

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as highlighted in this slide.

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This is established by law
by regulation (EC) 726/2004.

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The mandatory scope includes
the following products:

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new active substances for
the treatment of HIV,

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cancer, diabetes,
neurodegenerative diseases,

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autoimmune diseases,
and viral diseases;

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medicines derived from
biotechnology processes;

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advanced therapies;
orphan medicines;

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and innovative
veterinary medicines.

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For other medicines,

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companies have the option of
submitting an application

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through the
centralized procedure.

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This is possible for the
following categories:

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new active substance;
significant therapeutic,

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scientific, or
technical innovation;

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medicines whose authorization
would be in the interest

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of patients or animal health;
generic of a product

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authorized through the
centralized procedure;

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and marking authorization
applications,

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including a pediatric
indication.

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Once the marking authorization
application is submitted,

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the centralized
procedure follows

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an established
timeline and process.

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Before submission,

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there are a number of
activities taking place.

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One of them is so-called
pre-submission meeting.

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Pre-submission meetings
are voluntary.

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And if the company
wishes to have one,

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they need to come
six to seven months

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in advance of
the submission

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of a marketing
authorization application.

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During this meeting, the
company presents the product

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and can ask questions
related to scientific,

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regulatory, or
legal issues

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in order to facilitate
the subsequent validation

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and assessment of
the application.

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Other activities occurring
during the pre-submission phase

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include the appointment
of the rapporteur,

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who will take the lead in the
assessment of the application.

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The request for eligibility
to the centralized procedure,

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meaning that the company
needs to have the confirmation

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that the product is eligible
for the centralized procedure.

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Request for accelerated
assessment,

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meaning that if the company
would like an assessment

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quicker than the standard
timeline for assessment,

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it needs to provide a
justification before submission.

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Once the application is
submitted, it's then validated.

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The validation includes
the following:

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a technical validation to check
if the structure of the dossier

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is compliant with the use
specifications and rogatory

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and administrative
content validation.

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Once the application
has been validated,

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the review procedure starts.
During the primary evaluation,

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the rapporteur and co-rapporteur
will review the data submitted

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and produce independent
assessment reports.

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These assessment
reports will be shared

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with all members
of the Committee

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for Medicinal Products
for Human Use, the CHMP.

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The members have the opportunity
to provide comments,

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and these will be
followed by a discussion

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at the committee meeting.

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After this initial
phase of 120 days,

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the scientific committee
adopts a list of questions

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to the applicant

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indicating whether a medicine
is in principle approvable

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or whether major objections
have been identified,

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which preclude an approval.

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The clock is stopped and it's
then up to the applicant

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to prepare answers
to the questions.

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The applicant has a period
of three to six months

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to answer the list of questions.

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Once the applicant
submits his answers,

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the clock is started
at day 121,

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and the rapporteurs review
the complementary information

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provided by the company.

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The rapporteurs prepare
a joint assessment report,

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and if needed,

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the committee issues a list
of outstanding issues.

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The applicant can also be given
the opportunity to be heard

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by the EMA
Scientific Committee.

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An opinion, positive
or negative,

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i.e., recommending
the granting

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or the refusal of the
marketing authorization,

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needs to be adopted
by day 210.

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The CHMP opinion is then sent
to the European Commission

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who has 67 days to prepare
a binding decision.

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The decision to grant a
marketing authorization valid

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throughout the E.U. should
be given by day 277.

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The decision, including
product information,

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is given in all official
languages of the European Union.

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There are possible additional
steps in the procedure.

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This includes,
for instance,

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requests for good
manufacturing practice,

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good laboratory practice,

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or good clinical
practice inspections.

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The CHMP can also
decide to consult

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with scientific advisory
groups or doc expert groups.

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Scientific advisory groups
are groups established

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by the CHMP in connection
with the evaluation

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of specific therapeutic areas.
They consist of European experts

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selected according to
the particular expertise.

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For instance, we have
SAG, cardiovascular SAG,

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oncology SAG, and so on.

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The CHMP can also consult
other committees, for instance,

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the Committee on
Advanced Therapy,

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the Pediatric Committee,
and working parties.

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Working parties are groups
of experts in specific areas,

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for instance,

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quality working party,
methodology working party,

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biosimilars working party,
pharmacokinetics working party.

