The heart of a marketing authorization application
("MAA") is the pre-clinical and clinical data that proves
the drug's safety and efficacy. This data is collected through
substantial investments in time and money. The current and proposed
policies of the European Medicines Agency ("EMA")
threaten the confidentiality, and hence the business value, of
these investments.
At a workshop in November 2012, the EMA proposed to proactively
publish clinical data submitted with MAAs. Even worse, EMA
currently does not view pre-clinical or clinical data as qualifying
as commercial confidential data. EMA is therefore willing to
disclose the data in response to freedom-of-information
("FOI") requests. EMA is even of the opinion that data
owners do not have to be asked for comments before release.
EMA's position is inconsistent with EU legislation. It stands
in stark contrast to the regulations of the United States Food and
Drug Administration ("FDA"), and to Japanese regulations.
EMA's position endangers investments in drug development and,
in the mid to long term, risks cutting off European patients from
access to innovative treatments.
Originators therefore should strongly advocate protection of
commercial confidential data in the ongoing public consultation
process. In addition, if their data is subject to FOI requests,
they should consider taking legal action against EMA.
Background
The question of public access to data from drug development,
both clinical and pre-clinical, has turned into a battlefield where
the pharmaceutical industry risks losing out on their
multimillion-dollar investments in innovative therapies. While EMA
initially acknowledged that data submitted with the MAA is
commercial confidential information, EMA has since reversed
course.
In July 2012, EMA invited stakeholders to further discuss
proactive release of clinical data in a November 2012 workshop.
However, at the workshop, it became apparent that EMA had already
mapped its policy preferences, aiming for proactive disclosure of
clinical data upon marketing authorization.
EMA has taken similar legal and administrative positions in FOI
request cases. EMA has held that neither pre-clinical nor clinical
data are commercial confidential information of originators, and
may thus be disclosed on request. EMA considers this
"obvious," curtailing the right of the data owner to be
consulted. Accordingly, while in some cases EMA advised data owners
that it intended to release data from the MAA, EMA considered such
warnings to be voluntary. Thus, in other cases, originators learned
about the disclosure only when data they thought confidential was
presented to them by third parties.
EMA might thus release full sets of pre-clinical and clinical
data—thousands of pages that the originator would consider to
be commercial confidential information (unless already
published).
Legal Assessment
Current European legislation provides no legal basis for EMA to
proactively release clinical data, even after marketing
authorization. On the contrary, the Community Code on Medicinal
Products for Human Use (directive 2001/81/EC as amended) confirms
that data filed with an MAA enjoys data exclusivity. Even after
expiry of data exclusivity, generics may only reference data on
file with EMA—but not access it.
The proposed draft EU regulation on clinical trials reinforces
this conclusion. While the draft regulation proposes to set up a
database containing data submitted under the regulation, such a
database would contain only summary results of clinical trials (not
the full data set that has to be filed with an MAA), and the draft
explicitly protects commercial confidential information from public
access.
Regarding the release of data upon FOI requests, EMA's
position that such data does not constitute commercial confidential
data is fundamentally flawed and without basis in EU legislation.
Such data loses its status as confidential only if the originator
decides to publish it.
Transparency in the European authorization process is already
provided for through the European public assessment report
("EPAR"), which summarizes the basis of the decision of
the Committee for Human Medicinal Products. (An EPAR is comparable
to the Summary Basis for Approval released by the FDA and the
summary of clinical data released by the Japanese regulator,
PMDA.)
Providing an EPAR is itself an exception to the rule that
technological developments, even if of public interest, remain
confidential; nobody would seriously claim access to the building
plans for a department store (reviewed by the building authority)
or to the blueprints of an airplane or high-speed train (certified
by an aviation or public transport authority, respectively).
The special European rules on data exclusivity should take
precedence over the general rules on FOI requests. Until expiry of
data exclusivity, no data may be released except as explicitly
stipulated in the European legislation (e.g., safety data). Even
after expiry of data exclusivity, data must be treated as
commercial confidential, if it can be used as the basis for
marketing authorization applications in other jurisdictions.
