By: LSPR
Day
two of the 12th annual Bioprocess International (BPI) Conference
& Exposition featured a full day of exhibitions and continued high-level
technical discussions and presentations that attendees have come to expect from
the show. The day began on a high note with keynote speakers giving insight
into the next generation of manufacturing. Valuable conversations continued
during exhibit hours with the curtain rising on the BPI Theater. Of course,
there were technical sessions throughout the day, as well. Some of the
highlights from the second day of BPI 2015 are below.
Keynote Addresses
Bioprocessing
manufacturing facilities were the topic of the day during the keynote addresses,
as representatives from Amgen and Genzyme, a Sanofi company, built on the
keynotes presented on day one. Both day two speakers opened the door on
technologies and trends to provide a peak on what the future may hold for the
industry.
The
future is now was the theme of the first presentation, given by Kimball Hall,
Vice President Manufacturing, Amgen Singapore Manufacturing Pte. Ltd. Her address was on Amgen’s Next-generation Biomanufacturing Facility, which was four
years in the making and is scheduled to open its doors in 2017. In changing the
manner in which Amgen conducts bioprocessing manufacturing, the company is also
re-shaping the entire industry, according to Hall.
“Whereas
in the past, the focus was on high margins and capacity, today biomanufacturing
is centered on cost, speed, and operation flexibility,” she explained.
Hall
shared the thoughts of one of Tuesday’s keynote speakers, David J. Pollard,
PhD, Executive Director, BioProcess Development, Merck & Co., Inc., when
she spoke of a modular method for facility design.
“In
a conventional facility design, capacity becomes a consideration in Phase II.
That is not the case with a modular design as it allows facilities to expand or
contract as the market demands. Additionally, the modular format is agnostic to
a country or location,” she explained.
In
addition to a modular format, the Amgen Singapore facility incorporates other
design elements that have proven to create benefits in construction time, operations,
and environmental footprint. Among those elements mentioned by Hall were
integration of single-use technologies (95% of the equipment is single use),
incorporating connected processing, and real-time and remote monitoring.
Hall
explained that the disruptive approach taken by Amgen has cut the construction
time of the Singapore facility in half and capital costs are one quarter that
of a conventional facility. Operating expenses will be lowered by a third, as
well, according to Hall. The end result will be an approximately 60% reduction
in protein development cost.
“One
of the first questions I’m asked about is the environmental impact of the
facility. I am happy to say that it will use less water for heating, cooling,
and cleaning. Because it is a smaller facility, it will have a lower air
quality classification, and emissions will be lower due to reduced energy usage
and Singapore’s cleaner energy,” explained Hall.
All
told, the new facility in Singapore is expected to have an 80% reduction in energy
and water use.
In
the second keynote, Konstantin Konstantinov, PhD, Vice President, Technology
Development for Genzyme asked What is the
Future of Continuous Processing – What is the Time Frame for Implementing Fully
Continuous Processing in Commercial Production? He spoke of changes in
upstream and downstream processes that will help create a “dominant design” in
the next 5-10 years that will help shape bioprocessing.
“The
commercialization of innovation will lead to a dominant design where almost any
protein can be developed using a universal platform. It will take a lot of
courage and focus to accomplish this dominant design,” offered Dr.
Konstantinov.
The
dominant design outlined by Dr. Konstantinov is an end-to-end continuous
integrated upstream and downstream principle. While there has been promising
results in a pilot facility, Dr. Konstantinov noted, “Success is impossible
without a high-performance cell line.”
Thankfully,
Dr. Konstantinov believes there is tremendous opportunity to improve cell
lines. Success will be determined by three factors – stable productivity over a
long period of time, stable quality over a long period of time, and low cell specific
perfusion rate.
While
upstream processing improvements are one step, Dr. Konstantinov expects “a lot
of changes” in the downstream. He noted developments in equipment, and spoke of
a large scale continuous purification system with a very broad capacity range currently
in a laboratory at Genzyme’s Framingham, Massachusetts, campus.