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I've mentioned before
that the rapporteur

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and co-rapporteurs are
the ones taking the lead

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in the assessment
of an application.

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What is exactly the role of the
rapporteur and co-rapporteurs?

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The rapporteurs, together
with their assessment teams,

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lead the scientific assessment
of an application.

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The rapporteurs act as lead
reviewers on behalf of the CHMP.

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They draft the assessment
reports, as we have seen before,

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independent assessment reports
in the primary evaluation,

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and then a joint
assessment report

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in the secondary evaluation.
They propose objections,

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list of questions in the
need for inspections,

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the need to consult experts.

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They coordinate
input from experts

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and from the
committee members.

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And in certain
cases, for instance,

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for products that
are given prime,

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they also have an early
involvement in the --

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before submission
of the application.

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The rapporteurs are appointed on
the basis of objective criteria.

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And these objective criteria
include the ability

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of the rapporteur to
fulfill the role,

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the composition of
their assessment team,

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the scientific competence,
the regulatory experience,

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and also trying to obtain
an even distribution

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amongst the members
of the committee.

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We can also have rapporteurs
from other committees

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during the evaluation

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of an initial marketing
authorization application.

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This includes, for instance,
the PRAC rapporteurs.

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PRAC is the Pharmacovigilance
and Risk Assessment Committee.

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During the marketing
authorization application,

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they are responsible
for the assessment

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of the risk
management plans,

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focusing on the prospective
planning aspects

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like pharmacovigilance plan
and risk minimization measures.

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They're also responsible to
issue the list of questions

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related to the risk
management plans.

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And once a product
is authorized,

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they will be
[unintelligible]

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involved in post-authorization
safety-related procedures.

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We can also have
rapporteurs

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from the Committee
on Advanced Therapies,

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and this is specifically
for products that are ATMPs.

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For ATMPs, the CAT rapporteurs
are the ones leading

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in the scientific assessment

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of an initial marketing
authorization application.

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And then the CHMP acts as an
overarching peer reviewer.

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And what is the role
of the CHMP itself?

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The CHMP is the
EMA's Committee

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for Medicinal Products
for Human Use

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and is composed
by one member

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plus one alternate
from each member state.

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In addition, it also includes
five co-opted members

251
00:14:48,721 --> 00:14:51,056
that are nominated to CHMP

252
00:14:51,056 --> 00:14:54,026
on the basis of expertise
in certain areas.

253
00:14:54,593 --> 00:14:58,530
This could be, for instance,
expertise in medical statistics,

254
00:14:59,531 --> 00:15:04,770
pharmacokinetics, biologics,
on ATMPs, pharmacoepidemiology,

255
00:15:04,770 --> 00:15:06,372
and so on.

256
00:15:07,306 --> 00:15:09,008
What is the role of the CHMP?

257
00:15:09,908 --> 00:15:12,645
The CHMP is responsible
for the assessment

258
00:15:12,645 --> 00:15:14,513
of a marketing
authorization application

259
00:15:14,513 --> 00:15:17,783
and to give an opinion
on centralized marketing

260
00:15:17,783 --> 00:15:19,385
authorization applications.

261
00:15:20,085 --> 00:15:23,155
And as seen before, this is
based on the rapporteur's

262
00:15:23,155 --> 00:15:25,124
and co-rapporteur's
assessment reports,

263
00:15:25,624 --> 00:15:27,426
on the PRAC
rapporteur's assessment

264
00:15:27,426 --> 00:15:29,495
of the risk
management plans,

265
00:15:29,495 --> 00:15:32,031
comments from other
CHMP members,

266
00:15:32,031 --> 00:15:34,033
and consultation with experts.

267
00:15:36,368 --> 00:15:39,605
The CHMP is also
responsible for assessment

268
00:15:39,605 --> 00:15:42,608
and opinions for
post-authorization procedures.

269
00:15:42,608 --> 00:15:44,810
So, once a product
is authorized,

270
00:15:45,411 --> 00:15:49,548
if there are variations or
if there are, for instance,

271
00:15:49,548 --> 00:15:53,652
to include a new indication or
to include a new formulation,

272
00:15:53,652 --> 00:15:56,655
the CHMP continues to be
the main body responsible

273
00:15:56,655 --> 00:15:58,223
for this assessment.

