Interim EU measures needed to stem counterfeits

The EU institutions need to move more quickly to put in place at least some elements of the European Commission’s proposals for harmonised action against counterfeit drugs, insists one of the research-based companies whose products have fallen prey to counterfeiters.

"This is still taking us a long time to move through the system," said John Ricketts, associate director, government affairs for Lilly Europe.

"We would urge the Parliament and the other players in the system to try and bring forward a form of interim measures once we’ve got the overall agreement, so that we can give that reassurance to patients as soon as we can."

Ricketts’ position mirrors that of the European Federation of Pharmaceutical Industries and Associations (EFPIA), which believes any concrete measures to stem the flow of counterfeits EU-wide are unlikely to be in place until late 2013 - although some observers believe individual member states will move faster than that.

What EFPIA really wants to see is a ban on repackaging of medicines "as soon as possible", something the Commission has resisted in the proposals now before Parliament’s Committee on the Environment, Public Health and Food Safety (ENVI). In lieu of a repackaging ban, there should be interim measures to improve patient safety before the proposed directive and its implementing measures enter into force, EFPIA contends.

These should include requiring manufacturing authorising holders (e.g., parallel importers) that remove or cover up overt safety features to replace them with equivalent features and to be "held strictly liable in the case of counterfeits entering the supply chain as a result of their actions". With covert or forensic features, repackagers should supply their own versions (hence avoiding disclosure) of a "similar standard of complexity", EFPIA says.

Ricketts was addressing a meeting organised in the European Parliament last week by Aegate, the UK-based company that has launched a pharmacy-level drug authentication system, AegateProtect, in four European markets.

He cited the recall of counterfeit batches of Zyprexa (olanzapine), Lilly’s treatment for schizophrenia and bipolar disorder, by the UK’s Medicines and Healthcare products Regulatory Agency in May 2007. In that case, drugs seized by the MHRA contained only 50-80 per cent of active ingredient.

Significant gaps

The meeting on Making Patient Safety a Priority looked at "workable approaches" to the proposed anti-counterfeiting directive launched by the Commission as part of its pharmaceutical reform package last December.

It included a presentation by MEP Marisa Matias, the new rapporteur for the draft directive in the ENVI committee, who identified what she saw as a number of significant gaps in the Commission’s proposals as they stand.

Among these were provisions to block internet sales of counterfeit medicines; a definition of "falsified" medicinal products; a clear distinction between traders and brokers of medicines; measures addressing excipients (either on a comprehensive or risk basis); and more direction on mandatory safety features.

In Matias’ view, the legal basis for the proposed Directive should also be expanded from Article 95 of the EC Treaty, addressing the internal market, to Article 152 on human health protection.

Internal market arguments are believed to have prevailed in the Commission’s decision to reject the recommendation for a ban on both the repackaging and relabelling of patented medicines in a report commissioned from consultants Europe Economics. 

Matias also asked whether drug exports should be included in the proposals and whether, and to what extent, the directive should extend to generic and over-the-counter medicines. The question of whether compulsory safety features should be risk-based touches a particularly raw nerve, with EFPIA preferring a blanket requirement for prescription medicines to avoid trade distortions and counterfeiters switching their attention to unprotected products.

Generics manufacturers, on the other hand, argue that the financial burden of comprehensive security features would be disproportionate for an industry operating on tight margins and whose products have never been reported as counterfeited within the EU27 markets.

Compulsory baseline

Ricketts’ stressed there was "no one simple solution" to the counterfeiting scourge, which called for a "combination of robust measures" to protect patients.

The compulsory baseline, he suggested, should be "serialisation and seals", involving ‘end to end’ verification - as provided already by the AegateProtect system and as envisaged in EFPIA’s 2D data-matrix barcode pilot, which is due to launch in Sweden later this month - and a minimum level of tamper-evident pack security.

Medicines considered at particular risk of counterfeiting will need further protection, Ricketts added, noting that Lilly already takes a risk-based approach to counterfeiting with all of its products.

John Chave, secretary general of the Pharmaceutical Group of the European Union (PGEU), also favoured a precautionary approach, while cautioning that costs must be proportionate without pushing up drug prices.

"I believe that those of us in the supply chain, the industry, pharmacists, wholesalers and whoever else, we need to make some sort of sacrifice … we all benefit from as much integrity in the supply chain as possible," Chave told the meeting.

Moreover, he said, singling out particular medicines as high-risk could "merely push on the counterfeiters to other kinds of medicines", not to mention confusing patients:  "Do we create a sort of implied guarantee or warrantee that medicines that don’t have safety features are thereby safe and free from counterfeiting?"

The generics industry, stressed Hugo Carradinha, senior manager, health economics affairs for the European Generic Medicines Association, has been "extremely active" in the fight against counterfeiting through fora such as the Council of Europe, GS1 Healthcare and the World Health Organization’s IMPACT task force. 

While counterfeit drugs are undoubtedly a "huge problem", the market share in the EU27 countries has been estimated at less than 1 per cent and there is a danger of trying to "kill a mouse with a tank", Carradinha said.

Counterfeiters are interested in high-priced, high-profile brands, exploiting weaknesses in the distribution network and the criminal justice system. Moreover - and here Carradinha quoted Mike Muller, director of global anti-counterfeiting operations at Eli Lilly - anti-counterfeiting technology can be replicated within six to 12 months of launch.

As such, he insisted, the first line of defence should be "real" solutions such as more aggressive criminalisation of drug counterfeiting, enforcing laws on internet sales of medicines, improving business ethics in the supply and distribution chains, and tightening up requirements for wholesale licences.

Any safety features should be risk-assessed on the basis of price and past incidence. They must also, Carradinha emphasised, be cost-effective and achieved through an independent system that addresses concerns about commercial exploitation of transactional data.

Costs, logistics

Some idea of the cost and logistical implications of the Commission’s proposals for smaller manufacturers was given by Claudia Glasow, head of legal affairs at German company Ursapharm Arzneimittel.

Meeting the technical requirements of mass serialisation would entail at least two cameras and readers for each packaging line, at a minimum cost of €40,000, Glasow told the meeting. Manufacturers would also need to install software capable of handling the serialisation codes and quality control, which would cost between €80,000 and €120,000.

That amounted to minimum costs of €120,000 per packaging line, and even a medium-sized company such as Ursapharm ran 15 lines. So it would have to invest at least €1.8m to comply with the technical requirements for mass serialisation.

There were further complications, Glasow added, such as potential conflict with the EU’s readability guideline for drug labelling and packaging, under which certain information has to be printed on the pack in at least seven-point type.

For technical reasons, the minimum size of a 2D barcode was 43mm x 18mm, Glasow pointed out. This was unsuitable for small packages, which did not have enough space on the flap for the serialisation code. And putting the safety feature on the front or the side of the pack would encroach on the space needed for the labelling requirements in the readability guideline.