Inactive Ingredients in FDA-Approved Drug Products

The Inactive Ingredient Database (IID) provides information on inactive ingredients present in FDA-approved drug products. This information can be used by formulation scientists to develop a new drug product.

According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product other than the active ingredient. Only inactive ingredients in the final dosage forms of drug products are in this database.

Understanding the role of inactive ingredients in FDA-approved drug products is crucial for drug development and safety. While they do not provide the primary therapeutic effect, these components play a significant role in the formulation, stability, and delivery of medications. This article dives into the Inactive Ingredient Database (IID), its purpose, and key details to help pharmaceutical professionals, researchers, and curious minds navigate this essential resource.

What Are Inactive Ingredients in Drug Products?

Inactive ingredients, as defined by 21 CFR 210.3(b)(8), are components of a drug product that do not contribute to the therapeutic effect. Unlike active ingredients, which are designed to diagnose, treat, or prevent diseases, inactive ingredients support the drug’s structure, stability, or delivery. Examples include fillers, binders, preservatives, and flavoring agents found in the final dosage forms, such as tablets, capsules, or injectables. The FDA’s Inactive Ingredient Database exclusively lists inactive ingredients used in approved drug products.

What Are Active Ingredients?

As per 21 CFR 210.3(b)(7), active ingredients are the components responsible for a drug’s pharmacological activity or direct therapeutic effect. These ingredients may undergo chemical changes during manufacturing, but remain in the final product to deliver the intended health benefits. For instance, an active ingredient in a pain reliever would target pain relief, while inactive ingredients ensure the tablet’s proper formation or dissolution.

Purpose of the FDA’s Inactive Ingredient Database

The Inactive Ingredient Database (IID) is a vital tool for pharmaceutical companies and researchers developing new drug products. It provides detailed information on inactive ingredients used in FDA-approved drugs, including their routes of administration and dosage forms. Once an inactive ingredient is approved for a specific use, it is considered safe for similar applications, reducing the need for extensive safety reviews in future drug formulations. This streamlines the drug development process and ensures compliance with FDA standards.

How to Use the Inactive Ingredient Database?

Searching the IID is straightforward. Users can enter at least three characters of an inactive ingredient’s name to retrieve results, which are sorted alphabetically by ingredient, route of administration, and dosage form. The database pulls data from current FDA-approved labeling, ensuring accuracy. Key fields include:

• Route of Administration: How the drug is delivered (e.g., oral, topical, injectable).
• Dosage Form: The physical form of the drug (e.g., tablet, cream, solution).
• Maximum Potency: The highest amount of an inactive ingredient per unit dose in approved products.
• Maximum Daily Exposure (MDE): The total amount of an excipient a patient might consume daily, calculated as the dosage unit level multiplied by the maximum recommended daily dose.

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What Is Maximum Potency?

Maximum potency refers to the highest unit dose of an inactive ingredient (excipient) listed in the IID for a specific dosage form. For topical products, it is expressed as the highest percentage of the product formula. This value is dynamic and updates as the FDA approves new products with higher excipient levels. Note that maximum potency does not always reflect the maximum daily exposure (MDE) unless the product’s maximum daily dose is a single unit.

What Is Maximum Daily Exposure (MDE)?

Maximum daily exposure (MDE), also known as maximum daily intake (MDI) for oral drugs, is the total amount of an inactive ingredient a patient could consume in a day based on the maximum recommended daily dose of the drug. It is calculated as:

MDE = Excipient amount (mg) × Maximum number of dosage units per day

MDE values may change as the FDA collects new data on approved drug products, making the IID a dynamic resource for tracking exposure levels.

Can Inactive Ingredients Be Considered Active?

In some cases, an ingredient can serve as both an active and inactive component, depending on the drug’s formulation. For example, alcohol may act as an active ingredient in certain antiseptic products or as an inactive solvent in others. Ingredients like reactants in radiopharmaceutical kits or those that facilitate drug transport are classified as inactive, even if they interact with active ingredients. The IID only includes ingredients intended as inactive by the manufacturer.

Does the IID Include Contaminants?

No, the Inactive Ingredient Database does not list contaminants found in approved drug products. It focuses solely on intentionally added inactive ingredients.

What Is a CAS Number?

A CAS Number is a unique identifier assigned by the Chemical Abstracts Service (CAS), a division of the American Chemical Society. These numbers help identify chemical substances and are useful for cross-referencing inactive ingredients in other chemical databases. While many inactive ingredients have CAS Numbers, the identifier itself holds no chemical significance.

What Is a UNII?

A Unique Ingredient Identifier (UNII) is part of the USP/FDA Substance Registration System (SRS), designed to assign unambiguous identifiers to substances in drugs, biologics, foods, and devices. UNIIs support health information technology, including Structured Product Labeling (SPL), which requires UNIIs for all ingredients. Not all inactive ingredients have a UNII, as only distinct substances qualify. Products like “purified water” or proprietary blends (e.g., OPADRY II) are not assigned UNIIs.

How Often Is the Inactive Ingredient Database Updated?

The FDA updates the IID quarterly, by the tenth working day of April, July, October, and January. This ensures the database reflects the latest approved drug products and excipient data.

How to Access the Inactive Ingredient Database?

The IID is available for download in delimited text and Excel formats on the FDA’s website. Historical data since 2009 is also provided to track changes over time.

Key Takeaways

1. Inactive ingredients are essential non-therapeutic components in drug products, listed in the FDA’s Inactive Ingredient Database.
2. The IID aids drug development by providing data on approved excipients, reducing the need for extensive safety reviews.
3. Searchable by ingredient name, the database includes details like maximum potency, MDE, CAS Numbers, and UNIIs.
4. Quarterly updates ensure the IID remains a reliable resource for pharmaceutical professionals.

Stay informed and leverage this powerful tool to enhance drug development and ensure patient safety.

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