European Union Drug Approval: Overview of New European Medicines
Evaluation Agency and Approval Process (Letter Report, 04/05/96,
GAO/HEHS-96-71).

Pursuant to a congressional request, GAO reviewed: (1) the new European
Union (EU) procedures for approving new drug applications (NDA); and (2)
why the European Medicines Evaluation Agency (EMEA) was established, how
it operates, and how it is financed.

GAO found that: (1) because member states did not always accept EU or
other members' drug approvals, the EU Commission of European Communities
makes decisions on drug approvals and dispute resolutions that are
binding on all members; (2) EU has also established new approval
procedures for biotechnology, other high-technology, and innovative
products; (3) regulating drug prices and reimbursement policies remains
the responsibility of member states; (4) the centralized approval
procedure for biotechnology and some innovative products is expected to
take between 298 and 448 days; (5) the decentralized procedure allows
manufacturers to seek approval from member states and appeal denied
approvals; (6) the decentralized procedure is expected to take between
300 and 686 days; (7) industry officials are concerned about drug
evaluators' qualifications and whether EU-wide interests will be upheld
over national interests; (8) EMEA is responsible for the timeliness and
coordination of new drug approvals, administrative duties, ensuring that
drugs meet the highest standards of safety, efficacy, and quality, and
maintaining information on the drugs and their adverse reactions; (9)
the Commission and industry application fees fund EMEA, which has a
small permanent staff and 2 scientific evaluation committees that draw
on EU-wide scientific expertise; and (10) EMEA also provides advice to
companies on their trial procedures and other matters.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  HEHS-96-71
     TITLE:  European Union Drug Approval: Overview of New European 
             Medicines Evaluation Agency and Approval Process
      DATE:  04/05/96
   SUBJECT:  Pharmaceutical industry
             Foreign governments
             Product performance evaluation
             Drugs
             International cooperation
             International organizations
             Product safety
             Food and drug law
             Safety regulation

             
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Cover
================================================================ COVER


Report to the Chairman, Committee on Labor and Human Resources,
U.S.  Senate

April 1996

EUROPEAN UNION DRUG APPROVAL -
OVERVIEW OF NEW EUROPEAN MEDICINES
EVALUATION AGENCY AND APPROVAL
PROCESS

GAO/HEHS-96-71

European Drug Approval

(108235)


Abbreviations
=============================================================== ABBREV

  CPMP - Committee for Proprietary Medicinal Products
  CVMP - Committee for Veterinary Medicinal Products
  EMEA - European Medicines Evaluation Agency
  EU - European Union
  FDA - Food and Drug Administration
  NDA - new drug application

Letter
=============================================================== LETTER


B-261605

April 5, 1996

The Honorable Nancy Landon Kassebaum
Chairman, Committee on Labor and
 Human Resources
United States Senate

Dear Madam Chairman: 

The movement toward uniting individual European countries into a
single marketplace has made the European Union (EU) the largest
pharmaceutical market in the world.\1 With a population of about 370
million, the EU represents a consumer base that is one-third larger
than that of the United States.  Moreover, the EU leads the world in
the consumption of pharmaceutical products, using $82.7 billion worth
of pharmaceutical products in 1992, while the United States used
about $54.8 billion.\2

As part of its ongoing effort to establish a single European market
for pharmaceuticals, the EU recently modified its drug approval
procedures and created a new agency--the European Medicines
Evaluation Agency (EMEA)-- to provide a faster and more efficient
drug approval process that would benefit consumers and industry.\3

Given the size of the EU market and the recent regulatory changes,
advocates of reforming the U.S.  Food and Drug Administration (FDA)
have suggested that the new European drug approval process may
provide some alternative approaches for improving the timeliness of
FDA's drug approvals. 

To assist your Committee in considering various FDA reform proposals,
you asked that we (1) determine how the EU now reviews and approves
new drug applications (NDA)\4 and (2) explain why the EMEA was
established, how it operates, and how it is financed.  Because this
report uses European terms that may not be familiar to U.S.  readers,
we have defined these terms in a glossary at the end of this report. 

