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20 Cobert’s Manual of Drug Safety and Pharmacovigilance
may be created at multiple levels of government (fed-
eral, state, and local). Regulation of interstate com-
merce is the FDA’s main enforcement authority.
The law governing investigational drugs (“New
Drugs”) is found in Section 505(i) [21 U.S.C. 355], and
the law governing marketed drugs is found in Section
505(k) of the Food Drug and Cosmetic Act.
In addition to laws, the US Food and Drug Adminis-
tration (FDA) is empowered by Congress to create reg-
ulations. Regulations are rules issued by government
authorities under the power of laws. Regulations thus
have the force of law. To create a regulation, the FDA
publishes the proposed version of the new or amended
regulation in the Federal Register (https://www.federal
register.gov/). A period is defined during which time
the public may send written comments on the proposal
to the FDA. After review, a final regulation is published
in the Federal Register and in the Code of Federal Reg-
ulations (https://www.ecfr.gov). A long period may
elapse between publishing the draft and the final reg-
ulation (e.g., 6 months or more) and FDA is under no
obligation to finalize a draft regulation or guidance.
Also, a draft regulation or guidance may be withdrawn.
While a proposed or final regulation may be published
and put into force anytime, the Code of Federal Reg-
ulations is updated with final regulations once a year,
on April 1st.
Finally, the FDA issues guidances that contain FDA’s
preferences on how to comply with the agency’s inter-
pretation of laws and regulations. Regulatory guidances
are often offshoots of guidelines that are developed by
consensus organizations, e.g., the International Council
for Harmonization (ICH) or the Council of International
Organizations of Medical Sciences (CIOMS).
As the FDA states on its Center for Drug Evalua-
tion and Research (CDER) Guidance page: “Guidance
documents represent the Agency’s current thinking
on a particular subject. They do not create or confer
any rights for or on any person and do not operate to
bind FDA or the public. An alternative approach may
be used if such approach satisfies the requirements of
the applicable statute, regulations, or both.” However,
it is generally held in practice in the industry to be a
wise course of action to follow FDA guidances as they
outline what the FDA currently expects. Some of the
applicable pharmacovigilance (PV) guidances can be
found by simply looking through www.fda.gov.
European Union
The EU situation is different from that in the US, because
the EU is composed of 27 separate Member States (for-
merly 28 before the UK left the EU — Brexit) plus
three affiliated states that are organized differently from
the 50 United States. The EU member states are sover-
eign countries, whereas the states that make up the US
are not. The EU member states are Austria, Belgium,
Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Ireland,
Italy, Latvia, Lithuania, Luxembourg, Malta, the Neth-
erlands, Poland, Portugal, Romania, Slovakia, Slovenia,
Spain, and Sweden. Additional countries have indicated
a desire to become part of the EU: Albania, Bosnia and
Herzegovina, Moldova, Montenegro, North Macedonia,
Serbia, Turkey, and Ukraine. These countries are working
to adopt laws and values of the EU, albeit often with local
nuances. How this will affect PV is unclear at this time.
The European legislation often refers to and applies
to the European Economic Area (EEA), which consists
of the 27 EU member states plus Iceland, Liechtenstein,
and Norway. These latter three countries are not EU
member states but participate in much of the EU sin-
gle market and adopt the EU PV legislation. To com-
plicate matters further, one sometimes sees reference
to the European Free Trade Association (EFTA), which
was set up originally for countries not in the European
Union. The EFTA now includes only Iceland, Norway,
Switzerland, and Liechtenstein. (Note that Switzerland
is not part of the EU.) The Committee for Medicinal
Products for Human Use (CHMP)) which facilitates
scientific evaluation of medicinal products in the EEA,
using resources from the 27 EU countries and Iceland
and Norway.
EU “primary legislation” derives from treaties and
agreements among the Member States. This includes
the Single European Act (1987), the Maastricht Treaty
(1992), the Treaty of Amsterdam (1997), and the Lis-
bon Treaty (2007). “Secondary legislation” derives from
the treaties. There are several types. The ones that touch
most on PV are as follows:
https://avxhm.se/blogs/hill0
Regulations, Directives, Guidance, Laws and Consensus Documents 21
Regulations: Directly applicable and binding in
all EU Member States without the need for any addi-
tional national implementation legislation. That is,
the regulation as it is published is, word for word,
becomes the law in each of the Member States. Note
that this is different from the use of the word regu-
lation in the United States.
