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Regulators and industry move to require inspections of API manufacturing facilities.
European manufacturers of active pharmaceutical ingredients (APIs) have been campaigning for several years without much apparent success for the introduction of mandatory inspections of API plants. Such inspections by the European Medicines Agency (EMA) and the European Union's national regulatory authorities would help ensure manufacturers that they are meeting current good manufacturing practice (CGMP) standards.
European API manufacturers complain that the lack of proper GMP-compliance monitoring has led to their loss of the market share. Asia, in turn, has reaped the benefits. China and India, specifically, now account for more than two-thirds of the API market (by volume) in the European Union, according to industry sources.
(PHOTO: IMAGE SOURCE, GETTY IMAGES)
Representatives of European manufacturers, including the European Fine Chemicals Group (EFCG), believe that legislators finally seem to be paying attention.
Legislators are listening
In late 2009, the European Parliament moved to amend a proposed European Union directive tied to the EU Pharmaceuticals Package of 2008 that addresses counterfeit and substandard medicines. The amendment would make it mandatory for EU authorities to inspect API manufacturing facilities with the aim of preventing additional counterfeit and substandard drugs from reaching the market.
"EU public opinion and politicians are now taking a much greater interest in the issue," says Guy Villax, chief executive of Hovione, a Portuguese API producer, and a member of EFCG's board. "Members of the European Parliament seem to be far more aware of the need for mandatory inspections than the European Commission, the EU executive, which draws up legislation."
The European pharmaceutical industry is working internally as well to improve API facility audits. The popularity of Rx–360, the recently formed US-based international pharmaceutical supply chain consortium, and its proposed shared-audit information system is growing throughout Europe.
According to Villax, EFCG feels that the initiatives by regulatory authorities and pharmaceutical companies to collaborate more closely on the inspection of API plants is demonstrating support for its arguments within the sector itself. The proposed amendment, for example, would build upon the pilot project launched in 2008 by EMA, US Food and Drug Administration, and Australian Therapeutic Goods Administration (TGA) to conduct joint GMP inspections of API plants.
These efforts "are totally in line with our thinking because cooperation provides the better quality information needed to eliminate the fringe of API producers bypassing GMP standards," says Villax.
Audits can help, but are they enough?
Research- and develoment-based manufacturers and generic-drug suppliers agree that substandard APIs can be removed from the market with more effective auditing, particularly by more cooperation between companies.
Auditing by drug manufacturers as opposed to a full-regulatory GMP inspection, of API manufacturers is already required by EU law. The European Commission would like to ease the burden on manufacturers by allowing third-party audits as long as the auditors are accredited by a regulatory authority in the EU. Unfortunately, the majority of the European Commission's Council of Ministers, the second arm of EU legislature representing the EU's 27 member states, oppose the idea. The Council, according to a November 2009 EC press release, believes third-party audits would dilute the responsibility of pharmaceutical companies.
"Auditing by pharmaceutical companies, even if it is mandatory, is not sufficient," stresses Villax. "The pharma companies cannot have responsibility for setting standards. There must be a final arbiter of what minimum standards are required. Only regulatory authorities can do that."
Counterfeits create more urgency
Due to the rising influx of counterfeit medicines in to the EU—at an average annual increase of 10–20% by volume—regulators are beginning to tackle fake drugs as a public health matter.
"Production facilities of low-price API suppliers [in India and China] are, until now, rarely inspected by EU authorities," says Paolo Russolo, president of Cambrex Profarmaco Milano, a manufacturer of APIs and intermediates, and head of Aschimfarma, Italy's fine chemicals association.
In discussions regarding the proposed amendment to the EU Pharmaceuticals Package, members of the European Parliament have asked for more emphasis to be placed not only on the public-health responsibilities of regulatory authorities in fighting counterfeiting but also on the protection of the industry itself.
"It is important to prevent unfair competition from (non-EU) producers who place APIs on the EU market without them having been properly ascertained whether those producers comply with GMP—this will at the same time serve to protect public health," says Amalia Sartori, rapporteur for the parliament's industry, research, and energy committee.
The European Parliament is expected to give a first reading of the new legislation and its proposed amendments this spring. The Council of Ministers is also likely to reach an agreement on the controversial directive. European API producers are optimistic that both bodies will support mandatory API-facility inspections.
Sean Milmo is a freelance writer based in Essex, United Kingdom.