To gather this information, we reviewed background documents,
legislation, and status reports on the EU drug approval process and
interviewed senior officials at the EMEA and the Commission of the
European Communities, which oversees the EMEA's activities.\5 We also
interviewed representatives from two European-based pharmaceutical
companies and two pharmaceutical trade associations, as well as
several academics knowledgeable in European pharmaceutical policies. 
We conducted this study between April 1995 and March 1996 in
accordance with generally accepted government auditing standards. 


--------------------
\1 The European Union, formerly referred to as the European
Community, currently consists of 15 countries commonly referred to as
Member States.  The 15 Member States are Austria, Belgium, Denmark,
Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the
Netherlands, Portugal, Spain, Sweden, and the United Kingdom. 

\2 Eastern Research Group, Inc., Developments in International
Pharmaceutical Regulation:  Implications for the United States
(Lexington, Mass.:  Eastern Research Group, Inc., Sept.  12, 1995),
pp.  1-2. 

\3 The EMEA is also referred to as the European Agency for the
Evaluation of Medicinal Products. 

\4 The EU refers to its NDAs as marketing authorization applications. 
However, for the purposes of consistency, this report refers to both
types of applications as NDAs. 

\5 The Commission of the European Communities is the central
regulatory body in the EU that drafts legislation in the form of
directives and regulations designed to foster a single market in
Europe.  The Commission also enforces these rules. 


   RESULTS IN BRIEF
------------------------------------------------------------ Letter :1

Previous EU regulatory efforts to allow pharmaceutical companies to
market their products throughout Europe were unsuccessful because the
Commission did not require all Member States to accept the drug
approval decisions made by the Commission or other Member States.  As
a result, the EU enacted legislation in 1993 that created a new
approval process.  The legislation also made Commission decisions
binding on all Member States for both marketing biotechnology and
other high-technology products and resolving disputes among Member
States concerning drug approval decisions. 

The new drug approval process established two new procedures for
achieving EU-wide drug approvals--a centralized procedure and a
decentralized procedure.  Pharmaceutical companies must now use the
centralized procedure to obtain approval for biotechnology
products.\6 Companies may choose either the centralized or
decentralized procedure for other high-technology and innovative
products.\7

At the same time that it established new approval procedures, the
Commission created the EMEA to improve the timeliness of new drug
approvals and to ensure that biotechnology and other high-technology
pharmaceutical products meet the highest standards of safety,
efficacy, and quality. 

The new EU drug approval process and the creation of the EMEA
represent an important step toward creating a single European
marketplace for prescription drugs.  However, because the new system
has been operational for only a year, it is too soon to determine
whether it will enable pharmaceutical companies to more quickly
market their products throughout Europe. 


--------------------
\6 According to Commission regulations, biotechnology products
include those derived from recombinant DNA technology, controlled
expression of genes coding for biologically active proteins in
prokaryotes and eukaryotes, and monoclonal antibody methods. 

\7 According to Commission regulations, other high-technology and
innovative products include new delivery systems, new indications,
new manufacturing processes that represent significant innovations,
and new active substances not previously approved for human use in
the EU. 


   BACKGROUND
------------------------------------------------------------ Letter :2

Since its establishment by the Treaty of Rome in 1957, the EU has
tried to create a single market among its Member States to facilitate
the free movement of goods, services, capital, and people.  As part
of this effort, the Commission has attempted to consolidate and
harmonize many of the pharmaceutical regulations that have existed
among the Member States.  Specifically, the Commission established
two methods, called the multistate and concertation procedures,
allowing pharmaceutical products to be marketed in all the Member
States if approved by one Member State.  The Commission believed that
these methods would promote public health, by making drugs available
to patients in a more timely manner, and advance industry interests,
by stimulating investment in European research and development
activities.  However, these initial efforts were not successful
because the Commission did not require Member States to accept drug
approval decisions made by the Commission or other Member States. 

In 1975, the Commission established a multistate procedure to allow a
pharmaceutical company to market a product in all Member States if
just one of them approved the product application--a procedure
referred to as "mutual recognition." The Commission also created the
Committee for Proprietary Medicinal Products (CPMP)\8 to coordinate
the Member States' assessments of pharmaceutical products and
arbitrate disputes among the Member States regarding the marketing of
pharmaceutical products.  However, the multistate procedure was
unsuccessful in obtaining mutual recognition of drug approval
decisions because at least one Member State raised an objection to
every multistate application.  Moreover, the CPMP opinions were not
legally binding and, as a result, did not resolve disputes among the
Member States. 

