Just how effective is FMD legislation?

Dr Ash Ramzan, founder and principal consultant at regulatory affairs consultancy, Woodley BioReg looks at how the key requirements of the Falsified Medicines Directive are being fulfilled by stakeholders and manufacturers.

The Falsified Medicines Directive (FMD, 2001/83/EC as amended to 2011/62/EU), and its delegated regulation EU 2016/161, together set out the requirements that manufacturers of human medicinal products must meet, as part of their legal responsibility.

This applies throughout the EU and responsibilities extend to wholesalers, dealers and parallel importers. Requirements came into force on 9 February 2019, with a number having already been implemented over the past two to three years.

Why is preventing falsified medicines important?

There are several types of falsified medicines. They include any medicine that is not made by the approved manufacturer, or contains too much, too little, or no active ingredient.

It might also contain another or an undeclared active ingredient – or has passed its expiry date. Items that are deliberately mislabelled, have fake packaging, or are in some way not as the authorised manufactured intended, are also on this list. 

All of these can have a critical impact on the safety of patients. There have been many documented cases of harm – including death – caused by falsified medicines, which further underlines the importance of robust control measures to protect patients. 

Probably the first, and very well documented, example of falsification was the use of sulphanilamide elixir intended to ‘cure sore throats like never before’. 

The product used a diethyl ether as a solvent, that we know to be toxic to humans – resulting in hundreds of confirmed deaths. This event also sowed the seeds of the regulations and legislation to regulate and control modern medicines. 

A more recent example of falsification is 72,000 packs, containing 2.1 million doses of three medicinal products, with a retail value of £4.7 million. Only around 40,000 of these packs were seized, with the rest likely to have been distributed.

The Medicines and Healthcare products Regulatory Agency (MHRA) regularly sends notifications of product theft – and access to bona fide packaging, labelling, serial numbers and batch numbering facilitates this illegal trade.

Some of the products affected recently have included thousands of packs of Nexium, Co-Codamol and Voltarol.

What’s in place in the UK, EU and rest of the world to prevent falsified medicines?

Given the global nature and lucrative value of such counterfeits, local and regional initiatives have been developed and implemented to provide some level of assurance to patients and carers. 

These include a relatively simple application of codes by legitimate manufacturers, that are scratched off by customers to reveal details that can be texted to a central data centre, verifying products’ authenticity. This system was launched in several African countries in 2009, and to date has seen over 28 million verifications. 

In the EU, Directive 2001/83/EC allows safety provisions to be enacted. Amendments to this allowed the Falsified Medicine Directive 2011/62/EU to be defined with the key safety requirements. These came into force with the Delegated Regulation EU/2016/161, implemented by 9 February 2019. 

This system is active and in place throughout the EU, but following Brexit, the UK may no longer be able to access the database that manages serialisation and coding of legitimately manufactured pharmaceuticals. 

Spotting and stopping falsified medicines

Falsified medicines are notoriously difficult to stop and identify. With many tablets looking identical, the most effective way to spot illegitimate items is through small differences in packaging and labelling. 

This can involve official routes, such as customs and border controls, but also the supply chain including wholesalers and warehouses. Similarly, the MHRA operates a ‘yellow card’ scheme whereby patients and carers can report discrepancies and adverse events directly.

Once such events are logged, the agency will undertake investigations such as chemical analysis – and in extreme cases, product recalls.

How prevalent are falsified medicines?

After almost a year following its implementation, SecureMed – the EU body tasked with issuing serial numbers – noted that over 45 million medicines had been issued in the UK, and that there were no cases of any falsification. 

This is a clear indication that FMD measures have very effectively halted this trade in the EU and UK.  However, this is not the case in the rest of the world, where such measures don’t exist – and may not continue to be the case for the UK if its pharmaceutical industry and MHRA are not allowed continued access to the SecureMed databases. 

Trends for the future

In the EU, FMD legislation will continue to be enforced, to safeguard the quality, safety, and effectiveness of medicines. Meanwhile, it’s inevitable that those motivated to act fraudulently will continue to find ways in which the current system can be ‘beaten’ – and as with all regulations, FMD legislation will continue to be updated and refined.

The situation in the UK is less clear. Following the implementation of FMD – and before Brexit – there was clear evidence of the elimination of falsified medicines entering the country. However, this has depended on access to the EU databases. 

If this continues, Britain will continue to benefit from safe and effective medicines. If, however, Brexit means the UK is denied access, then industry and regulators will need to develop and implement alternative systems to mitigate the risk of falsified medicines.

In conclusion, the FMD has gone a long way to assuring patient safety and product efficacy.  Manufacturers and stakeholders have, in the meantime, responded positively.  However, while this system will continue to be implemented in the EU, the position for the UK is much less certain.