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 Solid
dosage form manufacturers have long relied on shape
and color as well as on-pill imprints of logos, product
names, or numbers for product identification. But in
these days of heightened counterfeiting concerns, the
industry has a growing interest in adding more difficult-to-duplicate
features to the pool of existing product identification
techniques. Added security is particularly important
on high-profile or high-cost drugs, as well as on pharmaceutical
products supplied in bulk for repackaging.
Advances in marking, coding, and inspection technology
have led to the development of new anticounterfeiting
tools for drug makers seeking ways to protect products
that are in pill form. The best of these versatile tools
help build brand identity and prevent medication errors
at the same time by making the product more distinctive.
Because drug makers are always concerned about making
postapproval changes to the drug product, the US Food
and Drug Administration is working on a guidance that
will clarify, and perhaps minimize, notification requirements
for manufacturers that want to add anticounterfeiting
techniques to their drug products or packaging. The
United States Pharmacopeia also has been studying the
imprinting of solid dosage forms to identify ways to
improve product identification. Its focus, however,
appears to be more on improving patient compliance,
reducing medication errors, and preventing response
delays to poisoning incidents.
Color-changing ink. Some companies are experimenting
with using a combination of color-changing materials
and laser beams to apply tiny two-dimensional Data Matrix
codes or other information such as dosage level directly
onto a tablet. The technique, which is patented in Europe
and the United States, involves the application of a
food-grade, color-changing material as a coating or
a coating additive by means of standard spray or tumble
methods.
When exposed to a low level of energy from a carbon-dioxide
steered beam laser, the color-changing material turns
black. These lasers, also known as scribing or vector
lasers, operate in the far-infrared range and generate
a 10-mm spot of energy. Using this tiny beam, sophisticated
control, and appropriate software, drug makers can apply
various images including logos, numbers, and Data Matrix
codes as small as 0.5-mm square to the product. Codes
of this size are difficult for counterfeiters to duplicate.
As an additional hurdle for counterfeiters, a different
Data Matrix code can be applied to each tablet.
Evaluations of the method are currently underway by
pharmaceutical manufacturers and suppliers of coating
and tablet production equipment. Commercial applications
are expected before the end of 2006. Future developments
could result in the application of microscopic photographic
images on solid dosage forms, a concept that has already
been prototyped. Other advances are likely to center
on food-grade formulas that transform into colors other
than black when exposed to laser energy (DataLase Edible
Laser Imaging Chemistry, Sherwood Technology Ltd., Widnes,
UK, www.sherwoodtech.com).
Microscopic markets. Another way to authenticate solid
dosage forms is by means of inexpensive, edible microscopic
markers that carry dense, easy-to-read information.
Markers are mixed with a liquid coating to enable spray-on
application.
Each marker has an irregular "Pac Man" shape
and measures approximately 16 [micro]m in diameter and
4 [micro]m thick, or nearly half the size of a human
hair. Irregularities around its circumference form a
pattern that can carry data. The patterns may be read
under a microscope or with pattern-recognition software
in machine vision systems and sensors that link to a
database for authentication. The technology also offers
multiple levels of security because modified markers
can detect physical, chemical, or biological threats
to drug products (Invisible Security Marker, Adhesives
Research, Inc., Glen Rock, PA, www.adhesivesresearch.
com; Burntside Partners, Inc., Ijamsville, MD, www.burntsidepartners.com;
reader-database, Complete Inspection Systems, Inc.,
Indialantic, FL, www. completeinspectionsystems.com).
Invisible tags. Optically and forensically invisible
markers (or taggants) are virtually impossible for counterfeiters
to detect and therefore are difficult to reverse engineer.
These odorless, colorless powder taggants are made from
an inorganic material and are used at levels of less
than two parts per million. In other words, 1-g of taggant
will cover a 30,000-[ft.sup.2] coating area.
As taggants flow with the coating fluid they arrange
themselves in random patterns that can be decoded by
a proprietary, pen-sized electromagnetic reader. The
reader uses edge-detection algorithms to record and
identify the image in 16-20 bits of code. A billion
unique codes can be stored in a 0.5 GB of memory. A
plug-and-play database system provides track-and-trace
capability from a standalone personal computer or as
a bolt-on module for an enterprise resource planning
system. Although the tiny taggants are currently targeted
for packaging materials and labels, they are expected
to be cleared as an acceptable component in drug formulations
by 2006 or 2007 (Creo Traceless Security and Authentication
system, Creo Inc., Vancouver, BC, Canada, www.creo.com).
Combination techniques
A multifaceted anticounterfeiting solution--which consists
of a combination of visual, electronic, chemical, flavor,
and aroma identification--allows overt and covert tools
to work in tandem, thus providing drug makers another
safe way to protect their products from counterfeiters.
For example, a visual tool such as a hard-to-duplicate
pearlescent coating may be combined with an electronic
identification tool such as a two-dimensional bar code
or a covert barrier (i.e., edible chemical markers that
are invisible to the naked eye). In addition, flavor
and aroma film coating additives provide unique profiles
and an additional level of authentication.
Film coating, colorant technology, and high-definition
printing and imaging systems are central to the implementation
of these tools. Transitioning to one or more of these
technologies may necessitate an investment in printing
and scanning equipment, but should add only a fraction
of a cent per tablet in material costs (Security inks
and coatings, Colorcon, West Point, PA, www.colorcon.com).
Pearlescent coatings are available in several custom
colors and provide a distinctive appearance that enhance
product branding and provide positive identification
at all supply chain levels. Strictly controlled production
secures supplies.
Several bar code inks have been tested and proven to
reproduce scannable Data Matrix codes. Successful combinations
include white ink on a purple film coat, black ink on
a red film coat, red ink on a yellow film coat, and
black ink on a white film coat. Code size and tablet
shape also affect scannability. Tests show that the
minimum size for a Data Matrix representation of a national
drug code ranges from 2.5 [mm.sup.2] for a flat tablet
to 4.0 [mm.sup.2] for a solid dosage form with complex
curves.
Bar codes can be combined with logos or numbers to
enhance recognition. With today's high-resolution printing,
logos can even incorporate coded images to provide a
product fingerprint (i.e., a covert chemical marker
added to the film coating). Such a marker provides a
means to authenticate the two-dimensional code and might
contain additional information such as manufacturer,
expiration date, and distribution channel.
Ink-jet printing. Food-grade inks combined with an
ink-jet printing system capable of high-definition microprinting
can produce alphanumerical, two-dimensional codes with
print heights of 0.8 mm. Such systems accommodate product
moving at 308 m/min. (Pinpoint inkjet coder with food-grade
ink, Domino Printing Sciences PLC, Cambridge, UK, www.
domino-printing.com).
Variable data can be printed on tablets using thermal
inkjet technology and food-grade inks. Printing may
take place on- or off-line. Variable data not only provides
an authentication tool, but also enhances track-and-trace
capability to meet electronic pedigree initiatives (Print-on-tablet
technology, HP, Palo Alto, CA, www.hp.com).
Additional two-dimensional codes. Other two-dimensional
codes also have potential for tablet marking. The technology
behind these printed codes is based on image recognition
principles and chaos theory. The printed marks may be
applied to smooth, rough, curved, or flexible surfaces
by means of laser. Data capacity ranges from 7 to >30
d; codes as small as 0.1 mm, which is invisible to the
naked eye, can be produced. Scanning requires a contrast
of less than 10% between the code and its background
and may be performed at speeds as fast as 12,000 codes/h
with commercially available equipment (2DMI, ORBID Corp.,
San Francisco, CA, www. orbidcorp.com).
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