In 1987, the Commission established another process--the concertation
procedure--designed to foster a single market.  Under this procedure,
the CPMP reviewed all biotechnology and other high-technology
pharmaceutical products for approval across the EU.  The EU decided
to centralize the review process for biotechnology and other
high-technology products because many of the Member States did not
have the scientific expertise needed to review such products. 
However, only 5 of 30 product applications reviewed under the
concertation procedure and approved by the CPMP were authorized for
marketing by all the Member States. 

Thus, neither the multistate nor concertation procedure achieved the
goal of free circulation of pharmaceuticals across all EU Member
States because these procedures did not compel the Member States to
accept a majority opinion of the CPMP.  While the Member States
professed allegiance to the principles of mutual recognition, their
national regulatory authorities continued to review product
applications and render their own opinions before allowing the
products to be marketed in their country.  Because the CPMP opinions
were not binding, Member States issued different decisions on drug
approvals, which prevented pharmaceutical companies from obtaining
EU-wide approval for their products. 


--------------------
\8 The CPMP was composed of representatives from each Member State's
national marketing authority. 


   NEW EU SYSTEM USES TWO DRUG
   APPROVAL PROCEDURES
------------------------------------------------------------ Letter :3

Under the new EU drug approval process, pharmaceutical companies may
use either a centralized or a decentralized procedure to obtain
approval to market their pharmaceutical products in more than one
Member State using one application.\9 These procedures modify the
former multistate and concertation procedures by (1) defining
specific review steps and establishing time limits for review
processes and (2) requiring Member States to accept as binding,
decisions that are issued by the Commission.  In addition, the CPMP,
which was formally an advisory arm of the Commission, now serves as
one of the EMEA's scientific committees.\10 The CPMP, composed of two
representatives from each Member State, renders opinions about the
safety, efficacy, and quality of human pharmaceutical products that
are binding on all the Member States. 

Although the new EU drug approval process changes the method for
obtaining a marketing authorization, it does not affect drug pricing
and reimbursement policies, which remain the responsibility of each
Member State.  Thus, in order to actually market a pharmaceutical
product approved under the new process, manufacturers must still
negotiate a product's price with individual Member States. 


--------------------
\9 Until 1998, pharmaceutical companies have a third option, called
the national route, which allows them to seek separate national
approvals to market their products in selected Member State(s).  This
report focuses only on the EU's two primary procedures for drug
approvals. 

\10 The EMEA's other scientific committee--the Committee for
Veterinary Medicinal Products (CVMP)--oversees the scientific
evaluation of pharmaceutical products for veterinary use.  This
report focuses only on the process for reviewing and approving new
drugs for human use. 


      THE CENTRALIZED PROCEDURE
---------------------------------------------------------- Letter :3.1

Pharmaceutical companies are now required to use the centralized
procedure for biotechnology products and have the option to use it
for other innovative products.  Under the centralized procedure,
Commission approval of a new drug application allows a pharmaceutical
company to market its pharmaceutical product in all 15 Member States
without having to obtain separate approvals from each Member State. 

   Figure 1:  EU Centralized Drug
   Approval Procedure

   (See figure in printed
   edition.)

As shown in figure 1, once the EMEA ensures that the application is
complete, the CPMP selects two of its members--known as
rapporteurs--to perform independent scientific evaluations of the
safety, efficacy, and quality of an application.\11 The rapporteurs
can draw on two sources of EU-wide scientific expertise in forming
their review teams--experts from the national marketing authorities
of Member States and any of the 1,200 outside experts located at
universities and institutes throughout Europe.\12

