THE CHANGING ENVIRONMENT
The days of single site integrated development, manufacturing and supply of medicines have long passed. Pharmaceutical imports to Europe now amount to over €170 billion (1). In volume terms, the extent of importation is clearly higher, with a greater proportion of lower cost generic products often coming from third countries, that is, those outside the EU. In the UK, two thirds of all dispensed medicines are now generic, with the single largest supplier being India, where no less than 25 per cent of all UK medicines are sourced. In addition to this dependence on imported finished products, there are few medicines which are not dependent on outsourced constituents. A telling example is the provision of penicillin and cephalosporin, with more than 50 per cent of global supply coming from China. The relentless drive to reduce costs in order to maximise profits has provided an opportunity to supply cheaper active pharmaceutical ingredients (APIs) and other constituents to which emerging countries, particularly China and India, have been quick to respond. The current economic crisis is likely to accelerate this outsourcing trend and our dependence on third country supply.
CUSTOMER CONFIDENCE
The average citizen remains largely unaware, or at least unconcerned by, this trend. They may in fact benefit from cost advantages. A 2009 opinion poll in the UK found that 85 per cent of respondents remain confident in the safety of medicines (2). This level has not changed since a previous survey in 2006.
While most patients may have limited understanding of the regulatory processes involved, they appear to be confident that the authorities are looking after their interests to ensure the safety of medicines. The exact licensing, inspection and market surveillance processes in developed countries, for the most part, have their origin in governments’ responses to threats to public safety. Most notably, the US Food, Drugs and Cosmetics Act of 1938 followed a tragic incident in which more than 100 children and infants died after taking a sulfanilamide elixir formulated with diethylene glycol. In the UK, the foundational Medicines Act 1968 was introduced following the devastating teratogenic effects of Thalidomide. Recent high profile events are once again focusing public attention on medicine safety. The deliberate contamination of Heparin with oversulphated condroitin sulphate (OSCS) in 2008 resulted in over 80 deaths and numerous serious adverse events, largely in the US.
The public are also understandably concerned by the growing awareness that they may be exposed to counterfeit medicines which, although physically indistinguishable from the authentic product, may at best be ineffective and, at worst, actually harmful. A less obvious, yet potentially equally serious threat to medicines’ safety is that of unacceptably poor standards for manufacturing and distribution. While poor standards still regrettably emerge from time to time in developed countries, the risk is clearly greater in countries that operate less mature regulatory systems.
This article addresses in particular the global phenomenon of pharmaceutical counterfeiting and outlines responses from regulators and industry which are required to maintain public confidence in the authenticity and safety of medicines, regardless of their country of origin.
THE THREAT TO PUBLIC HEALTH
The manufacture and supply of counterfeit medicines is a major international enterprise. In the legitimate supply chain, the World Health Organization (WHO) reports levels of counterfeit medicines exceeding 20 per cent in many African countries, in parts of Asia and Latin America, and in many countries of the former Soviet Union. The Pharmaceutical Supply Institute cites 1,759 reported incidences in 2007 involving 239 different pharmaceutical products (3). While the incidences of counterfeit medicines are much lower in countries with more effective regulatory and enforcement regimes, it would be a grave mistake to underestimate the threat. In a 2007 survey, seven of 13 EU Member States reported cases of counterfeit medicinal products in the legal supply chain (4).
In the UK alone there have been 15 known incidences of counterfeit medicines in the regulated supply chain in the past five years (see Figure 1). These have included products for a wide range of therapeutic indications and include a comparator used in a clinical trial. In 10 of these cases it was necessary to recall the medicines from the market. Although there is no evidence of actual patient harm from the use of these counterfeits in the UK, it should always be assumed that every counterfeit is dangerous. These products will generally have been manufactured in sub-standard conditions and will typically be sub-potent or even contain the wrong active ingredients and potentially harmful impurities.
Under-reporting makes it impossible to assess the full extent of public harm, but there are an alarming number of documented fatalities and serious adverse reactions from around the world (5). Criminals have also been quick to exploit the universal access to the internet, and the WHO has estimated that more than 50 per cent of medicines from sites which conceal their physical address are counterfeit.
COMBATING THE THREAT
In November 2007, the UK medicines and medical devices regulator, the MHRA, launched its anti-counterfeiting strategy. This incorporates strategic and operational measures designed to minimise the risk of counterfeit medicines and medical devices reaching patients in both the regulated and unregulated supply chains. The strategy has three broad focus areas: communication, collaboration and regulation (6).