Directives: This legislation binds member states
to the objectives of the legislation within a certain
timeframe but allows each Member State to create
its own form of national law to achieve it. That is,
each member state may modify the wording and
requirements of the directive as long as the objec-
tives of the directive are met.
Recommendations, guidelines, and opin-
ions: Similar to FDA guidances, though EU guide-
lines usually hold the force of law and are obligatory.
If Regulations and Directives are in effect for several
years while recommendations, guidelines and opinions
are frequently updated.
When translated into local law, each EU country
can include additional requirements which are then
country-specific. Thus, this can lead to somewhat dif-
ferent detailed requirements in various Member States.
The main EU website is, and the website cov-
ering legislation can be found at https://europa.eu/
european-union/law_en.
The key EU regulatory and procedural documents
relating to PV can be found at on the EU EMA website.
Guidelines can be found at www.ema.europa.eu
This site contains “Good Pharmacovigilance Practices
(GVPs)”, which consist of over a dozen “guidelines” for
post-marketing PV, which are referred to as “modules”, as
well as multiple other documents and “annexes”. These
annexes include other documents and templates. These
“guidelines” are soft law in the EU and are obligatory,
unlike the FDA “guidances”, as noted above, which are
not obligatory (although still within your best interest
to follow and implement). The modules are discussed in
the individual chapters ((in this manual covering each
module’s topics. Each module has requirements for reg-
ulators as well as for applicants (companies).
The EU situation regarding drug safety is, in many
ways, far more complex than the US situation. In the
US, the requirements for drug safety come primarily
from the FDA. Some state and local requirements apply
to PV for companies, but in practice, these do not touch
on drug safety as much as reimbursement, formularies,
health insurance, dispensing, and other non-PV areas.
There are, occasionally, requirements for registries or
other safety obligations imposed by other governmental
entities, such as the National Institutes of Health (NIH)
and the National Cancer Institute (NCI) for clinical
trials, as well as Risk Evaluation and Mitigation Strat-
egies (REMS) and other post-marketing obligations on
NDA or BLA holders. The US regulations are relatively
concise and far less detailed than the EU requirements.
Many of the US requirements actually fall under guid-
ances which, although strictly non-obligatory, have in
fact become standard practices and are de facto oblig-
atory. For example, Data Monitoring Committees
(DMCs) are described in a guidance but have become
more or less standard in most phase III clinical trials
and are expected by FDA.
In contrast, the EU requirements are highly detailed
and run to thousands of pages. Many people have
said that the US requirements are not detailed enough
(“Show me exactly where the regulations say that I have
to do this, some say the level of detail in the US affords
interpretive flexibility for different organizations while
others are of the opinion that the EU regulations are too
highly detailed. Another complaint is that many of the
EU modules have been revised several times since their
creation in 2012 whereas US regulations are revised far
less frequently.
The EU has the supra-national body of directives,
regulations, and such from the European Medicines
Agency (EMA) (empowered by the European Commis-
sion, Parliament, Council of Ministers in Brussels), as
well as legal requirements in each Member State, which
may differ from or add onto the European Union-level
requirements. EU documents are generally available in
many of the EU languages (of which there are 24 offi-
cial ones: Bulgarian, Croatian, Czech, Danish, Dutch,
English, Estonian, Finnish, French, German, Greek,
Hungarian, Irish, Italian, Latvian, Lithuanian, Maltese,
Polish, Portuguese, Romanian, Slovak, Slovene, Span-
ish and Swedish.) Interestingly, the working language
of the EU has largely been English. Translation has had
a few challenges. Now that the UK has left the EU, there
22 Cobert’s Manual of Drug Safety and Pharmacovigilance
are only two small English-speaking countries (Malta
and Ireland), one wonders if English will be used less
frequently though so far English still predominates.
Member State documents are published in the official
language(s) of the Member State but are not consistently
published in other languages. Local documents are often
not available in English. Most, if not all, EU-level doc-
uments are available in English. Summaries of Product
Characteristics (SmPCs), for example, are usually avail-
able in the official language of each country where the
product is approved. National documents may only be
available in that country’s The base SmPC language for
centrally-authorized products is English language.
