smaller number of patients. So the scale of
equipment is a challenge. You have to take
what was made in thousands of kilograms
and bring it down to say a hundred kilograms. So making PDFs requires specific
right-sized equipment. Halo has the capabilities to manufacture batches of PDFs
that typically range in scale from 5 kg to
1,000 kg, with many requiring multiple
Additionally, in nearly all cases, developing a PDF from an adult dosage form
requires additional product development
work. In many cases, it is necessary to provide the PDF in various strengths matched
to different pediatric age/weight brackets.
Also, in many cases the reformulation
requires changing the manufacturing process to turn the drug product into another
dosage form. So, for instance, an adult
tablet could turn into a mini-tablet or stick
pack, or powder in a bottle, or a solution in
a bottle for a PDF.
If you’re changing the dosage form,
that then requires having to redo your analytical methods. And in many cases the
packaging also changes to make it more
tailored towards kids.
There are also cleaning issues with
PDFs. At Halo we recently redid our cleaning validation in our Whippany, NJ, plant
because the carry over limits are different.
If you have residual drug and it goes into
the next batch and that next batch is only
5 kg versus 1,000 kg, everything changes.
Cleaning validation is a very important
part of the process.
CP: Are PDFs a global trend?
LK: Brand companies typically operate in
multiple geographic locations and juris-
dictions, so you have to have the regula-
tory approvals to make products for mul-
tiple countries and that involves not just
regulatory approvals for drug products
but also packaging and labeling opera-
tions. Because pediatric patient popula-
tions are smaller in a given geography
with the U.S. being the largest globally,
it’s still a relatively small patient popula-
tion. So to get the biggest bang for their
buck, pharma companies will apply for
the same indication in multiple coun-
tries so they can sell more of the product
across the globe. Having a plant that is
up to par with international regulatory
approvals is important. At Halo we pro-
vide specialized contract development
and manufacturing services that meet
the regulatory requirements of the U.S.,
Canada, and Europe, and are already
manufacturing PDFs for commercial sale
in these regions.
CP: Is the development and manufacture of
PDFs being outsourced for the most part?
LK: Pharma companies typically don’t
do this in-house. If you walk into a large
pharma manufacturing facility they have
these huge blenders and big packaging equipment. The plant manager never
wants to change his production line over.
He wants to make the same thing everyday. If I came in one day and said told him
he has to make this 10 kg batch, he’s got to
take everything apart and retool it. So yes,
PDFs are a heavily outsourced area.
I was telling somebody recently, pediatric products are typically smaller in
terms of the revenues that a contract manufacturing organization (CMO) sees. So
the PDF area isn’t large enough in terms of
revenues to get the largest contract service
providers out there excited about taking
on these projects.
Typically what companies have done is
they’ve gone to the smaller CMOs to do the
work. Well, many smaller CMOs typically
only produce for one market, the U.S. mar-
ket. One of the advantages we have at Halo
and one of the key attributes behind our fo-
cus on PDFs and our initiative with the Pedi-
atric Center of Excellence, is the fact that we
operate internationally independent of scale
restrictions. The smaller patient population
isn’t a problem for us and we have regula-
tory approvals in place internationally. We’re
kind of in that ideal sort of spot for pharma
companies, particularly large pharma com-
panies, to partner with.
CP: Tell me a little more about the center and
what it offers.
LK: The core fundamental formulation
and analytical support is in Whippany,
NJ. It has all the equipment and assets
there, and acts as the development center.
But both of our plants, the other being in
Montreal, can manufacture PDFs.
In addition to the reformulation and
development expertise and to-scale
manufacturing capabilities we offer, the
other thing we do is spend time advising large pharma on what to look out for
with PDFs. It’s a very specific thing. Do
I create a mini-tablet product, or granule? If I choose mini-tablets do I put two
mini-tablets in a pack or 3? If I do 3 does
that mean I’m going to have more or less
variability in the dose? Things like that.
We’ve actually gone through many of
these experiences. So a lot of times we act
as an advisor in many cases to pharma
companies because they’ve never done
it. Don’t get me wrong, they can create their own centers and do a lot of this
themselves, but it’s such a unique niche
thing that lends itself more towards outsourcing. And if you’re going to outsource,
you’re going to outsource to someone
that’s done it before. CP