I need some assistance with added additional or revision my paper, my paper is almost fully done. Refer to “Eli Lilly: Recreating Drug Discovery for the 2

I need some assistance with added additional or revision my paper, my paper is almost fully done. Refer to “Eli Lilly: Recreating Drug Discovery for the 21st Century.”
Doctoral learners are required to use APA style for their writing assignments. The APA Style Guide is located in the Student Success Center. An abstract is not required.
Refer to the Publication Manual of the American Psychological Association for specific guidelines related to doctoral level writing. The Manual contains essential information on manuscript structure and content, clear and concise writing, and academic grammar and usage.
This assignment requires that at least three scholarly research sources related to this topic, and at least one in-text citation from each source be included. Support for decisions should include appropriate current (within the last three years) or foundational, peer reviewed, and professional research.

Review the information in the case study.
Write a paper (1,500-1,750 words) in which you address the data-driven marketing as found in the case. Include the following in your paper:

An assessment of the internal and external data provided in the case. Is this enough to make a reasoned marketing decision? What else, if anything, is needed to make a more accurate marketing decision?

SINCE MY PAPER IS ALMOST FULLY DONE, I JUST NEED HELP IN THESE TWO POINTS BELOW: ONLY PERHAPS NEED 750 WORDS TO COMPLETE: I CAN UPLOAD MY PAPER ONCE I ACCEPT A BIT.

A discussion of what organizational culture adjustments are necessary for data-driven marketing to be successful in this case.
A summary cost-benefit analysis. Is the return worth the marketing effort? 07-043
March 13, 2008

This case was prepared by Cate Reavis under the supervision of Professor Rebecca M. Henderson. Professor Henderson is
the Eastman Kodak Leaders for Manufacturing Professor of Management.

Copyright © 2008, Rebecca M. Henderson. This work is licensed under the Creative Commons Attribution-Noncommercial-No
Derivative Works 3.0 Unported License. To view a copy of this license visit http://creativecommons.org/licenses/by-nc-nd/3.0/
or send a letter to Creative Commons, 171 Second Street, Suite 300, San Francisco, California, 94105, USA.

Eli Lilly: Recreating Drug Discovery for the 21st Century
Rebecca Henderson and Cate Reavis

The rise of personalized medicine is one of the most important developments in health care today.
Personalized medicine will change health care almost across the board…but nowhere, I would argue,
are the cross-currents of change more powerful or the stakes higher than in the development,
manufacture, and sale of prescription medicines. In my industry, we would be powerless to resist
personalized medicine, not to say foolish.

— John Lechleiter, President & Chief Operating Officer, Eli Lilly & Co. 1

Alone in this office on the last working day of 2007, Peter Johnson sighed as he finished reading the
rest of the recent talk given by John Lechleiter. It reflected more than five years of deep discussion
within Eli Lilly as to how to respond to the strategic challenges facing the industry – a discussion in
which Johnson, as Executive Director of Corporate Strategy, had been deeply involved. Johnson was
sure that a move to personalized medicine made sense for Lilly and for the patients Lilly aspired to
serve, but he was very much aware that implementing the strategy within Lilly was an ongoing
challenge with which he wrestled daily. With the move to “tailored therapeutics” now publicly
embraced by the senior team and with major investments in place what else, he wondered, could be
done to ensure that Lilly’s bold move proved to be successful?

Personalized Medicine

2008 found the pharmaceutical industry under increasing pressure. For more than 20 years the
industry had been dominated by the discovery of “blockbuster” drugs – drugs that embodied

1 John C. Lechleiter, “Markets of One: The Pharmaceutical Industry and The Pursuit of Personalized Medicine,” speech given at the Conference on
Personalized Medicine: A Call to Action, Boston, Massachusetts, November 29, 2007.