274
00:15:59,625 --> 00:16:03,028
The CHMP is also responsible
to give opinions

275
00:16:03,028 --> 00:16:05,164
regarding suspension,

276
00:16:05,164 --> 00:16:07,499
withdrawal of a
marketing authorization

277
00:16:07,499 --> 00:16:10,769
within the context of
European review procedures.

278
00:16:10,769 --> 00:16:12,938
Meaning that in
certain cases,

279
00:16:13,505 --> 00:16:16,008
even if a product is
nationally authorized,

280
00:16:16,975 --> 00:16:20,913
the CHMP can get involved
and do an assessment

281
00:16:20,913 --> 00:16:25,617
if this is considered of
interest for the European Union.

282
00:16:26,452 --> 00:16:28,821
For instance, when
a new safety issue

283
00:16:29,421 --> 00:16:32,825
arises in a specific member
state related to that product.

284
00:16:40,666 --> 00:16:44,570
The final CHMP opinion
and assessment report

285
00:16:44,570 --> 00:16:48,974
reflects the scientific review
of the submitted dossier,

286
00:16:48,974 --> 00:16:52,544
further information provided
during the assessment,

287
00:16:52,544 --> 00:16:55,114
the discussions held at CHMP,

288
00:16:55,114 --> 00:16:58,183
the information provided by
the applicant in a hearing.

289
00:16:58,817 --> 00:17:00,686
It also reflects
if there have been

290
00:17:00,686 --> 00:17:03,155
divergent views in the CHMP.

291
00:17:03,155 --> 00:17:06,525
And now, the committee finally
concludes on the benefit-risk.

292
00:17:07,226 --> 00:17:09,995
And of course, it also
explains how the CHMP

293
00:17:09,995 --> 00:17:13,665
arrived at specific statements
in the product information.

294
00:17:15,334 --> 00:17:19,538
The CHMP opinion is adopted
by consensus or majority vote.

295
00:17:20,406 --> 00:17:23,142
And in the case
of majority vote,

296
00:17:23,142 --> 00:17:26,678
the divergent views are included
in the opinion as well.

297
00:17:32,851 --> 00:17:35,954
I would like now to
highlight a few features

298
00:17:35,954 --> 00:17:37,990
of the centralized procedure.

299
00:17:37,990 --> 00:17:40,959
The first one is about
accelerated assessment

300
00:17:40,959 --> 00:17:43,328
that I mentioned also
at the beginning.

301
00:17:44,730 --> 00:17:48,400
Accelerated assessment
reduced the timeframe of CHMP

302
00:17:48,400 --> 00:17:50,969
to review a marketing
authorization application

303
00:17:50,969 --> 00:17:55,340
from 210 to 150 active days.

304
00:17:56,475 --> 00:18:00,112
Applications may be legible
for accelerated assessment

305
00:18:00,112 --> 00:18:03,415
if the product is of major
interest for public health,

306
00:18:04,049 --> 00:18:07,319
particularly from the point of
view of therapeutic innovation.

307
00:18:08,787 --> 00:18:12,825
Any request for accelerated
assessment should be made

308
00:18:12,825 --> 00:18:14,126
at least two to
three months

309
00:18:14,126 --> 00:18:16,829
before submitting a marking
authorization application.

310
00:18:17,963 --> 00:18:22,134
The applicant should provide
sufficient justification.

311
00:18:23,769 --> 00:18:26,705
And on that basis,
the CHMP will decide

312
00:18:26,705 --> 00:18:29,975
if this marking authorization
application is eligible

313
00:18:29,975 --> 00:18:32,010
or not for accelerated
assessment.

314
00:18:33,645 --> 00:18:35,447
The accelerated
assessment timeframe

315
00:18:35,447 --> 00:18:40,185
can be reverted to standard
assessment during the assessment

316
00:18:40,185 --> 00:18:42,287
of the marking
authorization application

317
00:18:42,287 --> 00:18:45,624
in case of major issues
with the application.

318
00:18:52,264 --> 00:18:54,132
Conditional marketing
authorization.

319
00:18:54,933 --> 00:18:57,469
EMA supports the
development of medicines

320
00:18:57,469 --> 00:18:59,705
that address unmet
medical needs.

