Molecular tagging could complement DSCSA serialization by adding a physical authentication layer to pharmaceutical supply chains.
The FDA’s physical-chemical identifier guidance provides a regulatory anchor for on-dose authentication in solid oral dosage forms.
DNA-tagged pharmaceutical ink has been demonstrated in capsules using swab-based recovery and molecular detection methods.
Raw-material tracking is an emerging frontier for DNA-based tags, particularly where conventional barcodes and RFID may be insufficient.
For biologics, the near-term opportunity is more likely to center on supply chain, packaging, and material-control applications than on direct embedding of molecular tags in biologic drug products.
The Traceability Gap: Digital Records Do Not Always Authenticate the Material
Pharmaceutical supply chain security has become increasingly data-driven. The U.S. Drug Supply Chain Security Act (DSCSA) describes a framework for achieving an interoperable, electronic system to identify and trace certain prescription drugs at the package level as they move through the supply chain. The stated purpose is to help prevent harmful drugs from entering the U.S. drug supply chain, detect them if they do enter and enable rapid response to remove them.1
That digital architecture is essential, but it also highlights a deeper question: how can the industry connect the integrity of an electronic record to the physical authenticity of the product, package, coating, ink or raw material itself? Serialization, barcodes, radio-frequency identification (RFID), and electronic product tracing can provide visibility into movement and custody. Molecular tags and DNA barcodes point toward a different layer of assurance: an identifier embedded in, applied to, or otherwise physically associated with the material being authenticated.
That distinction matters because falsified and substandard medical products remain a global health concern. The World Health Organization (WHO) states that at least one in 10 medicines in low- and middle-income countries (LMICs) are substandard or falsified and estimates that countries spend $30.5 billion per year on such products. The WHO defines substandard products as authorized products that fail to meet quality standards or specifications, while falsified products deliberately misrepresent their identity, composition or source.
2
Molecular tracking therefore functions best as a complementary layer to DSCSA, serialization, and conventional supply chain controls. A physical or chemical identifier can help authenticate selected dosage forms, coatings, inks, packaging-adjacent elements, or raw materials when documentary systems alone are not enough.
From Digital Traceability to Physical Authentication
The U.S. Food and Drug Administration’s (FDA) guidance on physical-chemical identifiers (PCIDs) provides an important regulatory anchor for this discussion. FDA describes the guidance as intended for pharmaceutical manufacturers that want to use PCIDs in solid oral dosage forms. It defines a PCID as a substance or combination of substances with a unique physical or chemical property that unequivocally identifies and authenticates a drug product or dosage form.3
That definition is useful because it separates the concept of authentication from any one technology. A PCID does not have to be DNA. It could be any qualifying physical or chemical identifier that serves the authentication purpose. DNA-based tags are one technologically sophisticated example within this broader idea, and their appeal comes from several attributes: they can carry sequence-specific information, be difficult to detect without the appropriate method, and be read using molecular analytical tools. However, in the pharmaceutical context, the evidence base is not equally strong across all product types. The most directly supported examples involve solid oral dosage forms, pharmaceutical inks, film coatings, and excipients or raw-material-like systems.
A key proof-of-concept was published in PLOS ONE in 2019 under the title “Rapid authentication of pharmaceuticals via DNA tagging and field detection.” In that study, the authors introduced a small polymerase chain reaction (PCR)–generated DNA fragment into pharmaceutical-grade ink as a molecular taggant and delivered the DNA-tagged ink onto capsule surfaces by standard high-speed offset printing. The printed ink was then sampled by swabbing, and the DNA-swab complex was analyzed without subsequent DNA purification.4
The same article reported that DNA recovered from the ink by swabbing was suitable for PCR–capillary electrophoresis (PCR-CE), quantitative PCr (qPCR), and isothermal DNA amplification when paired with portable devices similar to those used in environmental sampling and food safety testing. The authors framed the work as a precedent for introducing a small DNA fragment as an excipient into a pharmaceutical application and tracking it through the pharmaceutical supply chain using forensic DNA authentication.4
That example points to the central value proposition: the tag is not merely printed as visible information for a scanner to read. It is a molecular feature associated with the product surface. Authentication therefore requires detecting the tag itself, not just reading an external code.
