The Pharmaceutical Journal
Vol 272 No 7281 p31-32
3/10 January 2004

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American Society of Health-system Pharmacists

High-volume products likely to be the next target for medicine counterfeiters

Counterfeit medicines entering the legitimate market have become a serious problem in the US over the past year or so. Thomas McGinnis, director of pharmacy affairs, Office of Policy, Office of the Commissioner, US Food and Drug Administration, explained how the usual route of entry is through secondary wholesalers who were able to sell products back to primary wholesalers. Such products might then be sold to hospital and community pharmacies.

The active component in counterfeit products may be inactive, incorrect or present in smaller amounts than are stated on the label. However, the counterfeit products often look convincing, explained Mr McGinnis. When samples had been shown to congressmen they had been unable to distinguish between real and fake products.

Identifying counterfeit tablets

Counterfeit tablets can sometimes be identified by digital imaging. For example, a batch of counterfeit Viagra tablets could not be distinguished by visual examination but when the digital images of the die-stamped letters were superimposed the differences became obvious. Similarly, pharmacists had reported that some Viagra tablets seemed to be thicker than usual and digital images of the tablet profiles confirmed the difference.

Packaging differences often helped to identify fake products, although the differences could be subtle, said Mr McGinnis. The pack for the Amgen brand of epoietin contains a colour-shifting logo (similar to that used on one of the US bank notes) that changes colour when viewed from a different angle. One batch of counterfeit Epogen was identified when it did not fit well into a storage unit — the vials turned out to be 1/16 inch wider and shorter than the originals. Package inserts of fake products are sometimes printed on paper of different colour or quality from the original and in some cases the ink rubs off. If the manufacturer does not tell you about a packaging change, then the FDA needs to hear about it, because it might be a counterfeit product, he warned.

Anti-counterfeiting measures

Anti-counterfeiting measures can take different approaches: overt (on packaging), covert (a marker or dye in the product or packaging) or forensic (a dye in the tablets). However, better tracking of products though the supply chain is also important, said Mr McGinnis. Logistics companies such as Fedex and UPS are able to track every item at all times and the same should apply to medicines.

One way to achieve this would be through the use of electronic chips attached to products. Such chips can be the size of half a grain of rice and can be incorporated into labels. Once they are in place it would be possible to read the inventory of an entire warehouse at the flick of a switch. Mr McGinnis predicted that electronic chips would be in routine use within two years.

New “grey market”

In March 2003 a popular magazine had warned its readers that the medicines they obtained from reputable pharmacies might be “mishandled, tampered with or counterfeit”, said Gregg Jones, pharmaceutical programme manager, Bureau of Statewide Pharmaceutical Services, Florida Department of Health, Tallahassee. He went on to explain that 19 people have now been indicted in Florida for drug counterfeiting.

Counterfeit products are able to enter the distribution system because there is a “grey market” that functions alongside the usual market. In Florida, this secondary market is fuelled by a mixture of legitimate purchases, stolen drugs, drugs intended for export, counterfeit, outdated and repackaged products. Another source is “street drug brokers” who buy medicines that have been dispensed to Medicaid-funded patients. Special pricing deals also create an avenue for entry of counterfeit products, he added. Poor control over drug wholesalers has also contributed to this situation. For example, many states did not license drug wholesalers at all until 1987 and, even now, many do not routinely inspect wholesalers’ premises.

On one occasion large quantities of Neupogen and Epogen had been kept in a car boot in Miami for three days before being sold back to a wholesaler. Products that had been dispensed for patients are often “cleaned” by street brokers — this involves removing the dispensing labels using lighter fluid and a heat gun. Occasionally, however, labelled products have found their way through the systems and alerted pharmacists to this illicit trade.

Expensive products such as epoietin, growth hormone and anti-retroviral treatments are frequently implicated in counterfeiting operations. For example, a large batch of bogus Procrit (epoietin) was found in a major Texas wholesaler’s premises. The fact that there was a large quantity with the same batch number aroused suspicion. When the product was analysed it contained only one 20th of the labelled strength. This type of operation can be lucrative, explained Mr Jones. An investment of $2.6m, plus the repackaging costs, can be converted into more than $46m by astute counterfeiters.

Until recently counterfeiters have concentrated on high-priced, low-volume products, the recent discovery of fake Lipitor appears to signal a move into high-volume products, said Mr Jones. The goal of the enforcement authorities is to establish a closed distribution system in which all product movements can be tracked. Moves are already afoot in Florida to reduce the number of small wholesalers and to standardise the documentation required with medicines.

In the meantime, Mr Jones gave pharmacists worldwide some advice (see Panel).

