August 2024 SOCRA Source Journal - Journal - Page 35
2. Drug Development
Figure 2. Drug Figure
Development
upon the clinical trial design and
the therapeutic area. Phase IV
consist of collecting real-world
evidence of a marketed product
Collection of real-world evidence
before and after approval is part
of the product development
lifecycle. This provides evidence
of large-scale effectiveness,
safety, and additional riskbene昀椀t information. Before
commercializing the product,
it is necessary to complete
all of the clinical trial phases.
Commercializing means that
the doctor can now recommend
the marketed drug.
Figure 3. Clinical Trial Phases
as much research as possible
on the front end to determine
the chances of the drug being
groundbreaking or at least an
improvement over drugs or
biologics that are already on
the market (Figure 2).
Phase I clinical studies make the
shift from animal models into
humans. Typically, Phase I has
a dose escalation phase and a
dose expansion phase. During
dose escalation, researchers
determine the appropriate dose
(Recommended Phase 2 Dose
or RP2D) of the drug in humans
and how people respond to
the dose. Phase I is closely
monitored and participant
safety is the priority. There
are usually multiple cohorts
of participants randomized to
different treatment arms of the
drug in Phase I. A comparator
may be used to compare the
new drug to a marketed drug.
During the dose escalation
phase there are usually safety
management meetings
after each dose to evaluate
participants and ensure that
they are not at risk when
moving up to the next dose. If
the results from the data are not
favorable and if the participating
review members do not vote to
move forward the clinical trial will
be stopped or there could be a
protocol revision.
The dose expansion phase
occurs after researchers have
determined the appropriate
safe and effective dose for the
new drug. This part of a Phase I
study is open to a wider group
of participants, although the
number is still limited. During
the dose expansion phase there
16 management
are usually safety
meetings after each dose to
evaluate participants and ensure
that they are not at risk when
moving up to the next dose. If
the results are bad, the clinical
trial will be stopped.
If everything goes well in Phase
I, the product development
lifecycle moves into Phase II,
Phase III, and to generate data
in order to obtain drug approval
based on safety and ef昀椀cacy.
In general, it is necessary
to pass each phase before
moving into the next phase.
Sometimes two phases can be
run simultaneously. This depends
The drug development
landscape has changed
over the years. Before, large
pharmaceutical companies
would discover drugs and take
them through the product
development lifecycle. Now,
large pharmaceutical companies
have divested most drug
discovery efforts. Universities,
start-up biotech companies,
and pharmaceutical companies
are all involved in drug
discovery. In many cases, early
development work is done by
start-up companies and large
pharmaceutical companies
acquire drugs at the clinical
trials stage.
Drugs and biologics are different.
Drugs are manufactured by
chemical synthesis and have a
well-de昀椀ned chemical structure.
They have a straightforward pathway for therapeutic equivalence.
Biologics are extracted from
live (genetically-modi昀椀ed) cells,
requiring a longer research
and development process.
Characterizing biologics is
challenging. Biologics require a
new manufacturing structure;
they are not always therapeutically equivalent and, therefore,
they cannot be generic.
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