Cite as Judit Rius Sanjuan, James Love and Robert Weissman, Protection of Pharmaceutical Test Data: A Policy Proposal, KEI Research Paper 2006:1.
PROTECTION OF PHARMACEUTICAL TEST DATA: A POLICY
PROPOSAL*1
Judit Rius Sanjuan, James Love and Robert Weissman*2
KEI Research Paper 2006:1
21 November 2006
Table of Contents
Before a new drug is introduced into the market, evidence of its
safety, effectiveness and quality must be provided to the national
drug regulatory authorities. This can be done by generating and
submitting the pharmaceutical test data obtained from test and
clinical trials or, as usually done by the generic industry, by
relying on the test data submitted by others. There are economic,
practical and ethical reasons why second/generic entrants into the
pharmaceutical market should not attempt to reproduce the test
data. The tests may take several years to complete and delay the
entry of cheaper generics into the market; it will also generally
be unethical to replicate tests on human subjects for products that
have already demonstrated efficacy.
The tests, particularly those involving human clinical trials,
are relatively expensive and often require significant investments.
Many countries provide legal protection for the test data, which is
separate from the rights given to patented inventions.
Before 1984 in the United States, and before 1987 in the
European Union, pharmaceutical test data was protected as a
trade secret, and unfair competition law protections against
competition based on dishonest practices. There was no legal
prohibition against relying upon published data to establish the
safety and efficacy of drugs, and there were even some limited
situations where companies were effectively permitted to rely upon
unpublished “secret” data that had been submitted to
regulators.
Under current regulations, the United States and the European
Union grant a period of exclusive rights for the pharmaceutical
test data that “originators” (the company that developed the
product) generate and submit to national drug regulatory
authorities. These regulations prevent generic drug manufacturers
and national regulatory authorities from relying upon an
originator’s test data to approve generic applications during a
pre-determined period of time. If the generic entrant cannot obtain
a “right of reference” (permission to use the test data) from the
company that first marketed the product, they would have to
re-conduct the tests, including the human use clinical trials, or
wait until the data exclusivity period expires in order to obtain
marketing approval. The U.S./E.U. system, sometimes referred as
“marketing exclusivity” or “data exclusivity”1 is
clearly a generic delaying-approval mechanism.
The issue of exclusive rights to rely upon data has become
especially relevant since the United States and the European Union,
influenced by their brand-name pharmaceutical industries, are
urging countries to recognize this practice in a variety of trade
negotiations and forums.2
Although the U.S. system of exclusive rights in data was adopted as
part of a larger reform of the drug registration process that, on
balance, promoted generic competition, the U.S. and European
demands are intended purely to delay generic entry.
However, the granting of the exclusive right to rely upon test
data is not required and goes considerably beyond the minimum
obligations under the WTO Agreement on Trade-Related Aspects of
Intellectual Property Rights (TRIPS Agreement). The relevant
provision in the TRIPS Agreement is Article 39.3.
TRIPS – Section 7: Protection of Undisclosed
Information3
Article 39.3: “Members, when requiring, as a
condition of approving the marketing of pharmaceutical or of
agricultural chemical products which utilize new chemical
entities, the submission of undisclosed test or other
data, the origination of which involves a considerable
effort, shall protect such data against unfair commercial
use. In addition, Members shall protect such data against
disclosure, except where necessary to protect the public, or
unless steps are taken to ensure that the data are protected
against unfair commercial use.”
Article 39.3 by itself is not clear regarding the nature of
protection the TRIPS Agreement requires. Under article 39.3, a WTO
Member’ obligation is limited to the protection from unfair
commercial use of undisclosed data, the origination of
which involves a considerable effort and that is used
to register new chemical entities. Whatever the TRIPS
Agreement mandates, it certainly does not require Member States to
provide exclusive rights to the originator of the test data.
Experts who have examined this issue and the negotiating history
of article 39.3 have concluded that a country can satisfy its TRIPS
obligations by simply protecting regulatory data from disclosure or
“misappropriation”4.
Nothing in the TRIPS prevents a WTO member from allowing generic
competitors to rely upon public information, evidence of foreign
drug registrations, or non-disclosed data from another company (the
so-called Non-disclosure model).
This paper first explains the U.S. and European Union models of
data exclusivity in some detail. These accounts of the U.S. and EU
systems highlight their relatively recent adoption, and in the U.S.
case, how they were adopted in the context of other reforms
designed to speed up generic entry. Then, recognizing that several
countries are facing U.S. and E.U. pressures to implement a
TRIPS-plus model and to reject the minimum non-disclosure approach,
we briefly outline a series of measures that will lessen the harm
from grants of exclusive rights in test data. In the subsequent
section of the paper, and again in recognition of pressure on
countries to provide data protection beyond the nondisclosure
approach, we present a particular approach to implementing TRIPS
Article 39.35.
Similar to a system used by the United States for agricultural
pesticide test data, we advocate a cost-sharing model that would
provide a period of protection to data originators, but allow
generic companies during this period to rely upon originators’ test
data if they make reasonable contributions toward the cost of the
investments. The model presented in this paper would exceed the
minimum requirements of the TRIPS Agreement. It is a compromise
between the very modest obligations of the TRIPS and the very high
levels of protection given to data in the United States and
Europe,
6 and
explicitly offered as a strategy to offset the heavy political
pressure applied on developing countries by the United States and
EU to adopt systems of data exclusivity. After presenting the
proposal, we briefly outline its advantages and address potential
criticisms.
UNITED STATES7
Before 1984, U.S. legal protection for an applicant’s
unpublished safety and efficacy data was basically provided by a
limited trade secret protection regime8.
Prior to 1962, new drugs in the U.S. were approved by proving
safety only, and for generic competitors the existence of a drug on
the market was usually sufficient for that purpose. In 1962, the
U.S. Federal Food, Drug, and Cosmetic Act was amended to require
pharmaceutical manufacturers to demonstrate that their new products
were both safe and effective.
The 1962 amendments did not contain any provision for a separate
approval process for drugs that were identical to drugs previously
approved. Generic manufacturers were thus compelled to file a New
Drug Application (NDA) and to submit evidence proving that the
generic drug was safe and effective, even if their product was
chemically identical to one previously approved.
However, there were important exceptions to the 1962 safety and
efficacy requirements. The generic applicants were allowed to prove
only bioequivalence — that their product is pharmaceutically the
same and works the same in the body as the originator product — in
two situations:
a) Pre-1962 drugs. When relying on a drug that had been
approved before October 1962, the generic manufacturer had only to
demonstrate bioequivalence with the product already on the market,
while when relying on a drug approved after 1962, the generic
manufacturer also had to demonstrate safety and efficacy.
b) Special regime for Antibiotics. In the case of
antibiotics, the distinction between pre- and post-1962 drugs did
not exist. An abbreviated process for approving generic
antibiotics, which only required tests to show bioequivalence,
applied to all antibiotic drugs approved under section 507 of the
Federal Food, Drug, and Cosmetic Act.
Drugs could also be approved based on a “paper” new drug
application (NDA), which allows the applicant to rely on
published scientific literature demonstrating the safety and
efficacy of the drug and not on the result of the original testing
by the NDA applicant.
However, these sorts of studies were not available for all
drugs. Moreover, nothing in the FDA regulations prevented the
Agency from requesting additional studies. According to one
expert9,
getting a paper NDA approved was an uncertain and expensive
undertaking.
In 1984 a major pharmaceutical legislative reform took the form
of the Drug Price Competition and Patent Term Restoration
Act, also known as the Hatch-Waxman Act10.
The 1984 Hatch-Waxman Act effectively extended the Abbreviated
New Drug Application (ANDA) processes that existed for antibiotics
(and under certain conditions to pre-1962 drugs) to all generic
drugs, allowing generic manufacturers to gain FDA marketing
approval by relying on safety and efficacy data from original NDA,
so long as the generic drug was bioequivalent with the originator’s
drug11. The
1984 amendments also introduced a new kind of application: the
505(b)(2) applications 12.
Possible second applicants’ entrance into the U.S.
Market: Since 1984, there have been two possible ways a “second
applicant” company can file for drug approval: with an ANDA or a
505(b)(2) Application. Both ANDAs and 505(b)(2) applications imply
reliance, in full or in part, on the test data prepared by a third
party, usually the sponsor of the reference drug or originator.
The end of Paper NDA Applications: The introduction of ANDA and
505(b)(2) applications; which allow reliance upon unpublished data,
eliminated the need for FDA’s paper NDA applications, which
permitted the approval of duplicate drugs through reliance upon
published data.
The 1984 Hatch-Waxman Act also introduced several
non-patent-marketing exclusivity regulations (see box below). In
this paper, we are going to focus on the so-called “New drug
product exclusivity”. The inclusion of marketing
exclusivity regulations has been attributed to a political bargain
that took place in 1984 when the United States allowed second
applicants to register products when they establish bioequivalence
with a product that had already received marketing approval,
relying on that originators’ test data demonstrating the safety and
efficacy (the ANDA and 505 (b)(2) applications) and the “Bolar”
exception to patent rights
13. Both
measures were introduced to promote competition from the generic
industry.
The current U.S. marketing exclusivity regulations are quite
complex and co-exist with a number of other non-patent provisions
that extend marketing exclusivities, including:
– Orphan drug exclusivity: 7 years
– Pediatric drug exclusivity14
– Generic drug exclusivity15
– Drugs approved between 1982 and 1984
– Medical devices exclusivity
As well as special provisions relating to patent protection and
extensions of patent term.
The New Drug Product Exclusivity is regulated in Section 355 of
the Federal Food, Drug and Cosmetic Act. National regulatory
authorities are prevented from relying on the originator’s test
data to approve subsequent applications during a pre-determined
period of time. There are two categories of product
exclusivity:
a) A 5-year period of exclusive rights from the date of
FDA approval is granted to new drug products containing new
chemical entities.
The
main condition for receiving this 5-year exclusive right is that
the approved new drug application contains a new active ingredient
— that is, a New Chemical Entity (NCE)16or
new active moiety17
— not previously approved by the FDA alone or in combination with
other chemical entities.
“Relative” novelty: in the U.S., a drug is treated as an
NCE if it contains an active moiety that has not been approved by
the FDA, although it may not be “universally” novel because such
active moiety may already be known or described in scientific or
technical literature.
The effect of this exclusivity is that no ANDA18 or
505(b)(2)19
applications may be submitted during the 5-year exclusivity
period.
