The World Health Organisation (WHO) estimates that up to 10% of medicines worldwide may be counterfeit, costing the pharmaceutical industry about $2 billon annually.

The range of counterfeit products includes: antibiotics, hormones, analgesics, steroids, antihistamines, antimalarial and the so-called 'lifestyle' drugs.

It is often considered a problem of the developing world, where the percentage of counterfeit medicines can be as high as 40%, it is also a blight on more sophisticated markets. In the US, the FDA reported an increase of about six per year from 1997 to 2000 to more than 20 in 2001 and 2002.  

The recent cases of counterfeit medicines discovered in the US supply chain include: Lipitor, Neupogen, OxyContin, Procrit, Serostim and Zyprexa.

Counterfeiting these high value, high volume products provides an economic incentive for criminal activity. These US incidents have shaken consumer confidence, leading in some cases to lawsuits against distributors and pharmaceutical manufacturers by affected patients.

Counterfeiting is just one example of fraudulent supply of pharmaceutical products - this is a more common and widespread issue, which includes the following examples:

• Copies attempting to look like the genuine product
• Illegal imports, either from a non-approved supplier or manufacturer or where the active ingredient has not yet been approved for use in another country
• Illegally relabelled products: sometimes this is to extend the shelf life of short-dated products or to relabel the product with a label indicating a higher strength, which can be sold for more
• Substituted or diluted product: increasing the quantity in the original batch by addition of counterfeit product  
• Diverted product includes: product supplied overseas (at reduced cost) under access to medicines schemes. These do not reach intended patients but are diverted to a market commanding a higher price. In other markets pharmaceutical manufacturers supply free samples to hospitals which can end up being sold to patients
• Stolen product: here the product is genuine but not legally owned by the seller

In the UK there have been a few cases of counterfeit product, however, over 100 cases of fraudulent pharmaceutical product supply are investigated every year by the MHRA enforcement division.

A major concern is that fraudulent supply of pharmaceuticals will increase dramatically with the extension of EU membership.  After successfully growing from six to 15 members, a further 13 countries applied to become new members and the EU recently completed its biggest enlargement ever, in terms of scope and diversity. Ten of these countries - Cyprus, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, the Slovak Republic, and Slovenia joined on 1 May 2004; Bulgaria and Romania hope to do so by 2007.

This opens up thousands of miles of unprotected borders to the illegal entry of medicines into the pharmaceutical supply chain from former Soviet states where a recognised and significant counterfeit drugs problem already exists.

The almost unrestricted supply chain and legalised free movement of goods throughout the EU enables fraudulent supplies to be obtained from any unscrupulous source for trading, unchecked throughout Europe.

How are patients currently being affected?

There is a significant health risk to patients from fraudulent products, particularly counterfeits. Counterfeit drugs often contain harmful products, a different active, to be lacking an active ingredient or to contain less active than required for therapeutic effect. Additionally, the counterfeit product will not be made to the same quality standards. Injectable products will probably not be sterile and may even be contaminated with human material, particularly where used vials are fraudulently recycled.

The WHO estimates that as many as 20% of the annual deaths from malaria worldwide may be the result of taking ineffective drugs. A recent study in The Lancet concluded that up to 40% of artusenate (the best medicine to combat resistant malaria today) products contained no active ingredients.

A WHO survey found that between 20% and 90% of locally produced and imported antimalarial products in seven African countries, failed quality testing, many with insufficient active to kill the parasite. The implications are that patients buying the product will increasingly lose their protection against malaria as resistance builds up.  

What are manufacturers doing about it?

Manufacturers have been aware of counterfeiting for many years and are becoming increasingly concerned. Many have developed and use a range of features designed to prevent counterfeiting and to enable better identification. These features are referred to as:

• Overt: visible to the human eye eg, hologram label
• Covert: requiring the use of a specialised tool or instrument to visualise the feature, eg, UV marking
• Forensic: requiring the use of analytical technology and instruments to detect the feature, eg, biological marking of inks

The leading manufacturers use a rolling strategy of introducing new types of anti-counterfeiting measures on packs, acknowledging that the counterfeiters can soon discover the overt feature and copy it.

Manufacturers are also responsible for investigating and confirming the presence of counterfeits (in collaboration with local law enforcement officers), implementing recalls where necessary and providing advisory information to professionals and regulators

What are regulators doing about it?

The regulatory agencies work to ensure that marketed medicines are safe, efficacious and more recently meet the pharmacoeconomic evaluation that the patient benefit is worth the cost. Regulators and inspectors are involved throughout the supply chain in approving processes, manufacturing and distribution facilities, ensuring that the supply of pharmaceutical products meets internationally agreed standards.

When counterfeits are identified they work with the pharmaceutical industry to alert healthcare professionals and patients and carry out an investigation. They may also publish information on how to identify the counterfeit product, for example see:www.fda.gov/oc/initiatives/counterfeit/.   

The source of counterfeit medicines is frequently traced to developing nations where drug regulation and manufacturing controls are ineffective. Sentences for counterfeiting medicines are not considered a deterrent against the risks involved versus the potential financial gain.  

