A new draft guidance recently issued by the FDA regarding the use of inks, pigments, flavours and other physical-chemical identifiers1 means that a unique form of micro-tag technology developed by ARmark Authentication Technologies, LLC and Colorcon Inc. can now be applied to solid dose drug products to help fight counterfeiters and aid product traceability.

Q1: How is the technology developed by ARmark and Colorcon used?
ARmark's On-Dose ID covert markers, or micro-tags, act as a hidden fingerprint that contains a significant amount of information in a space of 75 to 110 microns — smaller than the diameter of a human hair. The information included in the micro-tag is specifically designated by the brand owner and proves that a product is authentic. Including data such as country codes and batch codes provides added intelligence about how a product moves through the supply chain to identify breeches leading to counterfeiting or diversion.

These tags are seamlessly incorporated directly into the film coating of a solid oral dose form, and enable manufacturers to follow their existing production processes and avoid additional machinery investments. Invisible to the naked eye, the micro-tags are identified with ARmark’s vision systems; hand-held, portable devices that magnify the micro-tags and enable accurate, in-field detection within a matter of seconds, without destroying the sample.

The micro-tags are virtually impossible to replicate or reverse engineer, and are compatible with other covert/overt identification technologies.

Q2: What principal advantages does the technology offer compared with other anticounterfeiting measures?
Adding micro-tags as physical-chemical identifiers (PCIDs) to an existing film-coated tablet enables drug manufacturers to quickly protect their products with unique data without changing existing processes or equipment.

The FDA’s draft guidance states that the post-approval incorporation of PCIDs is now considered to be an annual reportable (SUPAC Level 1) change. This enables pharmaceutical manufacturers to use micro-tags in an anticounterfeiting strategy without prior approval from the FDA when several critical considerations are met. One criteria is that the micro-tags must comprise approved excipient materials generally recognized as safe (GRAS) or included in the Center for Drug Evaluation and Research’s (CDER) Inactive Ingredient Guide (IIG) of approved substances. Another is that the micro-tags are intended to be added as a post-approval change to the tablet coating process without any modifications to the existing manufacturing process or product formulation. ARmark manufactures the micro-tags under cGMP conditions in a Class 10,000 clean room using a proprietary process.

Some other on-dose authentication techniques, conversely, require a manufacturing process change to apply the technology, leading to a more complicated, and timely, regulatory filing path with the FDA.

The micro-tag technology is not limited to use for on-dose application; it can also be integrated into product packaging, giving the brand owner added confidence of the product’s authenticity. Micro‑tags can also be formulated to be loaded into the materials used for drug blister packs, plastic labels or films, or can be applied to RFID labels.

Q3: The technology was developed through an alliance with Colorcon. How did each company contribute to the technology?
ARmark invented and owns the micro-tag technology, but partnered with Colorcon to benefit from the company's strong expertise in film coating technology and their excellent technical service reputation.

Colorcon developed a number of model studies to evaluate the inclusion of the micro-tags into various film coating systems, and determined the optimal methods of incorporation into existing manufacturing processes. In addition, Colorcon performed dissolution and stability studies on model drug products to provide supporting data indicating that the incorporation of the micro-tags into the film coating had no effect on drug product performance.

Q4: Since the FDA draft guidance was introduced, how have companies responded to the technology?
We have seen a marked increase in the number of major pharma companies contacting Colorcon or ARmark to begin investigating how they can take advantage of the flexibility provided by the FDA to incorporate these micro-tags. There was significant interest in the covert micro-tag technology prior to the new guidance, but some companies have been hesitant to advance because they were uncertain of the FDA’s position.

The guidance now provides a clear regulatory path for implementation because the FDA is encouraging the use of PCIDs, such as the ARmark micro-tags on drug products. This provides companies with the flexibility to incorporate these into film coatings on drug products as a low-risk way to increase product security without affecting drug product performance.

Q5: How does European legislation affect the use of physical-chemical identifiers on pharmaceutical products?
Currently, European legislation allows these types of micro-tags to be used; however, it does fail to provide the same flexibility that the FDA established in its draft guidance. Some labelling requirements in Europe state that there must be a notice on the product that says covert micro-tags are used. This type of labelling is often undesirable because it brings attention to the use of a covert technology and potentially puts the product security at risk.

Q6: Some companies have been slow to embrace anticounterfeiting measures. Why do you think this is?
Pharma companies are conservative and heavily regulated. They have been actively investigating different types of anticounterfeiting measures, but have also been waiting to understand the position of the FDA, or other regulators, regarding the use of these technologies. The FDA draft guidance answers many previously unanswered questions.

Also, every company has its own, confidential strategy for combating counterfeiting or diversion of their products. While it may appear that companies have been slow to adopt measures, we need to remember the extreme importance of confidentiality.

Q7: There are already different forms of anticounterfeiting technologies available to pharmaceutical companies. Do you think these are being used to their full potential?
Pharmaceutical companies are taking counterfeiting quite seriously; however, some are still confused by the regulatory guideline while others are reluctant to spend money on what is just an added cost of production unless they can clearly identify the dollar return. As this global problem continues to grow, however, most pharma companies will begin implementing initiatives that involve multiple layers of protective technology.

Q8: As well as covert micro-tag technology, what other anticounterfeiting methods do you think offer the most promise?
Other on-dosage technologies such as pigments, flavours and inks can be used to provide overt protection for the drug, which helps detect counterfeits.

It really is up to the brand owner to identify what their problems are and which of the available technologies provide the best solution to meet their needs. In any case, companies should at least be considering a layered approach that combines overt and covert features for added security.

Q9: Despite improvements in anticounterfeiting technology, counterfeit drug sales are still increasing. Why do you think this is?
First, many drugs products lack anticounterfeiting technologies, which makes them a target; second, the drug counterfeiting penalties are still too low and counterfeiters see it as a low-risk business with potentially large financial gains.

As more pharmaceutical companies adopt covert technologies, it will become more difficult for violators to integrate their fake products into the supply chain. These technologies will also provide companies and governments with the necessary proof to combat, subdue and prosecute these criminals.

Q10: Is it possible to completely eliminate the threat of counterfeits?
Eliminate? No. However, is it realistic for companies to limit the impact of counterfeit drugs to their patient population by incorporating a layered technology approach to better secure their supply chain.

www.rmark.org
www.colorcon.com

Reference
FDA Draft Guidance — Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting, July 2009.
www.fda.gov