Xavier Chaveton

The pharmaceutical sector faces increasing regulatory and economic pressures on compliance and traceability of its products. With drugs counterfeiting earning around $32 billion per year (~€26 billion), these regulatory pressures demand complete accountability from the sourcing of raw materials to the production process and the end-user.

				 This is not only to maintain brand integrity and supplier relations, but also to protect against the costly losses associated with counterfeiting and, ultimately, to ensure that the end-user — the patient — receives the best possible care. 

 Compliance with these regulatory demands creates economic pressures on manufacturers and distributors. Consequently, choosing the right marking and coding technology is a critical consideration. 

This article will look at how these pressures are brought to bear on the supply chain and and which technologies can best meet these challenges? 

The supply chain ideal is to account for the provenance of all the ingredients and the manufactured product at all stages, from raw material through to the patient's bedside. Then, if errors occur, the product in question can be traced to its point of origin or a process within its production so problems can be highlighted for correction. 

Historically, to meet this need for accountability, pharmaceutical manufacturers have generated their own codes for raw materials, ingredients, and part-finished and finished products. These codes were applied to, or marked on, the interim containers as well as all the packaging, from phials and bottles to cases. The use of codes allowed the quality standards of their suppliers and their own manufacturing processes to be effectively scrutinized and tracked. While proprietary codes worked within their own operational context, once the products entered the wider market it became very difficult to keep track of them.  

This diversity has also been vulnerable to exploitation by counterfeit drug producers. The long supply chains that occur during distribution from producer to point of dispensation are often open to substitution, switching and/or false labelling. Despite industry-wide initiatives for self-regulation in the past, true standardization and functionality were not achieved through the manufacture, distribution and dispensing systems. 

As a result, FDA has put the process on a legal footing. It has achieved this by instituting a regulation requiring drug packages entering the hospital healthcare system to display barcodes in a single format: the National Drug Code (NDC). This is intended to eliminate preventable patient errors and reduce healthcare costs. There are many other benefits including reduced manual tracking costs, improved tracking functionality and reduced costs of insurance and litigation in the event of an error. 

FDA's standard means that all drug manufacturers selling drugs to the US must ensure that their systems are totally compatible with the NDC bar code and be able to demonstrate this to FDA. This effectively has worldwide implications, as it affects most major manufacturers and is likely to be adopted by most countries outside the US. 

One case demonstrating this occurred in July 2005. UK health authorities tested and detected a batch of counterfeit statins and advised that all batches of the drug were returned to the UK manufacturer. FDA put an alert out because, although there was no evidence of the counterfeit drugs entering the US chain, some US residents were known to obtain the drug direct from the UK. 

While the FDA rule requires each bar code to contain at least the drug's NDC number, many companies are considering including other information, such as lot numbers and expiration dates. Identifying bar-coded information on each package and dose unit, integrated with a computerized database, is performed at the manufacturer and scanned at every point through the supply chain and hospital. 

Drug coding also helps with electronic pedigree compliance (FDA's 21 CFR part 211, section 211.150 distribution procedures and section 211.196 distribution records). As drug manufacturing and distributing companies move away from cumbersome paper pedigree systems, coding and data capturing technologies will eliminate manual record keeping and human error, making the process faster and more accurate. 

Control of the drug product begins with the manufacturer. There are a number of measures already well established that make drugs difficult to duplicate, such as unique dose shapes and colours. However, secure and robust coding and marking technologies form a highly important part of the solution too. 

Counterfeit drugs not only endanger patients' lives, they also destroy reputations and profits. Deliberate and fraudulent mislabelling of any pharmaceutical product to hide its true ingredients or origin is rife.  

Counterfeits may include products with the correct ingredients but fake packaging, with wrong ingredients, with insufficient or too much active ingredient or with no active ingredients at all. 

Combating counterfeiting through the implementation of a properly considered drug product-coding scheme is achieved by generating unique serial numbers for marking and tracking. This enables tracking along the supply chain, and blocks the progress of serial numbers identified as not coming from a legitimate source. 

Incorrect destinations or invalid lot codes would notify the system of the product's invalidity. Because of their capacity for large quantities of information, reduced space symbology (RSS) codes and radio frequency identification (RFID) tagging are ideal for use against counterfeiting as they are be more difficult to replicate. Using modern marking technology to achieve complex codes and images is an essential part of the security process, and new developments can improve patient safety. 

The drug codes would be cross-correlated with bar-coded identification issued to each patient on admission to hospital. This would allow drug dispensing to be matched with the patient's medication requirements and health record. 

