The Falsified Medicines Directive – What Does It Really Mean?

By Suzanne Elvidge, Contributing Writer
Follow Me On Twitter @suzannewriter

The trade in falsified medicines — medicines that look real but really aren’t what they seem — is a huge and growing one, and it is putting patients’ health and even their lives at risk. Along with regulatory authorities around the world, the European Union is putting directives into place that could begin to slow this deadly trade.

THE PROBLEMS WITH FALSIFIED MEDICINES
Falsified medicines are fakes that get into the supply chain, often via the Internet. These could be tablets or injectables that have the wrong amount of the right drug, with a dose that is too low or too high. They could include poor quality ingredients or completely different and potentially harmful active ingredients. Alternatively, they could be drugs that have been diverted from a legitimate source and repackaged, but not necessarily stored under the right conditions or with the right use-by date. The EU uses the term “falsified medicines” to differentiate these from counterfeits — copies of marketed drugs that do contain the right active ingredient but that infringe companies’ patents or trademarks.

Falsified and counterfeit medicines make up around 1 percent of the volume of the global market, according to the EU, and up to 60 percent in West Africa, putting already vulnerable populations of patients at risk. The WHO believes that falsified medicines could be the reason behind around 100,000 deaths per year in Africa.

The trade in falsified medicines is a highly lucrative one, as the drugs are generally high value, such as anticancer medications, or in high demand, such as antivirals or drugs for malaria or tuberculosis. The WHO estimates the global market to be worth around $77 billion, having doubled in size between 2005 and 2010. According to Craig Stobie, global account manager, Domino Printing Sciences, speaking at the SMi Group’s 8th annual conference on Parallel Trade in 2014, $1,000 investment in falsified medicines can lead to a return in $450,000, much more profitable for criminals than counterfeit currency, tobacco, and software combined. This money provides a source of income for organized groups that are hampering peaceful development, Andris Piebalgs, European Commissioner for Development, said in a statement.

THE EU FALSIFIED MEDICINES DIRECTIVE
Using legislation, countries around the world are working to combat the influx of falsified medicines into the supply chain. The approaches include track-and-trace and mass serialization, which use unique codes tied to central databases and allow genuine packs of drugs to be traced back to the license holders, manufacturers, and distributors. The addition of tamper-proof technologies on the packs confirms that the product hasn’t been repackaged or tampered with in any other way. In combination, these make sure that users (doctors, pharmacists, and patients) can verify the packs are authentic and contain the correct drug at the correct dose.

There are rulings coming in or already in place worldwide to stop the trade in falsified medicines:

• EU – Falsified Medicines Directive
• United States – Drug Quality + Security Act (HR3204)
• Brazil – ANVISA (Agência Nacional de Vigilância Sanitária)
• Saudi Arabia – SDC (Saudi Drug Code)
• China – CFDA (China Food and Drug Administration; previously SFDA)
• India – DGFT (Directorate General of Foreign Trade)

Around 80 percent of the requirements are common globally and tend to focus on item-level serialization and aggregation as measures for securing the pharmaceutical supply chain.

The EU Falsified Medicines Directive, adopted in July 2011 and put into place from January 2013, is the core of the EU’s legal framework for the licensing, manufacturing, and distribution of medicines. It is designed to include pan-European, harmonized safety-and-control measures to stop illegal drugs entering the supply chain. These measures begin with two key safety features — bar codes and tamperproof technologies. Under the directive, all legitimate product packs must include a unique 2D bar code that identifies the pack and that carries the manufacturer code, serialization number, national reimbursement number (if available), batch number, and expiry date. This needs to link with a repository system that stores and validates the bar codes end to end, from manufacturer to the point that the drug is dispensed to patients. The pack also needs to include a tamper-verification feature.

The directive also includes responsibilities for wholesalers and brokers, written confirmations for APIs manufactured outside the EU, and logos for legally operating online pharmacies.

In April 2014, the EU launched a three-year, approximately $5.3 million project targeted at developing strategies and legal frameworks and raising awareness of falsified medicines in developing countries.

IMPACTS AND OPPORTUNITIES
To comply with the directive, companies need to put a number of processes and protocols in place. They need to buy and install hardware and software that can generate and print unique bar codes or 2D codes. Then they need to be able to scan the codes and store and track the data. And all of this hardware and software will need to integrate with any existing enterprise resource planning (ERP) software.

Packaging designs may need to be rethought because they will have to include space for the bar codes. Furthermore, those bar codes need to be clear enough and contrast well enough against the background for easy scanning. That means companies will need to have quality control in place, and they will need to ensure the codes remain stable and legible in storage throughout the product’s lifetime. As Stobie explains, this is the biggest change in the pharma industry in the last 40 years, and any system is only ever going to be as good as its worst part.

Of course, compliance with the directive will come with a price tag. According to Maarten Van Baelen, medical affairs manager at the European Generics Association (EGA), he estimated the costs as:

• printing and serialization — around $331,000 to $397,000 per packaging line
• antitampering —around $199,000 to $265,000 per packaging line
• verification with repository systems — around $53 million/year.

The EGA believes this will make medicines, particularly generics, unaffordable by increasing the production costs. Van Baelen also suggested that the verification system could limit the ability of pharmacists to dispense medicines. His organization would like to see an optional application of the safety features, a waiver for the tamper-verification feature, and a phased-in approach of the implementation.

Another area where the Falsified Medicines Directive will have an impact is parallel trade, where traders import drugs from lower-value markets into higher-value markets in the EU (see “An Introduction to Pharmaceutical Parallel Trade in Europe” in Life Science Leader, May 2014). Traders may replace the packaging completely, which could involve the loss of the unique codes and damage to the tamperproof seals. To comply with the Falsified Medicines Directive, parallel traders will have to put more of a packaging and IT infrastructure in place. “This raises the bar for the parallel traders, as they will also need to invest in data and artwork management,” says Stobie.

Implementation also will take time. As Stobie warns, “Compliance is likely to take longer and be much harder than people think. As the directive will be enforced in 2018, companies that have not yet begun the process may not have enough time, and it could have a knock-on effect on the drug supply.”

However, there is a positive side to the process, too. As well as the protection for consumers, there could be advantages for both manufacturers and consumers. The system allows manufacturers to treat each individual pack as a “batch of one,” meaning they can access precise real-time data on the production process at every stage. And for consumers, the machine-printed codes could help those with vision, language, or cognition issues.

People with a visual impairment or cognitive problems could scan the code with a smartphone and hear spoken instructions, the product name and dose, a reminder to take the drug, or instructions to replace the pack because it is near the use-by date. This also could be a way to access instructions on-screen in simplified language or as a translation. “Including information for the patients via the codes could be a way to increase patient engagement and adherence,” says Stobie.

The Falsified Medicines Directive also could provide opportunities for contract packaging companies. These are amongst some of the earliest adopters of the directive, and many are already seeing the benefits of early compliance.

HOW WILL THIS AFFECT COUNTRIES OUTSIDE THE EU?
Under the terms of the directive, every batch of APIs imported into the EU from outside will have to be accompanied by a written statement issued by the regulatory authorities that confirms compliance to GMP standards equivalent to those in the EU. Alternatively, the manufacturing country will have to be “whitelisted” by the EU as a country that has GMP inspections equivalent to those in the EU.