Increasingly, the nature of excipients is changing from traditional, simple inert materials to more complex and specialised substances designed to perform highly specific functions within the drug product. As a result, more and more pharmaceutical companies are turning to these novel materials to assist in the development of more complex dosage forms and leading-edge products, and to improve existing products through reformulation. In fact, the reformulation of products is an increasingly common product lifecycle management technique as drug manufacturers strive to maintain or grow revenues in the face of patent expiries and competitive pressures.
Although new excipients are being developed specifically for pharmaceutical use, "novel" excipients by their definition have not yet been used and proven by the pharma industry. The established procedures listed for well-known excipients and APIs, such as compliance with a pharmacopoeial monograph, use of the Ph.Eur. Certificate of Suitability scheme or reference to food additive/GRAS status, depend on previous pharma use and, as such, novel excipients cannot use these procedures. Inevitably reviewers want to see more detailed information about these novel materials than for established excipients, which can lead to the perception amongst drug manufacturers that the use of a novel excipient could cause delays in their regulatory review and approval process. Another key issue for excipients is that, unlike APIs, there is no legally defined GMP standard or independent review procedure. Again, this presents difficulties — especially for novel excipient manufacturers who have to provide full and potentially confidential information directly to the user.
Overall the current regulatory environment can reduce incentives for both excipient manufacturers to develop, and pharmaceutical manufacturers to use, novel ingredients for the manufacture of innovative new products. This situation needs to be overcome and measures put in place to facilitate and standardise excipient review so that the advantages of novel materials can be utilised for the benefit of the consumer.
To this end, significant efforts by the biopharmaceutical industry and The International Pharmaceutical Excipients Council (IPEC) are ongoing, which are directed at standardising excipient manufacture, along with harmonising quality and safety assessment and data packages, a fundamental part of which is a proposal for Excipient Master Files (EMFs) in Europe. Master files allow for a more standardised and consistent approach for supplying excipient information to the regulators, and their use simplifies the system for excipient manufacturers, users and reviewers. They are invaluable to excipient manufacturers because they allow them to protect their confidential manufacturing know-how and manage their own product information. Unlike in many regions, such as the US and Japan, where master files can be submitted for a broad range of drug ingredients, the EU master file system is more restrictive and cannot be used for excipients. Establishing an EMF system in Europe would help reduce current EU regulatory burdens, removing the disadvantages compared with other territories in this area while also further aligning EU regulations with other global systems.
The current system for excipients is inadequate, especially for novel ingredients. The lack of globally aligned regulatory mechanisms for reviewing new excipients is currently creating significant challenges to the development of innovative, new pharmaceutical products. Therefore, harmonised global standards and a workable regulatory mechanism are needed to facilitate market and overall regulatory acceptance of these critical pharmaceutical components.
Kate Denton is Regulatory Affairs Manager at Novozymes Biopharma.