Excipients play a crucial role in formulation development, but what barriers to innovation in excipients exist and how is the industry addressing?

By Patricia Van Arnum, Editorial Director, DCAT, [email protected]

Innovation in excipients
Innovation in excipients is important to optimize a drug formulation, and the industry is pursuing ways to facilitate the use of novel excipients. While there have been some recent advancements in excipient innovation in specific uses such as in lipid nanoparticles in RNA molecules or custom excipients for bioavailability/solubility enhancements, there are still barriers to innovation, including regulatory barriers, which excipient manufacturers and users are seeking to address.    

To facilitate innovation in excipients, a key development occurred in 2021, when the Center for Drug Evaluation and Research (CDER) of the US Food and Drug Administration (FDA) launched a voluntary pilot program, the Pilot Program for the Review of Innovation and Modernization of Excipients (PRIME), as a means for excipient manufacturers to obtain regulatory review of certain novel excipients prior to their use in drug formulations. The premise behind PRIME was to enable manufacturers to submit safety and quality data of novel excipients through an independent regulatory review of that novel excipient prior to the regulatory review of a drug product in a regulatory filing, such as a new drug application (NDA). That pre-NDA review was considered an important component of reducing the hesitancy by pharmaceutical formulators to introduce novel excipients in their drug products and likewise, for excipient manufacturers to invest in novel excipient development given that hesitancy. The PRIME pilot program was cancelled by FDA for unknown reasons to the industry, and the industry is attempting to move forward with other ways to mitigate the regulatory barriers to excipient innovation that the PRIME program was seeking to resolve.

Scope of novel excipients
On a definitional basis, “novel excipients are essentially an excipient that does not have a precedence of use in an approved drug for that particular route of administration,” explains Dave Schoneker, President of Black Diamond Regulatory Consulting, LLC, which specializes in providing regulatory and quality consulting in formulation development and excipient selection and use. Schoneker is a past Chair of the International Pharmaceutical Excipients Council of the Americas (IPEC-Americas), a current Emeritus member of the IPEC-Americas Executive Committee, and has also been involved with the IPEC Federation for many years. The IPEC Federation is an industry association consisting of five independent regional industry associations (IPEC Americas, IPEC Europe, IPEC Japan, IPEC China and IPEC India) and composed of excipient manufacturers, distributors, and pharmaceutical companies, as well as other suppliers of specialized services related to the pharmaceutical use of excipients. Schoneker previously served as the IPEC Federation’s Global Expansion Coordinator, Chair of several  Committees of IPEC-Americas, and is currently the Chair of the Quality by Design/Composition Committee, where he is involved with the development of regulatory, safety, excipient GMP, and supplier qualification-related guidelines to improve excipient acceptability, safety, and global supply chain security.

“The term ‘novel excipients’ applies across the board to many different types of novel excipients,” he explains, such as co-processed excipients, slightly modified excipients, existing excipients used at higher levels of use than what has previously been used, or something being used in a different route of administration than previously has been used or even materials such as some pre-mixed excipients.” Schoneker shared the latest on excipient innovation in the latest episode of the DCAT Value Chain Insights podcast, Production to Prescription.

IPEC-Americas, along with the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium), a technically focused organization of bio/pharmaceuticals companies involved with advancing science-based and scientifically-driven standards and regulations, were instrumental in working with industry and FDA to bring the PRIME program to its initial pilot with the hope that it would be fully adopted to facilitate innovation in excipients.

“The program would have been probably one of the best things to happen to innovation and drug development and excipient development in many years,” says Schoneker, “for finally having a pathway for novel materials to come through that could then be brought forward with less risk into drug applications. It would have spurred the development of novel excipients.”

The pilot program has since been deprioritized in FDA and has not progressed further, so industry is examining other ways to facilitate innovation in excipients. “We were hoping that if PRIME were successful here in the US, that we could work with FDA and possibly get this concept into discussions with ICH [the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use], so that other countries could move in that direction as well,” says Schoneker. “But we are kind of back to the drawing board [now] and are trying to come up with other ways to address this.”

To that end, “IPEC-Americas is looking for other ways to try to mitigate some of the risk that is out there, or is perceived, I should say, with bringing forward novel excipients, so that we can try to get innovation back on track,” says Schoneker. He explains when looking at novel excipients, the focus is typically on the use of novel excipients with new chemical entities in a drug formulation under a NDA because the material does not have prior human use, but “that is only a small segment of real innovation and development in the excipient industry,” he says.

IPEC-Americas is currently working on an initiative to develop a guide for the use of what it is terming as “new excipient products,” which would entail other excipient types, such as modified excipients, co-processed excipients, pre-mixed excipients, higher levels of use, different routes of administration, materials used in foods or cosmetics for pharmaceutical use, with “all of these different types of materials that already have a lot of supporting safety data out there that could, in many cases, easily be bridged to the new use with different ways of justifying their use scientifically,” he explains. “The only type of newl excipient product, where there’s really a significant risk from a safety perspective because it may be unknown until studies are conducted, would be the truly novel new chemical entity type of excipient.”

IPEC-Americas has begun an initiative to develop a new guide on new excipient products by developing a process that could be applied to each type of new excipient product by building decision trees on the steps that companies would need to go through to understand the data needed for each type of new excipient product and what needs to be considered in evaluating whether to go forward with such a product. These would include not only scientific and technical considerations but also economic and marketing considerations that would be part of the decision-making to bring a new excipient product forward.

The IPEC-Americas team that is working on this initiative (under the Regulatory Affairs Committee) presented draft decision trees in a workshop at a recent IPEC conference, Excipient World, held in Nashville, Tennessee in May (May 2026) to gain feedback from the industry on the draft decision trees. The next phase of the initiative is to further build out these decision trees and the guide itself on how to use these decision trees with the goal of having the guide serve as a useful tool for both excipient manufacturers and users. The team is aiming for a draft of the guide to be potentially developed by the end of this year (2026) with the aim of presenting the guide at the 2027 installment of IPEC-America’s Excipient World conference.  Once the draft is developed, the team hopes to share it with FDA for its feedback as well before finalizing it for publication.