Once the rapporteurs have completed their respective evaluations,
they present the results to the CPMP, which then renders an opinion. 
The CPMP must render its opinion within 210 days after the
application was submitted.\13 \14 If a CPMP opinion is favorable, it
is transmitted to the applicant, all Member States, and the
Commission.  The Commission uses the CPMP's opinion to prepare a
draft decision.  If the Member States raise important new scientific
or technical questions, the Commission may refer the case back to the
CPMP for further consideration.  At this point in the approval
process, Member States may object to the decision only if they
believe the product poses a significant risk to public health in
their country.  If no objections are raised by the Member States, the
Commission's draft decision is submitted to its Standing Committee on
Medicinal Products for Human Use.  The Standing Committee either
agrees with the Commission's decision or, if there is no qualified
majority,\15 refers the decision to the Council of Ministers for
consideration.\16 Upon request, the EMEA will inform any concerned
parties about the final decision, and the public is notified when a
marketing authorization is granted through publication in the
Official Journal of the European Communities.\17

If, on the other hand, the CPMP renders an unfavorable opinion, the
applicant may appeal the decision to the EMEA.  During the appeal
process, the CPMP may obtain the views of additional experts who were
not involved in the first consideration of the application.  The
CPMP's final opinion is processed in essentially the same manner as a
favorable opinion; that is, the final decision is made by the
Commission or Council of Ministers.  The centralized procedure is
expected to take between 298 and 448 days depending on whether the
applicant appeals an unfavorable CPMP opinion, the Member States
raise important new scientific or technical questions, or the
Standing Committee cannot reach consensus on a Commission draft
decision and refers the matter to the Council of Ministers. 

According to an EMEA official, as of December 1995, almost 1 year
after the EMEA had become operational, pharmaceutical companies had
filed or intended to file 30 new applications under the centralized
procedure, and 20 had started the evaluation process.  In addition,
the EMEA had received 18 applications submitted under the former
concertation process.  The CPMP has given positive opinions on 8 of
these 18 applications, and the Commission has granted EU marketing
authorizations for three of those opinions. 


--------------------
\11 The CPMP may also arrange tests to verify a manufacturer's
control methods described in the application or inspect the
manufacturing site. 

\12 As of December 1995, the national marketing authorities were
estimated to have approximately 1,250 staff available for the review
of human pharmaceutical products. 

\13 The clock can be temporarily stopped if the reviewers request
additional information from the applicant. 

\14 In cases in which the CPMP cannot reach consensus, the opinion
becomes the majority view; divergent opinions may be recorded in the
formal record of the opinion. 

\15 The Standing Committee includes representatives from all 15
Member States.  The number of votes each Member State has depends on
its population.  Thus, the Member States with larger populations,
such as Germany, France, Italy, and the United Kingdom, have more
votes than the less populated Member States and therefore have
greater influence over the decisions about new drug applications. 
The Standing Committee currently has a total of 87 votes, 62 of which
constitute a qualified majority. 

\16 The Council of Ministers is composed of representatives from all
the Member States.  The Council analyzes Commission proposals and
enacts EU-wide legislation. 

\17 A marketing authorization license is valid for 5 years and
renewable for 5-year periods after consideration by the EMEA. 


      THE DECENTRALIZED PROCEDURE
---------------------------------------------------------- Letter :3.2

For optional innovative products, pharmaceutical companies can either
use the EMEA's centralized procedure or follow a decentralized
procedure to obtain mutual recognition of a new drug by the EU Member
States.  Under the decentralized procedure (see fig.  2) an applicant
can go directly to a national marketing authority to obtain
permission to market its product in that Member State and then seek
to have other Member States accept the marketing approval of the
first Member State. 

   Figure 2:  EU Decentralized
   Drug Approval Procedure

   (See figure in printed
   edition.)

Once an application has been submitted, a Member State's national
marketing authority has 210 days to decide whether or not to grant an
authorization to market the product in the Member State.\18 If a
Member State grants a marketing authorization, the applicant may seek
to have one or more other Member State(s) where the applicant wishes
to market its product recognize the authorization of the first Member
State.  Within 90 days of receiving the application, the other Member
State(s) must decide whether to recognize the approval. 