Creating safe names for products is still a challenge

At a packed session titled “Medication error prevention: can the pharmacist be separated from the system?” four speakers presented widely differing views.

Bruce Gordon, principal consultant, Supply Chain Performance Improvement, Premier Inc, Gambrills, Maryland, looked at the logic of system focusing. He defined task loading as the number of tasks performed in the time available and went on to demonstrate a positive correlation between the prescription work load per half hour and the number of dispensing errors in that same period. Other relevant factors include the task (hours worked, interruptions, breaks, paperwork), the environment (noise, disorderliness, lighting, heating), interpersonal relationships (social life, age, sex, experience, emotions, impulsiveness), organisational issues (attitudes to reporting errors, supervisory style, encouragement of the individual) and extra-organisational issues (lifestyle changes, influences of third parties). Dr Gordon concluded by posing a number of questions: What do you do with people? Should all pharmacists be able to do the same type of work and manage the same workload? Can we determine which type of pharmacy position or career will be most successful and satisfying to the individual? Finally, should all pharmacists be practising as pharmacists?

James Dettore, president and chief executive officer, Brand Institute Inc, Miami, Florida, discussed the significance of creating drug names to avoid confusion (look-alike and sound-alike errors). A large number of dispensing and drug administration errors occur as a direct result of drug name confusion. Since 1999, the Food and Drug Administration’s office of drug safety has reviewed all new drug name applications for potential confusion. Before a submission is made to the FDA, the manufacturer will have used many techniques to produce a name that can be used safely. The manufacturer requires a safe, distinctive, marketable name that is appropriate in different languages and cultures, that does not infringe other trademarked names and will be approved by the FDA and the European Medicines Evaluation Agency. Before the licence application for a new product, a creative team will have designed and tested a series of names. Focus groups, which include pharmacists, evaluate the proposals. Extensive phonetic trademark screening and look-alike and sound-alike assessments take place before the final list can be submitted to the manufacturer. The names are reviewed again for appropriateness and are screened in 18 languages. Even at that stage, said Mr Dettore, verbal and handwritten interpretation from practitioners is necessary before the final name is chosen. He concluded by saying that attempts to create safe names still remained a challenge and although specific protocols have been established by the industry, these do not guarantee success.

Who makes errors?

“To err is human, so why not pay attention to the human,” asked Robert Pihl, professor of psychology, McGill University, Montreal, Quebec, Canada, in a session on predicting the characteristics of pharmacists who make errors. Professor Pihl believed that the pendulum has swung too far towards system failure and needs to swing back towards human failure. The individual has to be considered as part of the system. Systems myopia leads us to believe that bar-coding and automation, for example, will solve many of the problems. Medication errors can be predicted by focusing on the individual and human engineering is not only possible but also necessary. There are a number of reasons for not focusing on the individual:

• Changing systems per se can be effective and are generalisable
• Focusing on individual factors can be punitive
• Focusing on individual factors can obviate reporting
• There is a philosophical conundrum: whereas we are a society based on individualism, we abhor individual differences
• Many methods for looking at individual factors are biased and error prone

A battery of tests can be performed on individuals that can identify those prone to making errors. Working memory measurements look at what individuals can do, not what they know. Learning ability, attention control and verbal organisation are all functions of the prefrontal cortex of the brain. Its primary role might therefore be regarded as abstract action, namely, the capacity to think before doing. Personality tests also provide some pointers. Anxious pharmacists are more likely to make mistakes whilst those working in sales are most successful if they are not very agreeable.

Professor Pihl went on to describe a small study comparing a group of pharmacists who had made dispensing errors with a control group.

The pharmacists from the dispensing error group were older, more experienced and had a reduced working memory. They also had associated learning deficiency that made it more difficult for them to distinguish between look-alike and sound-alike names. Their test results fell in the lower quartile on all neuropsychological factors. However, the personality tests showed no differences between the groups. In conclusion, Professor Pihl said that the characteristics of individual pharmacists were important in reducing medication errors.

Selection and intervention were the two areas where specific steps can be taken to reduce dramatically the risk of errors made by pharmacists said Dr Jordan Peterson, associate professor, Department of Psychology, University of Toronto, Ontario, Canada. At the point of hiring of both pharmacists and technicians, tests with predictive validity should be used. Further consideration should be given to a match between specific individual characteristics and job demands. Current employees should also be evaluated with relevant methodologies and where there are large discrepancies with job requirements, interventions should be considered. Techniques are available that could modify individual risk factors. He concluded by saying that individual differences are an important factor in medication errors and these differences are measurable. Working memory seems to be a critical attribute but the factors of concern can be remedied.