Lack of a co-ordinated global track and trace solu-tion continues to leave the pharma supply chain in a vulnerable position. Hilary Ayshford reviews latest developments
There are few industries where the security of the entire supply chain is as crucial as it is in the pharmaceutical sector. Whether the risk is from a faulty batch of drugs, medicines past their expiry date or counterfeit product, the ability to track, trace and authenticate pharmaceuticals from point of manufacture to point of consumption has never been more important.
Last month a further batch of fake Lipitor tablets was discovered in the UK - the second incident in as many months. Both batches were reported to carry authentic Lipitor numbers, so patients were unable to tell whether their tablets were fake or real.
Pfizer, the manufacturer, called for more effort to be made by authorities in the UK and Europe to ensure the safety of medicines. "Enough is enough," says Pfizer UK's managing director Dr Olivier Brandicourt. "We are calling for the MHRA and law enforcement agencies to conduct a full and thorough investigation into this incident and the general vulnerability of the medicines supply chain."
But the approach to finding a solution varies significantly around the world. US manufacturers are turning to radio frequency identification (RFID) technology to establish an "e-pedigree" for their products, whereas in Europe the trend is more towards effective coding and marking solutions, notably datamatrix codes applied by laser.
"From the point of view of pharmaceutical manufacturers, all sorts of things can be damaged by counterfeiting," said Lee Metters, pharmaceutical sector development director at coding and marking specialist Domino. "It is a great concern to the industry and we are now moving from the stage of lots of individual strategies to having a number of international bodies putting together coherent strategies. But those coherent strategies are at a very early stage of implementation.
"Coding and marking is like DNA in preventing counterfeiting and parallel trade because if you can identify the product you can then have an idea about how you control it. If you can't identify the product in a consistent way, how do you know if it's real or fake?"
In 2004 the FDA's Counterfeit Drug Task Force reported "an increase in counterfeiting activities and a more sophisticated ability to introduce finished dosage form counterfeits into legitimate drug distribution channels". In its first report in 2004 it stated that widespread use of electronic track and trace technology would help secure the integrity of the drug supply chain by providing an accurate drug "pedigree". It identified RFID as a promising technology as a means to achieve e-pedigree, and said that widespread adoption and use of electronic track and trace technology would be feasible by 2007.
However, take-up of RFID has been slower than expected and implementation of e-pedigree by the target date is unlikely, according to the recently published 2006 update to the report. Industry consensus in the US is that e-pedigree can be achieved using either RFID or barcodes, with the majority agreeing that it is necessary to adopt mass serialisation with unique identifiers on each package as an important step to facilitate e-pedigree.
"We understand the complexity in moving toward an e-pedigree and recognise that a hybrid approach using both paper and electronic pedigrees will be needed during a transition period," the report says. "We continue to believe that RFID is the most promising technology for electronic track and trace across the drug supply chain. However, we recognise that the goals can also be achieved by using other technologies, such as 2D-barcodes."
The report cites a number of obstacles to wider adoption of RFID, including a lack of standards for e-pedigree fields and format, data systems, international transmission standards and hardware specifications; privacy concerns; concerns about the ownership of confidential business transaction data; challenges in serialising all products; concerns over the accuracy and speed of electronic devices and systems; and a lack of definitive data to determine how RFID will affect sensitive products such as liquids, biologics.
"We are encouraged by the progress that industry has made to develop and adopt universal standards," said the report. "Once completed, we would expect to see a rapid growth in the implementation of RFID in the drug supply chain."
Mass serialisation - the incorporation of a unique identifier number on each individual drug package in order to track it as it moves through the drug supply chain - is a powerful tool in securing the nation's drug supply, according to the Task Force. But there are complex issues surrounding which numbers should be included in this unique identifier. For example, the National Drug Code (NDC) number is ubiquitous as an identifier of drug products but patient privacy and supply chain security could be compromised if it could be read surreptitiously.
These concerns can be addressed through IT solutions, the report suggests, and it therefore believes that for drug product packages using RFID or other non-line-of-sight technologies, the unique identifier should either include an encrypted NDC number or provide an accessible link to the NDC number that is readily available to pharmacies.
Whereas the FDA Task Force has stopped short of mandating RFID, the board of The European Federa-tion of Pharmaceutical Industries and Associations (EFPIA) last November came out in support of a 2D (datamatrix) system as a standardised and unique coding of medicines system across the EU. The pur-pose is to avoid different coding solutions being adopted in the EU Member States that would drive up production costs and limit production speed.
The recommendation was made by an informal ad hoc group representing a number of industry organi-sations with the mandate to assemble in a co-ordinated manner the respective industry associations" objectives and action plans in the fight against counterfeit medicines.
"With the Efpia system you wouldn't be able to prove that every pack is genuine, but you could prove that every pack is unique," Metters points out. "So if a counterfeiter produces a copy it has to be consistent with what is held on the database and if that shows that the original packet has already been dispensed then an alarm will be triggered."
Another group to come down firmly on the side of datamatrix codes is The European Association of Pharmaceutical Full-Line Wholesalers (GIRP). "Pharmaceutical full-line wholesalers are very concerned about counterfeits and advocate progressive actions on the ways to ensure that counterfeit medicines cannot enter the trusted legitimate supply chain," says GIRP.
The organisation keenly promotes the development and maintenance of a close, interlinked, collaborative early warning and information system involving health authorities, manufacturers, pharmacists and all other stakeholders. One of the main actions it advocates to achieve this is the development of a harm-nised tracking and tracing system.