Any company dealing in the EU must obtain exper-
tise at the European and Member State level to stay in
compliance with all safety obligations. In practice, this
usually means the creation of affiliates or subsidiaries or
the hiring of local companies or agents in the European
countries where the drug is sold or studied.
In particular, the EU requires the presence of a Qual-
ified Person for Pharmacovigilance (EU QPPV). Direc-
tive 2010/84/EU: “The qualified person (…) shall reside
and operate in the Union and shall be responsible for
the establishment and maintenance of the PV system”
and GVP Module 1: the EU QPPV “shall have sufficient
authority to influence the performance of the quality
system and the PV activities and to promote, maintain
and improve compliance with the legal requirements”.
The QPPV is the first EMA contact person for PV activ-
ities as well as for preparing reports and responding to
questions on safety matters, including the continuous,
ongoing risk–benefit analyses of authorized products.
Consensus Documents
These are reviewed elsewhere in this manual. Most of
the consensus documents that have been developed
have been done by international organizations, such
as CIOMS, ICH, or ISO. These documents represent
the agreed-on consensus for best/optimal practices by
governments and pharmaceutical companies and oth-
ers involved in pharmaceutical research, development,
and sales. Many countries and governments do indeed
adopt these documents as the laws or regulations in
their countries. Others adopt them with changes.
The key point here is that these documents them-
selves do not hold the force of law and do not have to
be followed unless a particular country or health agency
implements them into law or regulations. Thus, one
must examine the PV requirements in each country or
jurisdiction where one is working.
The Practice
In practice, the laws and regulations often leave areas
of ambiguity. No law or regulation is ever able to pre-
dict or account for every conceivable circumstance that
may arise. Where feasible, a “guidance” or some other
agency document is issued to clarify issues and intent.
However, it is a complex, time-consuming, and diffi-
cult bureaucratic process to create laws, guidances, and
regulations, and there is always a time lag between the
need for a clarification and the publication of such.
For example, the definition of serious would seem
fairly clear:
Any adverse drug experience occurring at any
dose that results in ... death, a life-threatening
adverse drug experience, inpatient hospitaliza-
tion or prolongation of existing hospitalization,
a persistent or significant disability/incapacity
or congenital anomaly/birth defect. Important
medical events that may not result in death, be
life-threatening, or require hospitalization may
be considered a serious adverse drug experience
when, based upon appropriate medical judg-
ment, they may jeopardize the patient or subject
and may require medical or surgical interven-
tion to prevent one of the outcomes listed in this
definition.
In fact, several areas are unclear, and there have
been a long series of dialogues, publications, and meet-
ings to address such ambiguities:
1. Is staying in a hospital emergency room over-
night considered inpatient hospitalization (and
https://avxhm.se/blogs/hill0
Regulations, Directives, Guidance, Laws and Consensus Documents 23
thus a serious adverse event, SAE)? The consen-
sus: No. It is highly recommended to address the
definition of “hospitalization” in the protocol
and to clarify if a <24 hr stay constitutes “hospi-
talization” or not.
2. Is a preplanned inpatient hospitalization that
occurs after an adverse event (AE) but perhaps
for a totally separate condition considered inpa-
tient hospitalization (and thus a SAE)? The con-
sensus: No.
3. Is a pre-planned inpatient hospitalization for a
cosmetic or elective procedure considered “hos-
pitlization” and an AE? The consensus: No.
4. What is an “important medical event”? Is throm-
bocytopenia, if the count is 5,000 platelets per
microliter? Yes. 50,000? Probably yes. 350,000
(where the normal is up to 400,000)? Probably no.
5. Is pulmonary embolism an important medical
event? Is the event considered to be clinically
significant enough to warrent further investiga-
tion as the ultimate outcome of the event could
adversely affect the patient?
6. What is “medically important” or “significant”?
There is no clear consensus on this. It is left to
individual reviewers’ and reporters’ judgments.
Thus, in circumstances where there is no clear
answer, the best approach is to take the most conserva-
tive course of action and “overcall”:
If the question is between serious and non-serious,
prefer serious.
If the question is between reporting and not report-
ing a case to the health authority, prefer reporting.
