Structured Product Labeling (SPL) is a document markup standard approved by Health Level Seven International (HL7) and adopted by the United States Food and Drug Administration (FDA) for the submission of product information in the eCTD format. SPL files contain essential product information such as active ingredients, dosage, route of administration, product labeling information, and product packaging information. SPL documents are designed to improve the safety and effectiveness of products by making the information easier to search and access.

A Structured Product Monograph (SPM) is a document that contains detailed information on the therapeutic use of a new drug or other health product, such as a medical device, biologic, natural health product, nutraceutical or veterinary drug. It is developed by the manufacturer and approved by Health Canada. The SPM outlines the product’s approved indications (uses), dosage and administration, pharmacology, safety and efficacy data, contraindications, warnings/precautions, adverse reactions, as well as other pertinent information. It is an important reference document for healthcare professionals, as it provides comprehensive product-specific information necessary for safe and effective product use.

SPL documents are created in XML and provide a standard way to exchange information about a product or product-related services, such as product labeling, prescribing information, and clinical trials. The SPL format is designed to improve the ability of healthcare providers and patients to access information about a product.

Structured Product Labeling (SPL) includes the following elements: 

• Product information: Name, active ingredients, dosage form, route of administration, strength, package size, and type of packaging. 
• Manufacturer information: Name, address, and contact details. 
• Clinical information: Indication(s) for use, contraindications, warnings, precautions, adverse reactions, drug interactions, and dosing. 
• Labeling information: Brand name, storage instructions, approved uses, and expiration date. 
• Regulatory information: FDA approval status, Drug Enforcement Administration (DEA) registration number, and/or National Drug Code (NDC) number. 
• Patient information: Safety information, dosage instructions, and potential side effects. 
• Miscellaneous information: Product images, professional articles, patient educational materials, reference materials, and links to other relevant resources.

Structured Product Labeling (SPL) requirements are a set of standards established by the FDA for the creation and distribution of product information in a standard format. They are designed to help healthcare professionals and consumers better understand product information, such as specific active ingredients, indications for use, dosing information, and other important safety information. SPL requirements are also used to help ensure product safety by providing traceability of the product back to its manufacturer.

Structured Product Labeling (SPL) submissions go to the Drug Registration and Listing System (DRLS) of the U.S. Food and Drug Administration (FDA).

Structured Product Monograph (SPM) submissions go to Health Canada.

Pharmaceutical companies must submit various kinds of SPL files to the FDA to obtain approval to market their drugs, including:

• Drug listing (FDA)
• Establishment registration
• NDC Labeler Code request
• Lot Distribution Report
• Wholesale Drug Distributor/Third Party Labeler registration
• GDUFA Self-Identification
• Blanket No Change Certification

In order to sell drugs and NDCs in the United States, drug companies must register their products with the FDA. This registration requires the submission of detailed product information, including the labeler, ingredients, application numbers, packaging configurations, and labeling content. This information is then stored in the National Library of Medicine’s DailyMed repository.

All drug manufacturers in the U.S. must register with the FDA, providing the address and contact information for their establishment, as well as details of any importers and U.S. Agents they work with. Each registration is only valid for a single establishment, even if the registrant owns multiple establishments.

The FDA assigns a unique three-segment National Drug Code (NDC) to each product or drug it regulates. The first segment, the Labeler Code, identifies the Labeler entity that owns the product or markets it under their name or the facility that produces it. Labeler Codes are obtained and maintained by submitting NDC Labeler Code files to the FDA.

The Lot Distribution Report (LDR) SPLs for biologic drugs must be submitted to CBER every six months, unless a waiver is granted for them to be submitted annually. This report should contain bulk, package, and label lot data, along with the bulk manufacturer’s details and product data elements as listed in the drug listing file. Additionally, all packages distributed during the reporting period should be included.

Every year, the FDA requires Wholesale Drug Distributors (WDD) and Third-Party Logistics Providers (3PL) to submit a single SPL file containing their license information for every state in which they do business. If the same facility operates as both WDD and 3PL, they must include the license number for each operation in the same file, even if the numbers are the same.

Human generic drug facilities must submit an Establishment Registration file and a GDUFA Self-Identification SPL file annually to the Generic Drug User Fee Amendments (GDUFA) in order to be registered. Although the two files contain similar information, they are distinct due to the differences in their operations and require separate submissions.

For a product to remain FDA-certified, its listing information must be updated to reflect any changes or recertified using a Blanket No Change Certification (BNCC) SPL file. This can only be used for drugs that have not been altered since the last submission and that have passed the current validation procedures. If an NDC Code hasn’t been submitted using these methods by the end of the calendar year, the product and its NDC Code(s) will lose certification on January 1 of the following year. Expired listings will be removed from the NDC Directory and may not be sold or marketed until the information is resolved.

Companies must submit WDD/3PL reports to the FDA annually between January 1st and March 31st.

To comply with GDUFA requirements and ensure their fees are accurate for the year, companies must submit their GDUFA files to the FDA between May 1 and June 1 annually.

Every year, organizations have between October 1 and December 31 to submit BNCC files.

Companies use pharmaceutical labeling submission software to ensure FDA and Health Canada compliance. This software helps streamline the process of creating, validating, and submitting the required Structured Product Labeling (SPL) in the U.S. and Structured Product Monograph (SPM) in Canada.