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40 Cobert’s Manual of Drug Safety and Pharmacovigilance
of output: (a) Simple counts; (b) Complex descrip-
tive analyses; and (c) Inferential analyses. ARIA was
launched at the beginning of 2016 and several hundred
analyses were run in the first 2 years.
The 2007 legislation also gave FDA the authority to
issue Post-marketing Requirements (PMRs). However,
FDA is required to consider the sufficiency of ARIA
to address the question before requiring an applicant
to conduct a PMR: “The Secretary may not require
the responsible person to conduct a study under this
paragraph, unless the Secretary makes a determination
that the reports under subsection (k)(1) and the active
post-market risk identification and analysis system as
available under subsection (k)(3) will not be sufficient
to meet the purposes set forth in subparagraph (B).” So,
for concerns that might result in a post-marketing obli-
gation for an applicant, FDA must use available tools
before imposing a requirement.
The Sentinel System is made available to others
through a public-private partnership. From an orga-
nizational perspective, the Reagan–Udall Foundation
offers access for FDA through the Innovation in Med-
ical Evidence Development and Surveillance (IMEDS)
program. The goal is to make the system a broader
resource for public health and medical evidence gen-
eration. IMEDS and Sentinel share the same analytic
coordinating center in Boston. Private users of IMEDS
have access to the same data as FDA and also the same
analytic tools. This approach also provides funding for
sustainability of the Sentinel System.
FDA continues to expand Sentinel and integrate
capabilities into the post-market safety monitoring
system.
In addition, there are other related projects, such as
the following:
European Network of Centers for Pharmacoepi-
demiology and Pharmacovigilance (ENCePP), a
network consisting of research and medical care
centers, healthcare databases, electronic registries,
and existing networks to strengthen post-marketing
monitoring and to facilitate the conduct of safety-
related post-authorization studies (particularly
observational studies);
Innovative Medicines Initiative (IMI), a public–
private partnership, has multiple projects that focus
on improving drug safety and other aspects of drug
development, for example, one project focused on
developing validated tools and methods that will
enhance adverse event data collection, active sig-
nal detection, standards for pharmacoepidemiology
studies, and integration of data for evaluation of
benefit-risk;
EU-ADR, a project to design, develop, and validate
a computerized system that exploits data from elec-
tronic healthcare records and biomedical databases
for the early detection of ADRs, which will be com-
plementary to existing systems with early detection
of safety signals; and
Drug Safety and Effectiveness Network (DSEN), a
virtual network to assess the risks and benefits of
marketed drug products.
Thus, the FDA will be able to initiate queries of
multiple databases to obtain safety information and to
do active and proactive surveillance using current and
emerging methods.
In March 2003, the FDA published proposed new
and comprehensive safety rules, sometimes referred to
as “The Tome” because of their breadth and length. See
“Safety Reporting Requirements for Human Drug and
Biological Products”, 68FR12405–12497, March 14,
2003. The proposal is now mostly of historical interest.
However, it did outline FDA’s thinking in that timeframe
and consisted of extensive and complex changes to the
current IND and NDA safety regulations. Major new
obligations on the part of the pharmaceutical industry
were proposed.
The FDA invited comments and received many
thousands. Many parts of the proposal are now clearly
out of date, especially with regard to electronic trans-
mission, risk management, and FDAAA require-
ments. However, some changes and new requirements
have been put in place via separate Federal Register
Notices.
In late 2012, the FDA issued a new final rule that
covers clinical trial safety reporting (21CFR312). Sub-
sequent guidance was issued to clarify requirements of
the rule. The rule is not fully consistent with ICH E2A
https://avxhm.se/blogs/hill0
The United States Food and Drug Administration 41
and requirements of other key regulators. This presents
special challenges for sponsors who entertain possibili-
ties for global development programs.
FDA has indicated that it will periodically issue
updated post-marketing regulations, as appropriate.
