The first thing to understand about biosimilars is that they are biological products.
A biological product is a very complex product.
It’s produced in a living system, such as bacteria, yeast, or a cell.
There is some inherent variability that’s with that because it’s a biological system.
It’s a living system.
It’s more difficult to control in the same way as you would something that’s going
to be chemically synthesized.
Again, these are complex molecules that are more complicated to manufacture than what
people typically think of in terms of a small molecule.
And that does make the data package a little bit bigger than you would expect for something
that would be a generic to a chemically synthesized product.
For biological products, we didn’t have an abbreviated approval pathway, so the only
way to come to market was to have that full data package, which can be very expensive
to develop those products.
And you see that respected in the cost of the products in the marketplace.
So what happened in 2010 was that Congress signed a law that allowed FDA to approve biosimilar
products.
For folks that use biological therapies, either prescribers or patients, it’s well known
that these are very expensive products.
So, it’s good to have that competition in the marketplace and, ultimately, that cost
reduction to patients.
A biosimilar product in the law that FDA needs to follow describes a biological product—describes
a biosimilar product as being a product that’s highly similar to the product they’re comparing
themselves to that we call the reference product.
And that would’ve been that originator product.
So it has to be highly similar and there has to be no clinically meaningful differences
between the two products.
So we look at the structure of the products.
We make those comparisons about the structure, how they’re functioning.
So that first step is to do that analytical comparison for the structural and functional
comparison to make sure that their structure is the same, they look the same, it has the
same primary sequence, same type of quaternary and tertiary structure that helps in its function.
After that, we want to look more closely at whether or not there’s clinically meaningful
differences between the products, because those analytical comparisons can tell you
so much about the molecule and so much about the comparison between the molecules and how
similar they are.
But there is some residual uncertainty that would remain about how it performs in the
body in a patient.
So we look for additional studies, including what’s called pharmacokinetics.
And that’s the exposure in the body.
Does it release in the body the same way?
Does it circulate in the body the same way?
Is it getting to the same place in the same way to exert its clinical effect?
And then, we can look at other types of clinical tests with different types of endpoints, where
we would be interested in certain populations or certain diseases.
We also look at differences in safety, making sure that it has the same safety profile between
the products.
Andthis all leads to the assessment that there's no clinically meaningful differences between
the products, but there is an expectation that when FDA approves a product, it will
work the same way in the body, whether they take the reference product or they take the
biosimilar.
There is no clinical difference between the products.
So FDA will not approve a biosimilar product if they don’t feel that the data support
that they are biosimilar and, ultimately, that the products can be labeled for safe
and effective use.
So while the data packages between a biosimilar product and a reference product or an originator
product are different, and that’s where the concept of an abbreviated approval pathway
comes in.
FDA’s standards to approve a product and be able to label a product as safe and effective
for its intended use is the same regardless of the pathway.
So, the health care community and the patient community should have confidence that FDA
is applying those same rigorous standards in terms of approving products and ensuring
that they are safe and effective.