321
00:19:00,405 --> 00:19:02,241
In the interest
of public health,

322
00:19:02,241 --> 00:19:05,511
applicants may be granted
the so-called condition

323
00:19:05,511 --> 00:19:07,112
marketing authorization

324
00:19:09,615 --> 00:19:14,086
for certain medicines on the
basis of less comprehensive data

325
00:19:14,086 --> 00:19:15,921
than normally would be required.

326
00:19:16,588 --> 00:19:19,558
Where the benefit of
immediate availability

327
00:19:19,558 --> 00:19:22,928
of the medicine outweighs
the risk in rent,

328
00:19:22,928 --> 00:19:25,964
in the fact that additional
data are still required.

329
00:19:27,666 --> 00:19:29,201
Medicines for human use

330
00:19:29,201 --> 00:19:32,170
are eligible for conditional
marking authorization

331
00:19:33,405 --> 00:19:37,476
if they are intended to
treat, prevent, or diagnose

332
00:19:37,476 --> 00:19:40,712
seriously debilitating or
life-threatening diseases.

333
00:19:41,647 --> 00:19:44,116
This includes
also for medicines,

334
00:19:44,116 --> 00:19:48,487
and its use is also intended
for public health emergencies.

335
00:19:50,489 --> 00:19:54,359
The CHMP may grant conditional
marketing authorization

336
00:19:54,359 --> 00:19:56,995
if all of the following
criteria are met.

337
00:19:57,796 --> 00:20:00,766
The benefit-risk balance
of the medicine is positive.

338
00:20:02,067 --> 00:20:04,536
It is likely that the
applicant will be able

339
00:20:04,536 --> 00:20:07,906
to provide comprehensive
data post-authorization.

340
00:20:09,141 --> 00:20:11,843
The medicine fulfills
an unmet medical need.

341
00:20:12,578 --> 00:20:16,915
The benefit of the medicine
becoming immediately available

342
00:20:16,915 --> 00:20:20,519
to patients is greater
than any risk in rent

343
00:20:20,519 --> 00:20:23,221
in the fact that additional
data are still required.

344
00:20:25,657 --> 00:20:27,326
Conditional market
authorizations

345
00:20:27,326 --> 00:20:29,328
are valid
for one year

346
00:20:29,328 --> 00:20:32,431
and need to be
reviewed annually.

347
00:20:33,665 --> 00:20:36,702
Once the conditional marketing
authorization has been granted,

348
00:20:36,702 --> 00:20:38,203
the marketing
authorization order

349
00:20:38,203 --> 00:20:40,572
must fulfill
specific obligations

350
00:20:41,306 --> 00:20:43,141
within defined timelines.

351
00:20:44,109 --> 00:20:47,913
These obligations could
include completing ongoing

352
00:20:47,913 --> 00:20:50,816
or new studies or
collecting additional data

353
00:20:50,816 --> 00:20:53,752
to confirm the benefit-risk
balance of the medicine.

354
00:20:55,420 --> 00:20:57,889
The marketing authorization
can be converted

355
00:20:57,889 --> 00:21:00,025
into a standard
marketing authorization

356
00:21:00,025 --> 00:21:03,395
once the marketing
authorization order fulfills

357
00:21:03,395 --> 00:21:08,734
the obligation imposed
and the complete data confirms

358
00:21:08,734 --> 00:21:13,038
that the medicine's benefits
continue to outweigh its risks.

359
00:21:18,844 --> 00:21:22,547
An authorization can be granted
under exceptional circumstances

360
00:21:23,081 --> 00:21:25,450
if the applicant
can demonstrate

361
00:21:25,450 --> 00:21:28,920
that he is not able to
provide comprehensive data

362
00:21:28,920 --> 00:21:32,424
on the efficacy and
safety of the medicine

363
00:21:32,424 --> 00:21:34,126
under normal
conditions of use

364
00:21:34,826 --> 00:21:37,029
because of one of the
following reasons.

365
00:21:37,763 --> 00:21:41,700
The indication for which the
product is intended is rare

366
00:21:42,300 --> 00:21:45,904
and therefore, the applicant
cannot reasonably be expected

367
00:21:45,904 --> 00:21:48,006
to provide
comprehensive evidence.

368
00:21:48,774 --> 00:21:51,843
Or in the present state
of scientific knowledge,

369
00:21:51,843 --> 00:21:54,680
comprehensive information
cannot be provided.

