> serving the global supply chain Biopharmaceuticals
Abstract
The biopharmaceutical industry continues to grow at
a healthy pace, with the biosimilars market predicted
to expand even more rapidly. As biologic drugs become
more complex, biosimilars become more important,
and downward cost pressures from both governments
and payers increase, biopharmaceutical manufacturers are turning more often to custom service provid-
Four Keys to
Successful
Biopharmaceutical
Outsourcing:
Technical Expertise, Quality,
Reliability and Timeliness
ers to assist in the development and manufacture of
biotherapeutics. While cost savings continue to be a
driver for increased outsourcing, the actual selection
of a contract development and manufacturing partner
is more often today based on other factors, including
their technical capabilities, reliability (such as financial
robustness), the quality of their products and services,
and their history of achieving on-time delivery.
Introduction
The value of the global biologics market reached approximately $230 billion in 2014 and is expected to
grow at a compound annual growth rate (CAGR) of just
over 10% to nearly $390 billion by the end of 2019.1 Biosimilars accounted for nearly $2.0 billion of the biologics market in 2014, and that number is predicted to double by the end of 2019, growing at a CAGR of 15%.2 One
market research firm estimates that there are 280 biosimilars in the pipeline, and the number of biosimilars
in clinical trials is increasing at a rate of 20% per year.3
The strong growth rates for the biopharmaceutical
market as a whole are in part due to the aging of the
global population and a worldwide increase in chronic
diseases, including diabetes, heart disease, and arthritis, that are better suited for treatment with biologic
drugs. In addition, continued expansion of the middle
class accompanied by growing wealth and improving
healthcare systems is leading to increased demand for
biopharmaceuticals in emerging markets.4
More significant growth is anticipated for the biosimilars market because numerous monoclonal antibody (mAb)-based drugs are coming off patent by
2020, including several with annual sales greater than
$5 billion each in the year of US expiry.5 The first mAb
biosimilar was approved by the European Medicines
> BY Greg Flyte Director, CMO Alliance and Program Management,
GlaxoSmithKline Biopharmaceuticals
Greg Flyte is the Director of Contract Manufacturing Organization (CMO) Alliance &
Program Management at GlaxoSmithKline (GSK). He brings over 18 years of technical
and business experience in engineering, validation, process development, alliance/
program/project management, manufacturing operations, and business development.
In his current role, he is responsible for the contract development and manufacturing
organization (CDMO) business, including several collaborations with both small and
large biopharmaceutical companies who are current clients of GSK. During his 16
years at the Rockville, Maryland, USA site (14 with Human Genome Sciences which
was acquired by GSK in August 2012). Greg has also been involved with managing the
design through validation phases during the construction of all GSKs’ manufacturing
facilities, in addition to managing the large scale manufacturing (LSM) facility validation
team from inception through commercial production.
Prior to joining HGS, Greg spent two years as a validation engineer consultant.
He holds a B.S. in Chemical Engineering from Drexel University.
6 American pharmaceutical review Supplement April 2015
Agency (EMA) in 2013 (Remsima/Inflectra from Celltrion/Hospira, a biosimilar of Johnson & Johnson’s inflixmab product Remicade).6 Now that the US Food and
Drug Administration’s Oncologic Drugs Advisory Committee has approved the first biosimilar drug in the
US (Sandoz’s Zarxio biosimilar of Amgen’s Neupogen
[filgrastrim]),7 more companies are expected to submit
applications through this new regulatory approval pathway, including mAbs, which account for approximately
40% of the biosimilars in development.8
Biopharmaceutical outsourcing on the upswing
With demand set to rise at a healthy pace, biopharmaceutical manufacturers are increasingly turning to
service providers for assistance with all aspects of the
drug development process, from discovery through to
recently found to be occurring along with a growth in
commercial manufacturing. In fact, the biopharmaceu-
interest in developing strong relationships with true
tical outsourcing market has increased at an annual
outsourcing partners.12 The survey of “outsourcing
rate of approximately 10% and is expected to grow at a
similar pace for the next several years.9
Many companies are investing in additional capacity
as a result, but it can be difficult to know what specific
Developing
Strategic
Partnership
facing pharmaceutical and biotechnology executives”
also revealed that biopharmaceutical companies, and
in particular emerging biotechs, are also interested in
developing strategic partnerships with service provid-
capabilities will be required in the future given the vari-
ers that offer integrated services from process devel-
able lead times for biotherapeutics. In fact, biologics
opment through to commercial manufacture.
