Drugdu.com expert's response:

To query FDA-approved natural drugs and their sources over the past decade through the FDA drug approval databases, the following systematic workflow can be followed, integrating FDA official resources with natural product classification logic for efficient retrieval:

I. Define Search Objectives and Natural Drug Categories

Natural drugs typically refer to active ingredients directly derived from plants, microorganisms, marine organisms, or minerals, as well as their structurally modified derivatives. Key focus areas include:

Plant-derived: Examples include paclitaxel (from Pacific yew) and artemisinin (from sweet wormwood).

Microorganism-derived: Examples include erythromycin (from actinomycetes) and cyclosporine (from fungi).

Marine-derived: Examples include trabectedin (from sea squirts) and eribulin (from sponges).

II. Leverage FDA Core Databases for Screening

Drugs@FDA Database

Steps:

Access the database and select "Advanced Search".

Set the "Approval Date Range" to the past decade (e.g., January 1, 2015, to December 31, 2025).

Enter natural product-related keywords in the "Active Ingredient" or "Product Name" fields (e.g., "plant extract", "microbial metabolite", "marine-derived").

Download the drug labels (Label) and review documents (Review) from search results, focusing on the "Drug Substance" section to confirm ingredient sources.
Example: Searching for "Crofelemer" reveals its origin as red latex from the Croton lechleri tree in Peru.

DailyMed Database

Advantage: Provides FDA-approved drug labeling information, enabling direct searches by drug name or active ingredient to quickly locate the "Source" field.
Tip: Use keywords like "Source of Drug Substance" or "Origin" in label searches. For instance, searching for "Paclitaxel" displays its source as Pacific yew bark.

III. Refine Searches Using Natural Product Classifications

Plant-Derived Drugs

Keyword Strategy: Use terms like "plant-derived", "herbal", "phytochemical", or specific plant names (e.g., "Ginkgo biloba", "Taxus brevifolia").
Case Study: Crisaborole (Eucrisa), approved in 2018, is a synthetic benzoborole compound inspired by natural product library screening. Literature verification is required to confirm its source.

Microorganism-Derived Drugs

Keyword Strategy: Employ terms like "fungal", "bacterial", or "actinomycete".
Case Study: Omacetaxine mepesuccinate (Synribo), approved in 2012, is derived from alkaloids in Cephalotaxus and produced via microbial fermentation.

Marine-Derived Drugs

Keyword Strategy: Input terms like "marine", "sponge", "tunicate", or "algae".
Case Study: Trabectedin (Yondelis), approved in 2015, is extracted from Caribbean sea squirts for treating soft tissue sarcoma.

IV. Cross-Validation and Source Tracing

Compare Multiple Databases

Cross-check results from Drugs@FDA, DailyMed, and third-party databases (e.g., PharmaCloud) to ensure consistent source descriptions. For example, eribulin (Halaven) is consistently labeled as sponge-derived across databases.

Consult Authoritative Literature

Validate source classifications using journals like Journal of Natural Products and Marine Drugs. For instance, the FDA label for ingenol mebutate describes its source as "Euphorbia peplus extract", aligning with literature reports.

Distinguish Semi-Synthetic Derivatives

Some natural drugs are semi-synthetic (e.g., dihydroartemisinin derived from artemisinin). Clearly differentiate between "natural origin" and "fully synthetic" in searches. For example, atorvastatin (Lipitor) is synthetic but developed based on natural statin structures like lovastatin.

V. Analysis and Report Generation

Trend Analysis: Quantify natural drug approvals over the past decade to observe shifts in source proportions (e.g., rising microbial-derived drugs due to antibiotic demand).

Source Distribution Mapping: Create visualizations categorizing drugs by source (plant/microorganism/marine) and therapeutic area (e.g., oncology,抗感染/anti-infectives, metabolic diseases). Marine-derived drugs, for instance, often target oncology.

Case Studies: Analyze representative drugs (e.g., Crofelemer) to outline their journey from natural resource to FDA approval, covering source identification, structural optimization, and clinical trials.

Key Considerations

Terminology Precision: FDA databases may use Latin names or technical terms (e.g., "Taxus chinensis" instead of "Chinese yew"). Basic biological knowledge is essential.

Data Lag: New approvals may take weeks to months to appear in databases. Regular rechecks are advised.

Semi-Synthetic Classification: Explicitly label drugs as "natural origin + synthetic modification" if applicable (e.g., semisynthetic penicillins).

By following this approach, researchers can systematically compile FDA-approved natural drugs and their sources over the past decade, supporting drug discovery, natural product chemistry research, or regulatory policy analysis.