Excipient Master File System Advocated for EU

An excipient master file (EMF) system in the EU would facilitate the review process, spur excipient R&D and harmonize with other regulatory systems, advocates are saying.

The current master file system in Europe encompasses only active chemical substances and does not extend to biological APIs nor to excipients and other components.

Other major world regulatory regions including the U.S., Canada, Australia and Japan have master file systems that accommodate a broader range of drug and biologic components, include packaging materials.  Japan added a master file system similar to the US model in updating its regulatory process under the 2005 Pharmaceutical Affairs Law (IPQ Jan./Feb. 2008 Report).

Advocates in Europe including the International Pharmaceutical Excipients Council (IPEC) have been urging that bringing the EU into alignment would benefit its regulators, suppliers of excipients and the manufacturers that use them.

The increasing significance, complexity and understanding of the role that excipients play in drug and biologic delivery systems together with a move toward a quality-by-design (QbD) regulatory paradigm are factors prompting regulators and industry to reassess how the relevant information should flow through the review and inspection process.  The EMF is being advocated as a vehicle for bringing into play the full range of excipient information needed in regulatory oversight and decision making.

Master files are voluntary vehicles for conveying product and manufacturing information from suppliers and contractors directly to regulators to support new drug and biologic product review, and may have open and closed sections. The later contain confidential information for regulator viewing only.

They are not generally reviewed and cleared separately, although advocates including IPEC have maintained that a separate approval process for new excipients in the U.S. and Europe would spur their development and improve the overall review process. Europe’s CEP procedure does involve a clearance process, but it is more oriented toward compendial conformance, and the more complex biologic and novel excipients are not candidates.

The lack of ability to protect confidentiality is felt most strongly by those excipient manufacturers who are willing to invest in pharmaceutical excipient R&D.  Among other concerns, the broad dissemination of their propriety process and product information potentially allows purchasers to shop the information to other suppliers in search of lower costs.

Addressing a PDA European regulatory affairs interest group teleconference in early September, Novozymes Biopharma Regulatory Affairs Manager Kate Denton discussed the problems inherent in the current EU approach and the benefits that excipient master files would offer.  Novozymes manufactures recombinant biopharmaceutical ingredients from yeast. Denton serves on IPEC Europe’s regulatory committee.

[Denton’s insights into the excipient review problem in Europe and the ongoing efforts by IPEC and others to address it are provided for subscribers here.]