manufacturers are turning to service providers to avoid
There are also many other reasons biopharmaceu-
the very high capital expenditures and long lead times
tical companies outsource to service providers. Some
needed to construct, equip, and validate manufactur-
are looking to improve quality, while others hope to
ing facilities.4
achieve faster time to market, particularly those out-
In addition, as biologic molecules become increas-
sourcing processes based on mammalian cell technol-
ingly complex and often more potent, branded drug
manufacturers are also looking to contract development and manufacturing organizations (CDMOs) that
have the specialized expertise needed for such projects. A 2013 survey of biopharmaceutical companies
CDMO
Selection:
Shift in
interest
ogy. Outsourcing can also enable more efficient use of
in-house expertise. In addition, service providers can
help biopharmaceutical manufacturers gain a competitive advantage, improve their regulatory positioning,
and mitigate supply chain risk.
revealed that they are increasingly outsourcing more
challenging processes to service providers with the
Characteristics of a true contract
appropriate technical expertise.10 A more recent study
biopharmaceutical CDMO partner
also revealed that biopharmaceutical companies tak-
Many of these benefits are not realized unless a true
ing the lead in the market are doing so through the de-
partnership is formed between the CDMO and the spon-
velopment of new products based on innovative new
sor company. Such partnerships require commitment
science that have demonstrated value for patients,
and trust on both sides. That trust and commitment
rather than through a diversification strategy.11 These
develop over time and as the CDMO demonstrates that
companies will clearly need the support of contract
manufacturers with advanced technical capabilities.
COST
it can meet or exceed the expectations of the biopharmaceutical manufacturer.
First, of course, the CDMO must clearly have the op-
CDMO selection no longer driven mainly by cost
erational, methodological, and therapeutic experience
The shift in interest to CDMOs with advanced tech-
and expertise that pertain to any project under consid-
nical capabilities rather than the lowest-cost bid was
eration. A strong quality record and positive regulatory
> Company Profile
Meet GlaxoSmithKline Biopharmaceuticals
Manufacturing Your Products Like Our Own
+
World-class biologics facilities
+
Advanced mammalian and microbial technologies
+
Drug product and drug substance development and
manufacturing capabilities
+
Industry-leading technical expertise
+
Flexible and agile relationship approach backed by leading
biopharmaceutical manufacturer
+
Excellent track record of development success
manufacturing and two plants in Europe able to provide a wide range of drug product
+
Proven quality systems
formulation and manufacturing services, GSK Biopharmaceuticals offers fully integrated
+
Demonstrated experience with technology transfer
+
Risk mitigation through depth of scientific experience
+
Comprehensive analytical/QC support
+
In-depth regulatory expertise
+
Release services from a global network
+
Fully integrated supply chain
GlaxoSmithKline Biopharmaceuticals serves as the manufacturing knowledge center
that enables the launch, supply, and management of GSK biopharmaceutical products
around the world. We leverage these capabilities to provide contract manufacturing
services with market-leading quality, cost, and timeliness.
With two facilities in the US capable of biologic drug substance development and
supply chain support.
We have the proven history, technologies, facilities, systems, people, and corporate
support you need to get your biologics products into development and out to patients
efficiently and with maximum quality and safety.
Americanpharmaceuticalreview.com 7
history are equally important. The demonstrated ability to meet project deadlines and deliver product on or
ahead of schedule is also a must, as is previous success in commercial manufacturing. Financial stability
is another key quality; without it, a CDMO will often
be passed over for short-term projects, and certainly
won’t be considered as a candidate for long-term strategic relationships. Finally, a CDMO must have adequate capacity and equipment and the ability to rapidly meet the changing requirements of its potential
strategic partner.