Why Oral Solid Dosage Forms Are Leading Early Adoption
Oral solid dosage (OSD) forms have become one of the clearest early proving grounds for molecular authentication in pharma. The FDA’s guidance on physical-chemical identifiers is specifically directed toward OSD forms, creating a defined regulatory context for considering how embedded identifiers may be used to authenticate a drug product or dosage form.3 That foundation matters because molecular tags are not simply supply chain tools; when applied to or incorporated into a dosage form, coating, or ink, they become part of a regulated product-control strategy.
Early pharmaceutical proof-of-concept work has also centered on this format. In the PLOS ONE study, researchers incorporated a small DNA fragment into pharmaceutical-grade ink and printed that ink onto capsule surfaces using high-speed offset printing. The DNA tag could then be recovered by swabbing and analyzed using molecular detection methods, demonstrating how an on-dose molecular identifier could be physically associated with the product surface rather than relying only on external packaging or labeling.4
Commercial development has followed a similar path. Colorcon’s 2019 announcement described an On-Dose Authentication capability in which molecular taggants from Applied DNA Sciences were integrated into an Opadry fully formulated film coating system, illustrating how molecular authentication can be positioned within familiar pharmaceutical coating and printing workflows.5
This OSD form focus also keeps the manufacturing conversation grounded. A molecular tag incorporated into a coating, ink, or dosage form would need to be introduced reproducibly, remain detectable over the intended period, avoid interfering with product quality, and be supported by appropriate analytical methods. Those requirements make molecular tracking more than an anti-counterfeiting concept. For pharmaceutical manufacturers, it becomes a chemistry, manufacturing, and controls (CMC) question: how to design, apply, detect, and document a tag in a way that fits within regulated production and quality systems.
The broader implication is that molecular authentication may enter pharma first through formats where the regulatory, analytical, and manufacturing pathways are most clearly defined. OSD products, printed capsule surfaces, and film coatings offer practical starting points because they can connect the physical identifier to established dosage-form technologies while preserving a clear line of sight to product control, quality documentation and supply chain investigation.
Extending Molecular Tracking Upstream
While on-dose authentication provides the most directly pharma-relevant foundation, raw-material tracking may be the more forward-looking frontier. Recent work on DNA-based anti-forgery systems points to the limitations of conventional identifiers, such as barcodes RFID, when the material being tracked is not a discrete finished product but a raw material that may be transferred, divided, blended, processed, or separated from its original packaging.6
In that context, engineered DNA mixtures could provide a material-associated authentication signal rather than relying solely on external labels or records. The approach described in that work uses DNA hybridization patterns to encode identifying information, with a paper-based readout that can fluoresce under a mobile phone and filter device. That combination of molecular encoding and field-readable detection suggests a possible path toward traceability tools that are harder to remove or falsify than conventional labels, while still being usable outside a centralized analytical laboratory.
Pharmaceutical supply chains extend well beyond finished products. They include excipients, active pharmaceutical ingredients, packaging components, processing materials, and a wide range of inputs whose origin, substitution, contamination, or diversion can have downstream consequences. Molecular tags could, in principle, allow certain materials to carry an authentication signal through parts of the chain where conventional labels are impractical, removable, or separable from the material itself.
Raw-material molecular tracking remains an emerging concept rather than a broadly established feature of regulated pharmaceutical manufacturing. The technical logic is compelling: a material-associated tag could help preserve identity through handling steps where external labels or package-level identifiers may be insufficient. Pharmaceutical use would still require product- and process-specific validation, including evidence that the tag can be applied consistently, remain detectable under relevant storage and processing conditions, avoid introducing quality or safety concerns, and fit within existing quality and regulatory systems. In the near term, selective deployment may make the most sense for high-risk or high-value materials where the added complexity of molecular authentication is justified by the need for stronger origin verification or anti-diversion controls. The most credible applications fall into three overlapping categories: anti-counterfeiting, traceability, and authentication.
Applying the Concept to High-Value Biologics Supply Chains
Biologics are an obvious area of interest because they are high-value, complex, and often move through tightly controlled supply chains. The WHO’s discussion of substandard and falsified medical products includes vaccines and cancer therapies among the types of products that can be affected.2 That makes the broader issue of biologics authentication highly relevant.
