already the drug of choice for that disease and that
everyone was already using it and that it would
even possibly be viewed as malpractice not to use
it. Nonetheless, the company could not promote the
drug for this use or mention it in publications. This
was not a commercial issue, as the FDA’s views
were correct, and moreover, there were very few
cases of Herpes encephalitis each year.
The speed of regulatory review depends on
the number of drugs in the queue in front of it,
the medical value of the drug and the quality of
the submission in addition to vegulations. Another
factor that few companies would want to try to
influence is the pressure from outside sources on
a regulatory authority. The US Congress pressured
the FDA to approve valproic acid for seizures in
children many years ago, even before the company
was ready to make its submission.
The medical value of a drug may be independent
of the efficacy and rarity of the disease. For exam-
ple, for Wilson’s disease there are several products
on the market that are effective and yet additional
ones are still being developed. Penicillamine is
often effective, but often causes serious adverse
reactions. Zinc acetate and trientine are newer
products and molybdenum is being evaluated for
the same indication.
21.11 Disincentives and
obstacles for orphan drug
developmentThere is no limit to the number of disincentives and
obstacles that could be described for developing
orphan drugs, several of which have already been
mentioned. Selected examples will be given to
illustrate several that are commonly encountered.
Disincentives include the following:
- The tax credit offered in the United States for
developing orphan drugs is not much more than
the tax credit for research and development of
any new pharmaceutical. - Resources of the company could be applied to
developing more profitable drugs.
3. Development may not be required if the drug is
already marketed for a more common use. This
implies off-label use, which is more easy to do
in some countries and very difficult or impossi-
ble in others.
4. Because the safety and quality standards of
manufacturing are the same, it may create too
many technical problems and costs for the
development of a specific drug.
5. The medical need for the drug may not be great
and/orthe medicaleffectiveness ofthe drug may
not be strong.
6. The regulatory authority may require more data
than the company thinks are warranted.
7. The liability risks may be unacceptably high. A
drug to treat patients with a rare disease that
causes a serious adverse event could increase
the exposureof the company toa major courtsuit.
8. Difficulty in finding a small number of patients
widely dispersed through the United States (or
other countries) for conducting clinical trials or
for marketing products.
Additional obstacles may include lack of a patent
or other proprietary position, availability of a gen-
eric equivalent, large amount of competition, tech-
nical difficulties in any area of formulation,
analytical, stability, scale-up or other related
issues. Manufacturing issues or costs of any aspect
of the manufacturing, from obtaining the raw pro-
ducts to final manufacturing and packaging to dis-
tribution, are other possible disincentives.21.12 The United States Orphan
Drug Act of 1983The Orphan Drug Act was signed by President
Reagan of the United States in 1983. In its original
form, the Act provided for the following:- A seven-year period of exclusivity for desig-
nated drugs.
272 CH21 ORPHAN DRUGS