In addition, to the extent data is relevant for obtaining patent
protection, and where public release might create prior art, such
data has to be treated as commercial confidential
information.
The confidentiality of commercial information is a property right
protected by the European fundamental rights, as acknowledged by
the Court of Justice of the European Union. The illegal disclosure
of information would violate this right. Therefore, EMA's
disclosure policy (and any parallel policy of national regulators)
would cause EMA to become liable for resulting damages. In
addition, officers of national authorities may face criminal
sanctions under national legislation protecting commercial
confidential information entrusted to authorities.
It further follows that EMA must consult the originator before
releasing data. There is no overriding public interest that would
dispense with such consultation; the general public interest of
access to information held by public authorities is outweighed here
by the public interest in maintaining a regulatory environment that
allows investment into drug development.
The International Perspective
EMA's proposal and current practice stands apart from
treatment of commercial confidential information by other
regulators.
The FDA is generally careful to protect the confidentiality of
submitted data, including data from clinical trials. Indeed, while
drug applications are pending, the FDA will not even disclose their
existence unless that fact is already publicly known. With limited
exceptions, regulations prohibit the FDA from revealing any data
contained within the pending drug applications.
Once a new drug application ("NDA") is approved, the FDA
automatically publishes a series of summary reports, including a
summary of the safety and efficacy data (a category that includes
all studies and tests of the drug). The summary reports, however,
are generally prepared by the company that submitted the NDA. The
summaries do not include the raw data, and "do not constitute
the full reports on which the safety or effectiveness of the drug
may be approved." If an application is abandoned, rejected, or
withdrawn, the FDA does not automatically publish data, but the
full safety and efficacy file is available to the public upon
request. The file likewise becomes available upon request following
approval of an abbreviated NDA ("ANDA") (which permits
the marketing of a generic), or after the date on which an ANDA
could have been approved.
A person who wants more information than is automatically
published may request disclosure under the Freedom of Information
Act ("FOIA"). With significant exceptions, FOIA requires
the government to disclose any document in its possession. The most
important exception shields from disclosure "trade secrets and
commercial or financial information obtained from a person and
privileged and confidential." The FDA defines "commercial
information" to include "valuable data or information
which is used in one's business and is of a type customarily
held in strict confidence."
The FDA has a well-defined procedure for responding to FOIA
requests. If the submitting party designated its data as
confidential, or if the confidentiality of the data is uncertain,
the FDA will notify the submitting party of any request for
disclosure. Should the FDA determine that the information is
subject to disclosure, the submitting party has the opportunity to
seek judicial review of this decision. The reviewing court will
then have the last word, and the FDA will not disclose the
information until the court determines the issue.
In court, the party resisting disclosure has the burden of proving
that the document is shielded by an exception to FOIA's
presumption of open access. Courts do not have a uniform rule
regarding how clinical data is to be treated. The outcomes depend
upon the evidence provided and often turn on whether there is proof
that disclosure will cause competitive harm to the company that
submitted the data.
Likewise, the Japanese regulator, PMDA, only discloses summaries
of clinical data proactively on its web site. Data submitted with
MAA is otherwise treated as commercial confidential information and
thus protected against FOI requests. Unlike EMA, PMDA is not
envisaging any changes to these policies.
Impact Assessment
If EMA were to deviate from international practice and release
data, whether proactively or on request, it would endanger the
multimillion dollar investments made in the development of the
drug. As competitors could freely use such data to file stand-alone
MAA of their own (NDAs in U.S. parlance), without patent protection
originators would quickly face competition in the market, long
before expiry of data exclusivity.
In the long run, however, industry might think twice about filing
with EMA before other relevant markets became open to generics.
This would deprive patients of access to innovative products in
Europe, or at least significantly delay introduction of new
drugs.
Possible Action
The consultation process on the proactive release of clinical data
runs through April 2013. Industry is well advised to engage in the
process and to clarify the impact an imbalanced aim for
transparency would have.
When fending off FOI requests, originators can take legal action
to protect their commercial confidential information; courts can
enjoin EMA from releasing such data. Where EMA has released data
without consultation, declaratory action should be sought to
prevent additional disclosures.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.