Unit Operations / cGMPs / QRM Process

Drug Security Gets (Nano-) Granular

Advances in nanoencryption technology have made on-dosage security more feasible and more affordable, says Dean Hart of NanoInk.

As the drug product security landscape broadens, many manufacturers are looking beyond packaging-level security features and looking for ways to secure the actual drug product itself. Advances in “on-dosage” technologies have made them feasible complements to tamper-resistant packaging, barcoding and other traditional security features.

NanoGuardian (a division of NanoInk, Inc.; Skokie, Ill.) has been at the forefront of the on-dosage movement. Pharmaceutical Manufacturing recently spoke with Dean Hart, the company’s executive vice president, about current challenges and market opportunities.

PhM: For those who might not be familiar with the company, tell us a little bit about the genesis of NanoGuardian.

D.H.: Certainly. The company really started about seven years ago as NanoInk, and the genesis of the company really was the focus on a proprietary technology dip pen nanolithography, or DPN. This technology was perfected through an alliance that NanoInk has and continues to have with Northwestern University School of Nanotechnology, one of the foremost leaders in the field of nanotechnology. And the key behind that was really the ability to take and place molecules ... on predefined substrates within a given pattern. And it has the greatest application within research and development. 

And at that point in time, individuals within the organization, many who had a strong pharmaceutical backgrounds, realized that the R&D component of our DPN, which is still very, very strong for us, was just one application where this incredible technology could be used, and so given their experience in pharma, and given the increasing concerns over counterfeiting and illegal diversion, looked at the ability to take that technology at its basic level and really evolve it into something that could be used to help manufacturers and authorities fight counterfeit medications and illegal diverted products. So over about four years of R&D on our part, we have now come up with what we term a nanoencryption technology, and we’ve perfected our technology. 

And basically, at the simplest, to kind of dumb it down, this technology applies directly to tablets, capsules and vial capsules. We are on-dosage technology, and we have a multilayered security feature, so we have overt and covert, which are used more on the authentication side and the counterfeit side of things. But then, at the deepest level of our technology is the forensic level, which is the nanoscale level. We place what we call nanocodes on dosages, on tablets, capsules and vial lids, and these nanocodes can be associated with an unlimited amount of information, both manufacturing data such as manufacturing date, location, batch, lot, strength, expiration date, as well as distribution data such as what specific country was this distributed in, and even to the extent of which particular distributor or wholesaler or retail chain, if you will, should the manufacturer determine that to be the case.

PhM: If you don’t mind, let’s break this down in terms of some of the things that you’ve just brought up. Explain a little bit more about what nanoencryption technology is and what it actually means to put a nanocode on a dosage, say, for example, a capsule, a tablet. Tell us as much as you can without, obviously, sharing too much with counterfeiters and your competitors.

D.H.: [Laughs.]  Certainly. ... First and foremost, we add nothing to the dosage. We add no chemicals, we add no additional product, if you will, to the particular medications that we’re encrypting. What we do is we have perfected a manner by which we make manipulations in the coatings of those tablets and capsules and vial caps, and by doing so, we’re able to, at a very high throughput — over a million encryptions per eight-hour period — be able to place our multilayered security features actually on the dosage. So manufacturers like it, and the fact that because we’re not adding anything, the development required and the regulatory requirement work that needs to be done is significantly minimized. ... 

PhM: So it’s a feature that’s on the surface of the dosage?

D.H.: It is on the surface of the dosage, exactly. And our nanoencrypter machine ... typically sits within the manufacturing line right before packaging. So the product is complete, it goes through our nanoencrypting, we place the nanoencryption codes and the other security features on the dosages, and then they go into the appropriate packaging.

PhM: And then how is the data read, and where would it be read if a manufacturer had your technology?

