European Fine Chemicals Group proposes certifiable standards for excipients

The manufacture of excipients destined for use in European medicines is neither regulated nor controlled as it should be and regulations and standards should be enforced to avoid any potential risk to the health of EU patients and consumers.

This view is put forward by the European Fine Chemicals Group (EFCG), a Cefic sector group, in a Position Paper on excipients used in pharmaceutical manufacturing.

With the implementation of EU Directive 2001/83/EC (amended by Directive 2004/27/EC) into national law, it is now mandatory that all active pharmaceutical ingredients (APIs), and the yet-to-be-defined list of Certain Excipients used in pharmaceutical manufacturing, must be produced in compliance with current Good Manufacturing Practice (cGMP).

However, normally a combination of excipients, beyond the before mentioned Certain Excipients, contribute by far the largest weight and volume in any pharmaceutical finished dosage form. The European Pharmacopoeia (EP) defines the excipient's specification and the required analytical methods to assure their quality, but in many cases only limited, general data on impurities are provided, and from a variety of different production processes used.

Based on the limited regulation of excipients and the lack of legal enforceability even by today's low standards, these chemicals pose a potential risk to the quality of pharmaceutical products. In addition to establishing higher standards, compliance will have to be enforced, the position paper says.

It proposes that:

• all common excipients, by far the largest grouping, conform to General Chapter <1078> USP, including certified ISO requirements;
• all Specific (includes Certain Excipients) and Novel Excipients, a much smaller defined group, are covered by EC Directive 2001/83 (amended by Directive 2004/27/EC);
• all these requirements are certified and effectively enforced.

Common Excipients are widely used pharmaceutically inactive substances, which are appropriately evaluated for safety using available standards and intentionally included in a drug delivery system. Specific Excipients and Novel Excipients, which have a higher risk potential, are excluded from this class.

In view of the increasing globalisation of the pharmaceutical industry and the harmonisation of pharmaceutical registration requirements, EFCG proposes to establish cGMP requirements for Common Excipients based on an amended General Chapter <1078> of USP to include:

• The formal release of every batch based on validated analytical methods or compendial methods
• Close monitoring of suppliers and manufacturing processes
• Assurance of the traceability and execution of comprehensive change control agreements along with the entire supply chain
• Assurance of hygienic excipients manufacture
• Minimisation of the known quality risk of the substances

In addition, appropriate stability data, comprehensive and appropriate product information for excipients should be made available for users as a basis for their internal qualification and registration processes.

EFCG believes that the consequences of the full implementation of its proposals not only supports the need to better protect the health of EU citizens, but it would also bring into law what is already the accepted practice for a wide range of reputable suppliers in the Far East, N America and Europe. As such, it should have an insignificant effect on product prices.