17924
Highlight

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

significant advances in medicine, were geared toward the mass market, and sold in the billions of
dollars. Plavix, for example, one of the most widely prescribed drugs in the United States, had 2006
sales of $3.2 billion and Lilly’s Zyprexa averaged $4.3 billion in revenue over a four year period
(2003-2006). Pfizer’s Lipitor became the world’s first drug to surpass $10 billion in sales in 2004 and
generated more than $12 billion in revenues in 2005 and 2006. While these kinds of drugs were
hugely profitable, it was proving to be difficult to find replacements for them as they came off patent.
Research and development costs were increasing dramatically and rates of new drug introduction had
failed to keep pace (Exhibit 1). In response, more and more industry observers were suggesting that
the industry needed to focus on personalized medicine.

There were almost as many definitions of personalized medicine as there were people defining it, but
in general the term referred to any therapy that was “tailored” to a particular subset of patients.
Physicians and researchers had long been aware that different individuals often react very differently
to the same drug. Some studies suggested, for example, that Plavix had almost no effect in as many as
40% of patients for whom it was prescribed. A patient’s response to a drug could vary widely
depending on factors such as the patient’s age, gender, physical condition and phenotype, or genetic
makeup. (Figure 1 shows average efficacy rates for select therapeutic areas.)

Figure 1 Efficacy Rates for Select Therapeutic Areas

0

10

20

30

40

50

60

70

80

90

100

A
na

lg
es

ic
‘s

(C
ox

-2
)

D
ep

re
ss

io
n

(S
SR

I)

A
st

hm
a

C
ar

di
ac

A
rr

hy
th

m
ia

s

Sc
hi

zo
ph

re
ni

a

D
ia

be
te

s

M
ig

ra
in

e
(a

cu
te

)

M
ig

ra
in

e
(p

ro
ph

yl
ax

is
)

R
he

um
at

oi
d

ar
th

ri
ti

s

O
st

eo
po

ro
si

s

H
C

V

(H
ep

at
it

is
C

)

In
co

nt
in

en
ce

A
lz

he
im

er
‘s

O
nc

ol
og

y

E
ffi

ca
cy

R
at

e
(%

)

Source: Spear B, et. al. Trends in Molecular Medicine, 7(5):201-204, 2001; Eli Lilly internal documents.

Lilly’s own research suggested, for example, that the efficacy of one of the company’s most
promising therapies, Strattera, the only non-stimulant drug approved to treat attention
deficit/hyperactivity disorder (ADHD) varied widely depending on the type of patient for whom it
was prescribed. In the general patient population, Strattera had a response rate somewhat lower than
that of its competitors. However, analysis of clinical trial results indicated that for ADHD patients

March 13, 2008 2

17924
Highlight

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

March 13, 2008 3

with co-morbid anxiety, the response rate to stimulants dropped while the response rate for Strattera
stayed the same. Developing a tailoring strategy for Strattera thus had the potential to turn what could
be seen as a slight disadvantage in perceived efficacy among the general population into a clear
advantage among a target group of patients.

One of the most challenging aspects of developing tailored therapeutics was obtaining a deeper
understanding of the factors that drove differences in patient response to particular drugs. Fortunately,
while the industry had long understood that segmentation by disease categories and patient groups
was often appropriate, the increasing availability of new tools, technologies, and knowledge appeared
to have the potential to dramatically expand the potential scope of personalization.

At one end of the scale, researchers were discovering that a particular patient’s response might be a
function of their genetic makeup. Genentech’s Herceptin, approved in 1998 for the treatment of
metastatic breast cancer, was one example of a drug that exploited knowledge of a patient’s genotype
to identify those patients who were most likely to respond to therapy. For patients whose genotype
led to the overproduction of a protein called HER2— something that could be determined with the aid
of a diagnostic test known as the HercepTest— Herceptin appeared to perform significantly better
than common alternative treatments; while for other women the drug performed no better than the
standard treatment. Herceptin therefore served a smaller market than a more conventional therapy —
by some estimates only 15% to 20% of breast cancer patients — and yet, sales of the drug topped
$2.5 billion in 2006. 2

While genetic profiling was a promising approach in some fields – particularly oncology – there were
many conditions for which researchers’ knowledge of the link between genetics and therapeutic
response was much harder to unravel. In response pharmaceutical firms were increasingly focusing on
other kinds of markers as potential differential response indicators. For example, in developing a new
compound to treat Alzheimer’s, Lilly researchers hypothesized that patients without evident “plaque”
— a waxy, translucent substance, composed primarily of protein fibers — were likely to respond very
differently to drugs designed to treat the condition than patients with a significant plaque presence.
The company was working to develop imaging techniques that would allow it to characterize the
plaque status of patients in clinical trials. Roughly 15% of patients with dementia indistinguishable
from Alzheimer’s did not demonstrate an amyloid plaque burden.