The same distinction becomes especially important for biologics. DNA barcodes or molecular tags should not be treated as established tools for direct incorporation into biologic drug products. The stronger near-term opportunity is likely to involve the supply chain around the product: packaging, labels, seals, cold-chain materials, container-associated elements, or other non-product-contact or lower-risk components that can support authentication without introducing the same level of direct product quality complexity.
Directly tagging a biologic drug product would carry a different level of complexity than applying a molecular identifier to an OSD form coating or ink. Potential questions would include product quality, analytical interference, stability, safety, and regulatory acceptability. For that reason, biologics are best understood as a high-value authentication context, with molecular tracking most plausibly applied first to the surrounding supply chain infrastructure rather than the biologic drug product itself.
What Molecular Tracking Would Require in Practice
For molecular tracking to become useful in pharma, the decisive issues will not be limited to tag design. Implementation will require answers to manufacturing, analytical, regulatory, and operational questions.
Where is the tag introduced? In existing pharmaceutical examples, the tag is associated with ink, capsule surfaces, film coatings, or model tablet systems, not broadly with all drug products.4 That matters because the location of the tag determines the regulatory and quality implications. A tag in a coating may be evaluated differently from a tag in packaging or a tag introduced into a raw material stream.
How is the tag detected? Suitability has been reported for PCR-CE, qPCR and isothermal DNA amplification using recovered DNA from capsule ink, as well as a paper-ticket fluorescence readout under a mobile phone and filter device.4,6 These examples show that detection is not only a laboratory question; field readability, operator training, cost and workflow integration may become central to adoption.
How stable is the tag? Early work supports the detectability of DNA tags in specific systems, but stability cannot be assumed across all pharmaceutical manufacturing and distribution conditions. Stability must be demonstrated for the specific tag, matrix, process, and intended use.
How does the tag fit into the quality system? Any authentication technology used in regulated supply chains must be controlled. That means defining the tag’s intended function, its acceptance criteria, how it is introduced, how it is detected, who is authorized to test it, how results are documented, and how out-of-specification or failed authentication events are handled. These are not simply technical questions; they determine whether molecular tracking can be used reliably in real supply chain investigations.
How does the tag interact with digital systems? The most compelling model is not molecular tracking alone, but layered authentication. DSCSA-style electronic traceability can document package-level movement. Conventional codes and labels can support scanning and data exchange. Molecular tags can add a covert or material-level authentication signal. Each layer addresses a different vulnerability.
A Layered Future for Supply Chain Trust
The most realistic future for molecular tracking is not a single universal tag applied to every pharmaceutical product. It is a risk-based model in which molecular authentication is deployed where the value justifies the complexity: high-risk markets, high-value products, vulnerable materials, frequently counterfeited products, sensitive supply chains, or selected products requiring forensic-level confirmation.
In that model, molecular tags would not replace serialization. They would help close a different gap: the space between the digital record and the physical thing. A serialized package can be scanned. A chain-of-custody record can be reviewed. But a molecular tag can help answer a more material question: does this object, coating, ink, or material carry the expected embedded identifier?
For pharmaceutical companies, CDMOs, excipient suppliers, packaging partners, and supply chain security teams, that shift is significant. It reframes authentication as something built into the product ecosystem rather than attached only at the level of documentation. It also creates new responsibilities. Molecular tracking would require coordination among formulation scientists, packaging engineers, analytical development teams, quality units, regulatory experts, supply chain partners, and security teams.
Those differences matter because the technology is not equally mature across every application. OSD forms, inks, and coatings currently offer the clearest pharmaceutical starting points. Raw-material tracking is an emerging frontier. Biologics create a compelling need for stronger authentication, but the most plausible near-term use cases remain packaging, labeling, cold-chain, and supply chain applications unless stronger evidence emerges for direct product tagging.
Pharma’s next generation of supply chain security may require a closer connection between electronic traceability and physical authentication. Molecular tags and DNA barcodes offer one possible path toward that connection: a way to make identity not only recorded, but embedded, detectable, and harder to separate from the material itself.
