The report is available in English with a French summary - KCE

KCE Reports 120 Plasma 7
Focus: status of plasma products with regard to the EU legislation
Legal status of plasma-derived products remains a sensitive and delicate subject both
from a legal and political point of view.
The main issue is to have a clear view on the legal nature of blood products, to be
specific of plasma-derived products. Whereas these products are blood products or
drugs might have far-reaching consequences, especially in terms of freedom of
circulation.
Until now, no case law of the European Court of Justice has been identified on the legal
status of blood or plasma products, as such.
The problem has really not been solved and the arguments listed below must be
considered with great care, and might be challenged by the ECJ in the future. To some
extent, one can rely on a body of legal evidence, considering the spirit of the existing
EU legislation on blood and blood products.
Directive 2004/33/ EC (22 March 2004) mentioned above sets out in Annex I a
long and precise list of what is considered as “blood” and “blood components”, to
which the directive’s requirements are applicable.
Directive 2001/83 /EC (6 November 2001) on medicinal products: it is clearly
stated in this directive that “medicinal products derived from human blood or human
plasma” can resort to “albumin, coagulating factors and immunoglobulin of human
origin”. We can easily draw the conclusion that all these products are considered as
medicinal products.
One can easily infer from the directives mentioned above that products that are listed
in the Directive are blood products (and not pharmaceutical drugs) and are a matter for
the EU Blood and Blood products legislation. Likewise, one can also infer that products
resorting to human plasma (alone or combined with other substances) that are sold by
pharmaceutical firms, after completion of the fractionation process, must be considered
as drugs.
Nonetheless, plasma fractionation is an extremely long and complex process, and the
range of plasma-derived products is very wide. Therefore, a “grey zone” can be
identified between blood and blood-components and plasma-derived drugs as described
in the previous paragraph. The main issue is to define accurate criteria to distinguish
“blood components” and “pharmaceutical drugs” and to draw a border between both
concepts. This is not an easy task, from a purely conceptual and legal point of view.
For lack of regulatory definition (or official case law of the European Court of Justice),
several EU Directives on health-related subjects can provide us with interesting clues on
that point, in several texts especially EU Regulation (EC) 1394/2007 on advanced
therapies (13 November 2007) on advanced therapy medicinal products (amending
Directive 2001/83 and Regulation 726/2004). The latter regulation deals with advanced
therapies resorting to cells or tissues. One of the key issues of this regulation is to
identify products that can be considered as “medicinal products”. To this end, the
regulation (Art.2 Definitions) resorts to the concept of “engineered products” (as
opposed to non engineered products).
To be more specific only cells or tissues that undergo “substantial manipulations” can be
considered as “advance therapy medicinal products”. Given that clinical practice or
scientific literature do not give a clear-cut definition of this concept, this regulation sets
out a list of practices (Annex I) that are not considered as “substantial manipulations”.
In practical terms, such practices as centrifugation, sterilization, filtering, and freezing
can be considered as “substantial manipulations” as such.
Then, a second criterion is used in the Directive, to be specific the volume of
production: the scope of the regulation clearly refers to the routine industrial
production of medicinal products (with a view to putting them on the market), and not
to custom-made treatments. Thus, a product that is used within a hospital in compliance
with a medical prescription and delivered to a patient is clearly excluded from the scope
of the regulation, since it is not considered as a medicinal product.