One concept in particular from the Tome is worth
noting and may eventually be enacted: the “Always
Expedited Report”. This new category requires sub-
mission of an ICSR within 15 calendar days of first
awareness, whether expected (labeled) or not, for these
events:
Congenital anomalies;
Acute respiratory failure;
Ventricular fibrillation;
Torsades de pointe
Malignant hypertension;
Seizures;
Agranulocytosis;
Aplastic anemia;
Toxic epidermal necrolysis;
Liver necrosis;
Acute liver failure;
Anaphylaxis
Acute renal failure;
Sclerosing syndromes;
Pulmonary hypertension;
Pulmonary fibrosis;
Transmission of an infectious agent by a marketed
drug/biologic;
Endotoxin shock; and
Any other medically significant “serious” adverse
events requested by FDA for specific investiga-
tional products or protocols.
What is Expected from Drug
Companies by the FDA?
The federal regulations noted above describe what the
FDA expects to receive from biopharmaceutical compa-
nies regarding the reporting of drug safety information.
In all cases, sponsors are expected to be 100% compli-
ant with regulations, i.e., submit complete reports on
time and do follow-up with due diligence to get com-
plete medically-relevant information:
Clinical trials — AEs reported to the IND
In 7 calendar days: deaths/life-threatening (at pre-
sentation), serious, unexpected, associated with
the drug;
In 15 calendar days: serious, unexpected, associated
with the drug;
For both 7- and 15-day reports: FDA requests that
sponsors submit one ICSR to the “parent” IND
rather than to all open INDs. (The “parent” IND
is the open IND for the subject active substance
that has the earliest filing date.) This is to avoid
duplicate reports that could confound safety sig-
nal detection; and
In annual periodic reports: summary of all studies,
tabular summary of the most serious and most
frequent serious AEs, deaths, discontinuations
due to AEs, and the 15-day reports submit-
ted since the last aggregate report. The general
acceptable format for the annual reports in the
US is now the DSUR format, originally adopted
in the EU. The content and format of the DSUR
is more comprehensive than the requirements
of the US IND Annual Safety Report and is now
generally accepted by the FDA.
Marketed biopharmaceuticals — AEs reported to
the NDA
In 15 calendar days: serious, unexpected. Note that
all spontaneous reports are considered to be
“associated with the drug”. The reasoning is that
if the reporter did not believe there was at least
some level of association (causality) with the
drug, he or she would not have reported it. This
comes from an earlier CIOMS recommendation.
In 15 calendar days: Reports from the medical liter-
ature that are serious and unexpected.
In the quarterly or annual periodic reports (PADERs)
or PSURs: A narrative summary and analysis of
the 15-day alert reports submitted since the last
periodic report plus all other reports that are not
serious and not unexpected. Foreign non-serious
AEs do not have to be reported. In general, clin-
ical trial AEs do not have to be reported to the
NDA. Note that, currently, ICH E2C PSURs are
42 Cobert’s Manual of Drug Safety and Pharmacovigilance
not required by FDA and PADERs are required
by regulations. FDA does accept PSURs with
the PADER-specific appendices; the ICH PSUR
(PBRER format) may be made obligatory at some
point in the future.
Solicited reports: AEs that are received from cus-
tomer engagement programs with the possibility
of two-way communication, e.g., disease man-
agement programs, patient support programs,
etc., should be reported as 15-day reports to the
NDA if they are serious, unexpected, and asso-
ciated with the drug. It is the latter causality
assessment that differentiates solicited reports
from spontaneous reports (FDA Guidance for
Industry, August 1997).
What is Expected from
Consumers and Healthcare
Professionals by the FDA?
Safety reporting by consumers and the healthcare com-
munity is purely voluntary, but strongly encouraged.
(Exception: The US National Childhood Vaccine Injury
Act (NCVIA) requires healthcare providers to report:
(a) Any event listed by the vaccine manufacturer as a
contraindication to subsequent doses of the vaccine;
and (b) Any event listed in FDA’s Reportable Events
Table that occurs within the specified time period after
vaccination (see www.fda.gov for the latest Report-
able Events Table).) Reports may be made to the FDA
directly via MedWatch (mail, online, fax, etc.) or to
the pharmaceutical company that manufactures, sells,
or packages the product. Once a manufacturer (NDA
holder or “Applicant”) or distributor, etc., learns of an
adverse event for one of its products, reporting to FDA
is mandatory.
