Laurence A Goldberg
HPE Editorial Consultant
This article is based on presentations focused on fraud and diversion in the pharmaceutical supply chain given by Captain Thomas J McGinnis (Director of Pharmacy Affairs, FDA), Rita Shane (Director of Pharmacy Services, Cedars-Sinai Medical Center, Los Angeles) and Marc Gonzalez (Director, Law Enforcement Liaison, Purdue Pharma, Stamford) during the American Society for Health-System Pharmacy Midyear Clinical Meeting, held in Orlando, Florida, in December 2004.
The rise of counterfeit drugs
Recent years have seen the arrival on the market of counterfeit drugs that are often visually indistinguishable from the genuine products. Organised criminal networks are now involved in counterfeiting. Their organisations are well funded; they employ sophisticated technology to make the products and often use the internet for marketing. Estimates of the extent of medicines counterfeiting are unreliable, said Captain McGinnis.
Typically, counterfeiters target high-cost drugs for which there is a big demand and which have a few years of patent life left. If the drug is in short supply, this provides an ideal opening for counterfeiters. Recent examples of counterfeit medicines include Lipitor(®), Procrit(®), Ortho Evra(®) patches and many antimalarials. One of the main reasons for counterfeiting is the huge profits that can be made. In one case, criminals had purchased 11,000 boxes of Epogen(®) at a cost of $2.4m. The product was repackaged, labelled as a more concentrated product and sold to a secondary wholesaler for $48.9m.
In the USA, 90% of medicines are supplied through three major wholesalers, the remainder being supplied through about 7,000 secondary wholesalers. Many secondary wholesalers are ethical organisations, but some function in the grey market and are often able to supply items at lower prices than the manufacturers. The sources of the medicines for the grey market can be charitable donations, institutions illegally reselling discounted products, Medicaid patients selling their drugs to street brokers, physician’s samples, expired products or stolen drugs. Secondary wholesalers supply both pharmacies and other wholesalers, thereby providing a route into the legitimate supply chain for counterfeit products.
Sources of counterfeit drugs
Experts estimate that it takes six months for counterfeiters to find ways round any new security measure and, therefore, multiple methods and frequent changes are needed. A combination of product authentication and product tracking, using barcodes or RFID methods, is needed. Product authentication techniques can be overt (such as holograms or colour- shifting ink that changes colour when viewed from a different angle) or covert (such as the use of invisible barcodes). Alternatively, forensic methods can be used, such as the incorporation of chemical markers or dyes. Product tracking should operate in a way similar to that in which FedEx and UPS track parcels. It can be done using barcodes, but radiofrequency identity devices (RFIDs), which are one-third the size of a grain of rice, would be ideal. At present, three manufacturers are planning to tag 31 products with RFIDs. Other measures include ensuring appropriate regulatory oversight and enforcement, increase penalties, heighten vigilance and awareness, and increase international collaborations.
In a recent FDA investigation, three products were ordered from the website of a pharmaceutical supplier that claimed to be “FDA-approved” and was apparently based in Canada. When the products arrived they were postmarked Dallas but gave a return address in Miami. The company’s telephone number was in Belize, the payment was processed in St Kitts and the server for the website was in China. All three products – supposedly Lipitor, Ambien and Viagra – were counterfeit. They contained variable quantities of active ingredients and failed tests for dissolution and impurities.
Medicines stolen from hospital pharmacies are one source for the grey market. In 2003, an investigation showed that epoetin alfa, filgrastim, leuprolide acetate and ondansetron hydrochloride valued at $2m had been stolen from the pharmacy department at the MD Anderson Hospital (Houston) by a small group of pharmacy staff. “We can no longer assume that the drugs we bring in are not walking out of the door,” said Dr Shane. She recommended automated cabinets for expensive drugs in pharmacy departments, along with security cameras, locked refrigerators and restricted (authorised) access to drug storage areas. In addition, packs should be opened and marked on receipt, to make them more difficult to resell, and staff should not be allowed to bring handbags or backpacks into drug storage areas.
Popular methods for diversion (theft) of drugs are substitution (removing the active ingredient and replacing it with something that looks the same) and modifying or forging patient records (eg, medication administration records), said Dr Gonzalez. Other methods include manipulation of wastage and disposal procedures. One of the most audacious methods is to trick accident and emergency department staff into issuing prescriptions for narcotic tablets.
One man did that by applying a phenol-containing mixture to his arm to mimic the appearance of a third-degree burn. Tablets were usually prescribed, but on one occasion he was given several pethidine injections by sympathetic staff, which made it difficult for him to concentrate on the deception. Another variant is to apply a spot of white correcting fluid to a tooth and then complain of root canal pain.
Identifying counterfeit drugs
One method to check that injections contain the correct drug and concentration is to use fluoroscopy. This can be used to check that narcotics are present when syringes or vials that could have been tampered with are returned to the pharmacy, but it could also be extended to cover other products, suggested Dr Shane.
A new tool, ValiMed, combines a new technology to validate medications, software to define and automate the testing process and a library of spectral fingerprints. The machine generates UV light that energises a given medicine. A consistent pattern of fluorescent energy is produced – a “spectral fingerprint”. These fingerprints are stored in a data library. Each medicine has it own unique spectral signature. By comparing the fingerprint of a tested medicine against the signature for that medicine in the data library, the machine immediately registers a match or a failure to match. The machine also has the ability to measure concentrations. A solution under test can be validated by comparing it with a standard concentration on file in the data library. ValiMed is also able to provide immediate validation of extemporaneously compounded high-risk intravenous infusions at the time of preparation in the pharmacy, or at the time of administration in the clinical area.