370
00:21:55,714 --> 00:21:59,518
Or it would be contrary
to the accepted principles

371
00:21:59,518 --> 00:22:02,621
of medical ethics to
collect such information.

372
00:22:04,056 --> 00:22:06,158
The marketing authorization
is granted subject

373
00:22:06,158 --> 00:22:07,959
to specific obligations,

374
00:22:07,959 --> 00:22:10,896
which will be reassessed
on an annual basis.

375
00:22:10,896 --> 00:22:13,198
However, the marketing
authorization

376
00:22:13,198 --> 00:22:15,067
is valid for five years.

377
00:22:19,304 --> 00:22:22,574
In this table, you have a
summary of the main features

378
00:22:22,574 --> 00:22:25,243
of the different types of
marketing authorization.

379
00:22:25,777 --> 00:22:28,013
So, you have the standard
marketing authorization

380
00:22:28,013 --> 00:22:30,682
where you have
comprehensive data

381
00:22:30,682 --> 00:22:32,317
at the time of the
authorization.

382
00:22:33,418 --> 00:22:36,154
The authorization is
valid for five years,

383
00:22:36,688 --> 00:22:38,323
and this is the
standard situation.

384
00:22:38,323 --> 00:22:39,558
And of course,

385
00:22:39,558 --> 00:22:42,360
the fact that it's a standard
marketing authorization,

386
00:22:42,360 --> 00:22:46,098
it still may have some
post-marketing requirements or

387
00:22:46,098 --> 00:22:48,366
some conditions for
post-authorization

388
00:22:48,366 --> 00:22:49,601
safety studies or

389
00:22:49,601 --> 00:22:52,404
post-authorization efficacy
studies to be conducted.

390
00:22:53,405 --> 00:22:56,441
Then we have the conditional
marketing authorization,

391
00:22:56,441 --> 00:22:59,878
where we do not have
comprehensive data

392
00:22:59,878 --> 00:23:01,313
at the time of
authorization,

393
00:23:01,313 --> 00:23:05,217
but it is expected that
the company will be able

394
00:23:05,217 --> 00:23:08,220
to get such data
after authorization.

395
00:23:09,087 --> 00:23:10,989
So, at a certain
point in time,

396
00:23:10,989 --> 00:23:14,826
this conditional marketing
authorization will revert,

397
00:23:14,826 --> 00:23:17,763
and it'll go to a full standard
marketing authorization.

398
00:23:19,331 --> 00:23:20,665
The conditional
marketing authorization

399
00:23:20,665 --> 00:23:24,436
is valid for one year, and
it's renewable every year.

400
00:23:25,570 --> 00:23:28,173
It's only possible in the
centralized procedure,

401
00:23:28,173 --> 00:23:30,642
and this conditional
marketing authorization

402
00:23:30,642 --> 00:23:36,481
is granted with specific
obligations to be completed

403
00:23:36,481 --> 00:23:38,350
according to defined timelines.

404
00:23:39,518 --> 00:23:41,153
And then the marketing
authorization

405
00:23:41,153 --> 00:23:43,555
under exceptional
circumstances,

406
00:23:45,056 --> 00:23:48,727
comprehensive data cannot
be expected to be obtained,

407
00:23:49,361 --> 00:23:53,532
meaning that pretty much
this marketing authorization

408
00:23:53,532 --> 00:23:57,035
will always remain under
exceptional circumstances.

409
00:23:57,903 --> 00:23:59,371
It's valid for five years,

410
00:23:59,371 --> 00:24:02,440
but there will be an annual
reassessment every year.

411
00:24:03,074 --> 00:24:04,676
It's possible
in all types

412
00:24:04,676 --> 00:24:07,946
of registration
procedures in Europe

413
00:24:08,480 --> 00:24:11,516
and as well can have
specific obligations

414
00:24:11,516 --> 00:24:13,885
and specific conditions
to be fulfilled.

415
00:24:20,158 --> 00:24:22,861
This slide illustrates
at a very high level

416
00:24:22,861 --> 00:24:25,363
how we monitor
safety of medicines

417
00:24:25,363 --> 00:24:27,532
once they come into the market.

418
00:24:27,532 --> 00:24:29,901
So, once marketing
authorization is given,

419
00:24:30,435 --> 00:24:34,005
how do we monitor the safety
of medicines in the E.U.?

