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E-drug: ICH and developing countries
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At each stages of the drug development, norms are designed by drug
regulatory authorities (DRAs) in order to protect the health of citizens.
The evaluation of a drug is bounded by the good clinical practices (GCPs)
and good laboratories practices (GLPs) in pharmaceutical trials ,
the industrial production process is framed through the good
manufacturing practices (GMPs) as well as various local technical
guidelines. The objective of regulations is to assure that safe and
effective drugs are available and prevent disastrous consequences derived
from mismanagements of drugs.
All of us know that the history of the establishment of the US regulatory
system (Food and Drug Cosmetic Act) is a " child of scandal "
(from the elixir of sulfanilamide dissolved in diethylene glycol and
killing 107 persons in 1937, to the thalidomide story in 1962).
To promote collaboration among DRAs and to improve the harmonization of
regulatory requirements, two movements have been initiated since the 1970s.
Firstly, there are regular discussions between developed and developing
countries, through the International Conference of Drug Regulatory Authority
(ICDRA), on various issues (counterfeit drugs, regulatory control measures,
safety monitoring, GMPs, exchange of information... etc.) . Secondly, there
is an integrated process of harmonization between Western countries DRAs
(European Union, United States, Japan and Canada) through the International
Conference of Harmonization (ICH), on the issues of research, clinical
trials and evaluation of new products.
The objectives of the ICH are to create an " easier flow of new products
into the international market " in harmonizing technical requirements for
the approval of medicinal products in the technical areas of safety, quality
and effectiveness. In theory such a movement of globalization leading to
more uniform standards and norms is obviously desirable. It should be
expected
that this harmonization process would give an important impulse to
technological development (avoiding the duplication of efforts for
pre-marketing evaluation) and would facilitate the exchange of information
and technical discussion. Moreover, costs of evaluation should be
significantly reduced and access of foreign pharmaceutical products to each
ICH country made easier (preventing any anti-competitive or protectionist
practices).
If the drug market necessarily requires normalization the impact of these
instruments can vary according to their specificity and origin, the decided
on set of norms will favor the evolution of one kind of market.
By way of example :
- GMPs cost money to establish and sustain, norms of too high level -
according to Western countries standards - would tend to be a barrier for
smaller pharmaceutical companies and even for the durability of
some Western production (e.g., melarsoprol). The higher standards of GMPs
which are set, the more delicate will be the economic situation of the local
small medium-sized firms in emerging countries.
- Clinical information on efficacy and safety required by DRAs when
requesting marketing approval incorporate greater numbers of patients into
studies of increasing length (e.g., according ICH, the cumulative total
number of individuals treated with an investigational drug should be about
1500). It is evident that international companies (" big pharma ") will
benefit from such standards to the detriment of smaller companies.
To a large extend this seems to be the tribute paid for safety but at a very
high price for developing countries :
. (i) so far artemisinin derivatives for malaria could not be approved by
FDA in spite of steps done by WHO/TDR,
. (ii) of the 1233 new chemical entities commercialized worldwide between
1975-1996, less than 1% were destined for tropical diseases, of which only a
minority may be claimed by Western pharmaceutical companies,
. (iii) eflornithine for sleeping sickness has been approved by FDA in 1990
by means of the Orphan drug act as an imported disease in the US !
L.G. Thomas found that between 1960 and 1980 larger US companies took
significant advantages in coping with the more and more stringent regulatory
regime, maintaining their R-D productivity in generating new products, while
R-D productivity of smaller companies fell dramatically (Thomas LG.
Regulation and firm size: FDA impacts on innovation. 1990 RAND Journal
of Economics, vol 21: 497-517).
Finally, increasing regulations do not necessarily conflict with big pharma
interests. On the one hand, the impact of more severe requirements in term
of costs have been amortized through price increases, more or less absorbed
by the Western markets. On the other hand, the high costs of development,
through high levels of standards, are used as a barrier to entry by large
companies. Then small companies which cannot follow, are eliminated.
The prevailing terminology ("globalization", "harmonization",
"standardization"... etc.) often disguises trade disputes. What we can
observe here is that current and future drug policies in emerging countries
will have less (or no) room for manoeuvre than in the past. The convergence
of norms among countries whose morbidity/mortality profiles diverge
considerably (developed ICH countries here and developing countries there)
ends up in a growing dichotomy between market structure and health needs.
The issue can be :
(i) Is - in all circumstances - Western registration necessary (right away
and without any critical acumen WHO/TDR says yes, arguing that the drugs for
developing countries must meet the same standards of quality and lack of
risk that are expected in the West) and (ii) who has to design and monitor
the GCPs, GLPs and GMPs, and through what mechanisms ?
Patrice Trouiller
Health-system pharmacist
Centre Hospitalier Universitaire de Grenoble, France
Fondation Medecins sans Frontieres, Paris
e-mail :pat.trouiller@wanadoo.fr
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