Counterfeit drugs: why on-dose authentication offers the most viable solution (part I)

Leading excipient and film coating manufacturer Colorcon has developed a solution to help in the fight against fake drugs through the inclusion of taggants embedded onto individual pills … and the use of smart readers to track and verify branded/authentic products

The issue of counterfeit drugs is moving higher up the pharmaceutical agenda owing to COVID-19; the ongoing pandemic is massively increasing the rate of online drug sales through illegal websites.

In the UK, for example, the problem will only get worse when we leave the EU and the Falsified Medicines Directive ceases to apply. Manufacturing Chemist’s Dr Kevin Robinson caught up with Colorcon’s Chief Scientific Officer, Dr Ali Rajabi-Siahboomi, and Global Product Authentication Lead, Gary Pond, to discuss the latest developments.

KSR: Wasn’t the serialisation and widespread implementation of track and trace legislation, which is now in place around the globe, intended to combat the problem of counterfeit drugs?

ARS: Manufacturing companies have put huge resources into meeting the legal requirements for serialisation and have seen benefits in terms of track and trace, but the supply of counterfeit drugs continues to rise.

Dr Ali Rajabi-Siahboomi

For instance, The Pharmaceutical Security Institute in the US estimates that during the past 5 years, the supply has increased by approximately 70%. Complex supply chains for many pharmaceutical products make them vulnerable to counterfeiting and diversion, and any security system focused solely on the packaging is open to abuse.

For criminals, counterfeiting is a low risk/high reward, with lenient sentences and the potential to make millions of dollars in successful operations.

Earlier this year, for example, Italian police seized 84 million Captagon pills that were allegedly produced by ISIS in Syria and contained amphetamines worth more than $1 billion.

Chinese efforts to restrict precursor chemicals used in making fentanyl (for illicit products) may be contributing to the rise of India as a supplier of fentanyl and fentanyl ingredients, and Mexican cartels are also getting in on the act. In 2019, more than 2000 products in a range of therapeutic areas were targeted by criminals.

KSR: What has been the impact of COVID-19?

GFP: There is widespread agreement that the Internet is the primary market for counterfeit pharmaceuticals. The World Health Organization has said that more than half of all drugs purchased from online pharmacies are potentially counterfeit, and 100% of online searches for medicines return links to illegal websites.

Since the beginning of the pandemic, online sales have increased dramatically and there’s compelling evidence to show that legitimate online pharmacies are several weeks and thousands of daily registered domains behind the scammers.

Every type of medicine is at risk of falsification; and, although counterfeiters often target lifestyle drugs, life-saving medicines are the fastest-growing category.

The Royal Pharmaceutical Society is also warning that the UK could see an influx of counterfeit medicines at the end of the Brexit transition period on 1 January 2021.

Criminals view Brexit and the COVID-19 pandemic as an opportunity to expand their operations. The widespread use of tablet presses means that we’re now dealing with counterfeiters who can change production and ingredients rapidly to satisfy market demand.

They are also using sophisticated printing technology that can easily replicate much of the on-package security that is being implemented with serialisation.

We believe that serialisation is important and that, as it matures, it will be a valuable track and trace asset; but, we need to expand our product security solutions to continue to improve patient safety.

Gary Pond

The COVID pandemic has resulted in a greater reliance on digital interactions and that lack of human connection harms consumer trust. Our goal is to give supply chain partners, caregivers and even patients the technology to show that their medication is real.

KSR: I’ve often questioned how workable serialisation can be in more remote parts of the world, so on-dose authentication and the use of smartphones seem like a good solution. How close is that to becoming a reality and what’s the prognosis in the new normal brought about by COVID?

GFP: Fortunately, it's not just a matter of proof of concept anymore – we’re beyond that. The technology is now available and could easily be implemented across the world.

We’ve been working with two different types of taggants, one produced from non-biologic DNA and one from silica. These taggants are not detectable with human senses, they are used in very small quantities and are easily detected using field instruments. A smartphone app is currently in development for real-time detection of the silica taggants.

Both taggant technologies are inactive, safe to use and easy to apply and detect. The structure of the DNA taggant means that different sequences of the same DNA molecule can make this product specific.

In effect, you can code to make it identify with a company, specific region, or individual manufacturing location, and these codes can then be detected using specific reagents (like a lock and key mechanism).

To add either DNA or silica taggants to tablets and capsules is simple, they are simply incorporated into the film coating that is applied onto the tablet, or into the ink used to print on the surface of the tablets or capsules. This is quite a straightforward process.

ARS: From an application point of view, we’re making it as simple as possible by leveraging current film coating and printing technologies. This means no new capital investment is needed and the manufacturing process stays the same; the tablet coating or capsule printing will be done anyway, so it's just a matter of the addition of the taggants.

The silica tagging technology differs from DNA in that it uses microparticles that are spectrally encoded and can be detected by the way they reflect light.

The interesting thing about silica is that it’s already used in the majority of tablet and capsule formulations. Silicon dioxide is typically used as a flow aid in core formulations as well as in many of our film coatings.

The development of these technologies using Opadry film coating is now at an advanced stage in terms of stability, application process and detection methods; and, through the SoteriaRx on-dose authentication platform, we’re ready to bring these solutions to the market.

KSR: In the case of DNA, how stable is it, for how long and in what conditions?

ARS: DNA molecules are complex structures made of nucleotides and their sensitivity to environmental conditions is well understood. There’s a large amount of data that demonstrates the stability of DNA for very long periods, and DNA technology has been used for many years in courts of law for legal cases.

We’ve tested coated tablets to demonstrate that the detectability and integrity of the DNA remain consistent throughout the shelf-life of the product and we have supporting data to confirm that standard manufacturing procedures don’t damage the DNA.

Also, we have developed know-how around the application process and cleaning procedures to ensure that no residues of DNA taggants are left, which could contaminate the next product in manufacturing lines. The same goes for the silica taggants, which are equally stable throughout a typical manufacturing process.

KSR: I'm assuming that because you’re not making any fundamental change to the production process, manufacturers using the tagged coating wouldn't have to revalidate their process to use it. Is it also safe to assume that the integration of the taggants does not affect the friability or the dissolution and disintegration of the tablets themselves?

ARS: The application of the taggants in coating or inks is seamless from the start to the finish of product manufacture.

The only thing that manufacturers need to do is validate their cleaning procedure to ensure no residues of taggants are left at the end of a batch, and we can provide support to assist in this.

Some companies may not want everybody in their manufacturing plants to know that the product has been tagged, and we can offer guidance on how to best manage this.

Even though the use of taggants is not a safety issue, manufacturers must notify the regulator that a product has been tagged as part of their annual disclosure.

There is a DMF (Drug Master File) and we’re already in discussions with the US FDA, so from a regulatory point of view, we don’t feel that there’s any significant hurdle to either the DNA or the silica approach. We can provide full advisory support to a client’s regulatory department to ensure smooth implementation.

The questions that might be raised by manufacturers will no doubt revolve around whether the use of taggants will affect how the coating is applied, if it will affect the stability of the product and/or the disintegration or dissolution.

Because the quantities of the taggants that are added to the film coatings or inks are small, there is no impact. There’s also the question of changes with time – do you get any instability; does it cause any degradation or any impurities? Again, the answer is that there's no impact on stability and we have not seen any evidence of degradation or impurities.

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