In the world of pharmaceuticals, consumers have certain expectations, and those include that the drugs which are approved and marketed have demonstrated safety and efficacy, that strength and potency are what they are advertised to be (so, if you expect 50 mg of active drug, you’re getting about 50 mg in your prescribed dose form). And also, maybe first and foremost frankly, that the product that you receive is “real” and not counterfeit. Consumers often take this for granted, but there are thousands of people behind the scenes in the industry who are the unsung heroes of making this assumption a reality.

Regulatory themes such as the Drug Supply Chain Security Act (DSCSA) exist to ensure that the supply of drugs to market, and the supply chains from which those drugs are made, are legitimate and not counterfeited. The DSCSA has undergone revisions recently (December 7th, 2023 for verification systems for certain prescription drugs), and was itself enacted by Congress on November 27, 2013. As stated by the FDA:

Title II of the Drug Quality and Security Act (DQSA), the Drug Supply Chain Security Act (DSCSA), outlines steps to achieve interoperable, electronic tracing of products at the package level to identify and trace certain prescription drugs as they are distributed in the United States. This will enhance FDA’s ability to help protect consumers from exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful. These requirements will also improve detection and removal of potentially dangerous drugs from the drug supply chain to protect U.S. consumers.

Regarding the recent guidance (Docket Number FDA-2018-D-3462), the FDA states that it includes, among other features, “the statutory verification systems requirements that include the quarantine and investigation of a product determined to be suspect and the quarantine and disposition of a product determined to be illegitimate.”

But what happens upstream of that? What countermeasures exist to protect consumers and the pharmaceutical companies’ assets?

Track and trace

At its most basic level, track and trace is pharmaceuticals’ way of proceduralizing (systems and processes) the products’ current and past locations. This includes from the site of manufacture through distribution, to the pharmacy shelves (or clinics, etc.). DSCSA requires pharmacies (“dispensers”) to use an electronic, interoperable system that tracks a drug at the unit level throughout the supply chain until it reaches the patient. Final compliance with all requirements was needed to be in-place by November 2023, which was a 10-year roll-out period from its initial 2013 inception.

Dispensers know to only accept product if the prior owner provides the “3Ts”: Transaction information, Transaction history, and a Transaction statement.

Serialization

This methodology provides unique serial numbers to each saleable unit of a product, which includes the provenance of such information as its batch number, origin, and expiration date.


Serialization itself helped bring the industry forward to some extent, because it required that computerized systems were implemented on production lines, which wasn’t always the case. Serialization itself works in conjunction with packaging, where there needs to be information printed on primary packaging and secondary packaging.

Secondary packaging

Secondary packaging refers to the container which houses the primary packaged medicine (hence its ordinal name). As a prime example, more that three-quarters of the world’s medicines are sold in a carton (secondary packaging). The secondary packaging must be serialized appropriately, and in most cases include tamper-evident features to help ensure integrity of the drug product within.


An example of secondary packaging is seen below. Inside you’ll find the primary packaging (blister pack), and within that, the dosage form:

 

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“The industry will continue to keep evolving, and hopefully that evolution will (mostly) outpace the counterfeiters. You’re only ever one step away from being counterfeited – if that. And it’s been only a scant couple of decades since we used to wonder why bags of fast food French fries can have barcodes on them, but we couldn’t barcode materials in the pharmaceutical drug supply chain.” — Ben Locwin

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Protecting the future by adapting

In these ways, compliance with DSCSA isn’t just “nice-to-have,” but present us with the continued case whereby we can trust the medicines we buy from the pharmacy. Other anti-counterfeiting tactics include the use of holograms and other hard(er)-to-duplicate printed formats, to further add friction to counterfeiting efforts. But taken holistically, the use of serialization in conjunction with track and trace, and appropriately-done primary and secondary packaging (and robust tertiary packaging), have helped to maintain confidence in hundreds of billions of supplied drug doses over the past decade. There is a bit of competitive evolution occurring (selective pressure), where the diversionary and counterfeiting tactics get more and more sophisticated, so needing to keep up with the evolution of nefarious agents will continue to necessitate the advancing of our industry’s best approaches to these methods.

If you’ve never thought about these things before, that’s a good thing, because it means that a) you don’t have a peculiar predilection with cartons and QR codes, and b) the technologies being used are quietly going about their anti-counterfeiting ways such that they don’t burden the end consumer. But if you notice over the course of time that your medicine’s primary container (bottle) or secondary packaging (outer carton) are subtly metamorphosing, it’s a good bet that it’s in order to thwart emergent threats to the safety and security of the pharmaceutical supply chain. 

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Ben Locwin is a pharmaceutical and healthcare executive, and has worked on final dosage forms, primary packaging, secondary packaging, serialization advances, and other cutting-edge drug supply protection schemes for companies and also federal agencies.