It should also be noted that biopharmaceutical companies looking to outsource mammalian and microbial
projects often consider different CDMO characteristics
as more important than others. So-called “soft traits” are
also important to sponsor companies. Good communication skills, a good understanding of customer requirements, and knowledgeable and professional experts
are all very important. Transparency, a good reputation,
and a willingness to go beyond the specifics in the con-
> GSK BIOPHARMACEUTICALS
tract are also very positive characteristics for CDMOs.
It is important to realize, however, that poor performance in many of these areas can be a source of dissatisfaction for biopharmaceutical manufacturers. Failing
to meet quality specifications and provide the product
on time are severe negatives for CDMOs, as is the
inability to provide the expected range of services and
capabilities. A lack of timely follow-through with respect to documentation, poor customer service and
technical support, and poor performance in safety
Rockville, MD
Located in the suburbs of Baltimore, MD and Washington, DC, our Rockville, MD facility
also offers both mammalian cell-based and microbial fermentation processes, with a
newly constructed process development laboratory. The site has been providing contract
development and manufacturing services to the biopharmaceutical industry for 8 years.
+ Five commercialized products
+ Support for yeast, NSO, and CHO-based host organisms from 650 L (microbial),
audits can also be very detrimental to any potential
1,600 L (mammalian), and 20,000 L (mammalian) scale
long-term partnership.
+ Full upstream and downstream process development capabilities to 200 L
+ Dedicated analytical team for supporting method development through validation
Demonstration of commitment
+ Disk-stack centrifuge, depth, and microfiltration skids for harvesting
Possessing the above attributes is not sufficient for
+ Flexible downstream operations
developing a true strategic partnership, however. A
CDMO must be able to demonstrate its willingness
to make a long-term commitment to the biopharmaceutical manufacturer. There are several ways that
a CDMO can do so, such as working with the sponsor company to develop operating procedures in a
collaborative manner, providing a project/program
Upper Merion, PA
Located in a suburb of Philadelphia, our Upper Merion, PA facility offers services to
support microbial fermentation and mammalian cell-based processes. The site has been
providing manufacturing services to the biopharmaceutical industry for 15 years.
manager who is dedicated to supporting the biolog-
+ Five commercialized products
ics manufacturer, developing customized protocols,
+ Support for multiple host organisms: yeast, CHO, mouse myeloma,
and providing dedicated development space and/or
insect, and cell cultures
production lines.
+ Support for multiple process platforms: batch, fed-batch, multiple
harvest, and perfusion
Understanding the marketplace
+ Seed labs and seed trains: shaker flasks and wave platforms with
As mentioned above, the interests of biopharmaceuti-
different scale-up ratios
cal companies looking to outsource mammalian and
+ 5000 L (mammalian) and 10,000 L (microbial) reactors
microbial processes often differ. An effective CDMO
must understand those different needs and preferences and be prepared to provide the expected capabilities and services. For instance, preferences for the
+ Disk-stack centrifugation and high-capacity, flexible depth filtration
for harvesting
+ Flexible downstream operations
stage of outsourcing, the use of stainless steel vs. dis-
+ Single-use disposable and stainless equipment options
posable equipment, and the types of services needed
+ Suite segregation
can vary widely for mammalian cell and microbial pro-
+ Campaign-dedicated equipment
cesses and even from one customer to another.
+ Analytical and release testing
8 American pharmaceutical review Supplement April 2015
Characteristics
of a true
CDMO partner
Technical
Expertise
Cost is still a factor
Finally, it should also be noted that, although cost is
Quality
It should also be noted that
biopharmaceutical companies
looking to outsource
mammalian and microbial
projects often consider different
CDMO characteristics as more
important than others. So-called
“soft traits” are also important
to sponsor companies.
and manufacturing resources associated with an established global manufacturer.
often considered to be less important than quality and
Such a CDMO is able to provide services from early-
reliability when biopharmaceutical manufacturers are
stage development to commercial production using
selecting a CDMO, cost is still a factor, particularly if
world-class, state-of-the-art equipment and facilities.
two CDMOs have equally attractive attributes other-
In addition, because such a CDMO has a tremendous
wise. There are few cases in which cost is not considered at all, but it is also unlikely today that cost will be
depth of scientific expertise in both mammalian and
Reliability
the only factor on which a CDMO is selected.
microbial technologies, biopharmaceutical manufacturers can minimize the risk of outsourcing more challenging processes. Access to top regulatory experts
The benefits of big biopharma backing
and analytical support is yet another benefit of part-
It can be challenging for CDMOs to possess all of the
nering with a CDMO that is associated with a major
desirable attributes outlined above. There is one very
biopharmaceutical company. Global marketing sup-
effective way to do so: have a connection to an established world leader in the development and scale-up of
port is another.