The use of biomarkers of this kind was one tool that was making patient segmentation easier. A
biomarker was any biological measurement that provided actionable information regarding disease
progression, pharmacology, or safety that could be used as a basis for decision making in drug
development.3 While the concept of biomarkers was nothing new, advanced technology and tools
were allowing them to be more pervasive and sophisticated and, thus, to come into play at much

2 Matthew Bell, “Unraveling the Pharmaceutical Industry,” Arthur D. Little, 2002.
3 Julia Boguslavsky, “Biomarkers as Checkpoints,” Drug Discovery and Development, September 1, 2004.

17924
Highlight

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

March 13, 2008 4

earlier stages of drug development. By 2006, 90% of Lilly’s compounds in preclinical trials had
identified biomarkers of some kind.

But biomarkers were just one aspect of personalized medicine. As Lilly’s President and Chief
Operating Officer John Lechleiter emphasized, “When you understand diversity and the wide
spectrum of personalized medicine, then you realize that it has implications in the labs and clinics,
certainly…but also in manufacturing, sales and marketing, and all kinds of external relationships.”4
Lilly concluded, for example, that a move to personalized medicine would not only require significant
shifts in the way that the firm approached drug discovery and development, but that there would also
be significant implications for participants at every stage of the drug delivery value chain. It was
likely, for example, that:

• Patients’ attitudes toward health and how they assessed pharmaceuticals would have great
variability, which would require relevant communications about the benefits of tailored
therapies.

• Payers would expect tailored therapies to demonstrate evidence linking their biomarker/tool
result to an actual outcome (e.g., lower cholesterol levels leads to less cardiac events).
Moreover, payers (and others with access to longitudinal healthcare data) were likely to have
increasingly quicker insights as to whether a treatment was resulting in the desired/promised
outcome, which could lead to cost-shifting and risk-sharing if a treatment did not live up to
expectations.

• Providers’ prescribing autonomy would probably continue to be further restricted by payers,
and providers might be measured/compensated based upon patient outcomes, which would
require that diagnostic/prognostic/monitoring tools be easy to use.

• While in general the regulatory bodies were intrigued with the potential of tailored
therapeutics, they were likely to operate with caution so as not to risk damage to their
reputation if personalized products proved not to be safer and/or more efficacious. Regulators
were also likely to be concerned about the potential misuse of tailoring tools and protecting
patient privacy.

• Diagnostic firms were likely to try and minimize the risk of developing companion
diagnostics through actions like seeking access to clinical samples so that they could develop
companion diagnostics, and having input into sales promotion efforts. They were also likely
to seek pharmaceutical funding for diagnostic development, and — perhaps —broad IP rights
on any biomarkers that might be developed.

Personalized Medicine at Lilly: A focus on “Tailored Therapeutics”

With 2006 revenues of $15.7 billion, 41,500 employees worldwide and medicines marketed in 142
countries, Lilly was one of the world’s 20 largest pharmaceutical companies. (Exhibit 2 gives key

4 John C. Lechleiter, “Markets of One: The Pharmaceutical Industry and The Pursuit of Personalized Medicine,” speech given at the Conference on
Personalized Medicine: A Call to Action, Boston, Massachusetts, November 29, 2007.

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

March 13, 2008 5

financial information for the firm.) The company, which prided itself on its strong record of science-
based research productivity, spent more on R&D as a percentage of sales (20%) than any other major
pharmaceutical company. (In 2006 GSK spent 15% and Merck 17%.) It had major research and
development facilities in nine countries and conducted clinical trials in more than 60. Lilly’s four
therapeutic areas included neurosciences (44% of revenue), endocrinology (31%), oncology (10%),
and cardiovascular (5%).5 Zyprexa, a treatment for schizophrenia, bipolar mania and bipolar
maintenance, accounted for 28% of Lilly’s revenue.