Because the FDA takes an average of 18 months to approve a
generic application, the five-year marketing exclusivity delays
competition by about 6.5 years following the date of the reference
drug’s approval.
The five-year period may be reduced to four years if the
second/generic application contains a certification of patent
invalidity or non-infringement (Paragraph IV Certification20).
b) A 3-year period of marketing exclusivity from the date
of the FDA approval is granted to new uses/indications of drug
products containing an active moiety that has been previously
approved, when the application contains reports of new clinical
investigations conducted or sponsored by the applicant that were
essential to the approval of the application or the supplement.
The main conditions for grant of this three-year period of
exclusivity are that a new use/ indication is discovered and
that the pharmaceutical company must have conducted or
sponsored
21new
clinical trials/investigations22
(other than bioavailability studies) which were essential for the
approval of the new drug application or supplement.
Contrary to the five-year exclusivity, this three-year
exclusivity allows the FDA to receive and review ANDA or 505(b)(2)
applications before market exclusivity has expired. The FDA can
even grant tentative approval, but the approval becomes
effective only after the three-year period has elapsed. The
second applicant can thus market its product immediately following
expiry of the three-year exclusivity.
How does this system work in practice?
-
The Center for Drug Evaluation and Research (CDER) makes
exclusivity determinations on all the relevant new drug
applications, with or without a request from the new drug
applicant. -
The generic companies use the FDA publication “Approved Drug
Products with Therapeutic Equivalence Evaluations”, commonly known
as the Orange Book, to find information on drugs that have
received New Drug Product Exclusivity23.
In a few words: Marketing exclusivity in the U.S.
provides the originator of a drug with a limited protection
precluding for a prescribed period of time the approval of
registration applications that rely on the originator’s test
data.
Five years exclusivity is provided for drugs with new chemical
entities; and 3 years exclusivity is provided for new
uses/indications in already approved drug products.
Special Regime: Antibiotics and U.S. Marketing
Exclusivity
The Title I of the 1984 Hatch-Waxman Law that introduced
marketing exclusivity in the U.S did not cover antibiotics because
an abbreviated process for approving generic antibiotics, which
only required tests to show bio-equivalence, already applied to all
antibiotic drugs approved under old section 507 of the Federal
Food, Drug, and Cosmetic Act24.
However, the Food and Drug Administration Modernization Act
(FDAMA) of 1997 made antibiotic drugs submitted after the FDAMA
effective date (November 20, 1997), eligible for Hatch-Waxman
exclusivities. The 1997 FDAMA repealed the old section 507 and
required companies that want to market new generic antibiotics to
file the same kind of application (section 505) as all other
generic drugs.
An application for a drug that
contains an antibiotic, in which the antibiotic was the subject of
any application for marketing received before November 21, 1997 (an
old antibiotic), is not eligible to receive marketing exclusivity
(and is not subject to certain Orange Book patent listing and
notification requirements) applicable to drugs approved under
section 505. Section 125 of FDAMA exempts from the marketing
exclusivity provisions, marketing applications for drugs that
contain old antibiotics, by providing that “[drugs that were
approved and marketed under former Section 507 of the FD&C Act,
as well as those that were the subject of applications that may
have been withdrawn, not filed, or refused approval under Section
507 of the FD&C Act are excluded from the patent listing and
exclusivity provisions.”
According to one expert25
because of the broad definition of antibiotic in section 125 of
FDAMA, FDA interprets26 the
exclusion from exclusivity for old antibiotics to be somewhat
broader than just the antibiotic drug products actually approved
under section 507. FDA interprets section 125 to exclude not only
specific drugs approved under 507 but also any drugs that include
the “active moiety” in a drug approved under 507. This means that
minor chemical variations (e.g., new salts and esters or other
non-covalent derivatives) of old antibiotics are also excluded from
eligibility for exclusivity.
For more information, see FDA Guidance for Industry and
Reviewers Repeal of Section 507 of the Federal Food, Drug and
Cosmetic Act27.
Recommended reading: FDA’s
Frequently Asked Questions for New Drug Product Exclusivity.
Available online at:
http://www.fda.gov/cder/about/smallbiz/exclusivity.htm
EUROPEAN UNION28
Before 1987, the European Union data protection regime was
basically a trade secret regime and varied considerably from
country to country.
Europe harmonized its medicinal products29
marketing authorizations in 1965 with the Council Directive
65/65/EEC30. The
1965 Directive established that a pharmaceutical company applying
for marketing approval should present results of test and clinical
trials demonstrating a product’s safety and efficacy.
The trade secret protection of test data was not addressed in
the 1965 Directive. The Directive did not consider use of such data
by drug regulatory authorities to approve another drug. However, in
1984 the European Commission recognized the concept of “indirect
use of such data” when it noted that “certain national authorities
tended not to be too demanding in their assessment of the adequacy
of published references, even where data on safety were
incomplete,” suggesting there was recognition that some regulators
allowed generic competitors to effectively rely upon data that was
controlled by the originator.
There were also exceptions. The 1965 Directive recognized one
application procedure that did not require applicants to present
the full efficacy and safety data testing – the “abridged
procedure”31 for
“published literature exemption” where adequate data existed in the
public domain (similar to the U.S. Paper NDA application).
The European Union introduced data exclusivity for the first
time in 1987 with the 87/21/EEC Directive32,
which amended the 65/65/EEC Directive.
The 1987 Directive, as well as several others, was consolidated
in 2001 in a single Community Code, the Directive
2001/83/EC33.
The 1987 Directive also introduced a new harmonized procedure
for abridged applications for “essentially similar” products, the
classic generic applications34.
Since 1987, European second/generic applicants for medicinal
products that show that their product is “essentially similar” to a
product already authorized can rely35 on
the test data submitted by the first applicant and present abridged
applications in the specific E.U. countries where the relevant
period of data exclusivity has expired and the product is
marketed.
In a 1998 case, the European Court of Justice (ECJ) defined an
essentially similar medicinal product as one: “where it
satisfies the criteria of having the same qualitative and
quantitative composition in terms of active principles, of having
the same pharmaceutical form and of being bioequivalent, unless it
is apparent in the light of scientific knowledge that it differs
significantly from the original product as regards safety or
efficacy” 36.
Possible second applicants’ entrance into the E.U.
Market:
The essentially similar abridged procedure is the typical
application for generic products in the European Union.
If, however, the generic medicinal product is intended for a
different use, or for different dosage forms or different forms of
administration, then the results of appropriate pharmacological and
toxicological tests and/or appropriate clinical trials, must be
provided. This proviso is known as the “hybrid
application“37.
As is the case in the United States, a second applicant with a
right of reference/use from the pioneer company is entitled
to rely on the latter’s data before the data exclusivity period has
expired38.
Second applicants may also seek marketing approval via the
“Published Literature Exemption”, where the second applicant
presents references to published scientific literature
demonstrating that the product has “well established medicinal
uses”, is also a possibility39.
After the Scotia40 and
Taxol41
litigations, however, the exemption was amended and E.U.
legislation now mandates42 a
minimum period of a decade to demonstrate a well-established use of
a constituent of a medicinal product. The period begins with the
first systematic and documented use of that substance as a
medicinal product in the E.U.
At the time of introduction in 1987, the data exclusivity regime
in Europe was justified to afford some degree of protection to
research-based pharmaceutical companies in European Member States
that did not confer patents to pharmaceuticals43 and
that were faced with the new process for approval of generic
competitors.
In July 2001, the E.U. launched an initiative to revise key
aspects of its pharmaceutical legislation, data exclusivity being
one of the key topics. The result was the 2004/27/EC
Directive44 that
amended Directive 2001/83/EC. Member States had until October 30,
2005 to implement the new revised Directive. However, the new data
protection harmonized periods will benefit only drugs submitted for
authorization after the implementation date. Originator drugs
approved before that date remain subject to the 2001 system.
Therefore, most abridged/generic applications to be filed
in the next ten years will be based on the old 2001
system.
The EU data exclusivity system is further complicated by the
fact that different forms of protection are provided depending on
how an originator product was granted marketing approval. These
different methods are summarized in the accompanying box below.
Possible applicants’ entrance into the E.U. market:
A pharmaceutical company wanting to get marketing approval for a
medicinal product in the European Union has several options:
a) National procedures to approve medicinal products that will
be sold only on the domestic market.
b) Mutual recognition procedure (decentralized) to approve
medicinal products that will be marketed in several Member
States.
c) London-based European Medicines Agency (EMEA) Centralized
procedure45 to
approve “eligible” medicinal products46.
Medicinal products obtain a single marketing authorization, in the
form of a Commission decision, valid in all Member States.
The data exclusivity regimes in Europe:
A) For Drugs Placed on the Market Before 2005: Directive
2001/83/EC
The E.U. period of data protection starts running with the first
marketing authorization of the medicinal product in any Member
State of the European Union. There are four different lengths of
exclusivity:
•a ten-year mandatory period: for high-tech
medicinal productsthat are approved by the EMEA through the
centralized procedure.
•a six-year minimum period47: for
all other drugs, drugs approved through either the mutual
recognition procedure or the national procedure of an individual
Member
State.
•a six-year minimum period capped by the patent
duration48:
Member States that apply the six-year minimum period may choose to
cap this period at the instant the
patent protecting the drug
expires, so data exclusivity will not extend beyond the period of
the patent protection.
•a ten-year optional period49:
based on a finding that it is “necessary in the interest of public
health”. Member States may decide to extend the six-year period of
protection up to a ten-year ceiling to all
eligible pharmaceuticals marketed in their territory; they may not
discriminate on the basis of the country of origin.
Contrary to U.S. law, current E.U. data exclusivity does not
grant additional periods of protection for subsequent improvements
brought to a drug, for example new therapeutic
indications, dosage forms, doses and dosage schedules
50 or
formulations51.
The current European regime has some ambiguities. To be awarded
a period of data protection, the first applicant must have obtained
marketing approval for a new medicinal product. The Directive does
not specify whether the product has to be an entirely new chemical
entity.
Furthermore, the European legislation does not make it clear
whether second entrants are authorized to submit their application
for review before the data exclusivity has expired, or if they have
to wait for expiry before filing their application. The European
Generic Medicines Association (EGA) argues that, in practice, the
rule is the latter. According to the EGA, “the effective period of
marketing exclusivity gained by the originator company is the
period of data exclusivity (6 or 10 years) plus the time it takes
to register and market the generic medicine – a further 1 to 3
years”52.