Timeliness
Of course, such a CDMO must have appropriate con-
biologics. This type of CDMO offers the flexibility of an
trols in place to ensure that the work it does for its
agile service provider combined with the financial sta-
customers remains confidential and separate from the
bility and depth of technical expertise, development,
activities of its parent company.
A
> references
1. BCC Research, “Biologic Therapeutic Drugs: Technologies
and Global Markets,” Jan 2015; http://www.bccresearch.
com/market-research/biotechnology/biologic-therapeuticdrugs-technologies-markets-report-bio079c.html. Accessed
2/15/2015.
2. BCC Research, “Biosimilars: Global Markets,” Jan 2015;
http://www.bccresearch.com/market-research/biotechnology/
biosimilars-global-markets-report-bio090b.html. Accessed
2/15/2015.
3. Daedal Research, “Global Biosimilar Market Trends &
Opportunities: 2015 Edition,” Jan 2015; http://www.daedalresearch.com//global-biosimilar-market-trends-opportunities2015-edition. Accessed 2/15/2015.
4. Challener C. How Will CMOs Provide Sufficient Capacity
for Growing Biologics Demand? BioPharm International.
Jan 31, 2014; http://www.biopharminternational.com/howwill-cmos-provide-sufficient-capacity-growing-biologicsdemand?rel=canonical. Accessed 2/16/2015.
5. Challener C. Monoclonal Antibodies Key to Unlocking
the Biosimilars Market. BioPharm International. Apr 1, 2014;
http://www.biopharminternational.com/monoclonal-antibodies
-key-unlocking-biosimilars-market. Accessed 2/16/2015.
6. Celltrion, “Celltrion’s RemsimaTM(infliximab) receives
positive opinion from EMA’s CHMP,” Press Release, July
29, 2013; http://www.celltrion.com/en/company/notice_view.
asp?idx=364&code=ennews&intNowPage=3&menu_
num=&align_year=all. Accessed 2/16/2015.
7. FDA, “FDA approves first biosimilar product Zarxio,” Press
Release, Mar 6, 2015; http://www.fda.gov/NewsEvents/
Newsroom/PressAnnouncements/ucm436648.htm,
March 6, 2015.
8. Dalgaard K, Evens M, da Sikva JS. Biosimilars seven
years on: where are we and what’s next? Feb 2013;
http://www.mckinsey.com. Accessed 2/16/2015.
9. HighTech Business Decisions, “Biopharmaceutical
Contract Manufacturing: HighTech Business Decisions’
New Report Indicates Improving Demand for Outsource
Services,” Oct 22, 2014; http://www.businesswire.com/news/
home/20141022006728/en/Biopharmaceutical-ContractManufacturing-HighTech-Business-Decisions-Report#.
VOE4nC6YYuc. Accessed 2/15/2015.
10. Langer ES. Outsourcing Trends in Biopharmaceutical
Manufacturing. Pharmaceutical Technology. Feb 1, 2014;
http://www.pharmtech.com/outsourcing-trendsbiopharmaceutical-manufacturing. Accessed 2/15/2015.
11. Accenture, “Four Keys to Biopharma High Performer
Success,” Oct 15, 2014; http://www.accenture.com/us-en/
Pages/insight-trends-life-sciences-four-keys-biopharma-highperformer.aspx. Accessed 2/15/2015.
12. National Law Review, “Nice Insight on Trends and
Expectations for Outsourcing in the Biopharmaceutical
Industry,” Feb 6, 2015; http://www.natlawreview.com/article/
nice-insight-trends-and-expectations-outsourcingbiopharmaceutical-industry. Accessed 2/16/2015.
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