Excipient Regulatory status

Some safety issues for excipients with a history of use may be addressed by citations of the clinical and nonclinical database, marketing history, or regulatory status of the compound, e.g., GRAS status as a direct food additive may support oral administration of that product up to the levels allowed in foods. 

Uchiyama M. Regulatory status of excipients in Japan. Drug Inform J 1999 33 27. 

In a recent article, the FDA stated For excipients with a history of use, it may be possible to adequately address some or all of the safety issues through citation of the existing nonclinical and clinical database, marketing history, or regulatory status of the compound (e.g., GRAS status as a direct food additive may adequately support oral administration of that compound up to the levels permitted in foods) (25). Therefore, it appears reasonable that the FDA would consider the use safety data based on the food additive regulatory status of an excipient to evaluate the safety of the excipient. If a new excipient has undergone a food additive safety review, this may reduce the perceived risks associated with the development and use of a new excipient. 

Many pharmaceutical excipients are food additives or GRAS substances that have been used in foods for many years. The Handbook of Excipients provides information in the regulatory status section for the accepted uses of excipients in foods (27). In addition, Appendix II of the Handbook lists the E number for excipients that are approved as food additives in the EU. 

CDs are not standard inactive ingredients, and their uncertain regulatory status causes hesitancy in their use in formulations. A common perception exists that an approval process is in place for the evaluation of new excipients, such as the CDs. In fact, there is no mechanism for submission and review of data on a new excipient that would lead to approval of that excipient. In the United States, the FDA reviews a new excipient only in relationship to the review of a drug formulation. Only the final drug product is approved by the FDA. By this method the excipient... 

It is also necessary to consider the regulatory status of excipients and any country-specific requirements or constraints. The U.S. and Japanese regulatory agencies publish lists of excipients used in medicinal pro-ducts. The materials listed in these compendia can generally be considered suitable for administration by the route for which they are already being used. For materials with no history of previous use, evidence must be provided that they do not compromise patient safety nor induce any other undesirable effects. 

Currently, regulatory agencies have not established safety-testing guidelines specifically for excipients. ° Under U.S. law, a new pharmaceutical excipient, unlike an active drug, has no regulatory status unless it can be qualified through one or more of the approval... 

Section 16, Regulatory Status, describes the accepted uses in foods and licensed pharmaceuticals where known. However, the status of excipients varies from one nation to another, and appropriate regulatory bodies should be consulted for guidance. 

Handbook of Pharmaceutical Additives Excipients used in prescription and OTC products approved by the FDA or recommended by USP/NF, BP and Ph.Eur. details manufacturers, composition, properties, function and applications, toxicology and regulatory status of additives Compiled by M. and 1. Ash Published by Gower, Aldershot, UK, and Vermont, USA... 

Microbial Considerations Does not support microbial growth Regulatory Status Cosmetic and pharmaceutical excipient Supplier Barnet... 

Regulatory Status PEG-6 to PEG-150 are USP/NF/FCC listed in the Handbook of Pharmaceutical Excipients and in the Handbook of Food, Drug, and Cosmetic Excipients not reviewed by CIR... 

In an attempt to increase the likelihood of regulatory and pharmaceutical industry acceptance of new excipients, excipient manufacturers have made several attempts to foster a regulatory environment that provides mechanisms for acceptance of new and novel excipients. Attempts to create a preapproval review or formal status for excipients have not been successful, and are likely not to be in the interests of the industry nor economically feasible for regulatory agencies. 

After the excipient has seen extensive utilization in multiple marketed products, the regulatory system has a process for review of the data resulting in possible inclusion of the monograph in the Japanese Pharmacopoeia (JP). The JP defines the mandatory standards for substances used in a pharmaceutical product. Inclusion in the JP establishes precedent status for the excipient and this notation permits use of the material in new drug products under defined conditions without the need to submit extensive supporting data. 

The Handbook of Pharmaceutical Excipients is a reference work containing a compilation of information on the uses and properties of pharmaceutical excipients, and the reader is assumed to possess the necessary knowledge to interpret the information that the Handbook contains. The Handbook of Pharmaceutical Excipients has no official status and there is no intent, implied or otherwise, that any of the information presented should constitute standards for the substances. The inclusion of an excipient, or a description of its use in a particular application, is not intended as an endorsement of that excipient or application. Similarly, reports of incompatibilities or adverse reactions to an excipient, in a particular application, may not necessarily prevent its use in other applications. Formulators should perform suitable experimental studies to satisfy themselves and regulatory bodies that a formulation is efficacious and safe to use. 

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