Calls to the agencies are possible to ask such
questions, but it is not always possible to reach the
right person to have a policy question answered. Most
agencies discourage this practice as it would be bur-
densome to them. If one does succeed in getting an
opinion from an agency on a tricky issue, try to get
a written confirmation. If that is not possible, write
detailed minutes of the telephone call and file them
with the case. For cases submitted to multiple health
authorities around the world, it is not practical to
call each authority to get an answer, and it is possible
the answers would be contradictory. Again, the best
course of action is the most conservative and, thus,
defensible course.
Over-the-Counter Drugs
Reporting requirements vary from country to country.
United States
In the United States, an over-the-counter (OTC) prod-
uct is sold based on whether it got to market via (1)
an approved New Drug Application (NDA) (Rx to
OTC switch) or an Abbreviated New Drug Application
(ANDA), or (2) the OTC drug monograph process. The
Time and Extent Application (TEA) is another method
to get a product onto the market via the monograph
process, but this is rarely used.
The safety obligations depend on which method is
used to get the product to market. If an OTC product
has an approved NDA, the requirements are the same as
for a prescription product (expedited reports, periodic
reports, etc.). For monograph products, the situation
is different. Until 2007, there were no obligatory safety
reporting requirements, though many manufacturers
voluntarily reported SAEs to the FDA.
The regulations and guidances changed when the
federal government put forth the following:
1. Dietary Supplement and Nonprescription Drug
Consumer Protection Act, December 2006.
2. Guidance for Industry Postmarketing Adverse
Event Reporting for Nonprescription Human
Drug Products Marketed Without an Approved
Application, July 2009.
These documents changed the reporting require-
ments for the monograph products:
1. A manufacturer, packer, or distributor whose
name is on the label (called the “responsible
24 Cobert’s Manual of Drug Safety and Pharmacovigilance
person”) must submit to FDA all SAEs with a
copy of the label within 15 business days.
2. All follow-up information received within 1 year
of the initial report must be submitted within 15
business days.
The requirements say one year, but FDA
expects reports with no time limit. That is,
report all follow-ups forever.
3. Report electronically, using E2B according to
FDA’s specifications (MedWatch forms are not
accepted from manufacturers, but can be used by
consumers and the healthcare community).
4. Use NDA definitions for minimum criteria,
reportability, and so forth.
For brand families need to know the active
ingredient to have a reportable drug.
If multiple suspect drugs, submit Individual
Case Safety Report (ICSR) to FDA and to
other manufacturers.
5. No aggregate reporting requirements, but FDA
has occasionally requested ad hoc compilations
or reports to address safety concerns.
6. Reporting requirements for NDA/ANDA prod-
ucts were unchanged because of the changed
OTC requirements.
European Union
In the EU, all marketed drugs (OTC or Rx) have a Mar-
keting Authorization (MA). Thus, all OTC drug products
have the PV requirements for prescription requirements
(expedited reporting, PSURs, signals and risk man-
agement, labelling etc.) Local requirements should be
checked for products, such as neutraceutical and herbal
preparations, etc. Agencies collect AEs on OTC products
(e.g., the Medicines and Healthcare Products Regula-
tory Agency, MHRA, collects them under its Yellow Card
Scheme). In other words, PV requirements for an OTC
drug in the EU are the same as for Rx drugs.
If a product is sold in both the US and the EU, in
practice, the product is handled as a drug with expedited
reporting, PSURs, and so forth, for global use, although
some documents (e.g., aggregate reports) would not be
submitted to FDA if not required.
Staying Up to Date
As noted in multiple places throughout this manual, the
world of drug safety is changing almost daily. Person-
nel handling drug safety and PV must stay up to date
with changes that occur both in the scientific and med-
ical world (new SAEs, new interactions, etc.) for drugs
they handle and in the regulatory–operational world.
The best way to do both is through journals, meetings,
conferences, networking, and the Internet. There are
also vendors who will survey the landscape and provide
updates to subscribers.
Scientific/Medical Literature
New and important medical information on areas that
involve drug safety are found in many medical journals
throughout the world, including major pharmacology
and medical publications, such as the New England Jour-
nal of Medicine, the Lancet, the Annals of Internal Medi-
cine, and specialized drug safety journals, including:
1. Drug Safety is published by Springer/Adis.
2. AdisInsight Safety is a worldwide resource for PV
literature monitoring. It provides access to pub-
lished adverse drug reaction case reports, drug
safety studies and regulatory news covering all
drugs and therapeutic areas, updated daily
3. Expert Opinion on Drug Safety) covers medical
issues on particular drugs.
