Seqens eBook - 10
What Could Possibly Go Wrong in
API Development?
Ed Price, CEO, Seqens CDMO North America
The quality of Active Pharmaceutical Ingredients (APIs) has a significant
Wrong temperature. Process chemists know all too well that you could
effect on the efficacy and safety of medications, and as such, poorly
follow all the steps correctly - but if you use the wrong temperature - too
manufactured or compromised APIs can result in serious issues, such as
high or too low - it could impact the product quality.
illnesses or even death.
Poorly defined Critical Process Parameters (CPPs). CPP refers to a
Since APIs are essentially the lifeblood of commercial drugs, the number-one
"process parameter whose variability has an impact on a CQA (Critical
goal of Contract Manufacturing Organizations (CMOs) and pharmaceutical
Quality Attributes) and therefore should be monitored or controlled,"
firms is to develop a safe and robust process that will eventually bring the
according to the FDA. There are a lot of variables here that need to be
API to market safely, effectively and as quickly as possible.
evaluated - such as particle size, moisture content, order of addition,
To accomplish this, the research scientist's job is to identify the process, or
filtration method, etc. All of these, if not clearly defined ahead of time,
development route that is robust, safe and scalable, while also providing a
could lead to major issues during scale up.
path that leads to the best yield and purity. This route selection is critical.
Expect the Unexpected
Yet, I would bet that no process chemist - ever - said that the route to
drug development and commercialization was easy and without a single
Unexpected challenges could really be anything from choosing the
bump in the road. As the famous quote goes, "the best laid plans of mice
wrong route and starting over, to getting a great process and in the end
and men often go awry." Sometimes, even with the best route selection,
being unable to identify the impurities. For these reasons, it's important
proper testing and method development, problems can occur through no
for the R&D scientist to work closely with the Method Development team
fault of the scientists or the processes.
to ensure they have analytical methods that can be relied upon and work
Six Issues That Can Arise During API
Manufacturing - and How to Resolve Them
for their intended use. The scientist may think he has a super product, but
once tested it could fail for low assay, residual solvents, impurities, etc.
The R&D team is in charge of determining the starting materials used -
Unexpected impurities. Sometimes, unknown impurities or a larger-
from the quality specifications to the vendor they are ordered from. When
than expected yield of impurities is produced during scale up. The very
the process is transferred to GMP, it is important to use the same source
process of scaling up can produce unexpected results, such as new
and quality of the starting material to ensure consistency. As it is, R&D may
impurities that weren't present during smaller-scale production or the
run into unexpected issues and problems that need to be solved along
amount of an impurity can increase significantly. At that point, the R&D
team needs to examine each step to determine if they can eliminate or
reduce the impurity to the expected level.
Problems with starting materials. A key starting material may not work
as intended, so in some cases, the team may need to evaluate the grade
or supplier to get the intended results. While it doesn't happen often,
sometimes if the initial work was conducted in a different facility or the
other provider took short cuts that were not documented, the CMO would
need to re-do the process to make sure the results produced are consistent.
The initial process may not be scalable. This would require re-evaluating
the process, including determining whether there are mistakes or if the
master batch records are sloppy. Another step to take may be to find out if
there is larger equipment available that will mimic the R&D size.
the way to ensure a successful technical transfer from the R&D facility to
the GMP group. In the land of R&D, the mantra is, expect the unexpected.
A structured approach also requires that companies don't look for
shortcuts or ways to streamline the critical processes. The costs associated
with the initial routing, familiarization or optimization of a process can be
well worth it in the long run, while short cuts may end up costing more
and causing unnecessary delays.
The API market is flourishing, thanks to expiring patents on global
blockbuster drugs and an increase in the adoption of generics,
among other factors. As competition heats up, drug developers and
manufacturers need to focus on sound and steady processes and testing,
while anticipating that problems can and most likely will occur despite
their best efforts. The key is in recognizing the possible challenges and
Time needed in production. A major focus should be on the stability
having a game plan in place to quickly get back on course on the road
of the material produced. In the quest to get material to the next step,
to product commercialization. Process chemists developing Active
sometimes teams will avoid asking whether the product is stable enough
Pharmaceutical Ingredients (APIs) for clinical trials today face a challenging
to be held or if it has the possibility of degrading.
array of business and regulatory hurdles.
Pharmaceutical Outsourcing |
10
| pharmoutsourcing.com
http://www.pharmoutsourcing.com
Seqens eBook
Table of Contents for the Digital Edition of Seqens eBook
Contents
Seqens eBook - 1
Seqens eBook - Contents
Seqens eBook - 3
Seqens eBook - 4
Seqens eBook - 5
Seqens eBook - 6
Seqens eBook - 7
Seqens eBook - 8
Seqens eBook - 9
Seqens eBook - 10
Seqens eBook - 11
Seqens eBook - 12
Seqens eBook - 13
Seqens eBook - 14
Seqens eBook - 15
Seqens eBook - 16
Seqens eBook - 17
Seqens eBook - 18
Seqens eBook - 19
Seqens eBook - 20
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Seqens eBook - 28
Seqens eBook - 29
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