The expanded definition of temperature-controlled product has led many
countries to pass laws mandating that
manufacturers ensure that drugs are kept
in the range stated on the label, according
to Orfanos. “Those governmental bodies
are saying if this product needs to be kept
at that temperature then you, the manufacturer, have delegated the temperature
requirement for that product,” he says. “If
you’re going to ship it from Point A to
Point B you need to maintain [the prod-uct’s] efficacy.” Regulators around the
world have taken the label designations
and said, “‘Okay, fine, but now you’ve got
to meet that requirement.’ ”
And if you don’t? “A product could
potentially be delayed in reaching its
destination, requiring analysis, or in the
worst case, being deemed spoiled,”
Orfanos says. Spoilage could occur
when a combined accumulated range
of temperature excursion reaches a
certain length of time deemed unacceptable by the manufacturer’s quality
assurance department.
“A number of regulatory and stan-dards-based guidance documents have
been published over the last two years,”
says Henry Ames, director of strategic
marketing for Sensitech (Beverly, MA),
which specializes in cold-chain solutions
for monitoring temperature-sensitive
products from the beginning to the end
of the supply line. These include the
November 2005 publication of USP
<1079>, the general guidance document
covering good storage and shipping
practices by the U.S. Pharmacopeia.
Other documents addressing product
efficacy and patient safety include
Technical Report 39 (“Guidance for
Temperature-Controlled Medicinal
Products: Maintaining the Quality of
Temperature-Sensitive Medicinal Products through the Transportation Environment,” revised in 2007), by the
Parenteral Drug Association, as well as
regulatory publications from Canada,
Ireland, and other countries.
Revised by a cold-chain working
group within the Parenteral Drug Association, Technical Report 39 harmonizes
supply-chain best practices with EU reg-
PHARMA-BIO TRANSPORT | February 2008
ulations. One of the key recommendations is that transportation companies
establish quality management systems
with a designated decision maker. USP
<1079> offers a range of storage and
shipping guidelines and recommendations. The 15-page document covers
areas such as establishing temperature
profiles, monitoring during shipping,
qualification protocol, and receipt of
pharmaceuticals. On this last topic, USP
<1079> recommends transfer of arriving
product to “a manufacturer-designated
storage environment within two hours
of receipt,” for instance.
“All supply-chain partners need to
work together to ensure product quality
and patient safety,” Ames says. These twin
Ames notes that ultimate
responsibility for product
safety, in the United States at
least, rests with the
pharmaceutical manufacturer.
goals have led Ames to argue that streamlining the cold chain and the pharmaceutical industry’s push for an anticounterfeit
electronic pedigree system are linked. The
majority of counterfeited drugs tend to
be temperature-controlled products, he
notes, because those typically cost more
than noncontrolled drugs.
“You need to look at all pressures to
streamline the pharmaceutical supply
chain, which would include a desire to
reduce counterfeit drugs as well as drugs
that have been adulterated through temperature abuse,” Ames asserts. “There is a
strong correlation between counterfeit
drugs and temperature-sensitive drugs.
Adulteration includes external factors
such as temperature, shock, vibration,
humidity, and pressure.”
An authentic product that’s been
“temperature abused,” even though it’s
the genuine article, “is worthless,” Ames
reasons. “You really have to [be vigilant
about] both to maintain product safety,
and streamlining the supply chain helps
to reduce the risk and address some of
the issues with either diverted product
entering the supply chain in complex
distribution channels or thermal excursions that may occur.
“The benefit to streamlining the supply chain can help address both problems,” he concludes, “and there are a
number of supply-chain partners that
have recognized the growth in this market and the need for more specialized
service offerings. FedEx Customer
Critical, UPS Health Care Shared Network, and DHL LifeConEx are all
good examples.”
Similarly, Keith Sinclair believes the
cold chain and e-pedigree matters are
“two distinct but related things.” The
director of operations for biopharmaceu-ticals distributor FFF Enterprises (
Temec-ula, CA), Sinclair agrees the industry has
been paying greater attention to maintaining product integrity throughout the
supply chain. “Once it gets out of the
manufacturer’s hands, it’s a matter of how
the wholesaler is handling it,” he says.
As a result, the regulatory spotlight has
shifted to the wholesaler, and “there’s
been talk of FDA stepping in,” Sinclair
says. “I think what’s happening is confusion between pedigree and channel
integrity. Pedigrees do not create channel
integrity. They just document who has
handled a product, but not how. And
how a product is handled, whether it’s a
cold-chain product or not, defines the
integrity of the channel. When [FDA] is
talking about getting involved, they’re
really talking about pedigree.”
Although Sinclair agrees with the need
for “a good pedigree system,” he says this
endeavor has mostly been left up to
states’ boards of pharmacy. FFF’s method
of narrowly defining the channel—from
manufacturer to distributor to healthcare
provider—contributes more to channel
integrity than any pedigree can, he says.
Sinclair does note that monitoring of
temperature during shipping “could tie
back to electronic pedigree” if RFID
technology were successfully developed.
There’s been industry talk that the