4. Pharmacoepidemiology and Drug Safety is the
official journal of the International Society for
Pharmacoepidemiology.
5. Therapeutic Innovation and Regulatory Science,
formerly known as the Drug Information Journal,
published by the Drug Information Association.
This journal carries articles on the whole field
of pharmaceuticals, including sections on drug
safety.
6. There is an expectation (and a requirement in
some jurisdictions) that relevant “local” jour-
nals (in the local language) will be identified and
periodically reviewed as part of an ongoing com-
prehensive literature survey.
https://avxhm.se/blogs/hill0
Regulations, Directives, Guidance, Laws and Consensus Documents 25
There are online and open access journals pub-
lished now that cover many medical areas including PV.
Some claim to be refereed.
There are also multiple blogs that cover PV news.
They vary in reliability. There are also many PV groups
on various websites, such as LinkedIn. They are gener-
ally not curated and also vary in terms of reliability.
It is likely AI will play a larger and larger role in
tracking PV sources, journals, courses, etc. As of now,
however, many of the AI sites do not yet connect
to the Internet and thus, the many of the large post-
marketing databases contain data that are incomplete as
of one to three years ago. This will likely improve over
time. Watch this space.
Meetings and Conferences
Many conferences cover drug safety only or have sec-
tions dedicated to drug safety.
1. Drug Information Association (DIA) holds
many conferences in the United States, Canada,
Europe, and Asia, as well as sessions before and
during annual meetings held in several regions.
Each year, conferences on drug safety are held in
the US and there are annual conferences in the
EU, Asia, and elsewhere.
2. Other private (non-profit) organizations offer
training, including the Pharmaceutical Education
and Research Institute (PERI) (www.peri.org),
the Uppsala Monitoring Centre (https://www.
who-umc.org/) and the Drug Safety Research
Unit (http://www.dsru.org/courses/).
3. The FDA, Health Canada, EMA and MHRA often
conduct PV training sessions or hold virtual
meetings to address relevant topics.
4. The International Society for Pharmacovigi-
lance (ISoP) holds meetings and training courses
(http://isoponline.org/).
5. The International Society for Pharmacoepide-
miology (ISPE) has conferences, meetings, and
training courses (https://www.pharmacoepi.
org/).
6. The FDA and certain other agencies hold advi-
sory committee meetings and hearings that are
open to the public. Some are also transmitted
online or are available as podcasts or webinars
on the respective websites.
7. The Regulatory Affairs Professionals Society
(www.raps.org) has training sessions and con-
ferences on the general field of regulatory affairs
and sometimes addresses drug safety.
8. Many private, for-profit organizations train in
drug safety on all continents. They are best found
by doing a Google search on drug safety confer-
ences. They vary in quality. Caveat emptor. Vari-
ous companies, institutions, individuals etc. now
claim to offer certification in PV, and some enti-
ties in Europe offer graduate degrees in Pharma-
covigilance (Eu2P for example), however there
is no “official” or “global” recognized body doing
this.
The Internet
There are many resources on the internet. They are
ever-changing, with new ones appearing, old ones dis-
appearing, and current ones changing:
1. Government e-mail alerts, e-newslet-
ters, Facebook, X (formerly known as
Twitter) and others: The FDA, EMA, MHRA,
Health Canada, TGA, and many other govern-
mental agencies issue periodic alerts in various
fora.
2. Fierce Pharma (https://www.fiercepharma.
com/): This is a set of daily publications on vari-
ous areas of the industry.
3. Blogs: There are many blogs on the pharma
industry, some serious, some outrageous, some
outraged, all opinionated. They change fre-
quently and their credibility varies. Best found
by a periodic Google search. Caveat emptor.
4. Google Alerts: An excellent Google function is
called Google Alerts. This is an automated mech-
anism that can be set up on Google to deliver,
as news becomes available, daily or weekly
26 Cobert’s Manual of Drug Safety and Pharmacovigilance
information found on the net. The use of key-
words such as “PV” and “drug safety” will bring
interesting news, press releases, blog addresses,
and sites (https://www.google.com/alerts).
It is easy to spend one’s entire day just reading blogs
and news on the Internet. A good compromise would be
to find one or two sources that provide the updates the
reader needs for his or her work. Attending (whether
live or on virtual media) a conference on drug safety
once or twice a year is also valuable for both updates
and networking.
