and labeling statements, a compound may be for-
mulated and marketed on the judgment of the
Sponsor alone. No further pre-approval or exam-
ination of any application to the FDA is necessary.
However, if the requirements set forth in the mono-
graph for a particular compound are to be changed
in any way by a different dosage, a new indication
or by changes in labeling, the formulation no
longer is covered by the monograph and it is
necessary to submit a full NDA. As long as the
monograph requirements are strictly met, the clin-
ician in charge will make the final judgment on
whether a new formulation is satisfactory for mar-
ket. This system exists only in the United States
and it provides for a striking amount of speed and
flexibility in the OTC marketing of products.
However, it also places a very substantial
amount of responsibility on the Sponsor. You
can never appreciate the value of having a regu-
latory agency review your work and make the final
decision to allow marketing until you do not have
them and must take the responsibility yourself.
This is particularly true with regard to the toler-
ability of new formulations. It is unlikely that
major safety problems will arise with well-
known drugs dosed at well-known levels for indi-
cations that are thoroughly understood. However,
with topical drugs, where irritation and allergeni-
city are a problem, the judgment of suitability for
market can be difficult. These drugs tend to be
very dependent on the contents of individual for-
mulations and be sure of enough information
before release them to market.
The need for specific clinical testing must be
determined by the clinician in each individual
instance. A wide variety of situations may arise,
varying from those in which no particular testing is
required to those in which an extensive series of
tests is needed before full confidence can be felt in a
formulation. In short, the American monograph
system provides unparalleled speed and flexibility
of drug development for those compounds which
are covered by it, but especial vigilance is also
needed on the part of the OTC clinician. For all
the delay and difficulty involved in obtaining
approvals from FDA, it does have the major advan-
tage that it provides a second source of learned
judgment prior to the marketing of products. Even
in the limited scope of monograph drugs, the clin-
ician can often find it necessary to use all his/her
abilities to ensure that adequate testing is done and
that careful judgments are made before individual
formulations are allowed to reach the marketplace.
Because of the monograph system, one of the
more striking features of OTC drug development is
the speed with which new formulations may be
moved from the conceptual stage to actual product
realization. This contributes in a major way to job
satisfaction, but also creates the need to act with
much more speed in advancing one’s own portion
of the development efforts. There is a need for the
clinician to participate in every phase of early
planning of a development program. This is the
only way to ensure that it is properly handled and
can be quickly executed. Frequently, several com-
panies will be moving forward with similar pro-
jects. Both commercial and personal success rely
upon being the first to market. Thus, the program
must be planned for success on the first try. If major
delays in research occur, the product will usually
be so far behind competition in reaching the market
that it will have little commercial value.
Several factors can accelerate the entire process
of research in the OTC area. As it is much quicker
and simpler for a product to remain within the
monograph requirements, every effort is made to
do so if it is possible. For research with monograph
drugs, it is perhaps surprising to learn that an
investigational new drug (IND) exemption is not
always required prior to undertaking research. This
is only logical, however, as for a monograph drug
there is pre-approval from the FDA to actually
launch the product into the market. It would not
be sensible to require special pre-approval to per-
form human research via the IND system. This
considerably speeds and simplifies the course of
the research effort but again results in greater
responsibility for the OTC clinician. The clinician
must ensure that the research undertaken will be
complete and adequate for both safety and efficacy
determination purposes and must make a solo judg-
ment as to the safety of the research subjects
involved, with no FDA oversight.
The details of the clinical research process are
little different for OTC and prescription work.
What changes most is the role of the Sponsor.184 CH14 THE UNIQUE ROLE OF OVER-THE-COUNTER MEDICINE