FDA Publications
and Updates
FDA has various publications and feeds freely available
without cost online, such as e-mail alerts and as RSS
feeds. “What’s New (Drugs)” comes out several times a
week with new drug-specific information. The relevant
publications are well worth receiving, particularly the
MedWatch and CDER notifications.
Others include the following:
1. CDER New: New items posted to the CDER
website;
2. Drug Information: Occasional drug infor-
mation updates on hot topics, frequently asked
questions, and more;
3. Marketing and advertising communica-
tions: Drug marketing, advertising, and com-
munication regulation information; updates to
the Office of Prescription Drug Promotion web
pages, which occasionally involve fair balance
with safety matters;
4. Drug Safety News (Podcast alert): Emerg-
ing safety information about drugs, broadcast in
conjunction with the release of Public Health
Advisories and other drug safety issues;
5. Drug Safety Newsletter: Post-market infor-
mation for healthcare professionals on new
drug safety information and reported adverse
events;
6. FDA Patient Safety News (video): TV
broadcasts for healthcare professionals about
recalls, alerts, and ways to improve the safety
of drugs, medical devices, vaccines, and diag-
nostic products;
7. MedWatch Safety Alerts: Product safety
alerts, Class I recalls, market withdrawals, and
public health advisories;
8. FDA Guidance Documents for the
industry;
9. FDA Warning Letters: FDA Warning Let-
ters and untitled letters issued to companies,
investigators, IRBs, etc.; and
10. Good Clinical Practice: Information about
the development of final rules related to FDA’s
regulations on good clinical practice and clini-
cal trials. These reference the ICH E6 guideline,
as revised.
The reports may change from time to time, with
new ones introduced and old ones phased out. Check
https://avxhm.se/blogs/hill0
The United States Food and Drug Administration 43
the FDA web site for updates. There are other alerts on
biologics, CBER, and specific diseases and conditions,
including HIV and infectious hepatitis, women’s health,
medical devices, research, food contamination, and
cosmetics.
This site offers sign-up for multiple subscriptions at
the same time from various health and human services
agencies and divisions, including the CDC, NIH, Med-
Line Plus, and others.
The FDA, the industry, and nearly everyone else is
now struggling with the newly and rapidly arising social
media (Twitter, Facebook, LinkedIn, Buzz, blogs, blog-
inars, eCards, podcasts, widgets, virtual worlds, etc.).
As of this writing, FDA had several Twitter feeds and a
Facebook page, and is expanding its use of social media.
The FDA’s influence on life in the United States is
extensive. The Agency oversees and regulates drugs, bio-
logics, vaccines, dietary supplements, radiation-emitting
devices, certain foods, cosmetics, and tobacco. They
cover both human and veterinary products. FDA’s influ-
ence outside the United States is obviously less strong
than within the United States but, nonetheless, is felt
through direct and indirect actions in international
entities (e.g., ICH, CIOMS, where FDA is a major player
either directly or indirectly), formal and informal inter-
actions and memoranda of understanding with other
health agencies (Europe, Canada, Japan, China, etc.),
and as a thought and action leader (e.g., a drug safety
restriction or withdrawal in the United States must be
addressed, in practice, rather quickly elsewhere around
the globe). FDA also has an extensive network of offices
outside the US (Mexico City, San Jose, Santiago, Lon-
don, Brussels, New Delhi, Beijing, among others).
For those in industries regulated by the Agency, the
FDA has an impact on actions every moment of the day
in just about all areas of business:
Approval of INDs and NDAs, 510Ks, and so on;
Regulations covering all aspects of manufacturing
(current Good Manufacturing Practices), clinical
research (Good Clinical Practices), animal research
(Good Laboratory Practices), quality systems, drug
safety (Good Pharmacovigilance Practices), the
supply chain(s), and so on;
Inspections (often unannounced) of factories, clini-
cal trial sites, safety divisions, clinical trial divisions,
licensing partners, contract research organizations,
and so on;
Drug safety;
Product labeling and packaging;
Product advertising, sales promotion, and other
professional communications;
Advice to the public; and
Communication to all stakeholders.
