The European Commission's decision last year to take a long, hard look at the pharmaceuticals sector in a widening European Union has left some uncertainty about how the industry will be regulated in the future. At the same time, the commission's recognition that globalization, an expanding internal EU market, and advances in science and technology are changing the pharmaceutical environment has opened up debate over regulatory issues that affect all stakeholders in the pharmaceutical business.
A seminar held by the European International Pharmaceutical Excipients Council (IPEC–Europe) at the end of January in Cannes, France, provided an opportunity to review Europe's regulatory environment for excipients and to highlight the emerging issue of counterfeiting, among other growing challenges.
Counterfeiting concerns growThe director of the European Directorate on the Quality of Medicines (EDQM), Dr. Susanne Keitel, told the IPEC–Europe audience that the Council of Europe has made counterfeiting a priority for EDQM as counterfeits entering the supply chain have become a major public health concern. EDQM is well-placed to coordinate anticounterfeiting efforts in Europe, said Keitel, particularly through its European network of Official Medicines Control Laboratories. "EDQM could contribute to knowledge sharing on analytical methods, setting of reference standards, and the coordination of testing and inspections, for example, as well as education and training exercises," explained Keitel.
Although the image conjured up by pharmaceutical counterfeiting is of bootleg copies of finished medicines, there is increasing concern about the possibility that raw materials, including excipients, may be present in the supply chain.
Counterfeiting of excipients is certainly a concern at the US Food and Drug Administration, according to Dr. Steven Wolfgang of the agency's Center for Drug Evaluation and Research. He said that recent cases involving the substitution of melamine for protein and diethylene glycol (DEG) for glycerin in drugs suggest that "commodity ingredients—not necessarily expensive drugs—are being targeted by unscrupulous individuals out to make a quick profit."
After last year's crisis, FDA issued guidelines recommending that a specific limit test for DEG be added to glycerin identity testing. The agency also now asks that glycerin be tested every time a shipment of the ingredient changes hands.
Wolfgang confirmed that supply chain integrity continues to be a hot topic in the United States. He noted the government's Interagency Working Party on Import Safety and the November release of an action plan that calls for a risk-based approach focused on prevention. Interestingly, among the proposals covered in the action plan are a certification system for foreign producers, expanded laboratory capacity for testing, and greater use of electronic track-and-trace technologies, all of which could have a bearing on excipient producers.
The World Health Organization (WHO) is also tackling drug counterfeiting via its IMPACT (International Medical Products AntiCounterfeiting Taskforce) program, set up in late 2006. Sabine Kopp of WHO issued an invitation to IPEC–Europe and its sister organizations IPEC–Americas and the Japan Pharmaceutical Excipients Council (JPEC) to contribute to that initiative.
At the seminar, the IPEC Good Distribution Practices Audit Guideline document on Good Distribution Practices (GDP) was introduced, developed by IPEC–Europe's GDP committee. The document is meant to help audit companies in the excipient supply chain when used alongside the IPEC GDP Guide, published in 2006. IPEC–Europe is also working with IPEC–Americas to draw up principles for a document on excipient pedigrees as part of a broader guideline on excipient qualification.
GMP space to be watched
A new IPEC Good Manufacturing Practice (GMP) Audit Guideline, prepared in collaboration with IPEC–Americas and the Pharmaceutical Quality Group, was also introduced at the IPEC–Europe seminar to complement the group's 2006 GMP guide. This is particularly timely as GMP is at the top of the agenda in Europe, with industry waiting to see how the European Commission plans to implement GMP standards for excipients, after years of discussion.
The fact that GMP must be implemented for "certain" excipients according to current regulation is beyond question—it already has been voted for by the European Parliament. The key questions are: What categories of excipients will be included, and what interpretation of GMP will be applied? Professor Henk de Jong, who last year acceded to the chair of the European Pharmacopoeia Commission, told the seminar audience there are four policy options on the table: legislation, adoption of guidelines, a risk-management approach, or self-regulation by industry.
"The indications are that there is little support for legislation. Based on the recommendations of the EC's Pharmaceutical Committee on Dec. 12, 2007, it seems that a risk-assessment approach is favored," he said, but stressed the matter is now in the hands of EC Industry Commissioner GFCnter Verheugen.
While this news is encouraging for excipient suppliers and users, De Jong cautioned that IPEC needs to keep an eye on the process and be prepared to react if events do not proceed as expected.