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 150 worldwide.
"FDA's publication of the draft guidance document emphasizes the need to look beyond traditional technology to prevent counterfeiting and illegal diversion," says Dean Hart, executive vice-president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.Physical–chemical identifiers
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 The draft guidance document also notes that PCIDs should be used at the levels prescribed in the IIG or CFR chapter on direct food additives and should not interfere with the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.
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According to the draft guidance, the addition of a PCID to packaging can be handled as a postapproval change.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.