The FDA has multiple “clients” to which it must
answer: the Secretary of Health and Human Services (in
the President’s cabinet), the Congress (which provides
funding and oversight), the American public, activ-
ist groups (consumer groups, lobbies, etc.), the media
(press, TV, Internet, blogs, etc.), the pharmaceutical
industry, other healthcare players, and, indirectly, for-
eign health agencies.
Pharmaceutical companies also have multiple cli-
ents but some are different: the stockholders (owners) of
the company, the Securities and Exchange Commission,
the American public, activist groups, the media, licens-
ing partners, academic collaborators, trade groups, the
FDA, and, for multinational companies, other health
agencies, insurance companies and other payers, and
foreign media.
The FDA’s fundamental viewpoint and raison d’être
differ from those of pharmaceutical corporations. The
FDA’s prime concern is protecting the American public
(and animals). They are, in theory, not concerned with
the viability or profitability of corporations or market
share, whereas companies, again in theory, have a pri-
mary fiduciary goal of increasing shareholder value.
Obviously, a company would not want to increase its
stock price at the expense of the public health. But, in
practice, decisions on what is good or bad for public
health are almost never black and white. Rather, they
are the subject of debate on the risks and benefits that
usually fall somewhere in the gray area between the
extremes. Nevertheless, it is in the interest of the pub-
lic health for the public and healthcare community to
have access to medical products when needed; all stake-
holders should strive to ensure that the benefits of these
products outweigh their risks.
44 Cobert’s Manual of Drug Safety and Pharmacovigilance
Other factors come into play. In general, salaries
and bonuses, particularly for professionals, are often
better in private sector companies than in the FDA or
academia. However, benefits, pensions, and retirement
packages are often better in government service. Private
sector companies tend to have more resources (peo-
ple, computers, parking spaces, etc.) than government
agencies.
As with other federal agencies, there is often a
steady flow of personnel leaving the Agency to go to
the private sector and, with the FDA, occasionally vice
versa. This is generally viewed as a good phenome-
non because it allows government workers to under-
stand the functions and pressures in private industry
and for private industry personnel to understand how
government agencies function. Others feel this is a bad
concept as it binds the regulators and the regulated too
closely together and influences the actions of regula-
tors who may want to get a job in industry after leav-
ing the Agency. Many people enter the industry or the
FDA from academia, often just after finishing training
(in medicine, pharmacy, nursing, pharmacology, toxi-
cology, statistics, IT, etc.) and, thus, the “first job” pro-
vides basic training that is essential for success in either
industry or the government.
There is a continuing debate, which varies in inten-
sity and persistence over time, on whether the FDA
works too slowly (“drug approval lag”) or too quickly
(“releasing dangerous drugs onto the market without
adequate evaluation”) and whether there are too many
regulations (“the biopharmaceutical industry is one of
the most regulated or over-regulated industries in the
United States”). This was very evident in the Covid era
with drugs and vaccines permitted for use often with
less than usual testing via waivers.
Most pharmaceutical companies live with a low-
level dread of the FDA and other health agencies com-
ing into their safety departments (or other departments)
to do an inspection (unannounced as a rule when done
by the FDA). The inspection may be routine, done
periodically (often every 1 to 2 years) or “for cause”
(wherein the FDA has a suspicion that all is not right).
The inspection may last from a few days to months if
major issues are found. The FDA may go to sites outside
the United States, if appropriate. Conversely, the EMA
and other agencies abroad inspect in the United States.
However, most companies now understand that build-
ing quality management systems is now obligatory, not
just in safety, but throughout the organization. They
also realize that periodic audits (including self-audits)
and governmental inspections are now part of the norm
and “a cost of doing business”. Such inspections not
only provide markers for compliance, but also serve to
promote trust in medical products and the regulatory
system.
There has been much controversy after the with-
drawal of Vioxx and other products from the US mar-
ket as well as contaminated products (e.g., heparin) for
safety reasons. Some (both from within the FDA and
from the outside) have accused the FDA of not suffi-
ciently protecting the American public from “danger-
ous” drugs, food, and other products. There have been
accusations of too rapid approval of drugs, insufficient
analysis of data submitted to the FDA, companies’ not
submitting complete or sufficient data to the FDA, and
other charges. Similar controversies have been seen
with other regulatory agencies in regard to financial reg-
ulation, air transport safety, and so forth. The PDUFA,
FDAAA, and other changes are a result of these contro-
versies. More will come.
