EFCG Meeting Wrapup

Drug ingredient safety was at the forefront in Lisbon

By Eize de Boer, Ph.D.

Long a gateway to global trade, Lisbon was recently the background for the European Fine Chemicals Group’s (EFCG) conference on the sourcing of pharmaceutical raw materials from around the world. Acting as the industry group for chemical manufacturers in Europe, the EFCG’s third annual Pharma Business Conference was host to more than a hundred delegates from the U.S. and Europe, including industry leaders and regulators from the U.S. Food and Drug Administration (FDA) and the EU’s European Medicines Agency (EMEA).

In light of the Heparin recalls earlier this year and other quality problems, the issue of good manufacturing practices (GMPs) in the sourcing of both active pharmaceutical ingredients (APIs) and excipients was front and center. The emphasis throughout the conference was on getting updates on the efforts taken by both the industry and government agencies to enhance the overall quality performance of third party manufacturers of APIs and excipients.

Aftershocks of a Global recall

The dust has just about settled from the March 2008 recall of Heparin, but nerves are still raw within the industry and especially within regulatory circles. Accordingly, this was the subject of several presentations at the conference. One focused on the Heparin supply chain, showing the vast number of companies involved in the manufacturing process in China and how hard it is to control such a distributed process. A second presentation, replete with photographs and process descriptions, went into more detail describing the results of audits conducted of manufacturers of crude Heparin in China.

In addition to these, a presentation from a Chinese API trading company showed that the current process for obtaining licenses to market certain pharmaceutical products in the U.S. and in the EU make it difficult to obtain a clear, consistent and transparent quality approach for foreign manufacturers.  While the FDA is responsible for licensing and controlling quality in manufacturing, these roles are split in the EU between the European Directorate for the Quality of Medicines & HealthCare (EDQM) and EMEA respectively.

Clearly there exists confusion over the approach to GMP compliance. The present approach in the EU, which makes drug companies in Europe responsible for the qualification of API and excipient producers in Asia, creates the serious risk that these ingredients can be imported by non-qualified organizations or by non-professionals.

Another serious risk is the multitude of auditing practices performed by individual drug companies and other consultants. This results in differing opinions on how to implement and optimize a compliant GMP organization, in many cases wasting precious time and money.

A Clear Path Forward

What the discussion among the attendees at the conference clearly demonstrated is that there is a need for enhanced and harmonized global GMP and Good Distribution Practices (GDP) standards.

For APIs, the obvious path forward is the International Conference on Harmonisation of Technical Requirements for Control of Manufacturing of Pharmaceuticals for Human Use (ICH) Quality Guideline Q7. Today, ICH Q7 is accepted by U.S., EU and Japanese authorities and has been incorporated into their national legislation. For excipients, the International Pharmaceutical Excipients Council and the Pharmaceutical Quality Group (IPEC-PQG) published detailed guidance this year for the manufacturing and distribution of excipients, including practical auditing guides.

At present it is generally accepted that the distribution chain of drugs, both finished and intermediate product, is critical. The call for harmonized standards regarding GDP is very strong, as pharmaceutical supply chains increasingly globalize. Harmonized storage and distribution standards are highly recommended to control the shipment of drug ingredients.

Global Standards

EFCG and IPEC presented a clear picture during the conference of how to control the manufacturing and distribution of both APIs and excipients. EFCG clearly stated that manufacturers of excipients should follow a path leading to quality certification. With certification against these standards being legally enforceable. EFCG claims that there will be little cost impact on the final product and the benefits for consumers will be huge in relation to the present uncontrolled state.

In addition, on June 11, EFCG and IPEC Europe announced an agreement to collaborate on the development of an international certification program that will cover both GMP and GDP for excipients. The program is to be developed in conjunction with other industry trade groups from around the world, with the objective of creating a global certification program.

What became crystal clear at this EFCG conference was both the industry’s and regulators’ desire not to see a repeat of the global Heparin recall. With the broadening and enforcement of GMP and GDP standards for drug ingredients, we can be confident that the right steps are being taken to ensure drug safety in today’s globalized pharmaceutical supply chain.

Eize de Boer, Ph.D. is the global manager for Life Science Auditing at SGS.