D.H.: There’s three different layers of security features. The first feature is an overt feature, and that can be seen with the human eye. We actually call it semi-overt, because if you didn’t know what you were looking for, you wouldn’t see it. But if you did, you would know that this particular medication or particular dosage had been encrypted. And the second layer is a covert feature. Now, both of these, the semi-overt and the covert, are used for authentication at the field level. And from that perspective, let’s say a manufacturer or a pharmacist, would be able to either use a loupe or a handheld microscope, 40x microscope let’s say, and be able to see the secondary forensic — excuse me — covert security feature, which is actually at the micron level, and be able to determine that this is an authentic tablet. 

Now, the third feature is where our nanocodes come in. And because we are at that nanoscale level, there’s really nothing, from a handheld perspective, that can be used to read that. And that’s seen by our organization as well as my clients as a good thing. And where we do that is at our NanoGuardian Authentication Center, the first of which has been established here in Skokie, Illinois, right outside of Chicago in our home office. 

PhM: So if you’re working with a large pharmaceutical company, and they had a product that was nanocoded, the product would have to go through your center?

D.H.: The product center, our center. And within hours of being able to receive it, not only can we quickly authenticate it ... but we would be able to read the nanocodes, report back those nanocodes, and we do that in a nondestructive fashion. So comparatively to, say, HPLC authentication methodologies and other chemical authentication technologies, ours is nondestructive. And not only does it authenticate, but what it also does is, again, it tells them all of the distribution and manufacturing data for that particular dosage that simply they cannot get today without something like our technology.

PhM: It sounds like a lot of data. And you know one of the issues that manufacturers have when they’re trying to track their products and trying to ensure security is how to handle all that data and how to manage it, how to integrate it with bar coding and other things that they might have on their packaging. What do you tell them in terms of how to manage this additional data?

D.H.: Well, and that’s a very good question. The key to any security feature is layering. And when we look at our technology, we believe our technology is very complementary to what’s being done on-package, if you will. And I think the nice thing is that our nanocode is just that: it’s a code. And that code is associated with an unlimited amount of data, as defined by the manufacturer. And every piece of this information, including whatever the e-pedigree initiative that they might be implementing for their on-package technology can be included in this nanocode. So we can capture an RFID code or tag or, for example, a 2-D bar code that can be associated with each of the dosages. And in addition, other information that they’re already capturing can be easily associated with our particular code. 

So we look at ours as being more complementary rather than additive ... they’re already capturing the information within other systems, and they simply have to utilize that system, or we actually are developing a software platform that will pull from those other disparate systems to feed into here, and then they will have everything that they possibly need within the NanoGuardian system to be able to couple our codes and associate our codes, if you will, with all that other information.

PhM: Forgive me for saying this, but it sounds expensive, which is a concern for a lot of manufacturers.

D.H.: It actually is not. We’re fractions of a penny per tablet. ... But the key is, what are you paying for? And I think you have to look at it not only as the raw expense, but also the benefit. I mean, today you have a technology in our technology which can not only authenticate at the field level, but can also trace back every single dosage that is manufactured by that particular organization.

And really, if you will, take a look at e-pedigree technologies, whether it be RFID, 2-D barcode or some other mass serialization technology, and what it ultimately tells you is that this is the exact same pallet, case, or bottle that came from the factory. And hopefully, sometime in the future, when all of the technology and databases are in place and processes are ferreted out, it will tell you where that particular packaging has been. But really, at its basic level, it does not tell you where that medication inside that package [has been]. That is an assumed acceptance of risk, if you will. 

... If you take a look at the cost for our technology, which is fractions of a penny per pill, and you place that in the overall benefit of being able to not only authenticate every dose, but also to be able to determine for every single dose where it came from, when it was made, what the expiration date is, what the strength is ... all of our clients have looked at that and said that it is certainly well worth the value. It’s a very strong cost-benefit ratio, if you will.

PhM: I think you would probably say that it can certainly complement RFID and bar coding, but are you also saying that it might actually replace them, in some instances?

D.H.: No, absolutely not. And I think your first statement is exactly correct. A security plan, whether it’s for a pharmaceutical manufacturing, your computer, your home, whatever, a financial institution, layering is the key. E-pedigree initiatives are absolutely important to be able to provide a greater security of that package flow throughout the system. Our concern is that e-pedigree, once that medication is repackaged — which happens in excess of 95% of the time here in the U.S., and of course repackaging is also supported through the EU in order to support parallel trade — all of those technologies are gone, they’re lost. ...

