Principles and Practice of Pharmaceutical Medicine

view; for example, expressing concern about
special programs that drive product costs upward
and when these costs are absorbed by the national
health services more easily in large countries than
in small ones. Within the EMEA, there are multiple
departments and divisions with responsibilities
that impinge on different aspects of risk manage-
ment programs; the CHMP maintains a Pharma-
covigilance Working Group, the COMP wants to
assure access to drugs for patients with rare dis-
eases, and the groups dealing with labeling have
the daunting task of ensuring that written descrip-
tions of how to mitigate drug hazards, mean the
same thing in more than 20 languages.
At the national level within Europe, the situation
becomes yet more complicated for both regulatory
and less tangible, cultural reasons. Each member
state has a National Competent Authority (NCA)
regulating pharmaceutical product price, label and
distribution. Each NCA can mandate product with-
drawal within its boundaries, and notify others
about its concerns. But such a decision is never
binding in any other part of the EEA, and there is
certainly no obligation for one member state to
implement a risk management program that has
been mandated at the national level elsewhere.
Academic, cultural (including religious), ethical
and medical attitudes also diverge within the EEA.
For example, with the exception of clinical trial
participation, in many European countries a
requirement for written informed consent is seen
as unethical: no informed consent means no ther-
apy, and therefore the patient may be under duress,
or provide uninformed ‘consent’ in order to gain
access to medical treatment. Furthermore, the
notion that some of the burden of responsibility
for drug exposure could shift to the patient can also
be seen as an abrogation of the responsibility of the
prescriber or pharmacist.
Patient registries and databases also run into
problems within the EEA. Regardless of whether
or not these rely on public funding, they are seen as
potential violations of patient confidentiality. In
some European countries, this is emphasized by
national privacy legislation. The entry of an iden-
tifiable patient into a registry, as a condition of drug
supply, can be seen as a situation where it is a
registry administrator, checking inclusion and

exclusion criteria, that ultimately decides whether

a patient is treated; this is seen asde factointer-

ference with the clinician–patient relationship. For

all these reasons, it can be impossible to operate the

same risk management program in every European

country.

41.3 Practical examples

What sorts of drugs and indications have special

clinical hazards and need special risk management

programs? At the pan-European level, the EMEA

now considers risk management plans more or less

routinely prior to Marketing Authorization. But in

general, the products for which detailed risk man-

agement plans will almost always be required are

biological products;

new chemical entities with novel mechanisms of

action;

significant changes in indication for older

products;

new target populations;

major issues of intolerability;

products undergoing the prescription-only to

over-the-counter ‘switch’; and

Orphan Medicinal Products(where clinical trials

patients are automatically few).

Although most of the ‘Sub-part H’ examples in

the United States fall into these categories, these

are good, general criteria which should stimulate

Sponsors to consider implementing detailed

risk management programs, regardless of whether

or not this is being mandated by a regulatory

authority.

Abuse liability. Psychotropic drugs with abuse

and dependence potential, and the associated

restrictions on product distribution (i.e. ‘Schedul-

ing’ under a Controlled Substances Act or equiva-

lent) form a well-established system of risk

41.3 PRACTICAL EXAMPLES 559