If the other Member State(s) recognize the marketing authorization of
the first Member State, an applicant may market its product in each
Member State.  If the other Member State(s) raise objections to
mutual recognition that cannot be resolved within 90 days, the case
is referred to the CPMP for arbitration.  Once the CPMP gets involved
in the process, the steps are the same as those followed for the
centralized procedure.  CPMP opinions under the decentralized
procedure, once accepted by the Commission, are binding on all the
Member States. 

The decentralized approval procedure is expected to take between 300
and 686 days depending on whether other Member States object to the
marketing authorization granted by the first Member State, objections
lead to a formal arbitration by the CPMP, the applicant appeals an
unfavorable opinion, the Member States raise important new scientific
or technical questions, or the Standing Committee cannot reach
consensus on a Commission draft decision and refers the matter to the
Council of Ministers.  According to an EMEA official, as of December
1995, the EMEA had not been involved in any arbitration proceedings
relating to disputes among the Member States under the decentralized
procedure. 


--------------------
\18 Member States that receive an application for licensing a product
that is already being assessed in another Member State may proceed
with an independent assessment or suspend their assessment until the
other Member State has decided to grant or refuse the license.  If a
Member State suspends its assessment, it must so inform the applicant
and the other Member State. 


      INDUSTRY CONCERNS
---------------------------------------------------------- Letter :3.3

Pharmaceutical industry officials acknowledge that filing NDAs under
the centralized procedure will allow a company to market its
product(s) in all Member States within a relatively short period of
time at approximately 60 percent of the cost of obtaining 15
individual marketing authorizations.  However, some officials said
they are hesitant to use the centralized procedure in the short term
to obtain approval for nonbiotechnology pharmaceutical products for
several reasons. 

First, under the centralized procedure, a company has less influence
over which rapporteurs will review its application than it does under
the decentralized procedure.  While a company can request particular
rapporteurs, the CPMP will ultimately make the selection.\19
According to industry officials, firms want their preferred
rapporteurs because of the significant time and resources they have
invested in establishing relationships with certain national
marketing authorities, particularly in countries with large
pharmaceutical markets.  Under the centralized procedure, drug
sponsors are concerned that the EMEA may assign an innovative product
to a less experienced rapporteur who cannot adequately review or
convincingly support the product before the full CPMP. 

Regulatory and industry officials believe that this concern will be
somewhat mitigated by the new procedures' use of two rapporteurs. 
They expect that using two rapporteurs, rather than the one used
under earlier procedures, will improve the quality of the drug
approval process in several ways.  First, by working independently,
the two rapporteurs--and the teams they assemble--should uncover most
concerns that might be raised at a meeting of the full CPMP.  Second,
being a rapporteur for an NDA carries great prestige, and the CPMP
and Member States will place pressure on the review teams to prepare
a thorough evaluation.  Third, rapporteurs will have access to the
scientific expertise available across the EU. 

Moreover, according to an EMEA official, the CPMP does consider drug
sponsor preferences in its selection of rapporteurs.  In 1995, the
CPMP was able to give drug sponsors one of their rapporteur choices
in every case.  However, the CPMP recognizes that this may not always
be possible in the future.  Under the centralized procedure, in 1995,
representatives from all of the Member States except Greece were
chosen as rapporteurs or corapporteurs for at least two applications. 
The United Kingdom was selected as a rapporteur or corapporteur most
often (nine times) with members from France and Germany involved in
eight and seven applications, respectively. 

A second concern voiced by industry and regulatory officials is that
the new procedures will function as intended only if members of the
CPMP and the Standing Committee, who are appointed by their Member
States on the basis of their scientific or regulatory expertise, are
able to look beyond their national identity to represent EU-wide
interests.  The members of these committees have to accept an
EU-based approval process and EU-based decisions in order for the new
procedures to successfully expedite the drug approval process. 
According to a senior EMEA official, the EMEA is doing all that it
can to encourage the CPMP members to act in the best interests of the
EU, regardless of their national identities.  However, the EMEA
official acknowledged that it will take time before the members feel
comfortable with one another and the new procedures. 

Finally, pharmaceutical industry officials told us that, in the short
term, industry will monitor progress with the centralized procedure
and may delay using it for nonbiotechnology product approvals until
the EMEA can establish a track record for drug approvals.  Industry
likes the multiple approval options for pharmaceutical products
because they create competition among the national marketing
authorities and the EMEA, encouraging them to be more efficient. 
Further, these options allow firms to pursue different marketing
strategies for their various pharmaceutical products. 