In a few words: The E.U. data exclusivity regime
guarantees market protection for originator medicines for either 6
or 10 years depending on the Member State national legislation. A
10-year period is granted to an originator gaining marketing
approval through the EMEA Centralised Procedure.
B) For Drugs Placed on the Market In 2005 or Later: Directive
2001/83/EC (as amended by Directive 2004/27/EC)
The new 2001/83/EC Directive53
introduces a harmonized “8+2+1” formula for new drugs
approved either through the centralized procedure or the mutual
recognition procedure.
The new E.U. pharmaceutical legislation establishes an
eight-year Data Exclusivity, starting with the initial
approval of the “European reference medicinal product”54 +
two-year Market Exclusivity. The second/generic applicant
can not submit its request for a marketing authorization
referencing the originator data during 8 years starting from the
initial approval of the reference medicinal product; after this 8
year period expires the generic can submit an application and get
preliminary approval but the authorization is not made effective
and the product can not be placed in to the market until the
following 2 year period expires55.
This effective 10-year market exclusivity can be extended by an
additional one year maximum if, during the first eight years
of those ten years, the data originator obtains an authorization
for one or more new therapeutic indications which, during
the scientific evaluation prior to their authorization, are held to
bring a significant clinical benefit in comparison with existing
therapies.
The 2004 legislation also provides that new strengths,
pharmaceutical forms, routes of administration, and presentations,
as well as any extensions or variations, are to be considered
as belonging to the same “global authorization” for purposes of the
abridged application rules56 and
therefore there is no data protection for these changes57.
Implementation: The 8+2+1 formula will apply to all
Member States, unless certain new Member States are awarded
derogations, which they can request following publication of the
new law.
In a few words: the New EU Pharmaceutical Legislation
adopted in 2004 has created a harmonized E.U. eight-year data
exclusivity provision with an additional two-year market
exclusivity provision. This effective 10-year market
exclusivity can be extended by an additional one year
maximum if the originator obtains an authorization for other
new therapeutic indications with a significant clinical
benefit.
Other Data Exclusivity Regimes:
The European revised legislation also provides that:
a) “Well-established” products are entitled to receive a
one-year data protection period if they are granted approval for a
new therapeutic indication. Contrary to new products, the
corresponding request (for approval of this new indication) can be
made at any time. The applicant must establish that “significant
preclinical or clinical studies were carried out” to demonstrate
the safety and/or efficacy of this new indication. This latter
provision is non-cumulative, it covers only the use of the new
indication, and can only be used once. It is not clear what
constitutes “a significant clinical benefit”.
b) The 2004 Directive also recognizes one-year data exclusivity
for products switching from “prescription-only” (Rx) to “over the
counter” (OTC) status, on the basis of significant pre-clinical
tests or clinical trials.
“Essentially Similar” v. “Generic”
Before the 2004 Directive, the typical generic abridged
procedure was available for “essentially similar” products. Since
2004, the abridged procedure is going to be available only for
“generics of reference medicinal products”.
A “generic medicinal product” is defined in article
10.2 as a product which “has the same qualitative and
quantitative composition in active substances and the same
pharmaceutical form as the reference medicinal product that is
bio-equivalent with the reference medicinal product and has been
demonstrated by appropriate bioavailability studies. The
different salts, esters, ethers, isomers, mixtures of
isomers, complexes or derivatives of an active substance should be
considered to be the same active substance, unless it differs
significantly in properties with regard to safety and/or efficacy.
In such cases, additional information providing proof of the safety
and/or efficacy…must be supplied by the applicant. The various
immediate-release oral pharmaceutical forms shall be
considered to be one and the same pharmaceutical form.
Bioavailability studies need not be required if the applicant can
demonstrate that the generic medicinal product meets the relevant
criteria as defined in the appropriate detailed
guidelines.”
The definition of “generic medicinal product” does not seem to
include different non-oral pharmaceutical forms, products
incorporating a different indication, strength, form or route of
administration that used to be considered “essentially similar”.
Therefore, these products now have to be authorized under the
Article 10.3 of the Directive (the “hybrid application”) and the
results of the appropriate pre-clinical tests or clinical trial
must be provided.
“Bio-similar medicinal products”: For the first time, the
2004 Directive recognizes that manufacturers of generic
bio-pharmaceuticals can follow an abridged procedure58.
OBJECTIONS TO DATA/MARKETING EXCLUSIVITY APPROACH
There are a number of objections to the imposition of a Data
Exclusivity/Marketing Exclusivity approach. These include:
-
*The granting of exclusive rights in test data will delay
the entry of generic products into the market, impeding access to
affordable medicines.
-
*It is both unethical and wasteful to ask for duplication
of clinical trials. Yet faced with data exclusivity rules, the only
way a generic entrant can get on the market during the period of
exclusivity without authorization of the originator is to repeat
already conducted clinical trials. -
*It is a form of double protection, since strong patent
rights are justified by the cost of investments in test data.
According to this line of thinking, stronger rights in the data
should be offset by weaker protections for the patent. -
*It is unclear whether the data exclusivity regimes
prevent a second entrant/generic from initiating the procedures for
the marketing approval “before” the expiry of the exclusivity
period. It could undermine the Bolar/Early Working Patent
Exception, which seeks to encourage quick access to the post-patent
market for generic medicines by exempting from patent liability
certain conducts. -
*Unless the exclusive rights in the data can be
overridden, it can make compulsory licenses of patents or
government use orders ineffective.
A real example: European Union Data Exclusivity &
Bird Flu Pandemic
An example of how data exclusivity regimes can harm public
health is contained in a letter that Martin Terberger of the
European Commission59 sent
to the European Generic Medicines Association (EGA). The
letter60
responds to an EGA inquiry on the role that data exclusivity regime
could play in case of a compulsory license of the Tamiflu
patents61. The
European Commission confirmed the worst fears of data exclusivity
critics by arguing that the regime will delay or prevent European
Member States’ ability to use compulsory licensing to permit
generic substitutes of Tamiflu on the market in case of a Bird Flu
pandemic. This situation is startling not only because of the
potential severity of a bird flu pandemic, but because concerns
surrounding Tamiflu focused less on high prices than on the fact
that the manufacturer, Roche, was unable to provide an adequate
supply to meet stockpile needs.
The letter contains the following language: “the European
Pharmaceutical legislation does not foresee any exception to the
above mentioned periods of 8 years of data exclusivity and 10 years
marketing protection in case of emergency situations or in case a
compulsory license has been granted by an EU Member State. This
means that a applicant for a marketing authorization in the EU
would have to provide the required documentation on pre-clinical
tests and clinical trials as required under Article 8(3)(i) of
Directive 2001/83/EC, or submit an informed application under
Article 10c of Directive 2001/83/EC” and concludes ”National
emergency provisions in a EU Member State may allow the granting of
a compulsory patent license which would allow a generic or other
company to use the patented product in the Member State in
Question. However, the Community pharmaceutical acquis does not
currently contain any provision allowing the waiver of the rules on
data exclusivity and marketing protection periods described above
in the case of a national or an EU-wide emergency”.
There are, moreover, heightened concerns about U.S. and E.U.
demands that developing countries adopt data exclusivity
regimes:
-
*There is no obligation in the TRIPS Agreement to grant
exclusive rights in test data, and it is inappropriate to ask
developing countries for more extensive and higher levels of
intellectual property protection for pharmaceuticals than were set
out in the TRIPS. -
*The export of the U.S. Hatch-Waxman regime to other
countries with very different income levels and health conditions
has been strongly criticized by one of its proponents,
Representative Henry A. Waxman, who has also noted that data
exclusivity was included in Hatch-Waxman as part of a deal that,
overall, eased generic entrance into the market.62 -
*Delays in generic competition in poorer developing
countries will have much more severe effects than the already
serious consequences in industrialized nations. To an extent far
greater than in industrialized nations with more evolves systems of
public and private insurance, in developing countries, the high
prices associated with marketing monopolies means that many people
simply go without medicines they need.
SAFEGUARDS TO A DATA/MARKETING EXCLUSIVITY
REGIMEWe believe countries should not include data
exclusivity/marketing exclusivity provisions in their national law.
The TRIPS Agreement does not require providing any such marketing
exclusivities, and they can exact a high public health toll by
delaying the introduction of price-lowering generic
competition.However, if countries decide that they must provide some type of
protection, for example as a consequence of trade agreements with
the United States or the European Union, there are several steps
that can be take to reduce the provision’s negative effects:-
*Shorten the period of protection: there is no
TRIPS obligation to impose five-or ten-year terms of
protection63. -
*Protect only undisclosed data, not data that is
already published or publicly available64. -
*Protect only the test data for which submission
was required and relied on by the national authority.
Therefore, if the national authority relies upon an approval
granted in a foreign country, the obligation of protection should
not apply65. -
*Protect only “New Chemical Entities66”
(NCEs), not new uses/indications. A restrictive definition of
NCE is necessary: molecules that were not previously
incorporated within a product or published; excluding second
indications, new formulations or dosage forms67. -
*Adopt a worldwide definition of NCEs: The data
exclusivity period should start at the time the originator drug is
first approved in anywhere in the world, or, at very least, at the
time the originator drug is first approved in a party to the
agreement68. -
*Establish a mandatory registration period. A
positive example is Chile. After ratification of the US/Chile FTA,
the government of Chile passed a law69
requiring that brand-name/originator drugs be registered within one
year of U.S. approval in order to benefit from market exclusivity
in Chile. -
*Clarify the existence of an early working
exception that allows generic companies to initiate the
application procedures and required studies during the data
exclusivity term in order to start commercializing immediately
after the expiry of the data exclusivity and patent
terms. -
*Clarify that compulsory or government use licenses
will include a compulsory license on underlying registration data,
so that data exclusivities do not function as a barrier to
compulsory licensing. -
*Create an exception for emergencies and public
health crises.