Despite
all the progress, Dr. Konstantinov noted that the industry is entering a “very
interesting stage.” New technologies still need to be developed to fill a few
gaps, including cell retention devices and viral inactivation.
He
also suggested the industry broaden its approach to the integration of
continuous processing. “Why stop at drug substance? We should also look at drug
product because continuous manufacturing can bring advantages there, as well.”
Technical Session
Highlights
In his session entitled High-throughput Process Development to Accelerate Speed to the Clinic
for Antibodies, Gregory A. Barker, Ph.D., Sr. Engineer, Biologics Process
Development, Bristol-Myers Squibb spoke of High-throughput Process Development
(HTPD) and how it allows scientists to examine 300,000 compounds per day so it
only takes a few weeks to screen millions of substances. Before HTPD, Bayer
researchers could take several months to develop special activity assays.
The goal of using HTPD, a computer-based
serial-testing method that incorporates robotic systems, is to determine
whether a substance reacts biochemically with the target, according to Dr.
Barker. During the HTPD process, robots fill millions of reaction vessels with
the assays.
“For example, a specific vessel may hold only
50 nanoliters of fluid with the vessels aligned on a plate that holds 1,536
wells. This would allow for 1,536 biochemical or cell-based assays to be
performed simultaneously on a single microliter plate. In fact, thousands of
these are often used in a single HTPD run,” said Dr. Barker.
As Dr. Barker explained, key benefits of HTPD
for chromatography unit operations include:
-
A platform
for rapid execution of experiments using sparingly small amounts of material to
enable investigation of a broad range of process conditions
-
Fundamental
data that may be used for scale-up via statistical modeling and process
simulate
-
Systematic
and highly reproducible execution of complex DOEs to survey the knowledge space
and enable multivariate understanding
Specific methods of HTPD for chromatography
were detailed, such as:
1. Isotherms
2. Batch uptake curves
3.
Batch chromatography
Dr. Barker described several HTPD methods that
are used to augment FIH process development packages, including protein
solubility, Protein A optimization and Sartobind Q membrane optimization. The
comparison between common data sets enables adaptation of the platform and
modification to process ranges.
In summarizing his remarks, Dr. Barker said
that HTPD methods are well-defined and are producing data aligned with
literature values. The data alone enables a broader PD knowledge space.
Empirical models built directly from batch chromatography data enable a first
level of prediction for large scale chromatography and rapid FIH timelines. One
thing he noted was that a comparison of HTPD campaigns across different
proteins reflected both commonalities and differences. As a result, the next
steps will be to explore the drivers of commonalities and differences based on
structural motifs.
Poster Highlight
One
of the more distinguished posters at BPI 2015 was presented by MedImmune and
was entitled The Final Push? Expelling
mAb Drug Product from Pre-Filled Syringe Configurations for Sub-Visible-Particle
Testing. The poster proposed that
a partial expulsion of drug products in pre-filled syringe (PFS) configurations
would more accurately reflect protein behavior.
The
poster showed that completely expelling a PFS generates a significant surge of
sub-visible particle (SVP) counts, stemming from the silicone oil (SiO) scraped
from the syringe barrel and forced through the needle. Conclusions drawn from
the experiment and published were that completely expelling a PFS results in
SVP counts as much as 50x greater than if PFS was partially expelled. Particles
in the surge are SiO droplets scraped off the barrel during the expulsion
process and introduced into the liquid upon complete expel. Other conclusions
drawn are that partially expelling a PFS is robust with respect to expel
volume. Removing the product through the stopper is an orthogonal method of
sampling without introducing the high artificial SiO background. The final
conclusion was that product stability should be monitored by partial expel
during the drug development process, as it best isolates the protein behavior.
Product Highlight
Roche
Custom Biotech made three announcements, two on products and a third on
partnership, at BPI 2015.
The
two new production introductions were:
Cedex Bio HT,
a highly reliable metabolite and substrate analyzer for cell culture analysis.
It offers unique photometric technology that delivers high data accuracy, as
well as a cost-saving expandable menu.
Tools for In Vitro
Glycoengineering that can be used after proteins have been
harvested. The tools increase productivity and can be used in early stage
development.
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