During the EMEA's first year of operation, however, there were
indications that industry was using the centralized procedure for
optional nonbiotechnology products.  According to EMEA status
reports, two-thirds of the 30 new centralized applications that
industry filed or intended to file could have been filed using the
decentralized procedure.  Nevertheless, industry officials contend
that future prospects for using the centralized procedure are
dependent on the EMEA's success in expediting the drug approval
process. 


--------------------
\19 According to industry officials, companies prefer rapporteurs who
are willing to interact with them throughout the drug development and
approval processes, are knowledgeable about a firm's clinical trial
procedures and products, have an open review process, share a common
language, and have a proven track record in approving pharmaceutical
products quickly. 


   EMEA TASKS, STRUCTURE,
   STAFFING, AND FINANCING
------------------------------------------------------------ Letter :4

The EMEA was created by the Commission in 1993 to administer the new
centralized approval procedure, which is mandatory for biotechnology
and optional for other high-technology and innovative pharmaceutical
products.\20 The EMEA also arbitrates disputes under the new
decentralized procedure in order to achieve mutual recognition of
Member State approvals for most other medicines.\21

The EMEA is funded by the Commission and industry application fees
and has a small permanent staff and two scientific committees that
draw upon EU-wide scientific expertise. 


--------------------
\20 The EMEA did not become operational until February 1, 1995, after
administrative and logistical issues had been resolved. 

\21 The EMEA's CPMP also reviews products of EU-wide interest, such
as treatments for AIDS, and products identified through
pharmacovigilance alerts. 


      EMEA TASKS
---------------------------------------------------------- Letter :4.1

The EMEA provides administrative, technical, and scientific support
for both drug approval decisions under the centralized procedure and
disputed decisions under the decentralized procedure.  Under the
centralized procedure, the EMEA is responsible for coordinating the
evaluation of the safety, efficacy, and quality of human
pharmaceutical products that will be marketed throughout the EU. 
Through its scientific committee, the CPMP, the EMEA also evaluates
assessment reports, summaries of product characteristics, labels, and
package inserts for pharmaceutical products.  Finally, the EMEA
provides advice to drug sponsors on issues relating to the conduct of
tests and trials necessary to demonstrate the safety, efficacy, and
quality of pharmaceutical products.  In 1995, the CPMP received 20
requests for scientific advice from pharmaceutical companies. 
According to EMEA and industry officials, this interaction between
the industry and the EMEA is beneficial to the European
pharmaceutical industry because it increases the industry's
interaction with the European reviewers of its product applications. 

In addition to coordinating the assessment of new drug applications
and resolving Member State disputes, the EMEA is responsible for
monitoring adverse drug reactions, an activity known as
pharmacovigilance.\22 The EMEA also ensures that the public receives
timely and accurate information about the safe and effective use of
these products.  While national pharmacovigilance systems have
existed for some time in the EU, the requirements and structure of
those systems have varied considerably.  According to a recent
report, these differences have made compliance with all the
regulatory requirements difficult for multinational pharmaceutical
companies, thereby endangering patients who may not have received
standard safety information about a particular product.\23

The new EU regulations are intended to strengthen and coordinate
existing pharmacovigilance systems.  As part of the new system, the
EMEA is responsible for creating a data-processing network for the
rapid transmission of information among the national marketing
authorities in the event of a pharmacovigilance alert.\24 The EMEA is
also responsible for formulating, as necessary, opinions on measures
to ensure the safe and effective use of such pharmaceutical products. 

The EMEA also performs several other functions.  It coordinates
Commission and Member States' responsibilities for verifying industry
compliance with good manufacturing, laboratory, and clinical
practices.  It also provides technical assistance for maintaining a
database on pharmaceutical products for public use and assists the
Commission and Member States in providing information about
pharmaceutical products to the public.  In addition, the EMEA is in
the process of developing ways to electronically transmit data
between its administrative arm, the secretariat, and the national
marketing authorities to track the flow of information during the
review process.\25 The EMEA also translates all documents into the 11
languages used in the Member States.  Finally, the EMEA promotes
technical cooperation among the Commission, Member States,
international organizations, and other countries regarding the
evaluation of pharmaceutical products. 