In the US, the FDA has responded to the increase in drug counterfeiting by introducing an anti-counterfeiting drug initiative. This is designed to identify the risks and threats from counterfeit drugs more effectively, coordinate the efforts of all involved against counterfeiters, identify tools and techniques to help combat counterfeiting and prevent fraudulent product from reaching patients. The final report is due to be published in January 2004.

The FDA believes that there is no single solution to the counterfeiting problem, and that a multi-pronged strategy will be the most effective. A combination of technology solutions tracking product through the supply chain to provide a product history, and authentication at point of dispensing may all be suggested.

In the meantime, US companies are considering various scenarios and waiting for the FDA report before changing their anti-counterfeiting strategy and selecting any one approach.

What methods currently exist for counteracting the problem and are they working?

Overt, covert and forensic features are added to products by manufacturers, but inspection of the overt features cannot be relied upon to prevent patients from receiving or taking fraudulently supplied medicines. Any system to prevent fraudulent and counterfeit products from reaching patients must not rely on manual inspection of pharmaceutical packaging for identification of counterfeit products. The reasons for this include:

• Counterfeit quality is very good: some are so good that they are almost indistinguishable from the genuine product. Guidance on the FDA website acknowledges that company packaging experts may be required to determine whether a particular product is genuine. Counterfeiters have access to component suppliers, technology and the ready finance to ensure that their copies are as close as possible to the real thing. The supply, use and destruction of packaging, including security features (eg, holograms) requires tight control. A consignment of packaging is very valuable to counterfeiters.  Discarded pharmaceutical packaging and product (eg, vials and labels) can be recycled and cleverly used by counterfeiters to reconstruct a genuine looking pack. Counterfeiters are also able to ensure that the paperwork (eg, certificates of analysis and export and import licenses, customs declarations, etc) that accompany consignments, is copied to a high standard.   
• The number of manufacturers, range of products and strengths make it an impossible task to remember the overt features associated with a particular product. There is no single standard for overt features, which include holograms, colour change inks and complex designs, with each manufacturer selecting and using different technologies. The Monthly Index of Medical Specialities (MIMS) published monthly in the UK lists over 250 manufacturers and 1,500 branded products; different strengths and generic products add to this number. This situation is complicated as manufacturers change packaging and generic products may be supplied from one of a number of companies with different packaging. Pharmacists dealing with so many products cannot be expected to know and remember how to check the overt pack features.    
• Human inspection is inconsistent. We are all different gender, age, dexterity, spatial ability, memory, eyesight, motivation, concentration, education, hearing, experience and language are some of the individual factors that mean the performance in carrying out inspection tasks varies from person to person. Our individual performance also varies from one time to the next and is conditioned by our experience.   

Inspection methods affect performance:

• When to inspect? On receipt at the pharmacy, before giving the product to the patient or by the patient when they obtain the dispensed product?  
• Where to do the inspection?  On the end of a cramped dispensing bench in a pharmacy or secluded, quiet area?   
• What to look for? What are the features that should be checked all of them or just a single, key feature?
• How to carry out the inspection for best results? Important factors include background noise and activity, interruptions, lighting, time available to carry out the inspection and whether more than one activity is being carried out at the same time. These will change with location, time of day and random events, such as a phone ringing, causing a distraction, leading to someone forgetting whether or not they have carried out the inspection. Use of best inspection practice and transfer of learning to pharmacists from other critical sectors (eg, aviation) would help improve inspection performance, but it is far from the foolproof system required to guarantee patient safety.
• Not all fraudulently supplied product has counterfeit packaging: stolen and diverted products will appear genuine. Products produced using stolen or recycled, used packaging components are further ways to pass manual inspection for overt features.

What can the pharmaceutical industry learn from other sectors?

Counterfeiting is not new and other industry sectors are already applying anti-counterfeiting measures. Whilst each industry has special characteristics, supply chain management and stricter methods of inventory control are particular areas where pharmaceutical manufacturers can learn from other industry sectors.

How can this issue be solved in the long-term?

Given the appropriate focus by governments and pharmaceutical companies, patients can be protected from receiving counterfeits and all fraudulently supplied pharmaceuticals.

Using existing, proven technology PA Consulting Group's authentication at point of dispensing approach will enable manufacturers to authenticate the product as genuine before it is given to a patient. This unique approach also provides the following checks:

• Product expiry date to ensure that only in-date product is given to patients
• That the pack being given to the patient has not been subject to a batch recall
• For changes in indications and contra-indications for the product
• For changes to labeling requirements

This approach:

• Improves patient safety providing a final layer of security and reassurance for healthcare professionals and patients, ensuring that fraudulently supplied medicines cannot reach patients.

• Embraces and enhances the UK government electronic agenda including: Electronic Transmission of Prescriptions, Drug Dictionary and Integrated Care Records.

• Protects the pharmaceutical industry and companies from the adverse publicity and enormous costs arising from fraudulent medicines getting into the supply chain and being given to patients.  

BY ANDY GILL

Tuesday , June 01, 2004