420
00:24:35,874 --> 00:24:39,411
European Medicines Agency is
responsible for coordinating

421
00:24:39,411 --> 00:24:42,113
the E.U.'s pharmacovigilance
system for medicines

422
00:24:42,681 --> 00:24:45,717
and can take action if
the information indicates

423
00:24:45,717 --> 00:24:48,854
that the benefit-risk balance
of a medicine has changed.

424
00:24:49,688 --> 00:24:51,423
How does the EMA do this?

425
00:24:52,557 --> 00:24:54,359
The safety of
medicines in the E.U.

426
00:24:54,359 --> 00:24:59,998
is constantly monitored
via reports from patients

427
00:24:59,998 --> 00:25:01,299
and healthcare professionals,

428
00:25:01,299 --> 00:25:03,635
clinical studies,
medical literature,

429
00:25:04,436 --> 00:25:07,572
patient resistors,
and collaboration

430
00:25:07,572 --> 00:25:10,108
with regulatory bodies
outside the E.U.

431
00:25:11,543 --> 00:25:13,245
The marketing authorization
audit, of course,

432
00:25:13,245 --> 00:25:15,714
also has specific obligations

433
00:25:15,714 --> 00:25:18,850
to submit adverse reactions
to the E.U. system

434
00:25:18,850 --> 00:25:22,420
and to submit periodic
safety update reports

435
00:25:22,420 --> 00:25:25,023
in accordance to
established timelines.

436
00:25:27,092 --> 00:25:29,761
EMA is also a
dedicated committee

437
00:25:30,362 --> 00:25:33,064
to the safety of
medicines for human use,

438
00:25:33,064 --> 00:25:34,366
the so-called PRAC,

439
00:25:34,366 --> 00:25:37,369
Pharmacovigilance and Risk
Assessment Committee.

440
00:25:38,503 --> 00:25:39,905
The PRAC is responsible

441
00:25:39,905 --> 00:25:43,642
for the assessment of periodic
safety update reports,

442
00:25:43,642 --> 00:25:46,411
any signals that arise,
pass authorization,

443
00:25:46,411 --> 00:25:49,214
safety studies,
risk management plans.

444
00:25:51,549 --> 00:25:56,955
PRAC can also give
recommendations

445
00:25:56,955 --> 00:26:00,825
regarding the changes
or suspension,

446
00:26:00,825 --> 00:26:03,128
or revocation of certain
medicinal products

447
00:26:03,128 --> 00:26:04,829
due to safety issues.

448
00:26:11,503 --> 00:26:13,805
And to finalize
my presentation,

449
00:26:13,805 --> 00:26:16,875
I would like to give
a brief overview

450
00:26:16,875 --> 00:26:19,878
of what we publish regarding
marketing authorizations.

451
00:26:23,248 --> 00:26:25,784
So, at the time an
opinion is adopted,

452
00:26:25,784 --> 00:26:27,986
an opinion recommending
the granting

453
00:26:27,986 --> 00:26:29,554
of marketing authorization,

454
00:26:31,222 --> 00:26:34,326
we announced in the
CHMP highlights,

455
00:26:34,326 --> 00:26:38,029
that a positive opinion
has been adopted by the CHMP.

456
00:26:38,563 --> 00:26:42,934
The CHMP meets once a
month, every month.

457
00:26:45,270 --> 00:26:48,006
And in addition to
the announcement

458
00:26:48,006 --> 00:26:50,108
in the so-called
CHMP highlights,

459
00:26:50,108 --> 00:26:52,077
we also publish
a patient-friendly

460
00:26:52,077 --> 00:26:53,712
summary of the opinion.

461
00:26:54,346 --> 00:26:57,882
And this is valid for positive
as well as negative opinions,

462
00:26:57,882 --> 00:27:00,618
meaning that if the
CHMP recommends

463
00:27:01,186 --> 00:27:03,488
that a certain product

464
00:27:03,488 --> 00:27:05,957
should not be given a
marketing authorization

465
00:27:05,957 --> 00:27:08,827
because the benefit-risk
balance is negative,

466
00:27:08,827 --> 00:27:12,731
we also made that information
available in the public domain.

467
00:27:14,632 --> 00:27:17,569
The EMA also publishes
information on applications

468
00:27:17,569 --> 00:27:19,804
withdrawn by the applicant.