However, Europe still lacks the affordable, proven and effective technology that would allow for the implementation of a seamless track and trace procedure throughout the supply chain without resulting either in sky rocketing costs or unacceptable delays for pharmacies and patients, says GIRP.
But the implementation of a harmonised track and trace system is about more than reducing counterfeiting - it also has the potential to improve delivery times, increase warehousing efficiency and cut distribution costs.
"The pharmaceutical industry is changing," asserts Metters. "In the past manufacturing efficiency wasn't important - manufacturing and distribution were seen as necessary but were not the focus of attention. Now we are finding that pharmaceutical companies are becoming much more interested in cost and efficiency." For example, the requirement to produce different batches for individual markets results in numerous coding and marking changes in the course of a day. "If it takes half an hour to change a piece of equipment, the effect on efficiency can be very great" he points out.
The key objective for pharmaceutical full-line wholesalers is to have harmonised, machine-readable data on every pack of medicine. These data are essential to capture automatically the relevant product information within the workflow in the warehouse. The national identification number, expiry date and batch number in machine-readable format are prerequisites for any kind of coding system, the organisation states.
In the future, RFID technology and its tags as carriers may allow wholesalers to automatically identify products. However, even though RFID could bring significant advantages to tracking and tracing of medicines in the future, it has presently proved not to be a technology mature enough to be embraced on the short run. Due to current technical difficulties, GIRP considers RFID to be a solution for the future.
The point of manufacture is the best place to apply codes to give proper traceability, which is where Domino sits. When it comes to the code format and the technology used to apply it, Simon King, director of Domino's Integrated Solutions Group, describes the company as "agnostic". As its name suggests, Integrated Solutions is aimed at supplying a total solution for an application, consisting of a coding system, verification system and data management.
"For example, on a complete packing line there might be a laser applying a data matrix code on the blisterpack, then a laser or an inkjet printer applying a data matrix code to the carton. The individual cartons go into a shipper and again the shipper has a unique ID relating to the contents," King explains. "We are looking at what the customer really wants to achieve. In some cases RFID will be the right solution, in others it won't - we try to select an appropriate code carrier."
One of the challenges is that the method of coding does not always give a clear result, leading to unnecessary rejection by the vision system. For example, most embossing equipment is now being replaced by laser or other coding technologies that not only give information that is easier to read but also gives improvements in OEE (overall equipment effectiveness) by speeding up changeover times and cutting rejects.
But the regulatory aspects of the pharma industry mean that change is bound to be slow - any change in a packing line is both expensive and has validation and record-keeping implications, and companies are also loathe to spend significant amounts of capital on implementing a technology that may be superseded in one or two years" time if a consensus on a standardised code format is reached.
"The EFPIA move means you will have some commonality of coding," Metters says. "It would be even better if they could move to a situation where that code is in a common place. You would then have something on the package that the pharmaceutical wholesalers and distributors, and even the pharmacies, could take advantage of. That should be a catalyst for change." But he also points out that Domino's coding equipment all has an upgrade path to enable it to be connected to a system that will print new codes in the future. "So you can take the benefit of quicker line changeovers today and still be able to do serialisation next year, even if you are not yet completely clear about what you want."
There are a number of technologies that can create the serialised codes that are key to future track and trace systems. One of the older methods, which is still widely used by the pharma sector because of its high line speeds, is continuous ink jet (CIJ). But although it is capable of coding 300 products a minute in black or white on a wide range of substrates, the print quality is not very sharp. Also, even though the ink is carefully packaged to minimise the risk of spills, it is still not an ideal system to use in a clean environment.
Thermal transfer is also a good technology in terms of code quality, but it is expensive and the cost goes up as the print area increases.
Scribing laser is becoming increasingly popular. It can print high quality graphics in an area up to 60mm square, and is faster and cleaner than CIJ. Although it does generate some particles, Domino offers shrouds and extraction equipment to prevent contamination of the cleanroom. However, lasers cannot mark some surfaces and a special area may have to be created on the pack on which to apply the laser code.
Domino is currently looking to introduce a new technology to the pharma sector: high resolution drop-on-demand (DOD). Widely used in the graphics industry, it can print in black and white and colour at very high speeds and high clarity, as long as the product handling is right. Again, the results are better on some surfaces than on others.
The company is also able to offer an RFID-based solution where appropriate, and was instrumental in tagging Pfizer's Viagra in the US and with a haemophilia product from manufacture through the supply chain to the point of use in a London hospital. It has two RFID pilot projects currently running in the US, and is constructing an RFID architecture in Europe, which is being funded by the EU, called Project Bridge.
The key to making serialisation a success is data management: the entire system will collapse if there is any duplication of serial numbers. But this is an area where Domino also has expertise - its technology is used for printing items such as lottery tickets.
"To date we have only used this expertise in commercial printing, but now things are changing and people in pharma are looking for the same structure around their high value products," Metters says. "Our eyes are fixed firmly on making serialisation a reality, and the big challenge is going to be making it work without having a detrimental effect on production efficiency.
"I hope that the EFPIA initiative will give us the opportunity to offer a systems- and solutions-based approach that improves record-keeping, that makes QC easier, simplifies the paper chain and improves line efficiency. Having to introduce serialisation should be a catalyst that accomplishes that. But it will require a major leap of faith."