PROPOSAL: Cost-Sharing Model for
Pharmaceutical Test DataRecognizing that several countries are facing U.S./ E.U.
pressures to implement a TRIPS-plus model and reject the minimum
non-disclosure model on the protection of their pharmaceutical test
data, we advocate consideration of a particular approach to
implementing TRIPS Article 39.3 obligation: a cost-sharing model
for pharmaceutical test data.The system we propose would provide compensation for data
originators, which is not required by article 39.3 of the TRIPS
Agreement. But for countries that cannot avoid TRIPS-plus
obligations on the protection of pharmaceutical test data, the
minimal TRIPS requirement of the nondisclosure approach is not a
realistic option. For these countries, it is vital to identify
other alternatives to the data exclusivity approach, and
particularly to identify alternatives that address data exclusivity
proponents’ claims that generic firms unfairly free ride on the
data generated by originators. In this context, we propose
consideration of a model similar to that which the United States
now uses for certain agricultural test data.Background:
The U.S. system for agricultural test data involves a mandatory
and automatic compulsory license on the originator’s test data
based on the principle of sharing the costs of originating the
data, under the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA)70, an
environmental protection law.The relevant provision reads in part:
“The administrator (EPA) may, without the permission of the
original data submitter, consider any such item of data (cited) in
support of an application by another person … if the applicant
has made an offer to compensate the original data submitter. …
The terms and amount of compensation may be fixed by an agreement
between the original data submitter and the applicant, or, failing
such an agreement, binding arbitration….If, at the end of ninety
days after the date of delivery to the original data submitter of
the offer to compensate, the original data submitter and the
applicant have neither agreed on the amount and terms of
compensation nor on a procedure for reaching an agreement on the
amount and terms of compensation, either person may initiate
binding arbitration proceedings by requesting the Federal Mediation
and Conciliation Service to appoint an arbitrator from the roster
of arbitrators maintained by such Service. The procedure and rules
of the Service shall be applicable to the selection of such
arbitrator and to such arbitration proceedings, and the findings
and determination of the arbitrator shall be final and conclusive,
and no official or court of the United States shall have power or
jurisdiction to review any such findings and determination, except
for fraud, misrepresentation, or other misconduct by one of the
parties to the arbitration or the arbitrator where there is a
verified complaint with supporting affidavits attesting to specific
instances of such fraud, misrepresentation, or other misconduct.
The parties to the arbitration shall share equally in the payment
of the fee and expenses of the arbitrator.If the Administrator determines that an original data submitter
has failed to participate in a procedure for reaching an agreement
or in an arbitration proceeding as required by this subparagraph,
or failed to comply with the terms of an agreement or arbitration
decision concerning compensation under this subparagraph, the
original data submitter shall forfeit the right to compensation for
the use of the data in support of the application…..If the Administrator determines that an applicant (second) has
failed to participate in a procedure for reaching an agreement or
in an arbitration proceeding …., or failed to comply with the terms
of an agreement or arbitration decision concerning compensation ….,
the Administrator shall deny the application or cancel the
registration of the pesticide in support of which the data were
used ….”7 U.S.C. Chapter 6, Subchapter II, § 136a. Registration of
pesticidesFIFRA § 3(c)(1)(F)(iii)
How do the data-sharing provisions of the FIFRA work71?
-
In order to obtain marketing approval for some agricultural test
data, originators provide the U.S. Federal
Government with the data and the cost to generate the
data (similar to the U.S. Orange Book obligations
to submit patent information72). If
the originators do not provide information on the cost of the data,
they can face a negative
presumption during the arbitration determination
of the actual cost. -
The originator gets ten years of market exclusivity, but for the
5 years afterward73 the
originator is granted a limited remuneration
right subject to procedures for
non-voluntary licenses by third
parties. -
During the 5 year period following the initial 10 years grant of
exclusivity, Generic/second applications have an automatic
right to use the data and can register products relying on the
data if they pay adequate remuneration to the test data
originator.
The issue, of course, is what “adequate remuneration” is. The
FIFRA system begins with a requirement for the generic entrant to
attempt to resolve this issue voluntarily. Once the EPA (US
Environmental Protection Agency) has issued a second entrant
registration, the second applicant has to make an offer of
compensation to the tests’ originator, which becomes the starting
point for a negotiation.However, if the parties do not reach an agreement 90 days after
the delivery of the offer74
either party can request binding
arbitration75 with
the Federal Mediation and Conciliation Service to establish
compensation levels.There is no explicit compensation standard set forth in FIFRA.
However, since 1975 arbitration decisions have often been resolved
based on a cost-sharing approach, meaning that the second
applicant should share the cost of generating the test data with
the originator.The concrete allocation of costs between the parties is a
controversial issue. The cost for the second applicant has
sometimes been based upon their relative/actual market
share76,
meaning that compensation is linked to the value of the data to
each company, which depends on resulting sales. The argument is
simple: if one party (A) has a market share larger than the other
(B), (A) will benefit more than (B) from its registration; and
since (A) can be expected to benefit more than (B), it should pay a
proportionately larger share of the costs of the data development
program.The usual practice is that:
-
*The arbitration decides the amount of compensation and
the second applicants’ entrance into the market is not
delayed, because the generic companies have an automatic right
to use the data and these disputes are resolved while the generic
product is on the market. -
*Arbitration costs are shared equally
between parties. -
*Arbitration decisions may not be appealed, except for
fraud, misrepresentation, or other misconduct by one of the parties
or the arbitrator, where there is a verified complaint with
supporting affidavits attesting specific instances. -
*The basis for establishing compensation is the actual
cost incurred by the originator, not how much it would cost to
replace the data. The arbitrators require originators to provide
evidence to support cost claims and the burden of
proof is on the originator, since they are in a better position
to know the actual cost of generating the data.
In at least one decision, a U.S. District Court has judicially
confirmed a FIFRA final arbitration order77. In
1984, the U.S. Supreme Court reviewed the FIFRA data-sharing
provisions on the Ruckelshaus case and declared that the provisions
were constitutional and that there was no improper “taking” of
property without just compensation.78The proposal:
We propose that countries pressured in trade negotiations or
other contexts to provide TRIPS-plus protection for pharmaceutical
test data use a modified version of the FIFRA approach.Under this system:
-
*Originators should be required to disclose their real
investment costs in generating the test data and provide
documentary evidence. -
*The generic/second applicants should have an automatic
right to use/rely upon the originators’ test data from “day one” —
the first registration by the originator anywhere in the world —
and no data exclusivity periods should be applicable. -
*The originator of the test data would get a remuneration
right during a limited period of time of 3 to 5 years. The
generic/second applicants would contribute to the cost of
generating this data by paying the originator an adequate and
reasonable remuneration.
Again, determining the adequate remuneration is the key point.
Two different approaches should be considered:a) A reseasonable royalty” model, where generics could pay a
percentage representing a modest share of the revenues on sales of
the generic product.b) A “pro-rata share of costs” model, where generics could pay a
contribution based upon their share of the global market sales for
the product.This second option is similar to the one that some FIFRA
arbitrators have designed for agricultural test data. A possible
adjustment could be introduced for risk of investments and cost of
capital79. The
adoption of an arbitration system, similar to the one used for U.S.
agricultural data, should also be considered for pharmaceutical
data, in order to speed decision-making an avoid bogging down
compensation determinations in the courts.For the second option, it is essential that implementing
legislation make it clear that a generic producer in a country
would only be obligated to pay for the fraction of the total costs
of the test data that is appropriate for their (likely small)
fraction of the total global market for the product.For example, if the costs80 of
test data for a particularly drug were $50 million, amortized over
five years in equal installments, and the generic producer had
sales that were .1% of the global market for
the product, the pro-rata share of the costs for one year would be
as follows:$50,000,0000 x 1/5 x .001 = $10,000 (a year for 5 years)
If the domestic generic firm’s share of the global market is
smaller, the contribution will also be smaller.Country-level determination of costs of conducting trials and
generating test data might be assisted by international
organizations, such as the World Intellectual Property Organization
(WIPO) or the World Health Organization (WHO). These organizations
could create a public database that would centralize the
collection of data on the costs of the clinical trials worldwide.
Such information might be collected in connection with a larger,
public database that would include clinical test medical
information.As compared to the data exclusivity approach, the proposed
cost-sharing model has several advantages:-
*During the period of protection, the test data
originators can benefit from reasonable contributions to the costs
of the test data — without conferral of monopoly rents that
overcompensate for the costs of generating data. -
*Countries adopting this approach can resist demands to
provide exclusive rights, because they are offering remuneration to
drug developers based on their actual investment costs — and
thereby directly addressing the “free riding” criticism of the
nondisclosure approach. -
*National regulators can avoid the creation of
monopolistic situations, and foster competition within the
pharmaceutical industry. -
*Generic competitors who share costs can enter the market
without delay because there is no exclusive marketing period. -
*Developing country generic companies’ contributions will
be affordable, because of their small share in worldwide sales. -
*Generic competitors can enter the market during the
period of data protection without unethically duplicating clinical
trials by eliminating the need to duplicate clinical trials.
Criticisms of cost-sharing approach:
Some persons81 have
criticized the cost sharing approach for developing countries on
the grounds that it represents a burden that is not required by the
TRIPS Agreement, and also because it could be implemented in a
manner that is complex or which leads to considerable litigation
costs. The responses to these points are as follows.First, if a country believes it can sustain a regime of no TRIPS
plus rights in the test data, they can certainly do so. However, it
is also true that faced with a choice between no economic rights
and exclusive rights, many countries have adopted exclusive rights
regimes. As a matter of strategy, a position of no-compromise may
fail, a costly outcome for patients. One has to be realistic about
feasible outcomes.Second, while it is true that a regime can be implemented with
complex rules or costly procedures, this is not at all necessary.
The fact that rules for data are TRIPS plus means also that
counties are free to design whatever rules they want, including
rules that are very easy to follow, and inexpensive to administer.
The U.S. approach to agricultural data is a case in point, where
decisions are made by arbitration, and appeals are not permitted.
Very simple royalty schemes are also reasonable alternatives, which
can be implemented without appeals, or with simple administrative
appeals. In this regard, it is worth noting that all of the
problems of determining remuneration levels and dealing with
procedure are also an issue for compulsory licensing of patents.
