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0:00
Hello. I will give you a talk
on the ICH guideline M3.
I will explain all these terms
in the course of my talk.
It's about the nonclinical
safety testing of
human pharmaceuticals in relation
to clinical development.
I'm Jan Willem van
der Laan, Retired.
I worked with the Medicines
Evaluation Board in Utrecht
and in that role, was participating
in the ICH for 30 years.
0:32
In Europe, we had some disasters
in the clinical trials,
which is one in 2016 in France
with the BIAL compound
BIAL 10-2474,
which was a small molecule,
but 10 years before, we
had a disaster in London
with an antibody TGN1412,
which was the main reason
to write a European
guideline about
dose selection and all
aspects in human trials.
That's an important aspect
that I will discuss.
1:13
How safe are human medicines?
Are there 100% safe medicines?
I will discuss the
concept of uncertainty,
the acceptable adverse effects
in relation to benefit
and the examples for
diseases to be treated,
short-term versus long-term,
small molecules versus
biotech-derived products.
1:35
First, the concept
of uncertainty.
Developing a drug is
reducing uncertainty
by gathering knowledge
step-by-step.
The starting point for a new
compound is 100% uncertainty.
No data are present
at that time.
We don't know.
We don't know anything
about the new drug.
In fact, you can see
all the gathering of the
data as risk mitigation.
What are the important
strategies first to
ensure adequate quality of
the investigational
medicinal product?
The knowledge of the structure
and purity is very important.
If needed, there are standard
animal testing approaches,
then you should also conduct
additional non-clinical testing
to support the relevance of
the animal models
which have been used.
Then apply a scientific
rationale in the selection of
the starting dose and
apply appropriate
risk mitigation
measures in the design.
These risk mitigation
measures can
be just the signals in
the clinical setting.
Be aware that 0% uncertainty
can never be reached.
There's no completely safe drug.
So you should always think about
what are the remaining risks.
That's what we did in the ICH,
