GMP Compliance In Europe
It’s no longer business as usual for suppliers of active pharmaceutical ingredients in Europe. New Good Manufacturing Practices will impact API manufacturers who want to conduct business in the European Union.
Tom Branna - Editorial Director
It’s no longer business as usual for companies that supply active pharmaceutical ingredients (APIs) to Europe. In October, EU authorities passed new directives to ensure that good manufacturing practices (GMPs) are met by any and every company that supplies APIs to Europe. In addition to ensuring the health of the European consumer, the directives are expected to help level the playing field between European, Indian and Asian API suppliers.
Terms of the new directives (2004/27 for human health and 2004/28 for animal health) call for inspections of API manufacturers, traders and brokers as well as “non-CEP APIs.” Moreover, the directives are intended to focus on incoming-API aspects during inspections at dosage-form manufacturers and keep an eye out for the possibility of fraud and counterfeiting. The directives also include API fingerprinting by the OMCL Network. Suppliers that fail in any of these measures could be subject to MAA withdrawals and rapid alert/recalls.
More specifically, under the new directives:
• A qualified person must declare the API in compliance;
• A GMP certificate from health authorities is not sufficient evidence that the the GMP requirements are being met; and
• Guidelines require that an audit report be on file and available to regulators.
The move was hailed by members of the European Fine Chemicals Group (EFCG), who called the directives a long time in the making and suggested that they are one way of ensuring that there is a level playing field for European API manufacturers. At the same time, EFCG board members pointed out that the U.S. has had similar standards in place for more than 50 years.
According to some estimates, more than 80% of APIs used in European pharmaceuticals now originate from China and India. EFCG estimates that there may be as many as 10,000 plants in these countries supplying APIs to Europe.
“The health of the European consumer is at the crux of all this,” explained Cefic’s Tony Scott, who also serves as a member of the EFCG board. “The new law will make us trust the system.”
Implications for the Industry
As a result of these new directives, pharmaceutical suppliers will no longer be able to “just buy the API from a trader,” according to Guy Villax, president of Hovione and president of the EFCG pharmaceutical business committee.
In fact, manufacturers must obtain a declaration and data to support directive compliance from the API producer.
 The new directives are expected to create a level playing field for suppliers and improve the supply of APIs throughout Europe, but EFCG members say many questions still remain. |
Although he hailed the passage of the new directives, Villax said they could still use some improvement. For example, there is no system in place for inspections and there is no provision for a random audit—there is only inspection when there is suspicion of failure to comply with the directives.
“With no random inspections,” Villax charged, “There can be no deterrence.”
Moreover, EFCG members are concerned that the EU member state health authorities may not be equipped to carry out the inspections called for under the new directive.
“The industry is asking regulators…are they adequately equipped to regulate?” he asked.
To answer that question EFCG is conducting a benchmarking survey to assess how well-equipped EU member state health authorities are to enforce the new directives.
To underscore his point, Villax said the next steps for regulatory authorities should be: “enforcement, enforcement, enforcement.”
Despite their shortcomings, Mr. Villax called the new directives a good start and he urged pharmaceutical suppliers to take an active role in ensuring the quality and integrity of the APIs that they formulate with.
“My advice to you is to make sure that the supplier you purchase ingredients from actually makes it,” he told the audience at a press conference held on Nov. 2 during CPhI in Madrid. “Be sure to conduct annual product reviews and keep copies of evidence of compliance.”
The High Cost of Compliance
Although the new directives are aimed at ensuring the health of European consumers, they also go some way in maintaining the health of European API producers. According to the EFCG, GMP compliance increases a plant’s operating costs by 25%, reduces its flexibility and lengthens time to market.
Although some may view the directives as direct attacks on the Indian and Chinese API market, Villax noted that every company must abide by the same regulations, pointing out that “in Europe, some API company facilities are substandard and some in Asia are excellent. So who knows?”
To help its members comply with the new directives, EFCG is carrying out an EU-wide benchmarking exercise with the inspectorates of the member states. Furthermore, it has made a third-party auditing plan available to both API producers and consumers. Both moves are intended to provide guidance on how to comply with the new legislation.
The EFCG Expands
The EFCG has expanded rapidly during the past year, growing from 20 to 37 member companies as well as several national associations and international groups. During that time, EFCG has formed four new committees, each with a mission, objectives and an action; integrated with the Active Pharmaceutical Ingredients Committee and formalized contacts with key stakeholders in the supply chain, government, NGOs and other international trade bodies. Despite these advances, board members insist the group still has much to do. Specifically, EFCG plans to double its membership and get more companies involved in the process; minimize regulatory bias favoring non-European manufacturers; promote EU citizens health through better law enforcement; promote the high quality added-value provided to customers by European producers and provide focus and help on innovation.