Drug Safety Inspections
The FDA has an extensive role in doing drug safety and
PV inspections. This is covered in a subsequent chapter
in this manual.
Frequently Asked Questions
Q: Is there too close a relationship between the
FDA and the pharmaceutical industry?
A: The answer depends on whom you ask. The FDA
would (most probably) say that they are not compro-
mised by maintaining correct and formal communica-
tions with the industry. Indeed, close communication
https://avxhm.se/blogs/hill0
The United States Food and Drug Administration 45
promotes an understanding of regulatory expectations
as well as practical challenges. The industry supplies
FDA with much of the post-marketing safety data and
nearly all of the pre-marketing safety data. There must
be communication between the industry and the Agency
to clarify ambiguous points, get further information on
critical cases, and so forth. The FDA also encourages
(and legislation even requires in some cases) meetings
with the industry during the development of regula-
tion and guidance. The FDA also regularly tracks drug
development and meets with sponsors to discuss prog-
ress and next steps with investigational drugs (in the
IND phases) and in post-marketing situations where
safety issues arise. It is a professional-to-professional
exchange of information to ensure the safety of the
American public.
The industry would say that its influence on the
FDA is slight. Companies go out of their way to be sure
the FDA gets what it needs (and wants) and companies
often submit more than regulations require to be sure
that the FDA gets what it wants and that the compa-
nies are not accused of hiding or under submitting data.
The industry often (privately) believes that the FDA is
rather tough and tends to not give the industry a fair
shake or a level playing field. Some feel the FDA treats
big pharma differently from small pharma or start-up
companies, cutting the latter a little more slack and giv-
ing them more “hand-holding”.
There has been speculation that the substantial
PDUFA fees provided by industry for scientific assess-
ment of new data by FDA “guarantee” new product
approval, i.e., payment for a positive opinion. For
example, in 2017 the fee for review of an application
with clinical data was $2,038,100. Of course, integrity
and objectivity of FDA reviewers is not adversely influ-
enced by payments to the Agency (not to individuals)
for operational expenses that improve efficiency of the
drug review process.
Others claim that there is too much interchange of
personnel between the FDA and industry, wherein some
people start their careers or spend some time at the FDA
and then move on to work for pharma companies, or
vice versa, carrying with them their contacts and inner
knowledge (which often becomes outmoded quickly)
of the other. Some feel that this may influence a person’s
actions in the company or FDA since his or her next job
may be for the “other side”.
The consumer groups and activists believe that
the FDA is indeed in bed with the industry and point
to the various “fiascos” in safety that have occurred,
such as Vioxx, Fen-Phen, suicide in pediatric patients
on antidepressants, and contaminated heparin, Oxy-
contin and other opioids, and vaping among others.
The FDA and the industry would (probably) counter
by saying, quite the contrary that these episodes have
shown that the drug safety system in place is indeed
functioning and functioning well; the real challenge
is to identify these problems earlier and manage the
emerging risks.
These criticisms have been made for many other
federal agencies, including regulators of banks, insur-
ance companies, Wall Street, the airline industry, and
car manufacturers. This is a fascinating and controver-
sial area that is and will remain a work in progress for
the foreseeable future.
Q: Should the FDA be broken up into an
approving body and a safety body, similar to
some other federal regulatory agencies?
A: This proposal has been advanced in the last several
years. The argument is that the people who approve a
drug have a vested (and emotional) interest in seeing
their drug stay on the market and may not act vigorously
on safety matters as this might be a tacit admission
that their original approval decision was incorrect or
too hasty. Organizationally, these functions are already
split, but within CDER. It is claimed that separate
reviewers should oversee safety, as they have no inter-
est in defending an approval decision and they would
be able to better interpret real world evidence, i.e.,
understand impact of bias and confounders, in data
from the post-marketing phase. Thus, the medical skill
set involved in post-marketing safety review is argu-
ably different from that required in pre-approval safety
review, which focuses on controlled clinical trial data.