And so the question is, what happens then? And that’s really where a technology like NanoGuardian comes in. You wouldn’t be able to track NanoGuardian throughout the supply chain, because it’s in the bottle. It’s just not feasible. On the other hand, whereas the drawback of e-pedigree technology such as RFID and 2-D bar code is that their protection is lost the minute they’re repackaged, well, that’s where NanoGuardian’s technology picks up. So it’s very complementary.

PhM: And that obviously leads into the topic of what has been the acceptance and interested from manufacturers, as much as you can tell us, and how are they coming to you? What’s the impetus for them coming to you, really?

D.H.: In 2008, we’ve really seen an increase in the awareness of NanoGuardian and our technology, and I think the appreciation of that technology. And first of all, I think it’s important that really, until this year, our technology was very much a ... nice concept. In February, we passed a factory acceptance test for our nanoencrypter for our number one client, who is a top ten pharmaceutical manufacturer, and we were able to have a proven throughput of one million encryptions per eight-hour time frame. Now, that’s one of the fastest nanoencryption performances period, in the world. So we went from a great concept to actually being commercially viable right there. 

In May of this year, our first client also received approval from the FDA for an sNDA [supplemental NDA] that was regarding the application of our nanoencryption technology to one of their blockbuster products. So now that was a next step, if you will, in the overall commercial viability of our technology. 

And I think what we’re also starting to see is people understanding that whereas on-package technologies are extremely important and need to be part of the overall brand protective mix, they’re not the silver bullet. And neither is NanoGuardian. But if we look at the recent Buyer-Matheson Bill that came out last year, entitled the “Safe Guarding America’s Pharmaceuticals Act of 2008”, in that particular bill they even state that 18 months after the enactment of this bill there needs to be a report done evaluating on-dosage technologies. 

So what we’re starting to see, I believe, is a wave of looking and saying, okay, what is the next step in security. And it has to be on-dosage because, again, the ultimate consumer in the supply chain is the patient, and e-pedigree technologies, quite frankly, stop the minute that the product is repackaged. ... We have a number of top ten pharmaceutical manufacturers, and even a larger number of the top 20 pharmaceutical manufacturers that not only have we spoken to but that are in different stages of evaluation. ... We expect to have a number of products that are nanoencrypted entering into the marketplace, the first by the end of this year, and several more by the beginning of next year.

PhM: And as you continue to grow, explain how your company might have to grow, at least geographically. You mentioned earlier that anything that is nanoencrypted has to go through your center in the Chicago area. Is that going to continue, or is it likely that you’re going to have to branch out and have other stations geographically?

D.H.: We also have already generated plans to open up authentication centers not only across the U.S., but also globally. The important thing is, in a suspected counterfeit case, time is of the essence. And so we have clients across the world that ... want to know that we’re going to be able to service them, and service them appropriately. 

And we’re very fortunate to have the appropriate funding. We’re a privately held organization, but we are privately held by a very strong foundation here called the Lurie Group in Chicago, and they’re very supportive of healthcare initiatives. They believe in what we’re doing and the value of what we’re doing, and we have big plans. ... We will be expanding our authentication centers, and then obviously looking at the importance of expanding into other countries, as necessary, from a commercial perspective.

PhM: You also mentioned earlier software and having some kind of data solution for this. Where are you in the development of this?

D.H.: We’re working to build that as we speak. And we believe that we’ll be ready to go when our first product goes live here at the end of the year.

PhM: Would this program be able to integrate to other programs that are key to manufacturing?

D.H.: Oh, absolutely. It must be. ... Our system will be able to pull from and interface very easily with other standard systems that are out there, whether those be ERP systems or production specific systems, to be able to feed and pull that information in and associate it with the particular nanocodes, and again, be completely customizable by the manufacturer so if there’s particular data they want to capture on Product A that might be different from Product B, they have the ability to do that and to do that very easily.

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