The worrisome headlines never stop. The first seven months of 2009 brought warnings about counterfeit products such as insulin-pen
needles in The Netherlands, malaria drugs in Ghana, and inhalers in the United Kingdom. In the United States in 2008, more
than 80 deaths and hundreds of allergic reactions were linked to counterfeit heparin. According to the Partnership for Safe
Medicines (Vienna, VA), batches of contaminated heparin were detected in 11 other countries, and the death toll reached nearly
As drugmakers and their suppliers ratchet up their defenses against counterfeiters, the battlefield appears to have moved
to the dose level. At Interphex in March 2009, at least three exhibitors displayed pill-level authentication tools. On July
13, 2009, the US Food and Drug Administration issued a draft guidance document titled Incorporation of Physical–Chemical Identifiers (PCIDs) into Solid Oral Dosage Form Drug Products for Anticounterfeiting (1).
Security features are built into CPI Security Foil during the rolling process.
"FDA's publication of the draft guidance document emphasizes the need to look beyond traditional technology to prevent counterfeiting
and illegal diversion," says Dean Hart, executive vice-president of NanoGuardian (Skokie, IL), a supplier of overt, covert,
and forensic anticounterfeiting technologies. "In order to be truly effective in the fight against counterfeiting and illegal
diversion, it's extremely important for manufacturers to employ on-dose technology," he adds, noting that every layer of security
makes it more difficult to successfully counterfeit or divert a product.
FDA's draft guidance document provides recommendations about the nature of the identifier itself and about the supporting
documentation needed for new drug applications, abbreviated new drug applications, and postapproval changes. The draft guidance
document focuses on pill-level defenses involving the addition of a trace amount of an inactive ingredient with a unique physical–chemical
characteristic that makes it possible to authenticate legitimate product and visually or automatically identify counterfeit
pills. Possible additions include inks, pigments, flavors, and molecular taggants. "FDA anticipates that many of the ingredients
that will ultimately be employed as PCIDs are already used as food additives, colorants, or excipients with established safety
profiles." In fact, the document recommends "using permissible direct food additives [such as those listed in 21 CFR parts 172, 182, and 184], including those affirmed as generally recognized as safe [such as those listed in 21 CFR part 184], or those ingredients listed in the FDA Inactive Ingredient Guide" (IIG) (1).
The online or stand-alone DTS 1200 printer can add security features to blister foil.
Caution should be used when selecting an ingredient that is not included in these lists or one that might cause an adverse
effect such as an allergic reaction or irritation. The draft guidance document also notes that PCIDs should be used at the
levels prescribed in the IIG or CFR chapter on direct food additives and should not interfere with the release rate of modified-release products.
Labeling changes may alert healthcare practitioners and patients to the presence of a PCID, but are not required. However,
labeling changes are subject to reporting and approval requirements under 21 CFR Part 314.70.
Solid dosage forms can be linked to the die that made them by comparing surface images.
Other provisions include "recommendations regarding (1) evaluation of toxicological and other concerns for PCIDs that are
incorporated into packaging and labeling and (2) procedures for reporting or requesting approval to add PCIDs to packaging
and containers as a postapproval change" (1).
A packaging-related PCID should not adversely affect the quality, performance, or stability of the solid oral dosage form.
If toxicology has not been established for the proposed PCID, then the manufacturer should provide assurance that the identifier
does not migrate into the solid oral dosage form.
According to the draft guidance, the addition of a PCID to packaging can be handled as a postapproval change. If the PCID
is a permitted direct or indirect food additive, listed in IIG, or previously approved for use in primary packaging, the addition
can be noted in the company's next annual report. If the PCID does not meet one of these criteria, the change may be submitted
on a CBE-30 supplement that should include data addressing toxicological concerns and provide assurance that the PCID will
not migrate into the product.
"If the safe use of a PCID cannot be ensured (i.e., if the toxicology has not previously been established and migration potential
exists), the applicant may not market the drug product using the PCID in primary or secondary packaging unless a prior-approval
supplement is submitted and approved" (1).
FDA accepts comments related to guidance documents at any time. To be considered by agency personnel preparing the final version
of the document, however, comments should be submitted by Oct. 13, 2009.