CHAPTER
27
4
The United States
Food and Drug
Administration
T
he “granddaddy” of drug safety
“regulatory agencies” dates back
to 18th century Japan, when the
eighth shogun, Yoshimune Tokugawa
(1716–1745), upon recovering from an
illness, awarded 124 medicinal traders
in Osaka special privileges to exam-
ine medicines throughout the country.
However, the safety of the medicines
was difficult to guarantee despite
these efforts. A shrine in Osaka, called
Shinno-san, was created and dedicated
to Shinno, the guardian of the phar-
maceutical industry and the divine
founder of medicine from China. This
information was found at the Osaka
tourism website.
Introduction
Very often governments have responded to misbehavior
or tragedies by strengthening laws intended to address
perceived shortcomings in protecting patient safety. In
the past 30 or so years, the number of organizations
devoted to drug safety has increased markedly outside
the United States. This chapter is focused on key activ-
ities of the US Food and Drug Administration (FDA),
which regulates biopharmaceutical products and med-
ical devices for human use. FDA also regulates certain
foods and veterinary products, for a total of more than
US $2.4 trillion worth of products each year. The latter
topics are outside the scope of this chapter.
28 Cobert’s Manual of Drug Safety and Pharmacovigilance
The FDA is a complex organization with over
15,000 employees strategically posted at US domestic
locations and overseas stations. Several distinct parts of
FDA handle safety matters. The largest areas touching
drug safety reside within the Center for Drug Evalua-
tion and Research (CDER) and the Center for Biologics
Evaluation and Research (CBER). In addition, within
CDER and CBER, functions are generally split between
pre- and post-marketing regulatory activities.
The FDA has undergone, and continues to undergo,
major changes following various scientific, public, and
political controversies, drug withdrawals, investiga-
tions, and changes in the law. This chapter will summa-
rize the key functions that deal with medical product
safety and will outline some of the initiatives that will
undoubtedly lead to further advances in “regulatory sci-
ence” in the coming years. The current organization of
the agency is posted on the FDA website and the infor-
mation is regularly updated with any changes.
Center for Drug Evaluation
and Research
This is the prime (and largest) center in the FDA for
handling the safety of biopharmaceutical products in
the US. The Center for Drug Evaluation and Research
(CDER) handles new drugs from the IND stage (when
a product first moves into human study) to the evalu-
ation of the NDA/ANDA or BLA for approval or rejec-
tion of the request to market the product in the United
States. A separate group within CDER then evaluates
the post-marketing safety of the product continuously.
Although simple in theory, the actual practice is com-
plex and has evolved over time. It continues to change,
often in response to Congressional mandate, and should
be viewed as a work in progress.
The FDA organization chart is posted online and
is quite useful. It gives names, addresses, and contact
information on the FDA organization and key person-
nel (www.fda.gov). The chart is updated regularly with
changes (see below). When this chapter was written,
there were 45 “offices” in CDER covering many areas,
including biotechnology, new medical product evalu-
ation, counterterrorism, pediatric drug development,
generic drugs (including biosimilars), compliance, bio-
statistics, prescription drug promotion, translational
sciences, and, of course, product safety.
See CDER’ s website (www.fda.gov/cder). In 2017,
there were 33 advisory committees made up of exter-
nal members, who provide consultation and give expert
and consumer advice to the FDA. The FDA generally
follows an advisory committee’s recommendation, but
is not bound to do so. There is an advisory commit-
tee on Drug Safety and Risk Management that evaluates
new products and safety concerns across the product
lifecycle continuum.
The FDA reorganizes periodically. As of 2024, the
structure was as follows (this content is easily accessi-
ble via fda.gov): the Office of the CDER Center Director
has under it approximately 13 offices and each office
has several further divisions and offices including the
Office of Surveillance and Epidemiology (OSE). OSE is
considered a safety “Super Office”, available for consul-
tation on safety concerns across all of FDA, not only
CDER-regulated products. In 2024, were two Offices
and eight divisions in OSE:
Office of Pharmacovigilance and
Epidemiology
Division of Pharmacovigilance I & II (two divisions):
The staff includes safety evaluators whose primary
role is to detect and assess safety signals for all mar-
keted drug products. They work closely with med-
ical reviewers in the Office of New Drugs so that
potential safety signals are placed in the context
of existing preclinical, clinical, or pharmacologic
knowledge of the drug(s) being evaluated.
