August 2024 SOCRA Source Journal - Journal - Page 27
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A substance intended for
use in the diagnosis, cure,
mitigation, treatment, or
prevention of disease.
A substance (other than
food) intended to affect the
structure or any function of
the body.
A substance intended for
use as a component of a
medicine but not a device
or a component, part or
accessory of a device.
Given that the probiotic was
going to be used to “cure,
mitigate, and or treat” the
irritable bowel syndrome, the
FDA stated that the probiotic
was considered a “drug.” As
such, an IND was required. The
FDA further required that before
the study could be done in
children, a safety trial in adults
with irritable bowel syndrome
was required as a phase I study
since the probiotic was not
labeled for use in children.
The SI had to re-evaluate the
study at that point.
As a result of the discussion
with the FDA, the investigator
petitioned the NIH to ask if he
could add an adult arm to study
the probiotic and proceed with
a child study that compared
昀椀ber versus placebo. The NIH
agreed and the child protocol
was modi昀椀ed to remove the
probiotic treatment arm. At that
point, the investigator became
a SI and needed to draft an
adult Phase I protocol and
Investigator’s Brochure in order
to obtain an IND to do the
adult study.
Fortunately, the probiotic
manufacturer provided its
preclinical data. Had this not
occurred, the SI would have had
to do the preclinical research as
part of receiving IND approval;
something that would not have
been possible given the SI’s
limited resources and time.
Luckily, as noted, the SI was
able to reference the probiotic
manufacturer’s preclinical data
when submitting the IND
application to the FDA.
Having a telephone call with
the FDA prior to working on an
IND is strongly recommended
to determine whether an IND
is needed and to get advice
on how to proceed. The FDA
recommended that the SI and
the author speak with the FDA
security of昀椀cer and medical
directors. Doing this helped
the SI develop a protocol
that met FDA requirements
without the need for multiple
amendments after submission.
The FDA can detail what is
needed in the protocol and
the Investigator’s Brochure.
Being that the submission of
the initial IND application is a
large undertaking, a SI needs
to consider who will assist in
preparation. When doing the
application on paper, 20 singlesided copies of the application
were requested.
IND Submission
Principal investigators are
familiar with completing FDA
Form 1572 for clinical trials. This
form is the attestation that they
are quali昀椀ed to conduct the
trial; agree to send the sponsor
certain information; and will
abide by federal regulations
and Good Clinical Practices
while conducting the study. As
a SI, they also must 昀椀le other
forms such as FDA Form1571
(the IND application) and for
some trials, FDA Form 3674.
The IND submission to the FDA
also includes:
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General investigative plan
Investigator’s brochure,
including basic science
background
Protocol
Chemistry/manufacturing
information
Pharmacology/toxicology
information
Previous human experience
Other important and
relevant information
The protocol must include study
methodology, background on
safety, risks, and bene昀椀ts, how
adverse events will be reported,
and the de昀椀nitions of severe,
serious, and mild adverse
events. If the manufacturer does
not provide the information
on chemistry/manufacturing
and pharmacology/toxicology,
the SI must provide it and that
involves preclinical data. If
the SI needs to provide the
preclinical data, it can halt an
application for some time since
preclinical data acquisition can
take years.
Previous human experience
with the product (probiotic) also
must be submitted with an IND
application. Since there was
no previous human experience
in children with irritable bowel
syndrome with the probiotic,
that necessitated the adult
safety trial.
After submitting the IND
application, the FDA places it
on a 30-day clinical hold, during
which time the FDA reviews the
application to decide if the trial
can proceed or the application
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