Indeed, the procedural rules for setting remuneration for test data
can be much simpler than is the case for patents, because there are
no TRIPS standards for doing so, unlike the case for patents under
Article 31 of the TRIPS. Given the shorter term of a test data
regime, and the ability to embrace systems of reasonable cost
sharing or remuneration, the most important issue may be to ensure
that generic entry is automatic, particularly when cost sharing or
remuneration payments are modest, relative to prices of
products.Conclusion:
Countries all over the world are facing pressure to implement
Article 39.3 of the TRIPS Agreement in ways that are harmful to
consumer interests. The most harmful outcome is one that involves
the granting of exclusive rights in test data — an approach to be
avoided whenever possible. Systems of remuneration and cost sharing
for the use of test data are not yet practiced by developing
countries, although many have accepted far worst outcomes, based
upon exclusive rights. The choices between various approaches,
including a regime that goes no further than that required by the
TRIPS, will depend upon a country’s assessment of both its self
interest and the political feasibility of sustaining different
approaches. The arguments against exclusive rights are strong,
particularly as an exclusive rights regime for test data can be an
even larger barrier to entry than a patent, and raises important
issues concerning the unethical nature of repeating human medical
experiments when the science is already known.MODEL LANGUAGE FOR A COST-SHARING
APPROACH821. Use of or Reliance on Undisclosed Test Data Submitted for
Pharmaceutical ApprovalParties shall be permitted to use or rely on undisclosed data
submitted by a prior party for the purpose of meeting government
requirements for marketing approval of pharmaceuticals, or to have
a government agency use or rely on the data. Such a right shall be
automatic and is not subject to appeal.2. Commercial Use of Undisclosed Test Data Submitted for
Pharmaceutical ApprovalWhen an agency requires parties, as a condition for the
commercial marketing of pharmaceutical products which utilize new
chemical entities, to submit undisclosed test or other data, the
origination of which involves a considerable effort, the agency
shall require subsequent applicants that use or rely upon the
originator’s data, or have the government use or rely upon such
data for registration of competing products, to contribute to the
costs of such tests, if the following conditions are met:a. Marketing approval was obtained within the past five
years.b. Marketing approval was obtained within one year of any
foreign approval.c. The person who seeks contributions to the cost of such tests
and data provides the agency with public disclosures ofi. the costs of such tests or data, supported by independent
verification,
ii. a reasonable estimate of the country’s likely share of the
global market, and
iii. the amount of global revenue the product has generated to
date, and in the previous 12 months.3. Contributions to the cost of tests
a.) Pursuant to section 2, parties using or relying, or seeking
to have the government use or rely, on data submitted by a previous
party shall make reasonable contributions to the costs of such
data. The amount of the contribution shall be based upon the
payment of a reasonable royalty for the use of the data, or payment
of a pro-rata share of the adjusted costs of the data. In the
absence of an agreement between the parties, the method and amount
of payment shall be determined by the agency.Reasonable royalty. If the reasonable royalty method is
selected, the royalty rate should be either a rate agreed to by the
parties, or 4 percent of the net sales of the generic product, or a
different rate determined by the agency.Pro-rata share of adjusted costs. If the pro-rata share method
is selected, the adjusted cost shall be the actual costs, with
reasonable and transparent adjustments for risks involved in
clinical trials, based upon evidence of typical success rates for
Phase I, II or III trials. The annual pro-rata share of the
adjusted costs shall be one fifth of the total adjusted cost,
multiplied by the generic company’s percentage share of the global
market for the product.b.) There shall be no compensation required where reliance on
the data is sought for government or non-commercial purposes.
SOME RECOMMENDED READINGS:
C. Correa: Protecting Test Data for Pharmaceutical and
Agrochemical Products under Free Trade Agreements (Included in the
book: Negotiating Health: Intellectual Property and Access to
Medicines, Pedro Roffe, Geoff Tansey, David Vivas-Eugui, Earthscan
Publications Ltd. 2006).J. H. Reichman: The international Legal Status of Undisclosed
Clinical Trial Data: From Private to Public Goods? (Included in the
book: Negotiating Health: Intellectual Property and Access to
Medicines, Pedro Roffe, Geoff Tansey, David Vivas-Eugui, Earthscan
Publications Ltd. 2006).M. P. Pugatch: Intellectual Property, Data exclusivity,
Innovation and Market Access (Included in the book: Negotiating
Health: Intellectual Property and Access to Medicines, Pedro Roffe,
Geoff Tansey, David Vivas-Eugui, Earthscan Publications Ltd.
2006).R. Weissman: Data Protection: Options for Implementation
(Included in the book: Negotiating Health: Intellectual Property
and Access to Medicines, Pedro Roffe, Geoff Tansey, David
Vivas-Eugui, Earthscan Publications Ltd. 2006).
ANNEX I: RELEVANT U.S. LAW
FEDERAL FOOD, DRUG, AND COSMETIC ACT
21 USCS § 355 New drugs83
New Drug Applications/ NDA/ Section 505(b)(2)
applications21 U.S.C. § 355(c)(3)(E)
(ii) If an application submitted under subsection (b) for a
drug, no active ingredient (including any ester or salt of the
active ingredient) of which has been approved in any other
application under subsection (b), is approved after the date of the
enactment of this clause [enacted Sept. 24, 1984], no application
which refers to the drug for which the subsection (b) application
was submitted and for which the investigations described in clause
(A) of subsection (b)(1) and relied upon by the applicant for
approval of the application were not conducted by or for the
applicant and for which the applicant has not obtained a right of
reference or use from the person by or for whom the investigations
were conducted may be submitted under subsection (b) before the
expiration of five years from the date of the approval of
the application under subsection (b), except that such an
application may be submitted under subsection (b) after the
expiration of four years from the date of the approval of the
subsection (b) application if it contains a certification of patent
invalidity or non-infringement described in clause (iv) of
subsection (b)(2)(A). The approval of such an application shall be
made effective in accordance with this paragraph except that, if an
action for patent infringement is commenced during the one–year
period beginning forty–eight months after the date of the approval
of the subsection (b) application, the thirty–month period
referred to in subparagraph (C) shall be extended by such amount of
time (if any) which is required for seven and one–half years to
have elapsed from the date of approval of the subsection (b)
application.(iii) If an application submitted under subsection (b) for a
drug, which includes an active ingredient (including any ester or
salt of the active ingredient) that has been approved in another
application approved under subsection (b), is approved after the
date of the enactment of this clause [enacted Sept. 24, 1984] and
if such application contains reports of new clinical investigations
(other than bioavailability studies) essential to the approval of
the application and conducted or sponsored by the applicant, the
Secretary may not make the approval of an application submitted
under subsection (b) for the conditions of approval of such drug in
the approved subsection (b) application effective before the
expiration of three years from the date of the approval of
the application under subsection (b) if the investigations
described in clause (A) of subsection (b)(1) and relied upon by the
applicant for approval of the application were not conducted by or
for the applicant and if the applicant has not obtained a right of
reference or use from the person by or for whom the investigations
were conducted.(iv) If a supplement to an application approved under
subsection (b) is approved after the date of enactment of this
clause [enacted Sept. 24, 1984] and the supplement contains reports
of new clinical investigations (other than bioavailability studies)
essential to the approval of the supplement and conducted or
sponsored by the person submittingthe supplement, the Secretary may not make the approval of an
application submitted under subsection (b) for a change approved in
the supplement effective before the expiration of three
years from the date of the approval of the supplementunder subsection (b) if the investigations described in clause
(A) of subsection (b)(1) and relied upon by the applicant for
approval of the application were not conducted by or for the
applicant and if the applicant has not obtained a right of
reference or use from the person by or for whom the investigations
were conducted.Abbreviated new drug application /ANDA
21 U.S.C. § 355(j)(5)(F)
(ii) If an application submitted under subsection (b) for a
drug, no active ingredient (including any ester or salt of the
active ingredient) of which has been approved in any other
application under subsection (b), is approved after the date of the
enactment of this subsection, no application may be submitted under
this subsection which refers to the drug for which the subsection
(b) application was submitted before the expiration of five
years from the date of the approval of the application under
subsection (b), except that such an application may be
submitted under this subsection after the expiration of four years
from the date of the approval of the subsection (b) application if
it contains a certification of patent invalidity or
non-infringement described in subclause (IV) of paragraph
(2)(A)(vii). The approval of such an application shall be made
effective in accordance with subparagraph (B) except that, if an
action for patent infringement is commenced during the one–year
period beginning forty–eight months after the date of the approval
of the subsection (b) application, the thirty–month period
referred to in subparagraph (B)(iii) shall be extended by such
amount of time (if any) which is required for seven and one–half
years to have elapsed from the date of approval of the subsection
(b) application.(iii) If an application submitted under subsection (b) for a
drug, which includes an active ingredient (including any ester or
salt of the active ingredient) that has been approved in another
application approved under subsection (b), is approved after the
date of enactment of this subsection and if such application
contains reports of new clinicalinvestigations (other than bioavailability studies) essential to
the approval of the application and conducted or sponsored by the
applicant, the Secretary may not make the approval of an
application submitted under this subsection for the conditions of
approval of such drug in the subsection (b) application effective
before the expiration of three years from the date of the
approval of the application under subsection (b) for such drug.(iv) If a supplement to an application approved under
subsection (b) is approved after the date of enactment of this
subsection [enacted Sept. 24, 1984] and the supplement contains
reports of new clinical investigations (other than bioavailability
studies) essential to the approval of the supplement and conducted
or sponsored by the person submitting the supplement, the Secretary
may not make the approval of an application submitted under this
subsection for a change approved in the supplement effective before
the expiration of three years from the date of the approval
of the supplement under subsection (b).