--------------------
\22 Pharmacovigilance involves collecting information on adverse drug
reactions at pre- and postmarketing stages, scientifically evaluating
these reports, and taking whatever regulatory actions may be
appropriate following the analysis of the reports. 

\23 Developments in International Pharmaceutical Regulation: 
Implications for the United States, pp.  5-1, 5-2. 

\24 In 1995, the Commission requested bids on a $2 million
feasibility study to determine how to establish an information
network on adverse drug reactions and what resources would be
necessary to fund such a network.  The European Community Joint
Research Center in Ispra, Italy, was selected to conduct the study. 

\25 According to an EMEA official, a prototype Automated Tracking
System is undergoing testing at the EMEA.  The information from the
system will be available only to those inside the evaluation and
decision-making process. 


      EMEA STRUCTURE AND STAFFING
---------------------------------------------------------- Letter :4.2

The EMEA is composed of a Management Board, two scientific
committees, and a permanent secretariat.  The Management Board is the
EMEA's governing body and is responsible for budgetary and resource
matters.  It consists of two representatives each from the European
Commission, the European Parliament, and the Member States, for a
total of 34 members. 

The scientific committees, the CPMP and the CVMP, each consist of 30
members--two from each Member State--who are primarily responsible
for acting as rapporteurs to coordinate the review of NDAs.  The
rapporteurs have access to the staffs of national marketing
authorities in other Member States, as well as to any of the 1,200
outside experts on the EMEA's European experts list. 

By the end of 1995, the permanent secretariat consisted of about 67
staff but was expected to grow to 250 staff by the year 2000.  The
secretariat is charged with providing general administrative and
logistical support to the scientific committees, as well as
administering the day-to-day activities of the EMEA.  The permanent
secretariat consists of four units: 

  the Administration and Logistical Unit, which is responsible for
     personnel, administration, budget, accounting, and organization
     of and interpretation for conferences and meetings;

  the Human Medicines Evaluation Unit, whose two sections support the
     centralized and decentralized procedures for approval of
     pharmaceutical products for human use;

  the Veterinary Medicines Evaluation Unit, which supports
     centralized and decentralized procedures for approval of
     pharmaceutical products for veterinary use and monitors the
     maximum residue levels in foodstuffs of animal origin; and

  the Technical Coordination Unit, which is responsible for
     inspection, pharmacovigilance, and technical documentation
     activities. 


      EMEA FINANCING
---------------------------------------------------------- Letter :4.3

Initially, the EMEA was expected to be financed equally by industry
application fees and Commission funds.  However, the EMEA reported
that about one-third of its funding for 1995 actually came from
industry fees, while about two-thirds came from the Commission.  The
EMEA's budget for 1995 was approximately $17 million.\26

The application fee for authorizing a pharmaceutical product for
human use under the centralized procedure ranges from about $165,200
to approximately $236,000, depending on how many different product
strengths and forms, such as tablet or liquid, are being considered. 
The EMEA receives half of the fees to support its operations, and the
other half are split between the two review teams formed by the
designated rapporteurs.  Other fees, which are detailed in Commission
regulations, are charged to process application variations,
extensions, and renewals; inspect manufacturers' facilities; and
arbitrate Member State disputes. 

According to industry and regulatory officials, the Member States
differ in how they would like to see the EMEA funded.  Some of the
Member States, particularly the United Kingdom, would like the EMEA
to be fully financed by industry fees.  Other Member States have
resisted a total fee-based financing scheme because they view
industry support of a public health agency as a conflict of interest. 
Consequently, they want the Commission to maintain oversight
responsibility of the EMEA through its funding mechanism.  The Member
States and Commission agree that the EMEA's financing should be
reviewed in about 3 years, with the objective of increasing the
proportion of the budget financed by the industry.  However,
according to a senior Commission official, the Commission is likely
to retain its oversight control by funding at least 20 percent of the
EMEA budget in the future. 


