When the principle of marketing authorisation for medicinal products
was first adopted in Europe, the first recital of Directive 65/65/EEC,
dated 26 January 1965, stated that the overriding aim was to "safeguard
public health".
Over the last forty years the regulations governing marketing authorisation
have become increasingly complex, but this aim has never been explicitly
challenged. However, we have noticed a tendency on the part of the
European Commission to neglect public health in favour of industrial
competitiveness. In particular, during the drafting procedure for
Directive 2004/27/EC and Regulation (EC) 726/2004, the Medicines
in Europe Forum and other representatives of civil society were
hard pressed to ensure that the legislative framework now governing
medicinal products for human use did not overlook the public health
imperative.
The draft regulation currently proposed by the European Commission
for conditional marketing authorisation of medicinal products again
places European public health at risk and must be opposed with force.
Conditional marketing authorisation already
exists, but conditions are rarely enforced
Many marketing authorisations granted through the European centralised
procedure are already subject to conditions. However, these are
only mentioned in the last few lines of the relevant European Medicines
Evaluation Agency (EMEA) assessment reports (EPARs), with words
to the effect that the Committee for Medicinal Products for Human
Use only granted a favourable opinion provided the company conducts
further clinical trials, or completes ongoing trials, or conducts
postmarketing pharmacovigilance studies of the first patients to
receive the drug.
As we have pointed out elsewhere, this procedure is particularly
risky because it allows inadequately assessed drugs to enter the
European pharmaceuticals market. Conditional authorisation may be
acceptable in urgent situations, in which no other therapeutic options
are available, but it should remain the exception and not the rule.
We have also underlined the difficulties encountered when trying
to verify whether companies actually fulfil the conditions to which
they their marketing authorisations are subject. The available evidence
suggests that many of these requested studies are postponed or never
even launched.
Official endorsement of a harmful procedure
Regulation (EC) 726/2004 endorses the principle of conditional marketing
authorisation, stipulating in article 14.7 that marketing authorisation
(European centralised procedure) can be granted if the applicant
is subject to certain obligations that are to be revised annually
by the Agency. The Medicines in Europe Forum initially believed
that this article simply raised a possibility, to be used in exceptional
circumstances. The Forum nevertheless succeeded in imposing the
following sentence: "the list of these obligations must be
made public". A paragraph of article 14.7 does state that conditional
marketing authorisation would be further defined in another regulation,
the first draft of which was recently released by the Commission.
In the light of the growing number of pharmacovigilance affairs,
the current draft regulation presented by the Commission is simply
unacceptable from the standpoint of population health. As it stands,
the aim is clearly not to help patients who find themselves in exceptionally
difficult situations, but rather to open the floodgates to inadequately
assessed drugs:
- field of application too large: according
to draft article 2, the procedure will apply to all drugs intended
for the treatment, prevention or diagnosis of any chronic, severely
incapacitating or life-threatening health disorder; all orphan drugs
and all drugs for emergency use (probably in case of pandemics,
bioterrorism, etc.). The last part of this definition (orphan drugs
and emergency situations) is acceptable, but the first part is far
too wide-ranging and therefore unacceptable;
- vague approval criteria: draft article 4 states that the procedure
will apply if the applicant is able to demonstrate the presumed
positive benefit-risk balance of the medicinal product. And draft
article 5, which is very brief and concerns the appraisal of marketing
applications, offers no details on the type of evidence to be provided
by the applicant, or on the endpoints to be covered. It simply states
that any new trials that are requested as a condition for conditional
marketing authorisation must not be more demanding than for normal
marketing authorisation. However, as this regulation concerns medicines
intended for serious health disorders, the least one would expect
is a requirement for comparative trials versus a reference treatment
based on clinical endpoints;
- flimsy follow-up requirements: draft article 6 stipulates that
conditional marketing authorisation will be granted for one year,
renewable, but that the marketing commission can also modify the
conditions and confirm the marketing authorisation without further
conditions. And draft article 9, dealing with pharmacovigilance,
only requires applicants to provide reports at least every six months.
- patients poorly informed: draft article
7 states that the conditional nature of the marketing authorisation
will feature on the summary of product characteristics and on the
patient information leaflet. In our opinion, this information should
also be provided on the pack, as a warning to patients.
An unacceptable draft in the current pharmacovigilance climate
We demand that the draft regulation be profoundly reconsidered,
especially concerning its field of application, evaluation criteria,
and follow-up of imposed conditions. The few guarantees of transparency
in the draft represent the strict minimum, yet will serve no useful
purpose if the underlying aim of the text is not to help patients
but rather to facilitate market access for inadequately assessed
drugs.
The conditional marketing authorisation procedure, as defined in
the current draft, places European public health at risk. La revue
Prescrire and other concerned health care professionals are deeply
opposed to this project. Too many patients already fall victim to
the adverse effects of drugs that are rushed to market.
©La revue Prescrire 15 January 2005
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