In all instances, however, safety assessment must always
be considered in the context of benefit. Separating the
functions would discount the knowledge the reviewing
46 Cobert’s Manual of Drug Safety and Pharmacovigilance
group has obtained over months and years of review of
a product, moving post-marketing follow-up to people
unfamiliar with the drug. This also would increase the
bureaucracy and be more costly. In addition, complete
separation would introduce additional challenges in the
pre-approval phase when non-routine safety interven-
tions, e.g., REMS, are under discussion. Clearly, each
side has valid points. What will evolve will most likely
be a political decision. There has also been talk of sepa-
rating the food part of FDA into a separate agency. This
too is under evaluation. It is possible, given the many
issues on vaccines, waivers, communication with the
public, new untested or minimally tested products that
appeared during the Covid period in the early 2020s,
that a whole new look at FDA and CDC will occur.
CHAPTER
47
5
The European
Medicines Agency
I
n 1995, the European Medicines
Evaluation Agency (EMEA), now
called European Medicines Agency
(EMA) but also “the Agency,” was cre-
ated and based in London, England but
was moved to Amsterdam, The Neth-
erlands after Brexit. Now, over two
decades later, the face of drug regula-
tion in Europe has totally changed. In
2010, a new PV Regulation was issued
generating hundreds of associated
Directives, Guidances, Q&A, etc. This
“tsunami” continues to evolve with
ongoing new or updated regulatory
documents which continue to be pub-
lished. See the very extensive website
of the EMA. In addition to English, the
EMA website is available in official
languages of the EU. Regulators in the
Member States have their own websites.
We will examine the EMA in detail and
take a brief look at one Member State’s
Health Agency: France.
Introduction
Like the US FDA, the EMA’s main responsibility is the
protection and promotion of public and animal health
through the evaluation, supervision, and safety moni-
toring of medicines throughout the European Union.
The EU comprises 27 countries (Member States), as
well as the three European Free Trade Area (EFTA)
nations of Iceland, Liechtenstein, and Norway. These 30
countries are also referred to as the European Economic
Area (EEA).
48 Cobert’s Manual of Drug Safety and Pharmacovigilance
Switzerland also works closely with the EMA,
particularly in areas regarding inspections, but is not
within the EU.
Due to Brexit, the EMA
moved from London
to Amsterdam, The
Netherlands and the
number of EU countries is
back to 27. Note that there
is a pathway for additional
jurisdictions to enter the EU.
Registration Procedures in
the EU
All medicines must be authorized (“approved”) before
they can be marketed. There are two main ways for
authorizing medicines: a centralized process and a
national one (that is, non-centralized).
Centralized Authorization Procedure (CAP):
Pharmaceutical companies submit one single Marketing-
Authorization Application (MAA) to EMA. EMA’s Com-
mittee for Medicinal Products for Human Use (CHMP)
then, using scientific resources provided by the Member
States), carries out a scientific assessment of the appli-
cation and makes a recommendation (an “opinion”) to
the European Commission on whether the medicine
should be marketed or not, i.e., the EMA functions as a
coordinating agency and does not have direct authority
to authorize medicinal products.
Once granted by the European Commission, the
centralized MA is valid in all EU Member States as well
as in the European Economic Area (EEA). The new
or innovative medicines pass through the centralized
authorization procedure in order to be marketed in the
EU. This allows the marketing authorization holder
(MAH) to market the medicine throughout the EEA
on the basis of one single marketing authorization. The
centralized process is required for certain medicines,
e.g., biosimilars, gene therapies, etc.
National Authorization Procedures: Many
medicines available in the EU have been authorized
at national level, either because they were authorized
before EMA’s creation (1995) or they were not within
the scope of the centralized procedure. Each EU Mem-
ber State had, and still has, its own national authoriza-
tion procedures. If a company wishes to request a MA in
several EU Member States for a medicine that is outside
the scope of the centralized procedure, it may use one
of the following routes:
Mutual Recognition Procedure (MRP), whereby a
marketing authorization granted in one Member
State can be recognized in other EU countries; or
Decentralized procedure, whereby a medicine that
has not yet been authorized in the EU can be simul-
taneously authorized in several EU Member States.