Lilly was one of the only major pharmaceutical companies not caught up in the merger and
acquisition activity of the late 1980s and 1990s. (See Exhibit 3.) The company was able to safeguard
its independence by looking internally for core capabilities it could develop and exploit, including
improving speed to market, leveraging existing products, narrowing its R&D focus from eight to five
therapeutic areas, spinning off its non-core medical device and diagnostic businesses, and creating
multi-functional, product-focused teams (known internally as heavyweight product development
teams) which focused exclusively on the development of a single compound. These teams combined
all activities related to drug discovery, manufacturing, sales, marketing, and distribution.6 These
activities were complimented by an internal alliance management organization, charged with
managing Lilly’s external alliances. Alongside remaining independent, partnering was a big part of
the Lilly’s strategy.

Lilly’s strategic shift was coming at a time when several of the company’s blockbuster drugs were
facing patent expiration. The company expected to lose patent protection on seven products between
2011 and 2013, including Zyprexa, the company’s best selling product. Between them the seven
accounted for roughly 50% of forecast 2010 revenues. (See Exhibit 4 for revenue breakdown by
product, and Exhibit 5 for a comparison of results between Lilly and some major competitors.) As a
result the company was under significant strategic pressure. One widely cited company goal, for
example, was to reduce the cost to develop a new drug from over $1 billion to around $800 million.

Lilly’s first public commitment to personalized medicine came in a July 2005 interview, when Lilly’s
Chairman and CEO Sydney Taurel went public with the company’s new strategy telling the New York
Times, “The challenge for us as an industry, as a company, is to move from a blockbuster model to a
targeted model…We need a better value proposition than today.”7 Internally, however, the strategy
dated from the summer of 2004 when an internal project known as “Project Resilience” had
recommended that the company pursue a strategy focused on what at that time was characterized as a
“niche high value” business model. (For a more detailed account of Project Resilience and the
strategic thinking that it embodied, please see Sloan Case #07-040, Eli Lilly’s Project Resilience:
Anticipating the future of the pharmaceutical industry.)

5 Animal Health and “other pharmaceuticals” made up the remaining 7% of revenue.
6 Matthew C. Verlinden, “Eli Lilly: The Evista Project,” Harvard Business School, Case No. 699-016.
7 Alex Berenson, “Blockbuster Drugs Are So Last Century,” The New York Times, July 3, 2005.

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

March 13, 2008 6

The Project Resilience team described the niche high value strategy as:

A fully integrated firm that focuses on highly valued niche products. Research efforts
focus primarily on targeting therapies to specific subpopulations of patients and capturing
those niche opportunities completely with highly effective products. While the total
patient number might be smaller, product responsiveness will drive greater market share
and premium pricing may be possible for highly effective treatments. Relationships with
diagnostic firms are critical to utilize biomarkers and identify the appropriate patients.
Marketing messages must focus on identifying the right patient and using a diagnostic
and be geared toward B2B capabilities. Buyers will want to ration drug use, particularly
of innovative products, so therapies that can identify the right patient will be attractive.

The recommendation followed extensive analysis of the future facing the industry and of Lilly’s
particular competitive strengths. The Resilience team felt that the niche high value strategy allowed
the company to capitalize on its traditional strength in research while giving it some competitive
insulation from what was expected to be an increasingly cost conscious world. While the team had
considered strategies that might enable the company to thrive in a world in which innovation was
much less central to the firm’s mission, the senior team had been very reluctant to embrace them. In
reflecting on the decision a year later, John Lechleiter recalled “if we had really believed that (a much
less innovative world) was the future we would have looked for another option. I couldn’t imagine
taking the company there…”

Internal reaction to the new strategy was mixed. Lilly’s marketing organization was skeptical about
the term “niche high value” and its implication that Lilly would be going after smaller markets and,
therefore, selling less. Many wondered how the company would make money from the new strategy.
Lilly’s research organization, Lilly Research Labs (LRL), was further concerned that the Resilience
team had put too much weight on a business model and approach that might be appropriate for
leading edge cancer therapies but that had little relevance for other therapeutic areas. As one scientist
recalled thinking at the time, “You can’t just change our business model. You don’t know how to do
discovery. Furthermore, we have this ongoing pressure to accelerate products to the market.” Steve
Paul, executive vice president for science and technology and president of Lilly Research
Laboratories, was even more direct: “We thought this was biotech b.s. – just another fad.”