ANNEX II: RELEVANT E.U. LAW
DIRECTIVE 2001/83/EC OF THE EUROPEAN
PARLIAMENT AND OF THECOUNCIL OF 6 NOVEMBER 2001 ON THE COMMUNITY CODE
RELATING TO MEDICINAL PRODUCTS FOR HUMAN
USE84OLD REGIME
Article 10 of the 2001/83/EC Directive:
“1. In derogation of Article 8(3)(i), and without prejudice to
the law relating to the protection of industrial and commercial
property:(a) The applicant shall not be required to provide the results
of toxicological and pharmacological tests or the results of
clinical trials if he can demonstrate:(i) either that the medicinal product is essentially similar to
a medicinal product authorized in the Member State concerned by the
application and that the holder of the marketing authorization for
the original medicinal product has consented to the toxicological,
pharmacological and/or clinical references contained in the file on
the original medicinal product being used for the purpose of
examining the application in question;(ii) or that the constituent or constituents of the medicinal
product have a well established medicinal use, with recognized
efficacy and an acceptable level of safety, by means of a detailed
scientific bibliography;(iii) or that the medicinal product is essentially
similar to a medicinal product which has been authorized within
the Community, in accordance with Community provisions in force,
for not less than six years and is marketed in the
Member State for which the application is made. This period
shall be extended to 10 years in the case of
high-technology medicinal products having been authorised according
to the procedure laid down in Article 2(5) of Council Directive
87/22/EEC (1). Furthermore, a Member State may also extend this
period to 10 years by a single Decision covering all
the medicinal products marketed on its territory where it considers
this necessary in the interest of public health. Member States are
at liberty not to apply the six-year period beyond the date
of expiry of a patent protecting the original medicinal
product.However, where the medicinal product is intended for a different
therapeutic use from that of the other medicinal products marketed
or is to be administered by different routes or in different doses,
the results of appropriate toxicological and pharmacological tests
and/or of appropriate clinical trials must be provided.(b) In the case of new medicinal products containing known
constituents not hitherto used in combination for therapeutic
purposes, the results of toxicological and pharmacological tests
and of clinical trials relating to that combination must be
provided, but it shall not be necessary to provide references
relating to each individual constituent.2. Annex I shall apply by analogy where, pursuant to point (ii)
of paragraph 1, (a), bibliographic references to published data are
submitted.”NEW REGIME
Article 6.1 of the 2001/83/EC Directive (after the 2004
Amendment):“No medicinal product may be placed on the market of a Member
State unless a marketing authorization has been issued by the
competent authorities of that Member State in accordance with this
Directive or an authorization has been granted in accordance with
Regulation (EEC) No. 2309/93.When a medicinal product has been granted an initial marketing
authorisation in accordance with the first subparagraph, any
additional strengths, pharmaceutical forms, administration routes,
presentations, as well as any variations and extensions shall also
be granted an authorisation in accordance with the first
subparagraph or be included in the initial marketing authorisation.
All these marketing authorisations shall be considered as belonging
to the same global marketing authorisation, in particular
for the purpose of the application of Article 10(1).”Article 10 of the 2001/83/EC Directive (after the 2004
Amendment):“1. By way of derogation from Article 8(3)(i), and without
prejudice to the law relating to the protection of industrial and
commercial property, the applicant shall not be required to provide
the results of pre-clinical tests and of clinical trials if he can
demonstrate that the medicinal product is a generic
of a reference medicinal product which is or has
been authorised under Article 6 for not less than eight
years in a Member State or in the Community.A generic medicinal product authorised pursuant to this
provision shall not be placed on the market until ten
years have elapsed from the initial authorisation of the
reference product.The first subparagraph shall also apply if the reference
medicinal product was not authorized in the Member State in
which the application for the generic medicinal product is
submitted. In this case, the applicant shall indicate in the
application form the name of the Member State in which the
reference medicinal product is or has been authorised. At the
request of the competent authority of the Member State in which the
application is submitted, the competent authority of the other
Member State shall transmit within a period of one month, a
confirmation that the reference medicinal product is or has been
authorised together with the full composition of the reference
product and if necessary other relevant documentation.The ten-year period referred to in the second subparagraph
shall be extended to a maximum of eleven years
if, during the first eight years of those ten years, the
marketing authorisation holder obtains an authorisation for one or
more new therapeutic indications which, during the
scientific evaluation prior to their authorisation, are held to
bring a significant clinical benefit in comparison with existing
therapies.2. For the purposes of this Article:
(a) “reference medicinal product” shall mean a medicinal product
authorised under Article 6, in accordance with the provisions of
Article 8;(b) “generic medicinal product” shall mean a medicinal
product which has the same qualitative and quantitative composition
in active substances and the same pharmaceutical form as the
reference medicinal product, and whose bioequivalence with the
reference medicinal product has been demonstrated by appropriate
bioavailability studies. The different salts, esters, ethers,
isomers, mixtures of isomers, complexes or derivatives of an active
substance shall be considered to be the same active substance,
unless they differ significantly in properties with regard to
safety and/or efficacy. In such cases, additional information
providing proof of the safety and/or efficacy of the various salts,
esters, or derivatives of an authorised active substance must be
supplied by the applicant. The various immediate-release oral
pharmaceutical forms shall be considered to be one and the same
pharmaceutical form. Bioavailability studies need not be required
of the applicant if he can demonstrate that the generic medicinal
product meets the relevant criteria as defined in the appropriate
detailed guidelines.3. In cases where the medicinal product does not fall within the
definition of a generic medicinal product as provided in paragraph
2(b) or where the bioequivalence cannot be demonstrated through
bioavailability studies or in case of changes in the active
substance(s), therapeutic indications, strength, pharmaceutical
form or route of administration, vis-à-vis the reference medicinal
product,the results of the appropriate pre-clinical tests or clinical
trials shall be provided.4. Where a biological medicinal product which is similar
to a reference biological product does not meet the conditions in
the definition of generic medicinal products, owing to, in
particular, differences relating to raw materials or differences in
manufacturing processes of the biological medicinal product and the
reference biological medicinal product, the results of appropriate
pre-clinical tests or clinical trials relating to these conditions
must be provided.The type and quantity of supplementary data to be provided must
comply with the relevant criteria stated in the Annex and the
related detailed guidelines. The results of other tests and trials
from the reference medicinal product’s dossier shall not be
provided.5. In addition to the provisions laid down in paragraph 1, where
an application is made for a new indication for a
well-established substance, a non-cumulative period of one year
of data exclusivity shall be granted, provided that significant
pre-clinical or clinical studies were carried out in relation to
the new indication.6. Conducting the necessary studies and trials with a view to
the application of paragraphs 1, 2, 3 and 4 and the consequential
practical requirements shall not be regarded as contrary to patent
rights or to supplementary protection certificates for medicinal
products.”Article 10a of the 2001/83/EC Directive (after the 2004
Amendment):“By way of derogation from Article 8(3)(i), and without
prejudice to the law relating to the protection of industrial and
commercial property, the applicant shall not be required to provide
the results of pre-clinical tests or clinical trials if he can
demonstrate that the active substances of the medicinal product
have been in well-established medicinal
use within the Community for at
least ten years, with recognised efficacy and an
acceptable level of safety in terms of the conditions set out in
the Annex. In that event, the test and trial results shall be
replaced by appropriate scientific
literature.”
NOTES
*1 This work is licensed under the Creative Commons Attribution
2.5 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/2.5/
or send a letter to Creative Commons, 543 Howard Street, 5th Floor,
San Francisco, California, 94105, USA.*2 This work was requested by the “International Seminar on
Development and Vulnerability: Outlooks for Resuming Development in
Southern Countries” organized by the Institute of Economics (IE) at
the Federal University of Rio de Janeiro (UFRJ), September 2006 in
Rio de Janeiro. This paper is a modified version of two previous
CPTech proposals: “US and EU Protection of Pharmaceutical Test
Data” (CPTech Discussion Paper No. 1, 2006) available online athttp://www.cptech.org/publications/CPTechDPNo1TestData.pdf
and “A cost sharing model to protect investments in pharmaceutical
test data” (CPTech Policy Brief No. 1, 2006) available online
at
http://www.cptech.org/publications/policybrief-no1-cost-sharing.pdf1 The terms “marketing exclusivity,” “market exclusivity,” “new
drug product exclusivity,” “Hatch-Waxman exclusivity,” “sui generic
protection,” “data exclusivity,” and “data protection” are all
found in the U.S. and E.U. legal literature. The term “marketing
exclusivity” is used more often in the U.S. regulatory system, and
both the terms “data protection” and “data exclusivity” are used in
the E.U. system. According to one expert (Interview with Ann Witt,
U.S. House of Representative Government Reform Committee, Minority
Staff, November 2006): “Hatch-Waxman never mentions the concept
of “data” exclusivity. The law prohibits the marketing of certain
generic drugs during a specified period, but does not expressly tie
that exclusivity to the data submitted in the application. For
example, a new drug that was approved solely on the basis of
publicly available data could be entitled to 5-years of exclusivity
under Hatch-Waxman and the data supporting the application would
remain public. The only requirement for the exclusivity is that the
drug contain a never-before-approved active moiety. There is no
requirement that the data belong to the applicant. It seems
preferable to call Hatch-Waxman exclusivity “marketing
exclusivity.” Calling it “data exclusivity” could make it harder to
argue that FDA could release or use the data in the applications
for public purposes”.2 In addition to various bilateral and regional trade agreements
negotiated by the U.S. or the E.U., and the continuing negotiations
over WTO accession, the U.S. makes this issue a leading focus of
its Special 301 Report, which is a unilateral listing of countries
that do not provide “adequate” intellectual property
protection.3 Emphasis added.
4 For example, Carlos Correa: “Protection of Data Submitted for
the Registration of Pharmaceuticals: Implementing the Standards of
the Trips Agreement”. (2002, South Centre). Available at: http://www.southcentre.org/publications/protection/toc.htm5 CPTech began working on problems relating the data exclusivity
in 1991, in connection with the registration of Taxol, an
unpatented cancer drug, and in a number of cases has advocated
consideration of compensatory liability or mandatory compulsory
licensing of rights in test data, including, for example, October
21, 1997 US Senate hearing (Ibid), and as an option for the
CAFTA-US Free Trade Agreement in 2004(http://www.cptech.org/ip/health/trade/cafta/joyspencercafta.html).
6 Alternative models to the “EU/US exclusivity regime” have been
presented (at least) by: J.R. Reichman: Undisclosed Clinical Trial
Data Under the TRIPS Agreement and Its Progeny: A Broader
Perspective, (UNCTAD-ICTSD Dialogue on Moving the Pro-Development
IP Agenda Forward: Preserving Public Goods in Health, Education and
Learning, 2004). Available online at:
http://www.iprsonline.org/unctadictsd/bellagio/docs/Reichman_Bellagio4.pdf;
R. Weissman: Data Protection: Options for Implementation (Included
in the book: Negotiating Health: Intellectual Property and Access
to Medicines, Pedro Roffe, Geoff Tansey, David Vivas-Eugui,
Earthscan Publications Ltd. 2006); A.X. Fellmeth: Secrecy,
Monopoly, And Access To Pharmaceuticals In International Trade Law:
Protection Of Marketing Approval Data Under The Trips Agreement (45
Harvard International Law Journal 443, 2004); and R. Dinca: The
“Bermuda Triangle” of Pharmaceutical Law: Is Data Protection a Lost
Ship? (8(4) Journal of World IP 517, 2005). Earlier proposals for
capping exclusivity when sales reach a certain level, and providing
for compulsory licensing of the data were presented in an October
21, 1997 US Senate hearing, “Health Registration Data Exclusivity,
Biomedical Research, and Restrictions on the Introduction of
Generic Drugs,” statement of James P. Love, Consumer Project on
Technology, before the Subcommittee on Labor, Health and Human
Services and Education and Related Agencies, Committee on
Appropriations, U.S. Senate. Available online at: http://www.cptech.org/pharm/senhregd.html7 For some background reading: A. Engelberg: Special Patent
Provisions for pharmaceuticals: have they outlived their
usefulness? 39 J.L. & Tech. 389 (1999); A. Engelberg: Data
Exclusivity under Article 39.3 of TRIPS – Does current US law
comply? Working Paper, October 22 (2001); G. Mossinghoff: Overview
of the Hatch-Waxman Act and its impacts on the Drug Development.