Note: For issues that occur after authorization (e.g.,
safety concerns), the CHMP handles centrally-licensed
products. The Coordination Group for Mutual Recogni-
tion and Decentralized Procedures — human (CMD(h))
handles nationally-registered medicines and reports to
the Heads of Medicines Agencies (HMA). The Pharma-
covigilance Risk Assessment Committee (PRAC) (see
below) is the senior committee that then handles all
authorized products and makes recommendations to
both CHMP and CMD(h).
European Medicines Agency
The EMA serves a market about 510 million people liv-
ing in the EEA. The terminology in Europe can be a bit
confusing as the EU/EEA is not the European equiv-
alent of the United States. The EEA is composed of
sovereign nations, which still retain many powers and
functions. They are linked by a variety of treaties. Some
governmental functions are devolved in full or in part
to the “central” authority (in Brussels and Strasbourg)
and others are retained by the national governments.
Not all countries devolve the same functions to the cen-
tral authority. Thus, the EU/EEA’s handling of drugs and
drug safety is like but, in many ways, quite different
from that of the FDA or other single, national health
agency.
https://avxhm.se/blogs/hill0
The European Medicines Agency 49
Organization and Structure
The EMA handles human and veterinary medicinal
products (but not food, unlike the FDA). Whatever the
registration status, the EMA goal is to ensure harmo-
nized safety surveillance for all EU countries.
The EMA principle is based on a central organi-
zation (~900 EMA permanent employees), supported
by ~4,500 experts, who conduct the detailed, work of
the Agency by sitting on scientific and medical com-
mittees, working groups, and assessment teams. These
experts are made available by the Member States, and
usually reside in the Member States but may attend
periodic meetings in the Member States, at the EMA,
or elsewhere.
The EMA is headed by an executive director with
seven reporting divisions: The Advisory Functions,
the Human Medicines, the Veterinary Medicines, the
Stakeholders and Communication, the Task Forces, the
Information Management and the Administration and
Corporate Management. “Inspections, Human Med-
icines Pharmacovigilance & Committees Division”
handles drug safety. The other Divisions are “Human
Medicines Research & Development Support”, “Human
Medicines Evaluation”, “Veterinary Medicines”,
“Administration and Corporate Management”, “Infor-
mation Management” and “Stakeholders & Communi-
cation”. See the organization chart below or on the EMA
website for an organogram snapshot as of late 2023. As
with any organization, changes occur over time (http://
www.ema.europa.eu/ema/). As of 2023, seven scientific
committees, with members from all 31 EU/EEA states,
handle the main scientific work of the Agency:
· Committee for Medicinal Products for Human
Use (CHMP);
· Pharmacovigilance Risk Assessment Committee
(PRAC);
· Committee for Medicinal Products for Veterinary
Use (CVMP);
· Committee for Orphan Medicinal Products
(COMP);
· Committee on Herbal Medicinal Products
(HMPC);
· Paediatric Committee (PDCO);
· Committee for Advanced Therapies (CAT).
Note 1: Within these committees, the role of each
EU country representative is not to defend a local rec-
ommendation but to ensure that the EU decision is
actually applicable to and valid for all EU countries.
Note 2: The EMA has a number of working parties
and related groups in place. They advise EMA’s scientific
committees on issues relating to their fields of expertise
(e.g. Biologics or Biosimilar Working Parties, etc.).
Note 3: The CMD(h) covers a variety of issues
related to new applications, variations, renewals and
pharmacovigilance activities for nationally-authorized
medicines. It is not strictly-speaking an EMA Commit-
tee even if CMD(h) meetings are held at the EMA.
The highest-level committee handling human med-
icines is the Committee for Medicinal Products for
Human Use (CHMP). It is responsible for the following:
Conducting the initial assessment of EU-wide
(i.e., centralized process) marketing authorization
applications,
Assessing modifications or extensions (“varia-
tions”) to an existing marketing authorization.
Considering the recommendations of the Agen-
cy’s PRAC regarding the safety of medicines on the
market and, when necessary, recommending to the
European Commission (EC) changes to a medicine’s
marketing authorization, or, in extreme instances,
its suspension or withdrawal from the market. The
EC is the senior level of management, is above the
CHMP and PRAC, and can act on the opinions of
the CHMP, i.e., has the authority to authorize a
product.