IPEC e-newsletter - Excipients Insight April/May 2018 - 15-05-18


Inside this issue


Novel excipients - why a master file system could remove regulatory obstacles

In the last 20 years, the number of novel excipients that have successfully been brought to market has been vanishingly low. While there is no shortage of high-quality R&D work on new excipients that could improve the quality, safety and ease of manufacture for medicinal products, regulatory challenges make it hard for pharmaceutical manufacturers to use them in their products.

The main reason for this is that novel excipients – by their very nature – have not been through any prior regulatory assessment for pharmaceutical use, so drug developers cannot reference pharmacopoeias or other ingredient compendia, or earlier drug approvals. In Europe there is still no simple way to demonstrate the safety and efficacy of a new excipient, other than to win approval of its use as part of a medicinal product via the usual marketing authorisation application (MAA) procedure.

What is lacking is a regulatory mechanism for independent review and qualification of new excipients. For many years, IPEC Europe has advocated the need for a master file system in the EU that can be used for excipients, but with Europe increasingly out of step with the rest of the world on this issue the organization believes it is time to raise the issue once again.

“All of the IPEC Federation regions have a master file system open to excipients – including US, Japan, China and India – except for Europe,” notes Kate Denton (pictured), who represents Albumedix Limited on IPEC Europe’s Quality and Regulatory Affairs Committee.

Given that many other regions including Australia, New Zealand, Canada and Korea also have excipient master file (EMF) systems, the EU is increasingly looking like an outlier on this important issue - and as a result - "the needs of both developers and users of novel excipients are not met in Europe compared to other global regions,” she adds. The situation means new and improved treatments are reaching patients in other countries that are not penetrating the EU market.

In jurisdictions that operate EMFs, a pharmaceutical manufacturer has two ways to apply to use a novel excipient in a medicinal product. It can file the supporting data as part of a marketing application or alternatively reference a master file which the excipient supplier has already lodged with the regulatory agency.

Most excipients are used in pharmaceutical products in Europe on the strength of a Certificate of Suitability (CEP) that can be submitted to the European Directorate on the Quality of Medicines and Healthcare (EDQM) in order to demonstrate that the excipient meets the monograph requirements laid out in the European Pharmacopoeia (Ph. Eur.). However this approach is not possible for a novel excipient.

“IPEC Europe recognises that an EMF would not necessarily be of value for compendial excipients for which a CEP can be obtained and therefore it envisages its use mainly by novel excipient manufacturers,” says Denton.

She would like to see a system where the EMF contains a closed portion that could be accessed only by the regulator, with an open part provided to the excipient user, namely the marketing authorization holder (MAH), similar to the system that is already used for active pharmaceutical ingredients (API), i.e. active substance master files (ASMFs). IPEC Europe believes that, as for APIs, such an approach would allow the MAH access to all the information needed to take full responsibility for the excipient’s use in a drug product, whilst also helping the supplier protect confidential information about its product. A master file system is used successfully in this way in all other major world regions as discussed above.

“Given that data requirements for active substances and novel excipients are equivalent, and that the European legislation specifies that information in relation to a novel excipient must be supplied according to the active substance format, IPEC Europe believes that novel excipients should be treated the same in terms of their assessment procedure and that submission via a master file procedure should be possible,” according to Denton.

“The rationale for allowing manufacturers of active substances significant advantages that are not open to novel excipient manufacturers is unclear.”

An EMF system would also allow the regulator to have all the complex information on the excipient in one centralised location where it can be reviewed in conjunction with drug licence applications. That would reduce the need for duplicative assessments of the same information if the excipient is cited in more than one marketing application.

IPEC Europe also believes that as it stands EU reviewers may not have access to the same level of information on the excipient as their counterparts in other EMF-using countries. That is because excipient manufacturers seeking to protect their intellectual property may not be able to hand over confidential details to the MAH. This could have a negative impact on the EU assessors’ ability to ensure the safety and quality of the finished pharmaceutical product.

“Implementing an EMF system in Europe by extending the use of the ASMF to novel excipients would benefit a large proportion of the pharmaceutical industry—excipient manufacturers and users alike—by reducing the barrier to innovation in this area and bringing Europe in line with other global markets,” concludes Denton.

“This would encourage the development of improved drug products thereby increasing EU citizens’ access to better safer medicines.”

IPEC Europe is drawing up a position paper to reflect that viewpoint. If you are an IPEC Europe meber and would like to learn more, or to get involved in the EMF project, please contact the Secretariat.




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