When drugs are coded at the unit-of-use level, and when healthcare providers can easily compare product codes with codes from patient profiles, medication errors can be reduced significantly. Problems such as incorrect medication dosages, timing, allergies, medication regime changes or problems with the drug itself (such as recall or expiry) could be immediately flagged. 

The higher the quality, complexity and detail of the marking and coding, the more it provides information and enhanced protection against counterfeiting. At the same time, the variety of substrates that must be marked is continually expanding — be it the cardboard packaging or the actual drugs themselves. 

On top of this need for more complexity, manufacturers require higher speed production for increased efficiency without incurring quality or reliability penalties. Scannable codes applied directly to oral dosage formats or fluorescent markings to avoid consumer confusion may be appropriate solutions. Marking and coding technologies are evolving rapidly as manufacturers strive to meet the changing demands of the industry — but which system should you choose? 

The pharmaceutical sector can make use of the four most common marking and coding technologies: ink jet, laser, thermal transfer overprinting and RFID. 

This is dot-matrix, non-impact technology that can be used to transfer a very wide variety of codes and other information at a range of production speeds. The advances in ink jet coding machines over the last few years have greatly increased their efficiency, especially with the reduced ink usage and maintenance requirements of small character, continuous printers. 

Features such as automated nozzle cleaning and auto-flushing printheads deliver maintenance-free starts and minimize manual cleaning requirements. Speeds have increased to 4 m/s or more over this period, yet character generation and print quality have improved through better ink drop placement over increased ink throw distances, thanks to printhead design modifications. 

Ink jet technology variations include: 					

 Continuous ink jet printers that provide optimum efficiency at high line speeds and use a curtain of ink. 

 Large character ink jet printers for secondary packaging. 

 Binary array is a more recent introduction that offers enhanced coding with a high-resolution image at fast drying times and with no smearing. This is often used in high-throughput environments. 

One recent ink jet application refers to contact lens cleaning solutions. The product was unsafe if put directly into the eye — although once it had cleaned the lens it was harmless. As safety information was shown on the label, which could be obscured by the hand, and on the security wrapping, which could be discarded, it was felt additional safety coding was needed. 

Consequently, it was determined that a third warning should be placed on the shoulder of the high density polyethylene (HDPE) bottle, where it would be seen as the bottle was raised to the eye. Ink jet technology was not only able to offer consistent quality but also codes that were resistant to the solvents in the cleansing solution and could adhere to the HDPE plastic bottle. 

 refers to the production of breath strips — fragile edible films that deliver breath freshener when they dissolve in the mouth. To ensure freshness of the product and traceability, it was specified that the strips are individually coded. The solution was a non-contact print ink jet system that could deliver individual codes — whilst making use of 'edible' inks that are safe for human consumption. 

In fact, the variety of inks now available also simplifies the coding process. A specific advance is the use of invisible inks that fluoresce under ultraviolet (UV) lamps. This solves one of the dilemmas of overprinting packages where the original graphic design can be compromised by excess printed data. It also allows the manufacturer to be selective about what the customer needs to know, for example, the simple use-by or expiry dates remaining visible, while the mass of manufacturing data can be hidden. 

Industrial laser marking started in the early 1970s and is now used in thousands of production lines worldwide. Modern sealed CO

 laser coders can be used to generate all types of codes and graphics with incredible precision, as the resolution of the high-energy beam means it can be focused to dimensions within fractions of a millimetre, creating high resolution, sharp images, with considerable complexity. 

With no requirement for maintenance or consumables, laser marking is precise, permanent and non-smearing. It is ideal for printing smaller characters onto smaller items, and particularly important in printing 1D and 2D barcodes and RSS codes.  

One example is printing lot/expiry codes on labels used for asthma medication. The code height was 1.6 mm and had to be clear enough to be read by an optical character recognition (OCR) system prior to automatic packing. A clear, crisp result was achieved by laser marking through a black ink panel on the label (which ablates the black ink from the label) and used thin, precise lettering that could be easily read by the OCR system. 

Similarly, laser technology can be used when marking directly onto a product, such as a gel cap or tablet. In one instance a production line had previously used ink jet printers to mark two capsules that were presented simultaneously to the printing head, at a rate of 18 pills/min. However, as there was a variety of pills and materials on the same production line, the ink did not adhere well to all of the substrates and could often be rubbed off when in contact with other pills. 

The production requirement was for a permanent code on all the products, with minimal disruption to the existing production line. By adopting a laser solution, the permanent marking of any gel surface was easily achieved. The laser was minimally modified to the simultaneous twin-pill presentation by setting up the coding through the top and bottom lines of the marking field. The laser was directly incorporated into the line. 

Articles

This article looks at the different types of marking and coding techniques used in the pharmaceutical supply chain and their role in helping to prevent counterfeiting.