Food and Drug Law Journal, Vol. 54; How Increased Competition from
Generic Drugs has affected process and returns in the
Pharmaceutical Industry. CBO (1998); M.P. Pugatch: Intellectual
Property and pharmaceutical data exclusivity in the context of
innovation and market access. ICTSD-UNCTAD Dialogue on Ensuring
Policy Options for Affordable Access to Essential Medicines
Bellagio (2004); R. Strongin: Hatch-Waxman, Generics, and Patents:
Balancing Prescription Drug Innovation, Competition, and
Affordability. NHPF Background Paper (2002); and V. Junod: Drug
marketing exclusivity under United States and European Union law.
59 Food & Drug L.J. 479 (2004).8 FDA regulations 21 CFR § 314.14 (f), codified in 1984 in the
Section 21 U.S.C. § 355 (l).9 Interview with Alfred Engelberg (April 2006)
10 Pub. L. No. 98-417 (98th Congress, 1984).
11 Abbreviated new drug applications (ANDA) are regulated
in section 21 U.S.C. § 355(j). These are the most common form of
generic applications. Applications must contain information to show
that the proposed product is identical or almost identical in
active ingredient, dosage form, strength, route of administration,
labeling, quality, performance characteristics and intended use,
among other things, to a previously approved application (the
originator or reference listed drug). ANDAs do not contain clinical
studies but are required to contain information establishing
bioequivalence to the originator. In general, the bioequivalence
determination allows the ANDA to rely on the agency’s finding of
safety and efficacy for the originator.12 505(b)(2) Applications are
regulated in section 21 U.S.C. § 355(b)(2). These applications are
for drugs that are only somewhat similar to another drug (e.g. the
same composition but a new indication), and for which one or more
of the investigations relied upon by the applicant for approval
“were not conducted by or for the applicant and for which the
applicant has not obtained a right of reference or use from the
person by or for whom the investigations were conducted”. When
approving a 505(b)(2) application, the FDA can rely on data not
developed by the applicant such as published literature or the
agency’s finding of safety and effectiveness of a previously
approved drug. For more information: “Guidance for Industry
Applications Covered by Section 505(b)(2)” (1999). Available at
http://www.fda.gov/cder/guidance/2853dft.pdf13 Certain practices related to obtaining FDA approval that
would otherwise constitute patent infringement are exempted from
infringement liability under the patent laws. Most importantly, the
U.S. “Bolar” exception is in Section 35 USC 271(e)(1), which reads
in part: “It shall not be an act of infringement to make, use,
offer to sell, or sell within the United States or import into the
United States a patented invention . . . solely for uses reasonably
related to the development and submission of information under a
Federal law which regulates the manufacture, use, or sale of drugs
or veterinary biological products”.14 Pediatric exclusivity is six months and can be added to other
exclusivities or patent protections. It is the only exclusivity
that runs from the end of other exclusivity protection (New Drug
Product and Orphan Drug) or patent protection (and thus may
function as a de facto patent extension).15 To encourage generic producers to seek early entry of their
products onto the market (including by challenging the validity of
patents with a paragraph IV certification), the first generic
company that successfully applies for approval of a generic version
of an originator product may have a 180-day period of exclusivity.
21 USC 355 (j)(5)(B)(iv)(I)16 The FDA interprets the term “New Chemical Entity” as a
drug that contains no active moiety that has been approved by FDA
in any other application submitted under section 505(b) of the
Act.17 The FDA interprets the term “active moiety” as the
molecule or ion, excluding those appended portions of the molecule
that cause the drug to be an ester, salt (including a salt with
hydrogen or coordination bonds), or other noncovalent derivative
(such as a complex, chelate, or clathrate) of the molecule,
responsible for the physiological or pharmacological action of the
drug substance.18 21 U.S.C. § 355(j)(5)(F)(ii)
19 21 U.S.C. § 355(c)(3)(E)(ii)
20 Section 21 U.S.C. § 355(c)(3)(E)(ii) stays that: “….except
that such an application may be submitted under subsection (b)
after the expiration of four years from the date of the approval of
the subsection (b) application if it contains a certification of
patent invalidity or non-infringement described in clause (iv) of
subsection (b)(2)(A)….” U.S. Law provide that second
applicants/generic have four certification options, Paragraph IV
certification indicates that the generic intends to market the drug
as soon as the FDA approves the application because the patent is
invalid or will not be infringed by the generic drug for which the
applicant seeks approval. For more information see CPTech
Discussion Paper N.2 on Patent-Registration linkage (2006),
available online at:http://www.cptech.org/publications/CPTechDPNo2Linkage.pdf
21 The FDA interprets “conducted or sponsored” as
involving clinical trials where, before or during the
investigation, the applicant was named in Form FDA 1571 as the
sponsor of the investigational new drug application under which the
investigation was conducted, or the applicant or the applicant’s
predecessor in interest, provided substantial support for the
investigation. An applicant who has purchased exclusive rights to a
study should also be able to obtain new drug product exclusivity.
Applicants cannot qualify for exclusivity by simply collecting and
submitting to FDA information from the literature or buying the
results of tests already done and submitting them to FDA without
obtaining exclusive rights for those tests. The applicant is not
required to conduct the complete study to obtain exclusivity; it is
enough when the applicant has provided 50 percent of the funding or
by purchasing exclusive rights to the study.22 The FDA interprets “new clinical investigation” as an
investigation in humans, the results of which (1) have not been
relied upon by the FDA to demonstrate substantial evidence of
effectiveness of a previously approved drug product for any
indication or of safety in a new patient population and (2) do not
duplicate the results of another investigation relied upon by the
FDA to demonstrate a previously approved drug’s effectiveness or
safety in a new patient population. A clinical investigation that
provides a “new” basis for approval of an application can qualify
for exclusivity. In this context, “new” is intended to convey a
lack of prior use of a clinical investigation rather than any
temporal requirement.23 The electronic version of the Approved Drug Products with
Therapeutic Equivalence Evaluations/ Orange Book is available at
http://www.fda.gov/cder/ob/default.htm24 Source: FDA FAQ on patents and exclusivity, available at:
http://www.fda.gov/cder/ob/faqs.htm25 Interview with Ann Witt, U.S. House of Representative
Government Reform Committee, Minority Staff (November 2006)26 A useful description of FDA’s understanding of the situation
is found in the preamble to its proposed (not finalized) rule to
implement section 125 of FDAMA, available at: http://www.fda.gov/cder/fdama/fedreg/01242000.pdf27 Available online at: http://www.fda.gov/cder/guidance/2468fnl.pdf
28 For background reading, see: I. Dodds-Smith: Data Protection
and abridged applications for marketing authorizations in the
pharmaceutical industry (from the book: Goldberg, Richard and
Lonbay, Julian, (Eds.): Pharmaceutical Medicine, biotechnology and
European Law, Cambridge University Press, 2000); M.P. Pugatch:
Intellectual Property and pharmaceutical data exclusivity in the
context of innovation and market access. ICTSD-UNCTAD Dialogue on
Ensuring Policy Options for Affordable Access to Essential
Medicines Bellagio (2004); and V. Junod: Drug marketing exclusivity
under United States and European Union law. 59 Food & Drug L.J.
479 (2004).29 In E.U. terminology, “pharmaceutical products” are refereed
to as “medicinal products”.30 Council Directive 65/65/EEC of 26 January 1965 on the
approximation of provisions laid down by Law, Regulation or
Administrative Action relating to proprietary medicinal products.
Available at:31 In Europe, subject to certain conditions, applicants
submitting “abridged applications” are not required to provide the
results of pharmacological and toxicological tests or the results
of clinical trials and can rely on the data presented by a pioneer
application. The abridged applicant remains obliged to provide the
other particulars and documents listed in Article 8.3 of Directive
2001/83, including physico-chemical, biological or microbiological
tests.32 Council Directive 87/21/ECC of 22 December 1986, amending
Council Directive 65/65/EEC on the approximation of provisions laid
down by law, regulations or administrative action relating to
proprietary medicinal products. Available at:33 Directive 2001/83/EC of the European Parliament and of the
Council of 6 November 2001 on the Community Code Relating to
Medicinal Products for Human Use. Available at:
http://pharmacos.eudra.org/F2/eudralex/vol-1/DIR_2001_83/DIR_2001_83_EN.pdf.
In 2003, the 2001/83/EC Directive, and more specifically its Annex
I, was modified by the Commission Directive 2003/63/EC of 25 June
2003, 2003 O.J. (L 159) 46. The text is available at:
http://pharmacos.eudra.org/F2/review/doc/2003_June/direct_comm_2003_63_es%20.pdf34 Article 10.1(a) of Directive 2001/83 (formerly Article 4.8(a)
of Directive 65/65, as amended by Directive 87/21) provides for an
abridged authorization procedure.35 The E.U. interprets the notion of “reliance” in much the same
way as the United States; indeed, the notion refers to reliance by
the drug agency, and not to direct access and use of the data by
the second applicant.36 C-368/96 Generics (UK) and Others [1998] ECR I-1967
37 Regulated in second subparagraph of Article 10.1(a)(iii) of
the Directive 2001/83/EC38 These types of applications are referred as “informed
consent” abridged applications. Article 10.1(a)(i). This had always
been possible although before 1987 it was not expressly
mentioned.39 Article 10.1(a)(ii) of Directive 2001/83 (formerly Article
4.8(a)(ii) of Directive 65/65, as amended by Directive 87/21)
regulated the published literature exemption.40 Case C-440/93 R v. 1. Licensing Authority of the Department
of Health and 2. Norgine Ltd, ex parte Scotia Pharmaceuticals LTD
(1995) ECT I-285141 Bristol-Myers Squibb BV v. Het College ter Beoordeling Van
Geneesmiddelen (Medicines Evaluation Board) and Yew Tree
Pharmaceuticals BV. Ultrecht District Court, 200042 Article 10a of the Directive 2001/83/EC, as amended
43 For example, until 1992, Spain and Portugal did not grant
product patents to medicinal products. Product patents for
medicinal products are now available in all 25 Member States.44 Directive 2004/27/EC of the European Parliament and of the
Council of 31 March 2004 amending Directive 2001/83/EC on the
Community code relating to medicinal products for humanuse.
