Unique Ingredient Identifier (UNII)

The Unique Ingredient Identifier (UNII) is an alphanumeric identifier linked to a substance’s molecular structure or descriptive information, generated by the Global Substance Registration System (GSRS) of the Food and Drug Administration (FDA) . It serves as a standardized, non-proprietary, and unambiguous identifier for substances, ensuring consistency across regulatory and scientific domains. The UNII system classifies substances into distinct categories, including chemicals , proteins , nucleic acids , polymers , structurally diverse materials , and mixtures , adhering to the standards outlined by the International Organization for Standardization (ISO) in ISO 11238 and ISO DTS 19844.

Overview

The UNII is designed to be unique, permanent, and free to generate and use, making it an essential tool for regulatory agencies, researchers, and industries involved in drug development, biological products, and other regulated substances. The system is broad enough to encompass any substance, ranging from simple atoms to complex organisms, ensuring comprehensive coverage across scientific and regulatory applications.

Classification of Substances

The GSRS classifies substances into the following categories:

1. Chemicals: Defined primarily by their two-dimensional molecular structure, including stereochemical information.
2. Proteins: Identified by their amino acid sequences and essential modifications, though heterogeneity in protein structures may result in shared UNIIs for non-biosimilar substances.
3. Nucleic Acids: Defined by their sequences and any modifications present.
4. Polymers: Characterized by their structural repeating units and physical properties such as molecular weight or viscosity.
5. Structurally Diverse Materials: Includes heterogeneous preparations from natural sources, such as plant extracts and vaccines.
6. Mixtures: Combinations of substances that are not easily separable or defined by a single molecular structure.

Generation and Application

The GSRS generates UNIIs by analyzing molecular structures, protein and nucleic acid sequences, and descriptive information. For chemical substances, the preferred method of identification is through their two-dimensional molecular structure, as it provides critical information about the substance’s identity and stereochemistry. Nucleic acids are defined by their sequences and modifications, while proteins are identified by their end-group modifications and other essential features due to their inherent heterogeneity.

Polymers are defined by their structural repeating units and physical properties, such as molecular weight or viscosity, which are crucial for their characterization. Structurally diverse materials, such as plant extracts and vaccines, are inherently heterogeneous and are defined by their composition and source.

Examples of UNIIs

Collaboration and Governance

The GSRS is a freely distributable software system developed through a collaboration between the FDA, the National Center for Advancing Translational Sciences (NCATS) , and the European Medicines Agency (EMA) . The system was designed to implement the ISO 11238 standard, which is a core component of the ISO Identification of Medicinal Product (IDMP) standards.

The GSRS Board, which governs the system, includes experts from the FDA, European regulatory agencies, and the United States Pharmacopoeia (USP) . This collaborative approach ensures that the GSRS remains a robust and reliable tool for substance identification and regulation.