In an important step to modernize drug formulation and biopharmaceutical development, the FDA is launching a program to test the safety and suitability of new excipients for use in new drugs and biologics. This latest initiative, first proposed two years ago, will support a pilot program to test up to four new excipients with the potential to improve the efficacy and safety of important new drugs (1). The goal is to encourage clinical trial sponsors to test new drugs formulated with excipients that the FDA deems acceptable for use in this program.
The FDA announced the pilot program on September 7, 2021 and clarified the application process in a Federal Register notice (2). The advisory explains that the pilot is open to new excipients that have not previously been used in foods or in products approved by the FDA. Excipient manufacturers wishing to participate in the pilot project should submit information on the new inactive ingredient and its potential to improve health by providing pharmacokinetic characteristics important for the development of new drugs, as described in an outline of a proposal. initial (3). The sponsor must also show that it can produce a complete information package within the time limit for weighing the pilot proposals. Initial pilot review proposals must be submitted to the FDA by December 7, 2021.
The FDA defines a new excipient as an inactive ingredient that is not fully supported by existing safety data regarding a proposed level of exposure, duration of exposure or route of administration. Manufacturers should describe how the product meets a public health need and advances drug development, for example by increasing the solubility of an oral formulation taken chronically. Sponsors should also describe the available quality and toxicology information that supports the safety of the product, such as pharmacokinetic / toxicokinetic data and other non-clinical information, as presented in the FDA guidelines published in 2005 (4 ).
From these submissions, the FDA will select four products for a full review as part of the pilot, with two scheduled in the first year. Selected participants must then provide a complete set of toxicological and chemical grade, manufacturing and control (CMC) data, as required for the excipients. If the excipient passes the test, the FDA will determine that it can be used in the formulation of an investigational drug during clinical trials, provided the sponsor demonstrates that it is safe to use in this therapy. Once the FDA approves a new drug or biologic using the new excipient, that excipient would then be added to the FDA’s inactive ingredient database, making it available for use by other manufacturers, including those who produce generic drugs.
Manufacturers of drugs and biologics, as well as developers of excipients, have long sought a process for the FDA to assess new inactive ingredients before using them in a new drug or biologic. A continuing difficulty is that promoters of new drugs are reluctant to delay or complicate the review and FDA approval of a new investigational drug (IND) for investigational therapy due to the need to assess an ingredient. inactive not tested in the product formulation. Yet these companies are finding it increasingly difficult to formulate innovative products with available and established excipients. Biopharmaceutical companies have expressed support for the pilot project as a way to address these development challenges, such as the need for new ways to stabilize proteins for bioavailability in new formulations. Excipient manufacturers also recognize that they would be more willing to invest in the production, controls and characterization of new excipients if it were possible to obtain FDA review of the product’s benefits outside of clinical trials for a new molecular entity.
The FDA first proposed this process to assess new excipients separately from new drug applications in a Federal Register notice published in December 2019 (5). This draft plan asked manufacturers to comment on the proposed program, its definitions and scope, and the FDA sought to address these issues in this final proposal.
It seems appropriate that the FDA is launching this new pilot excipient program as the International Council for Pharmaceutical Excipients, IPEC-Americas, celebrates its 30th anniversary. IPEC held its first meeting in March 1991, with the aim of harmonizing excipient standards set by different pharmacopoeias and addressing important global issues for the use of excipients. The manufacturers of these essential ingredients in pharmaceutical formulations note that many well-known excipients that have been in use for decades are unsuitable for the new dosage and parenteral forms under development today (6). The industry would also like to see an update to the 2005 FDA guideline on safety testing of excipients, mentioned earlier. These initiatives, along with ongoing efforts to establish international standards for the use of excipients, have the potential to improve drug formulation and support modern manufacturing and quality control efforts.
1. FDA, New Excipient Review Pilot Program, FDA.gov, accessed September 14, 2021.
2. FDA, Office of New Drugs Center for Drug Evaluation and Research New Excipient Review Program, Avis, September 8, 2021.
4. FDA, Guidelines for non-clinical industry studies for the safety evaluation of pharmaceutical excipients (CDER, CBER, May 2005).
5. FDA, Proposal for a review program for new excipients; Request for information and comments, Federal Register, 84 FR 66669, December 5, 2019.
6. C. Challener, PharmTech 45 (3) (March 2021).
About the Author
Jill Wechsler is the editor-in-chief of Pharmaceutical Technology in Washington, firstname.lastname@example.org.
Book 45, Number 10
When referring to this article, please cite it as J. Wechsler, “FDA Moves to Advance Innovative Excipients, Pharmaceutical technology 45 (10) 2021.