|
 High
research and development costs and lengthy time-to-market
challenges make it difficult for pharmaceutical companies
to successfully introduce new drugs to market. To expedite
the process, these companies rely on a highly structured
clinical trial system to collect, analyze, and categorize
data about a new drug as it progresses through development,
testing, and trials in the field.
Yet like a massive pipeline that's equipped with a
myriad of inbound and outbound valves and conduits,
the clinical trial system depends on precise timing,
monitoring, and coordination efforts as well as a cataloged
flow of information and materials. If just one critical
step in the clinical trials process goes awry and slows
or stops the pipeline, the drug manufacturer could lose
tens or even hundreds of millions of dollars in potential
revenue and profit. The longer it takes for a new drug
to go through clinical trials, the shorter the amount
of time is available to enjoy protected sales on the
market before its patent expires--an industry rule of
thumb pegs the opportunity cost as high as $1 million
per day in lost revenues.
To help keep the new-drug pipeline flowing freely and
improve time-to-market and profitability, pharmaceutical
manufacturers often rely on various technologies to
help connect clinical trial management with manufacturing.
Among the most popular systems are those that aid collaborative
communication and planning, simulation and subject compliance,
clinical supplies, packaging, and manufacturing.
Integrated communication is key
The clinical trial system requires the input, output,
and cooperation of diverse groups, including personnel
from the pharmaceutical company's medical department,
biostatisticians, investigators, trial subjects, representatives
of domestic and nondomestic regulatory organizations,
manufacturing personnel, packaging personnel, and sometimes
representatives from contract research organizations
(CROs) and other third-party vendors.
To juggle the needs and requests of these groups during
the clinical trial process, a pharmaceutical company
reties on the knowledge, experience, and involvement
of its in-house clinical supply group or CRO packaging
and clinical supply group. Often, this job requires
as much explanation as it does expertise. For instance,
even the most experienced pharmaceutical personnel may
be unaware that decisions made at the study-design level
can have a significant effect on manufacturing and packaging
operations and profitability down the line. It's the
job of those in clinical supply to explain the cost-
and time-effectiveness of alternative decisions, as
demonstrated in the following group-specific examples.
Medical personnel. When medical personnel design a
clinical study, they often request complex packaging
designs that will take a significant amount of time
to produce; for example, blister packs with detailed
instructions printed on each blister. Bottles that contain
a preprinted instructional leaflet are usually less
expensive and faster to package. Moreover, medical personnel
often do not understand the extensive lead times for
formulation, validation, and stability efforts that
are needed to obtain and blind comparative products
(i.e., to develop a product that is visually identical
to a competitor's drug).
Biostatistics personnel. Biostatisticians who work
closely with medical staff to design a clinical trial
hold considerable sway over how a clinical drug is packaged
and distributed. However, their decisions may not always
be optimum. For example, they may request a randomization
scheme that could inadvertently make the setup of packaging
runs difficult, time-consuming, and expensive.
Clinical investigators. Clinical investigators--the
physicians who provide the drug to the patient--may
have difficulty keeping track of various standard operating
procedures, storage conditions, minimum inventories,
and other rules related to a range of studies and products.
In addition, investigators are sometimes responsible
for reordering new-drug supplies. They may assume that
a product is sitting on a shelf in a warehouse and is
ready to be distributed when in fact a reorder may require
a full manufacturing and packaging run because of limited
available supplies.
Trial subjects. Responsible for taking the investigational
drug, trial subjects present multiple challenges to
the packaging and clinical supply group. For example,
subjects might misplace their drug supplies or not take
the product as labeled. The clinical supply group must
carefully consider the packaging with trial subjects
in mind as well. Historically, clinical materials were
exempt from regulations concerning child-resistant pharmaceutical
packaging. However, today's clinical materials often
must adhere to the same guidelines as those for marketed
products. Thus, trials for certain demographic groups
such as arthritis patients may require special packaging
materials to ensure that the packaging will comply with
both trial and regulatory requirements.
Regulatory organizations. Regulatory organizations
during the clinical trial process are critical stakeholders.
The documentation, tracking requirements, and import-export
considerations for clinical supplies are extensive.
Insufficient or inaccurate documentation during a trial
can delay or cancel it, thereby resulting in huge losses
to the study sponsor.
The manufacturing group. The manufacturing group within
a pharmaceutical company is unique in that it is both
a supplier and a customer of the clinical trial materials.
The facility that supplies the clinical trial material
usually is not the same facility or even the same company
that will manufacture the drug for the market. However,
the manufacturer must know how the drug is produced
and, therefore, will be a customer for the production
data from the clinical material facility. For this reason,
the manufacturer also may want to be involved in decision-making
for producing the trial formulations.
CROs and third-party vendors. CROs and third-party
vendors hired by the pharmaceutical company to assist
with manufacturing, packaging, labeling, and distributing
clinical materials rely on data about the clinical trial
and supplies to plan and execute their work. Any break
in the process such as a delay in the delivery of the
investigational drug from the pharmaceutical company
can seriously disrupt the timing and success of their
work.
Challenges of international production, marketing,
and distribution
The packaging and clinical supply group must design
ways to cost-effectively meet the needs of multiple
groups involved in the process. In addition, it must
deal with the unique challenges of manufacturing and
distributing an investigational product. Because pharmaceutical
companies typically plan worldwide marketing and sales
of a new drug, this poses a host of issues related to
international production and testing.
Before a drug can be sold in a country, it may first
need to go through a clinical trial under the rules
that are specific to that country. Sourcing issues for
new drugs are complex because many countries do not
permit the use of certain compounds. For example, most
European countries require excipients, capsule shells,
and bulk drug products to be certified as free of bovine
spongiform encephalopathy and transmissible spongiform
encephalopathy. Country-specific requirements such as
these pose unique challenges when drugs are still in
research and development because it is typically not
cost-effective to manufacture different batches for
each country. Thus, most pharmaceutical manufacturers
follow the requirements of the country having the most-strict
regulations.
However, drug companies often do not decide which countries
will participate in a clinical trial until late in the
process. By that point, it may be difficult to obtain
sufficient quantities of the drug material in time to
make and deliver the first batch to the first investigator
in time for the first patient visit.
Sometimes, a company will manufacture different clinical
trial batches for different countries. However, this
can lead to supply challenges if the sites in one country
are running short on the drug while another country
has an oversupply. Often, the oversupply cannot legally
be sent to the sites that are in need. Thus, companies
must track which batches may legally go to which site
and ensure that material is not sent to the wrong location.
Mistakenly sending the wrong batch to the wrong country
not only may result in a large fine from the regulatory
agency for that nation, it also may invalidate the clinical
study data.
|
