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ROUNDTABLE

Can you tell us about some new oral solid dosage
manufacturing technologies and/or processes that
are helping pharmaceutical companies bring new
products to market or are reviving older products?
Childers: Two technologies that have seen an increase over the last
three years are extended release beads in a capsule and sublingual
tablets. With the early detection of many diseases, the extended
release beads appear to be on the rise for both pediatric patients, as
well as those with difficulty swallowing tablets. Another advantage
is the release rate can be optimized, reducing the initial dose spike
with immediate release tablets and target the therapeutic rate. The
increased control is intended to reduce the side effects. A second
technology is sublingual tablets which are capable of delivering
medication quickly, bypassing the harsh environment of the
digestive track. This technology is mainly used in pain management
applications with APIs that have good absorption in the mouth.
Considering nitro-based tablets have been around for decades, the
sublingual tablet has opportunity to grow in the coming years.
Nuno Matos, Head of Continuous Manufacturing, R&D, Hovione:
Amorphous solid dispersions (ASDs), commonly produced via spray
drying (SD) or hot-melt extrusion (HME), provide drug formulations
with higher apparent solubilities, faster dissolution rates and the
stability required for safe and efficacious medicines. There are cases,
however, where neither HME nor SD is ideal, particularly APIs with
high melting points (>200°C) and limited solubilities in volatile
organic solvents. For these increasingly prevalent compounds,
either an alternative ASD method or a non-ASD approach, such as
nanomilling or complexation with cyclodextrins, must be adopted.
Co-precipitation of an API and a polymer is a scalable, attractive
option for problematic APIs. Improvement of the co-precipitation
process is needed, however, to make the technology more attractive
for commercial drug formulation and manufacturing. Hovione is
developing new techniques for co-precipitation that will allow its use
as a robust and reliable third platform technology for ASD generation.
Our approach involves the use of microfluidization, a solventcontrolled precipitation (SCP) process, in microreactors rather than
the traditionally used stirred reactors. With this method, the particle
size, size distribution and morphology and the level of nanoparticle
aggregation can be finely controlled, enabling enhancement of the
bioavailability of BCS Class II compounds with poor solubilities.

When a pharmaceutical company is choosing an
oral solid dosage manufacturing/service provider,
what questions should they ask? What qualities
and expertise should an oral solid dosage
manufacturer/service provider have to ensure
that their client gets the best quality product?
Childers: Choosing a solid dosage manufacturing service provider
should focus on two questions, with the first being: "What is your
most complex operation being completed?" Understanding that
Pharmaceutical Outsourcing |

CMO's cannot reveal client information, it is important for the
provider to be able present the most complex operation in order to
get a general understanding of the knowledge level of the workforce.
A site manufacturing a simple formulation (i.e. direct compressed or
granulated - compressed products) is not going to have the required
knowledge base of a site manufacturing an extended release
spheronized bead product that is encapsulated. The presentation of
the process is important to gain an understanding of the expertise.
The second question is: "What is the defect rate or deviation rate for
the complex process over the last 6 to 12 months?" This question
focuses on how the success of a process is being run. If the process
has a high defect rate, the follow-up question would be: "What is
the average time to close the issues?" We all understand that issues
happen in manufacturing, however, the telling signs for the second
question is how quickly do you resolve them and can the team get to
the root cause.
Tim Tyson, Chairman, Chief Executive Officer, Avara: It is essential
but not sufficient to be a highly flexible CDMO that provides excellent
quality and on-time delivery. CDMOs must be fully integrated service
providers in order to be able to serve as strategic, long-range partners
for biotech and pharmaceutical companies. Drug manufacturers
seeking outsourcing partners should look for a provider with a
demonstrated track record of excellent performance across all
activities - development, manufacturing and formulation capabilities,
product and service quality, program management, technology
transfer, problem solving and cost-effectiveness, to name a few.
For OSDs in particular, the CDMO should have extensive knowledge
and expertise and advanced technical capabilities for overcoming
solubility issues. A CDMO should also recognize the importance of
speed to market and have systems designed to facilitate accelerated
development, manufacturing and commercialization, even for
complex and difficult OSD formulations, while still ensuring full
regulatory compliance and maintenance of an effective quality culture.
Ultimately, beyond the necessary expertise, technological capabilities
and available capacities, pharma companies should be looking to
partner with CDMOs that repeatedly delivery on their promises.
Gregory: Service providers must be able to provide real value and
continually anticipate the changing needs of their pharmaceutical
customers. To be one of the chosen, CDMOs must have the expertise
to support fully integrated capabilities, be able to form truly
collaborative relationships and provide highly customized solutions
to meet aggressive development and commercialization timelines
and project budgets. Flexibility, responsiveness and innovation are
crucial. Consequently, CDMOs that have expertise in preformulation/
formulation development and are also able to provide clinical trial
supplies and achieve seamless scale-up and technology transfer for
commercial manufacturing will have a distinct advantage. CDMOs,
with specialized capabilities, such as the production of highly potent
compounds and controlled substances, the ability to overcome the
challenges posed by poorly soluble APIs and the development of
innovative dosage form technologies will be further differentiated.
23

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Seqens eBook

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