--------------------
\26 Throughout this section, we use an exchange rate of $1.18 U.S. 
dollars per European Currency Unit. 


   AGENCY COMMENTS
------------------------------------------------------------ Letter :5

We obtained comments on a draft of this report from the EMEA, FDA,
representatives of the European-based pharmaceutical industry, and
experts in international drug regulatory policies.  In general, they
found the report to be accurate and complete and provided specific
technical comments, which we incorporated into the report where
appropriate. 


---------------------------------------------------------- Letter :5.1

This report was prepared by John C.  Hansen, Assistant Director;
Thomas J.  Laetz; and Mary W.  Freeman.  Please call Mr.  Hansen at
(202) 512-7105 if you or your staff have any questions about this
report. 

Sincerely yours,

Sarah F.  Jaggar
Director, Heath Financing and
 Public Health Issues


GLOSSARY
============================================================ Chapter 0


      COMMISSION OF THE EUROPEAN
      COMMUNITIES
-------------------------------------------------------- Chapter 0:0.1

The central regulatory body in the EU that (1) drafts legislation in
the form of directives and regulations designed to foster a single
market in Europe and (2) enforces EU rules.  The Commission also
prepares draft decisions, on the basis of CPMP opinions, on the
licensing of pharmaceutical products. 


      COMMITTEE FOR PROPRIETARY
      MEDICINAL PRODUCTS (CPMP)
-------------------------------------------------------- Chapter 0:0.2

Committee within the EMEA, composed of two representatives from each
Member State, that renders scientific opinions about the safety,
efficacy, and quality of new pharmaceutical products.  The CPMP also
has a role in pharmacovigilance issues, developing guidelines, giving
scientific advice to companies developing pharmaceutical products,
and providing quality information to health professionals and
patients. 


      COUNCIL OF MINISTERS
-------------------------------------------------------- Chapter 0:0.3

European Council composed of representatives from all the Member
States.  The Council analyzes Commission proposals and enacts EU-wide
legislation. 


      EUROPEAN MEDICINES
      EVALUATION AGENCY (EMEA)
-------------------------------------------------------- Chapter 0:0.4

Central agency within the EU that supports the CPMP in its scientific
evaluations of pharmaceutical products.  The EMEA also verifies
compliance with EU good clinical practices and good manufacturing
practices and provides technical support to the Member States'
national marketing authorities. 


      EUROPEAN UNION (EU)
-------------------------------------------------------- Chapter 0:0.5

Formerly known as the European Community, the EU was established by
treaty to create a single market.  The EU currently consists of 15
countries commonly referred to as Member States.  The 15 Member
States are Austria, Belgium, Denmark, Finland, France, Germany,
Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain,
Sweden, and the United Kingdom. 


      NATIONAL MARKETING AUTHORITY
-------------------------------------------------------- Chapter 0:0.6

The regulatory authority in each Member State that is responsible for
the approval of new human and veterinary pharmaceutical products in
that Member State.  National marketing authorities also inspect
manufacturing facilities, monitor quality control, and perform
pharmacovigilance activities.  The size and structure of each
national marketing authority vary among Member States. 


      PHARMACOVIGILANCE
-------------------------------------------------------- Chapter 0:0.7

The process of collecting information on adverse drug reactions at
the pre- and postmarketing stages, scientifically evaluating these
adverse drug reaction reports, and making the regulatory decisions
that result from this analysis. 


      RAPPORTEUR
-------------------------------------------------------- Chapter 0:0.8

A CPMP member selected to lead the scientific evaluation of a new
drug application and discuss its merits and shortcomings before the
CPMP. 


      STANDING COMMITTEE ON
      MEDICINAL PRODUCTS FOR HUMAN
      USE
-------------------------------------------------------- Chapter 0:0.9

Committee within the Commission, comprising representatives from all
15 Member States, that is responsible for approving draft licensing
decisions for pharmaceutical products on the basis of the
Commission's draft decisions. 


      SUMMARY OF PRODUCT
      CHARACTERISTICS
------------------------------------------------------- Chapter 0:0.10

The EU's version of the full prescribing information for a product
that is supplied to physicians separately from the product. 


*** End of document. ***