Report from Europe

Three years after first being drafted, new regulations on combating the growing menace of fake medicines have finally been approved by the European Union. It has involved intense lobbying by trade associations in the sectors most affected by the legislation—the drug manufacturers themselves, producers of active pharmaceutical ingredients (APIs) and excipients, and packaging suppliers. There are still, however, issues to resolve.

(PHOTO: NEIL BEER / GETTY IMAGES)

Many of the details of the legislation, the Falsified Medicines Directive (FMD), have yet to be worked out. The EU legislative body, which consists of the European Parliament and the Council of Ministers, represents the governments of the union's 27 member states. The legislature has decided to delegate the task of finishing the job to the European Commission, the EU's executive body. After that task is complete, any additional details will still have to be approved by the two legislative arms before finalization and implementation can occur.

"We're pleased with what we have got but we've got reservations about the details because there are a lot of unanswered questions about how the legislation will be implemented," says Tony Scott, adviser to the European Fine Chemicals Group (EFCG), which represents European-based API producers.

During the next 18 months and before the FMD's implementation, EU states will have to incorporate the directive into their national statutes. Some experts believe that the Commission could take much longer than this allotted timeframe to fill in the gaps, particularly with regard to the new rules regarding APIs and packaging.

Most APIs used in Europe are imported, mainly from India and China. The European fine-chemical manufacturers failed to persuade the legislators to agree to a mandatory system of official inspections to ensure that API plants comply with GMPs. European API producers have long complained about unfair competition from substandard Asian imports.

Instead, the legislation makes auditing of API plants by drug manufacturers obligatory. It also requires countries exporting APIs into Europe to have plant-inspection systems and GMP standards equivalent to those in the EU.

The Commission will have to decide what is "equivalent" and establish a process for verification of equivalence. The legislation appears to be flexible on this matter. It does not lay down, for example, that GMP standards for active ingredients will be the same as those in existing EU regulations.

"The Commission will certainly need to consider a transition period for implementation of this provision (on equivalence in standards of API exporting countries)," says Julie Marechal-Jamil, senior manager for quality and regulatory affairs at the European Generic Medicines Association (EGA).

FMD also makes GMP for excipients obligatory. But it has left to the Commission the decision about what GMP standards must be applied. Excipient producers seem confident that the existing GMPs for food production will be permitted.

With regard to packaging, the legislation stipulates that packaging should enable verification of authenticity, identification of individual packs, and capacity to show tampering evidence. These features would be backed by a pan-European information-technology network that is linked to a central database.

The exact nature of the safety features and the verification system, including any data-matrix characteristics and the size of the centralized databank, still needs to be finalized. The details are likely to be a controversial because they could trigger costly changes in packaging processes and equipment.

Already, the generic-drug sector is demanding exemptions from the scheme on the grounds that generic drugs are the least likely to be counterfeited and that producers of high-priced drugs should bear most of the costs of the changes.

"Manufacturers that have medicines considered at high risk of being falsified should pay (for the costs of the system) by the value of the medicine and not by the volume in the market," says Hugo Carradinha, EGA's senior manager for health economics affairs.

Tighter supply-chain controls for finished medicines as well as for raw materials will offer new openings to chemical distributors, particularly those adhering to good distribution practice, which is also a requirement of the new legislation.

"This legislation is a positive development for us," says Michael Cooke, who is responsible for the pharmaceutical sector at Univar, a leading chemicals distributor in Europe. "Traceability will become of even greater importance with pharma customers needing to be assured that suitable GMP standards are applied to all materials. We've invested in creating robust traceability systems."

Drug manufacturers will be seeking help from suppliers and distributors to reduce the extra costs of the legislation. "Funding of the FMD is a key concern," says Marechal-Jamil. Already, the enforcement of the new regulations faces delays because of a limited budget. Scarcity of funds could be major factor holding up the implementation of FMD as well.

Sean Milmo is a freelance writer based in Essex, UK