469
00:27:19,804 --> 00:27:23,341
Meaning if at any time during
the assessment of the procedure,

470
00:27:23,341 --> 00:27:26,611
the company decides to
withdraw the application,

471
00:27:26,611 --> 00:27:29,414
we also put that information
in the public domain.

472
00:27:31,616 --> 00:27:35,954
In addition to this,
we also develop

473
00:27:35,954 --> 00:27:37,222
and prepare
what we call

474
00:27:37,222 --> 00:27:39,491
the European Public
Assessment Report,

475
00:27:39,491 --> 00:27:41,092
or the so-called EPAR.

476
00:27:41,726 --> 00:27:45,463
The EPAR is published once
the commission has issued

477
00:27:45,463 --> 00:27:47,966
the decision granting the
marketing authorization.

478
00:27:49,434 --> 00:27:51,036
And then in the
post-authorization,

479
00:27:51,036 --> 00:27:53,905
we also publish information
on new safety issues,

480
00:27:53,905 --> 00:27:57,976
suspensions, or any other
changes to the products.

481
00:28:02,614 --> 00:28:03,848
Regarding the EPAR.

482
00:28:03,848 --> 00:28:06,785
The EPAR is the European
Public Assessment Report

483
00:28:06,785 --> 00:28:10,588
for each product
authorized through

484
00:28:10,588 --> 00:28:13,258
the centralized
procedure in the E.U.

485
00:28:13,258 --> 00:28:16,928
Once the commission decision
gives the authorization,

486
00:28:16,928 --> 00:28:20,131
we publish this
comprehensive report.

487
00:28:21,066 --> 00:28:24,769
The EPAR includes information
about the product,

488
00:28:24,769 --> 00:28:27,639
and this is, for instance,
the presentations,

489
00:28:27,639 --> 00:28:29,707
the strengths,
formulations available.

490
00:28:30,475 --> 00:28:32,444
The proved product
information,

491
00:28:32,444 --> 00:28:34,312
meaning the information
to the doctors,

492
00:28:34,312 --> 00:28:37,082
the so-called summary
of product characteristics,

493
00:28:38,249 --> 00:28:41,719
the information to the patients
or package leaflet,

494
00:28:41,719 --> 00:28:43,488
and the labeling information,

495
00:28:43,488 --> 00:28:45,790
the information that will
appear on the boxes.

496
00:28:47,525 --> 00:28:50,662
We also publish any conditions
to the marketing authorization.

497
00:28:50,662 --> 00:28:53,498
So, if the marketing
authorization was granted

498
00:28:53,498 --> 00:28:55,733
under specific conditions,
for instance,

499
00:28:55,733 --> 00:28:59,838
studies that the companies still
need to complete or others,

500
00:28:59,838 --> 00:29:03,675
these will be also published
as part of the EPAR.

501
00:29:05,543 --> 00:29:07,612
We published a full
scientific discussion

502
00:29:07,612 --> 00:29:10,115
based on the CHMP
assessment report.

503
00:29:10,748 --> 00:29:13,885
And then once the
product is authorized,

504
00:29:13,885 --> 00:29:17,489
we'll keep updating the EPAR

505
00:29:17,489 --> 00:29:21,326
according to the latest
post-authorization procedures.

506
00:29:23,828 --> 00:29:26,464
In addition to the
EPAR for each product,

507
00:29:27,165 --> 00:29:29,601
we also publish clinical data.

508
00:29:31,336 --> 00:29:34,272
Since 2010, EMA had
already been releasing

509
00:29:34,272 --> 00:29:35,807
clinical trial reports,

510
00:29:35,807 --> 00:29:40,011
but on request, meaning under
the access to documents policy.

511
00:29:40,945 --> 00:29:45,917
However, since January 2015,

512
00:29:45,917 --> 00:29:47,886
we are also
proactively publishing

513
00:29:47,886 --> 00:29:54,159
the clinical overview summary
and study reports of products

514
00:29:54,159 --> 00:29:57,362
for which we gave a
marketing authorization

515
00:29:57,362 --> 00:29:59,063
under the centralized
procedures.

516
00:29:59,631 --> 00:30:01,466
So, as I said,
this is applicable

517
00:30:01,466 --> 00:30:03,501
for all marketing
authorization applications

518
00:30:03,501 --> 00:30:06,905
submitted after the
1st of January, 2015.

