Issue link: https://www.e-digitaleditions.com/i/1035980
34 October 2018 Tablets & Capsules cessing to amplify a 1-molecule sample from an SODF or packaging to millions of molecules and analyze the sam- ple within 30 to 45 minutes. This same PCR technology can cost-effectively produce DNA at the scale required to support widespread adoption of DNA molecular taggants by the pharmaceutical industry. A proven technology DNA molecular taggant technology has been proven in a range of other supply-chain applications, including: • more than 830,000 microcircuits for the US Defense Logistics Agency to provide counterfeit risk mitigation in critical supply chains; • 200 million pounds of cotton at nine gins in the US and Australia that supply more than 1,000 retail stores, with purity testing proven through to finished goods; • 20 million pounds of polyester and recycled polyes- ter masterbatch, tested through to finished home and auto goods fabric to prove claims of authenticity and sus- tainability; • 60,000 metric tons of fertilizer in Belgium, with detection of tagging and blending performed at the prod- uct's destination in Africa; • cash-staining dye in more than 40,000 ATMs/cash degradation devices and asset marking solutions, provid- ing supporting evidence in UK and EU courts in the con- victions of 117 criminals to more than 550 sentence years; • 60,000 luxury automobiles upon importation to Sweden, providing linkage to vehicle identification num- bers and helping to solve several crimes, including one that involved criminals operating from Sweden, Lithuania, and China selling stolen parts as new. DNA molecular taggants are formulated to be compati- ble with their host carriers and protected against environ- mental or process conditions but extractible for authenti- cation purposes. In many industrial applications, DNA authentication occurs after the taggants have been sub- jected to chemical processing or harsh solvents or cured in a military-grade epoxy. By comparison, SODF ingredients need to be digestible, so pharmaceutical DNA molecular taggants use less-resilient, more-accessible matrices such as film coatings, food-grade inks and shellacs, and hydroxypropyl methylcellulose (HPMC) capsules. Many industries and companies use DNA as an infor- mation carrier, including life sciences and healthcare, law enforcement forensics, data storage technology companies, and even national data archive organizations. This focus means that significant funding is being put into DNA technology, resulting in a proliferation of smaller, faster, less expensive, and more mobile authenti- cation methods, which may result in more widespread use of DNA molecular taggants for pharmaceutical authentication in the future. Safety DNA molecular taggants are essentially a new use for an ancient substance. The short, unmodified DNA sequences used are biochemically generated using large- The US Drug Supply Chain Security Act, the EU Falsified Medicines Directive, and other regional initia- tives have created a groundswell of industry focus on authentication and traceability of packaging for solid oral dosage forms (SODFs). In contrast, there has been rela- tively little discussion about technologies for authenticat- ing and tracing the SODFs themselves. In 2011, the FDA issued a guidance for industry titled, "Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting" [2]. The guidance primarily focuses on dosage-form iden- tification and defines a physical-chemical identifier (PCID) as "a substance or combination of substances pos- sessing a unique physical or chemical property that unequivocally identifies and authenticates a drug product or dosage form." Examples of PCID substances include "inks, pigments, flavors, and molecular taggants." A molecular taggant is a unique microscopic material added to a product in small concentrations that can be detected for traceability purposes—essentially a molecu- lar barcode. A recent development in PCID technology is the use of DNA as a molecular taggant. DNA molecular taggants can help pharmaceutical companies address the counterfeit drug problem by providing a means to iden- tify and trace both SODFs and packaging throughout the supply chain. Why DNA? DNA molecular taggants function the same way as standard digital barcodes but with far richer authentication capabilities. A traditional black-and-white-striped barcode uses the digital language of the binary system (ones and zeros) to form letters, numbers, and characters in accor- dance with standard symbologies. DNA, on the other hand, uses four molecular bases—adenine (A), guanine (G), cytosine (C), and thymine (T)—in combination to form unique sequences. To give an example of DNA's cod- ing capacity, the human genome (haploid) uses 3 billion base pairs to encode 4^(3 billion) bits of information— equal to approximately 1 gigabyte of digital code [3]. Just as different sequences of human DNA can be used to identify a unique individual, a DNA molecular taggant added to a drug product's active pharmaceutical ingredi- ent (API), fillers, coatings, inks, and/or shells can be used to authenticate and trace that particular product. The DNA molecular tags used in pharmaceutical products are orders of magnitude smaller than the human genome, typ- ically less than 200 base pairs in length. In most cases, this PCID identifier is used like a car license plate, referring to a database that contains much more contextual informa- tion about the product, such as the owner, manufacturing facility, year of manufacture, or other relevant data. DNA molecular taggants offer several benefits over other PCIDs. DNA is a common molecule that is highly resolvable. While pharmaceutical applications may use only trace amounts of DNA (approximately 10 -16 parts DNA per part SODF excipient), devices either in a lab or in the field can use polymerase chain reaction (PCR) pro-