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

March 13, 2008 7

Targeted Therapeutics

Through 2005 Peter Johnson and his team focused their attention on communicating the importance
of the new strategy as an integral part of Lilly’s response to the changing pharmaceutical
environment. Responding to concerns that the term ‘niche’ was both misleading and inaccurate, the
strategy was renamed “targeted therapeutics.” Johnson presented the idea of targeted therapeutics—
and the strategic rationale behind it — to over 3,000 Lilly managers as part of the executive program
“Leading in Lilly,” and to more than 5,000 employees in a series of town hall style talks. A DVD was
developed and made available to all Lilly employees on the company’s intranet which dealt with
questions such as: what drove Lilly to a targeted therapeutics strategy? How does the new strategy fit
in with Lilly’s strategy overall? How is Lilly implementing the new strategy particularly in R&D and
sales and marketing? How do the economics of moving to a targeted therapeutics model work?
Sidney Taurel, Lilly’s CEO, also took a very active role in advancing the new strategy – presenting it
to his board and to over 800 people at Lilly’s Global Leadership Conference, and actively talking
about its implications throughout the company. These communication efforts were followed up by
continual updates to Lilly’s board and its top managers.

As Table 1 below indicates, the targeted therapeutic and the conventional FIPCO (Fully Integrated
Pharmaceutical Company) models took very different approaches to R&D, sales and marketing, and
manufacturing.

Table 1 FIPCO vs. Targeted Therapeutic Models

Conventional FIPCO Targeted Therapeutic FIPCO
• Large patient populations
• One size fits all products
• Few, large products generate majority of

revenue
• Mid-sized R&D portfolio
• Dedicated manufacturing focused on few, high

volume products
• Primary care, large sales force
• One size fits all marketing

• Targeted patient populations
• “Customized” treatment
• Many, equally sized products generate most revenue
• Large R&D portfolio
• Highly flexible manufacturing capability
• Specialty, technical, smaller sales force
• Targeted marketing positioning and messages
• Marketing with companion diagnostic or biomarker
• Relationships with diagnostics companies
• Generally lower development costs and improved

probability of technical success
Source: Internal Lilly documents.

As with the “niche high value” model, reactions to the targeted therapeutics strategy were mixed.
Researchers within LRL took issue with the term “targeted” since they were already focused on trying
to find biological targets to guide drug development. “Aren’t we already doing this?” was a common
response from this group. There was also a feeling in the marketing and sales organization that the
company had immediate problems that needed solving before it could worry about transitioning to a
new model. As one example, Lilly’s potential blockbuster, Xigris, launched in 2001 for the treatment

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

March 13, 2008 8

of sepsis, had 2005 revenues of $214 million, far from the blockbuster mark of $1 billion. Lackluster
sales were blamed on the drug’s delayed launch and poor efficacy results. As one executive
recounted, “The company was trying to find the right language for the strategy. We needed to figure
out what we were really talking about when we referred to the term targeting.” There also continued
to be concern that “targeting” was fine in cases such as oncology in which it was possible to imagine
finding a link between an individual’s genotype and how they might respond to a drug, but was not a
very useful approach in many other cases.

Tailored Therapeutics

As Johnson and his colleagues grappled with these issues they came to the realization that the strategy
that they were advocating was best captured using the word “tailored.” Lechleiter used an analogy to
put the tailored therapeutics strategy in perspective:

A traditional tailor can sew up some cuffs, extend the sleeves, or even—on very rare occasions—
take in the waist. In that same spirit, tailored therapeutics can narrow the target population of
patients, tighten up dosing guidance based on various criteria, address the timing of therapy, or
provide better information to patients—for example to improve adherence. And, of course, none
of these scenarios is mutually exclusive. With regard to the degree of tailoring: There’s quite a
range between buying whatever’s on the rack and ordering a custom made-made suit—just as
there’s quite a range between ‘one-size-fits-all’ medicine and truly patient-specific therapies and
treatment regimens.8

(Exhibit 6 depicts how Lilly characterizes its ranges of tailoring involving drug discovery and
development.)