519
00:30:07,739 --> 00:30:10,341
We only do that after the
decision on the application

520
00:30:10,341 --> 00:30:11,543
is taken,

521
00:30:11,543 --> 00:30:15,547
and we have also done that for
COVID-19 vaccines and products.

522
00:30:20,318 --> 00:30:23,555
And just to test
your knowledge,

523
00:30:24,956 --> 00:30:29,093
just a few questions on the
topics of my presentation.

524
00:30:31,262 --> 00:30:34,699
All medicines
authorized in the E.U.

525
00:30:34,699 --> 00:30:38,036
are assessed by the EMA
Committee for Human Medicines.

526
00:30:39,270 --> 00:30:42,840
True or false? False.

527
00:30:44,008 --> 00:30:45,910
In the E.U., there are
two main processes

528
00:30:45,910 --> 00:30:47,245
of authorizing medicines.

529
00:30:47,245 --> 00:30:50,882
There is the centralized
procedure, and there indeed,

530
00:30:50,882 --> 00:30:53,151
the Committee for
Human Medicine, CHMP

531
00:30:53,151 --> 00:30:55,853
is the main body responsible
for the assessment.

532
00:30:56,654 --> 00:31:00,325
But we also have the so-called
national reauthorized products

533
00:31:00,325 --> 00:31:02,594
that are authorized
at the national level

534
00:31:02,594 --> 00:31:06,531
by the regulatory authorities
of the member states.

535
00:31:07,332 --> 00:31:10,034
And these are not
seen by the CHMP.

536
00:31:12,937 --> 00:31:14,405
The EMA is responsible

537
00:31:14,405 --> 00:31:17,175
for the granting of marketing
authorizations for products

538
00:31:17,175 --> 00:31:19,344
assessed through the
centralized procedure.

539
00:31:20,645 --> 00:31:24,515
True or false? False.

540
00:31:26,251 --> 00:31:30,021
The EMA is responsible to
give a scientific opinion

541
00:31:30,021 --> 00:31:32,357
or a scientific recommendation.

542
00:31:32,357 --> 00:31:35,760
The legal act of giving
a marketing authorization

543
00:31:35,760 --> 00:31:38,463
is the responsibility of
the European Commission.

544
00:31:41,299 --> 00:31:44,402
A conditional marketing
authorization can be recommended

545
00:31:44,402 --> 00:31:47,138
when it is expected
that comprehensive data

546
00:31:47,138 --> 00:31:49,340
can be obtained
after authorization.

547
00:31:50,775 --> 00:31:53,745
True or false? True.

548
00:31:54,712 --> 00:31:58,049
Indeed, if there is
an unmet medical need,

549
00:31:58,049 --> 00:32:02,320
and if it's considered
that after authorization

550
00:32:02,320 --> 00:32:05,223
that the information
submitted at the time

551
00:32:05,223 --> 00:32:07,158
of the marketing
authorization application

552
00:32:07,158 --> 00:32:08,760
could be complemented,

553
00:32:08,760 --> 00:32:12,230
and as far as on the basis
of the available data,

554
00:32:12,764 --> 00:32:16,067
the benefit-risk of the product
is considered positive,

555
00:32:16,067 --> 00:32:19,270
then we can -- the
CHMP can recommend

556
00:32:19,270 --> 00:32:21,239
a conditional
marketing authorization.

557
00:32:25,076 --> 00:32:28,513
An authorization under
exceptional circumstances

558
00:32:28,513 --> 00:32:31,849
will be reverted to a standard
marking authorization

559
00:32:31,849 --> 00:32:35,320
after a few years once
further data is obtained.

560
00:32:35,320 --> 00:32:38,923
True or false? False.

561
00:32:40,758 --> 00:32:43,594
The authorization under
exceptional circumstances,

562
00:32:43,594 --> 00:32:46,664
it is not expected
that comprehensive data

563
00:32:46,664 --> 00:32:48,266
will become available.

564
00:32:49,867 --> 00:32:52,937
The EMA publishes proactively
clinical stat reports

565
00:32:52,937 --> 00:32:54,972
for authorized products.

566
00:32:54,972 --> 00:32:57,044
True or false? True.

566
00:32:58,972 --> 00:33:00,044
Thank you very much.