Properties of the study drug
Another factor to consider when determining the need for an IND
is how the study drug will be physically modified for the purposes
of the study. This may actually place the subject in a situation
of unanticipated risks. Consider if the following issues:
Changing the Form of the Drug
Some drugs have an encapsulation or coating that can be a protectant
or can have special properties that determine the location and rate
at which the drug is absorbed.
Coumadin® is very unstable in high humidity,
which is why the pills are coated. Crushing of these caplets can
change them chemically and result in unanticipated safety risks
and a lack of efficacy.
Example: Niaspan® pills
are specially formulated to control the rate of absorption of
the drug to reduce side effects and maintain consistent drug delivery
over a 24-hour period. Crushing the Niaspan® pill (such
as one might do to put a drug in a gelatin capsule for study blinding)
would cause the drug to be absorbed much more rapidly. This would
lead to significant side effects, a markedly shortened duration
of drug delivery, and wide variations in peak drug concentration.
Good Manufacturing Processes (GMP) dictate that proper controls
are in place to ensure the product is safe, the stability is known,
and that the product’s storage or delivery system is effective.
These regulations are just as important as regulations on clinical
drug development in the protection of human patients/subjects.
Example: A cytotoxin
used in a psoriasis study would not only have potentially
unacceptable toxicities in that setting but it might also expose
the research team, who is not familiar with the safe handling
of cytotoxins, to be at increased risk.
Example: The packaging
of some drugs is very important to preserve its chemical composition.
Some drugs are in blister packs, for example, because they decompose
when they come in contact with air. Other drugs must be maintained
in a dark brown glass bottle, as they are photosensitive.