Division of Epidemiology I & II (two divisions): The
staff conducts active surveillance using the Sen-
tinel System and also conducts epidemiologic
studies using observational data sources. An
increasingly important activity is the review of epi-
demiologic study protocols, which are conducted
by applicants as post-marketing commitments or
post-marketing requirements. The Division evalu-
ates various post-marketing surveillance tools that
may be incorporated into non-routine risk mini-
mization strategies, such as patient registries and
restricted distribution systems. They estimate the
https://avxhm.se/blogs/hill0
The United States Food and Drug Administration 29
public health impact of safety signals by evaluating
digital claims databases, healthcare datasets, and
the published literature, etc.
Office of Medication Error Prevention and
Risk Management
Division of Medication Error Prevention and
Analysis (I and II) (DMEPA I & DMEPA II): The
staff provides pre-marketing reviews of all pro-
prietary names, labels, and labeling for CDER-
regulated products to reduce the potential for med-
ication errors of a proposed product. The division
also provides post-marketing review and analysis
of all medication errors received by the Agency.
Division of Risk Management (DRM): DRM serves as
the focal point for risk management activities in
CDER. DRM provides risk management expertise
on design, development, and implementation of
programs and initiatives to support the Center’s
policies related to Risk Evaluation and Mitigation
Strategies (REMS) authorities under the Food and
Drug Administration Amendments Act (FDAAA) of
2007. DRM provides input on the need for a REMS
for all new molecular entities (NMEs), original
BLAs, and post approval for serious risks that war-
rant consideration of a REMS. Additionally, DRM
reviews sponsor-proposed REMS and REMS modifi-
cations for all products with an approved REMS for
conformance with current FDA standards. REMS
decision-making is a joint decision between the
Office of Surveillance and Epidemiology (OSE) and
the Office of New Drugs. DRM serves as the REMS
experts within OSE and the scientific lead for CDER
on all new REMS and REMS modifications. In con-
junction with the Division of Mitigation Assess-
ment and Medication Error Surveillance (DMA-
MES) and Office of New Drugs, DRM participates
in the review of REMS assessment reports. DRM
consists of healthcare professionals with varied
backgrounds, including: pharmacists, physicians,
nurses, and health communication specialists.
1
Division of Mitigation Assessment and Medication
Error Surveillance: (DMAMES)
1
Office of Surveillance and Epidemiology (OSE) — Divisions | FDA
“DMAMES provides expertise to evaluate risk miti-
gation strategies and recommend regulatory actions
to ensure safe and effective use of drug products.
Our focus is on identifying and mitigating medica-
tion errors and assessing Risk Mitigation and Eval-
uation Strategies (REMS) for marketed products.
We are the lead for medication error pharmacovig-
ilance, and collaboratively work on safety signal
detection, assessment, understanding, and preven-
tion of medication errors. We also collaboratively
review proposed new REMS and REMS modifica-
tions, REMS assessment methodologies, and REMS
assessment reports. We develop standards, policies,
and approaches related to health informatics and
data management tools and techniques to support
REMS standardization and integration initiatives,
medication error prevention and analysis, use of
structured product labeling, and electronic health
record interoperability. We also work closely with
other entities, including the Institute for Safe Med-
ication Practices (ISMP), to support research and
innovation to advance the science of risk assess-
ment and mitigation and protect public health.”
FDA’ s SOP list is available (www.fda.gov). In fact,
almost all of FDA’s policies and procedures are available
on their website. The FDA has an extensive, useful web-
site, although the information tends to be scattered and
difficult to find. There is a search engine that is some-
what useful. The website has extensive information on
how the FDA works, its history, drug availability, coun-
terfeits, Internet purchases of drugs, labeling and med-
ication guides for drugs on the market, signals, REMS,
guidance, laws and regulations covering pharmaceuticals
(as well as devices, biologics, radiologic agents, over-the-
counter (OTC) products, nutraceuticals, and more). The
main CDER website lists late news and provides a jump-
ing off point to other CDER information, including:
1. FDA Basics: This provides fundamental infor-
mation on the various divisions, functions, and
leaders at FDA.
2. Drug-Specific Information: This is an
alphabetical list of drugs that have an information
sheet, Early Communication about an Ongoing
Safety Review, or other important information.