Available at:
http://pharmacos.eudra.org/F2/review/doc/final_publ/Dir_2004_27_20040430_EN.pdf45 European Commission, Notice to Applicants, Centralized
Procedure, in Vol. 2A, PROCEDURES FOR MARKETING AUTHORISATION, ch.
4, at 2-3 (Dec. 2002). Available
at:http://pharmacos.eudra.org/F2/eudralex/vol-2/A/v2a_
chap2%20_r3_2004-02.pdf46 Presently, only so-called “high-tech” products are eligible
for approval through this centralized procedure. These are drugs
derived from biotechnology (e.g., recombinant DNA), and products
with a significant innovation or therapeutic advance, including new
active substances, new therapeutic indications, new delivery
systems, and new manufacturing methods.47 Austria, Denmark, Finland, Greece, Ireland, Portugal, Spain,
Norway and Iceland and the 10 new 2004 Member States (Cyprus, the
Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland,
Slovakia, and Slovenia) have opted for this solution.48 Greece, Spain, and Portugal have opted for this solution.
49 Belgium, Germany, France, Italy, The Netherlands, Sweden, the
United Kingdom, and Luxembourg have opted for this solution.50 C-368/96 R v. The Licensing Authority established by the
Medicines Act 1968 (acting by the Medicines Control Agency), ex
parte Generics (UK) Ltd; R v. Same, ex parte Wellcome Foundation
Ltd; R v. Same, ex parte Glaxo Operations UK Ltd and Others (E.R.
Squibb & Sons Ltd, Generics (UK) Ltd, intervening) [1999] ECR
I-7967 (“The Generic Case”)51 C-94/98 R v MCA ex parte RPR and R v MCA ex parte RPR,
Trinity Pharmaceuticals and Norton Healthcare Intervening (“The RPR
Zimovane Case”)52 Available at: http://www.egagenerics.com/gen-dataex.htm
53 A not official consolidate version is available at:
http://pharmacos.eudra.org/F2/eudralex/vol-1/CONSOL_2004/Human%20Code.pdf54 The 2004 Directive creates the “European reference
product”. Now, a generic applicant can apply for a marketing
authorization in any Member State and rely on the dossier already
submitted from the European Reference Product in another Member
State. The other Member State will be obliged to supply the
documentation requested.55 See chart and summary from the European Generic Medicines
Association. Available at: http://www.egagenerics.com/gen-dataex.htm56 Article 6.1 of the Directive 2001/83/EC, as amended.
57 This provision is in line with some recent ECJ decisions
which held that a generic application could rely on data relating
to a reference product even though the generic product was not
essentially similar to the reference product (for example, due to a
difference in their pharmaceutical forms. C-106/01, Novartis
Pharmaceuticals (ECJ Apr. 29, 2004) and Eli & Lilly & Co.
(ECJ Dec. 9, 2004).58 Article 10.4 of the Directive 2001/83/EC, as amended. See
also several EMEA/ Committee for Medicinal Products for Human Use
(CHMP) Guidelines on Similar Biological Medicinal Products.
Available at:
http://www.emea.eu.int/htms/human/biosimilar/biosimilarfin.htm59 Head of Pharmaceuticals Unit. Enterprise and Industry
Directorate-General, European Commission60 Letter available at: http://www.cptech.org/ip/health/dataexcl/ec-de-tamiflu.pdf
61 Tamiflu is the trade name under which Roche is marketing
oseltamivir, an antiviral drug
that is used in the treatment and prophylaxis of both
Influenza
virus A and B.62 Statement of Congress Representative Henry A. Waxman at the
House Committee on Ways and Means (June 2003). Available at:
http://waysandmeans.house.gov/hearings.asp?formmode=printfriendly&id=110763 The TRIPS legislative history had a prior Brussels draft
(1990) providing that data exclusivity had to run “for a reasonable
time, generally no less than five years”. The exclusion of this
language from the final version of TRIPS endorses the reading that
members are free to determine a period of protection that they
consider in accordance with their national interest.64 Such a limitation, however, is prohibited by the
US/Singapore, US/Morocco, and US/Central America Free Trade
Agreements, which require exclusivities for “information” submitted
by originators — without the “undisclosed” qualification.65 For example, Canada grants exclusivity only if there is
actual reliance, in that the authority has actually reexamined the
file submitted by the first applicant to approve a second entrant’s
application.66 The term ‘new chemical entity’ is understood broadly to mean
a chemical compound not previously known or described. The IUPAC
Recommendations (1998) define an NCE as “a compound not previously
described in the literature”, available at http://www.chem.qmul.ac.uk/iupac/medchem/ix.html67 An example of a bad practice is the US/Singapore FTA with
“pharmaceutical chemical product” wording.68 By contrast, the U.S.-Central America Free Trade Agreement
Countries requires member countries to provide five years of data
protection from the date a product is given regulatory approval in
their country. It also requires that member countries grant five
years data exclusivity protections to originator companies if their
product has received marketing approval anywhere in the world –
even if the originator company has not introduced the product in
their country. Pharmaceutical companies may maneuver in this system
to extend the period of monopoly control over the data to 10
years69 Ley No. 19.996, VIII, Article 91(e) (2005). Available (in
Spanish) at:
http://sdi.bcn.cl/boletin/publicadores/normas_publicadas/archivos/19996.pdf70 The FIFRA Act is available online at:
http://www.access.gpo.gov/uscode/title7/chapter6_subchapterii_.html71 For an analysis of the FIFRA cost sharing model read M.
Cresence Stanfford and James C. Wright: “Data Citation,
Compensation and Cost Sharing: Pitfalls and Traps for the Unwary”.
Available online at: http://www.pesticide.net/x/article/stafford20021210.pdf72 As described in the CPTech Discussion paper on linkage. See:
“Patent-Registration Linkage” (CPTech Discussion Paper No. 2,
2006). Available online at: http://www.cptech.org/publications/CPTechDPNo2Linkage.pdf73 To be compensable, the study must have been submitted to EPA
within fifteen years of being cited. A study may be cited and
relied upon by another company, without any obligation to pay
compensation, if it has been on file with EPA for more than fifteen
years. (source: M. Cresence Stanfford and James C. Wright, supra
note 75)74 Or 60 days after a party offers to share the cost or
jointly develop the data for FIFRA § 3(c)(2)(B)(iii) situations:
“If, at the end of sixty days after advising the Administrator
of their agreement to develop jointly, or share in the cost of
developing, data, the registrants have not further agreed on the
terms of the data development arrangement or on a procedure for
reaching such agreement, any of such registrants may initiate
binding arbitration proceedings by requesting the Federal Mediation
and Conciliation Service to appoint an arbitrator from the roster
of arbitrators maintained by such Service. The procedure and rules
of the Service shall be applicable to the selection of such
arbitrator and to such arbitration proceedings, and the findings
and determination of the arbitrator shall be final and conclusive,
and no official or court of the United States shall have power or
jurisdiction to review any such findings and determination, except
for fraud, misrepresentation, or other misconduct by one of the
parties to the arbitration or the arbitrator where there is a
verified complaint with supporting affidavits attesting to specific
instances of such fraud, misrepresentation, or other misconduct.
All parties to the arbitration shall share equally in the payment
of the fee and expenses of the arbitrator. The Administrator shall
issue a notice of intent to suspend the registration of a pesticide
….if a registrant fails to comply with this clause.”75 For the official arbitration rules of FIFRA test data
compensation/ cost sharing disputes (29 C.F.R. Part 1440) see:
http://www.pesticide.net/x/cfr/arb_rule.htm76 For example, Dupont v. Griffin and Drexel/Docket No.
16-171-0080-86M (1988) Decision available at http://www.pesticide.net/x/comp/dupont1.htm.
American Cyanamid v. Aceto / Docket No. 13-171-0800-85 (1989)
Decision available athttp://www.pesticide.net/x/comp/aceto.htm.
Ciba-geigy v. Drexel Chemical / Docket No. 16 171 00321 92G (1994).
Decision available at http://www.pesticide.net/x/comp/ciba.htm77 U.S. District Court for the District of Columbia in Cheminova
A/S v. Griffin L.L.C., 182 F. Supp. 2d 68 (D.D.C. 2002) available
online at: http://www.pestlaw.com/x/comp/cheminova02.html78 Ruckelshaus v. Monsanto Co., 467 U.S. 986 (U.S. 1984). Some
relevant language: ”But Monsanto has not challenged the ability of
the Federal Government to regulate the marketing and use of
pesticides. Nor could Monsanto successfully make such a challenge,
for such restrictions are the burdens we all must bear in exchange
for the advantage of living and doing business in a civilised
community.”79 See, for example, the Microgen v. Lonza arbitration Decision
(2000) available online at http://www.pesticide.net/x/comp/microgen3.html80 Calculated with appropriate adjustments for risk.
81 Among others: Initiative for Medicines, Access &
Knowledge: “The Impact of Article 39.3 in India: A Practical
Perspective” (2006, I-MAK); and B. Baker: “A critical analysis of
India’s probable data exclusivity/data compensation provisions”
(2006, Health Gap), available at:
http://www.cptech.org/blogs/ipdisputesinmedicine/2006/10/critical-analysis-of-indias-probable.html82 This model language was proposed in “A cost sharing model to
protect investments in pharmaceutical test data” (CPTech Policy
Brief No. 1, 2006) available online at
http://www.cptech.org/publications/policybrief-no1-cost-sharing.pdf.
For an earlier proposal see also R. Weissman: Data Protection:
Options for Implementation. Included in the book: Negotiating
Health: Intellectual Property and Access to Medicines, Pedro Roffe,
Geoff Tansey, David Vivas-Eugui, Earthscan Publications Ltd.
2006.83 Titles and emphasis added. Only most relevant sections
included.84 Titles and emphasis added. Only most relevant sections
included. -