Intense conversations inside the firm generated the insight that there were many ways in which a drug
could be personalized, and that the level of tailoring of any particular drug was likely to vary
significantly across the company’s four therapeutic areas—neurosciences, oncology, cardiology, and
endocrinology. The recognition that drugs such as Insulin had been “tailored” for many years – in that
dosage, for example, was carefully calibrated to a patient’s blood sugar level – also helped build
support for the new strategy. Lilly began to use the model shown in Figure 2 to illustrate the
complete spectrum of potential tailoring opportunities.

Framing things this way made it clear that a tailored therapeutics model was not solely about drug
development. It could also include an information delivery system in which the overall message,
information provided and language used to market a drug was customized to particular patient
populations. A tailored therapeutics model could also include the way information was provided
through Lilly’s sales force or various e-channels. As Johnson noted, tailoring drug delivery could

8 John C. Lechleiter, “Markets of One: The Pharmaceutical Industry and The Pursuit of Personalized Medicine,” speech given at the Conference on
Personalized Medicine: A Call to Action, Boston, Massachusetts, November 29, 2007.

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

include giving providers and pharmacies choices as to how they received Lilly products, including the
size and shape of pills and how they were packaged. It could also include tailoring messages.
Johnson explained:

For example, different cultures have different approaches, attitudes and beliefs about healthcare
and medicine, and it is important to speak to these communities in ways that are meaningful to
them – and one size fits all messages and information don’t do that. Our desire is to identify those
patients that have the highest probability of being helped by any of our medications, as well as to
identify those who may have a higher probability where the medication will not work either
because they are non-responders or because they may have a higher likelihood for a particular
side effect.

Figure 2 Tailoring Scenarios

Tailoring “Drug”

Engineering therapies with a specific patient
subpopulation in mind

Identifying “Patient” best suited
for drug

Special case

Identifying those patients for whom benefits
outweigh risks

Identifying responders for targeted therapies
(essentially highly tailored therapies)

Tailoring “Dose”

Optimizing dosing regimen for patient
subpopulation(s) to achieve optimal benefit/risk

Tailoring “Time”

Identify the time to intervene during disease
progression, the time to complete therapy, or the
time to alter treatment regimen

Tailoring “Information/Tools”

Accommodate information for patient diversity,
questions specific to payers or providers, or
provide tools to meet needs of customers

Source: Internal Lilly documents.

Identifying and Building Capabilities

As the company educated employees about the new strategy, the process of operationalizing it began.
In early conversations the tailored therapeutics strategy had been presented as a significant shift for
the company, or as a new “S curve.” Thought was even given to creating a separate business unit
within the company devoted to tailored therapeutics. As it became clear that the new strategy would
require exploring the possibility of tailoring a drug in multiple ways across the value chain, the
decision was made to implement tailored therapeutics within the existing organization. As a result,
Lilly made few changes to its organizational structure to accommodate the new strategy.

March 13, 2008 9

ELI LILLY: RECREATING DRUG DISCOVERY IN THE 21ST CENTURY
Rebecca Henderson and Cate Reavis

March 13, 2008 10

Lilly’s organizational structure was fundamentally functional, with research and development
structured as a tightly integrated matrix (Exhibit 7). Within this context, Lilly put together a strategic
team charged with “watching over” the implementation of tailored therapeutics. The team was chaired
by Johnson, and included Eiry Roberts, Vice President in charge of early clinical development and
Bert van den Bergh, VP of Global Customer Solutions. The team decided to pursue two parallel
tracks in supporting the company’s transition to the new strategy. The first was to ensure that every
team working on a potential new therapy continually considered the potential for tailoring in its plan,
while the second was to ensure that each team had access to the capabilities that it needed to execute a
tailored strategy.

Integrating “Tailoring” …

Looking for this or a Similar Assignment? Click below to Place your Order