Structured Product Labeling (SPL) is a document markup standard developed by Health Level Seven (HL7) and adopted by the FDA as the required format for submitting product and facility information. Currently, the following submissions must be filed with the FDA in SPL format. DCL can convert your data and prepare these files to meet all FDA requirements:
Drug listings
Establishment Registrations
NDC Labeler Code Registrations
Lot Distribution Reports
Annual Reporting by Prescription Drug Wholesale Distributors and Third-Party Logistics
REMS Documents
Self-Identification of Generic Drug Facilities
The following submissions MUST be provided to the FDA in SPL:
Drug listings
Establishment Registrations
NDC Labeler Code Registrations
Lot Distribution Reports
Annual Reporting by Prescription Drug Wholesale Distributors and Third-Party Logistics
REMS Documents
Self-Identification of Generic Drug Facilities
For drug listings and REMS documents, submissions should include both the Word documents used for review and the final SPL file. Negotiations are done in Word, but the FDA requires that the SPL version be submitted as well.
Drugs and APIs, once initially listed, must be certified every year. This can be done either by submitting an updated listing at least once during the year or, if there are no changes, by submitting a Blanket No Change Certification (BNCC) SPL file that includes the product code.
Establishment registrations, Prescription Drug Wholesale Distributors, and Generic Drug Facilities must file annually, according to the schedule specified in the regulations.
NDC Labeler Code registrations, after their initial submission, only need to be updated when information changes. However, we recommend reviewing these registrations at least once a year to ensure that all details—especially contact information—remain accurate.
See FDA’s Structured Product Labeling Resources page for more information and links.
All drugs and API must be listed by the manufacturer (foreign or domestic), using their labeler code (the first segment of the full NDC). If the manufacturer is not the labeler for the final product sent to pharmacies, hospitals, and other health care providers, it is a manufacturer listing, containing only the drug product information, and package labels. They do not require the Content of Labeling (such as package inserts for prescription drugs, and Drug Facts for OTC Monograph drugs).
See 21CFR207.41(c)(2) for additional information.
Manufacturer listings are done where the manufacturer’s shipped product is:
A bulk ingredient (used for APIs [Active Pharmaceutical Ingredients]); its listing is document type and marketing category Bulk Ingredient
Drug for further processing (manufacturer’s product needs additional work such as packaging and/or labeling by another establishment before being commercially distributed); its listing is document type and marketing category Drug for Further Processing
Manufactured under contract (product is ready for commercial distribution under a different labeler code); note that:
The product may be commercially distributed by another drug manufacturer, that contracted with another manufacturer to manufacture this particular drug; in that case, the manufacturer distributing the drug manufactured by another company is, in that context, a private label distributor The NDCs in the drug product information use the manufacturer’s labeler code, the document type is the same as the PLD’s (such as Human Prescription Drug Label) and the marketing category is xxx Drug Product Manufactured Under Contract (xxx is based on the PLD’s marketing category - “Approved” for any drug approved under an application, “OTC Monograph” for any OTC Monograph drug, Unapproved for any unapproved drug (such as a homeopathic drug).
See 21CFR207.41, (c)(2) for additional information.
A distributor listing is the one done for the drugs provided to pharmacies and health care providers. In SPL, prescription drugs are listed with their application type and number, OTC drugs compliant with a monograph are listed as OTC Monograph Drug with their monograph number, all other drugs are listed with the approved “unapproved” marketing category.
See 21CFR207.41(c)(1) for additional information.
Distributor listings are done where the marketing category is any of the other marketing categories other than bulk ingredient, drug for further processing, or manufactured under contrac. Those marketing categories are OTC Monograph Drug, any of the application type marketing categories such as NDA or BLA. The NDCs in drug product information use the distributor’s labeler code. If the manufacturer is the distributor, only the distributor’s listing is done.
Under certain circumstances, a product distributed by a domestic manufacturer that is produced by the manufacturer at a foreign site that it fully owns may have both listings for import reasons – the manufacturer’s listing for the domestic manufacturer’s foreign site and the distributor’s listing for the domestic manufacturer/distributor that distributes the product.
When a manufacturer fully manufactures and commercially distributes its products, the listings are normally handled by the manufacturer or someone with whom they contract. In our experience, the only exception is the drug sponsor who takes on that responsibility, but they need to make sure the manufacturer is aware of that. In all other cases, the various parties (manufacturer, US agents, and distributors) need to know who is handling the listings. As indicated previously, there are manufacturer and distributor listings handled by a party other than the manufacturer. In other cases, the distributor listing are contractually assigned by the distributor to the manufacturer.
If a company is already tracking whatever listings it is handling, all is well and good. In practice, though, we are finding that many companies have not been doing that tracking; if the listing is not certified in a given year, it will automatically be inactivated early in the following year,
See 21CFR207.41, (c)(1) for additional information.
Per FDA requirements, the manufacturer is responsible for all drug listings, including listings done for private label distributors (PLDs) using the PLD’s National Drug Code (NDC) labeler. The actual listings may be done by
Private label distributors
US agents for the manufacturers
Importers of the manufacturers, regulatory consultants, and drug sponsors acting on behalf of the manufacturers or distributors
Placing the requirement on the manufacturers means that if a listing is not done it is the manufacturer that is responsible, even if it is a listing for a private label distributor.
See 21CFR207.41, (c)(1) and (c)(2), at this page; (c)(1) is for distributor listing, (c)(2) for manufacturer listing.
The FDA charges manufacturers of Over-the-Counter drugs an annual fee. Please see FDA’s Over-the-Counter Monograph Drug User Fee Program (OMUFA) webpagefor detailed information, but the contact points at FDA:
For questions about the program, or regarding refunds and waiver requests, contact FDA by email to CDERCollections@fda.hhs.gov or call to 301-796-7900
For questions about paying the fee or confirming the status of a payment, contact FDA by email to the User Fee Helpdesk at userfees@fda.gov or call to 301-796-7200.
In August of 2016, the FDA published the Final Rule for drug listings in the Federal Register. That rule became effective in 2017. In broad terms, the requirements of the Final Rule are not much different from the previous regulations, in that manufacturers need to keep their listings up to date, revising them by the June or December that follows any revision. While the previous regulations required that listings be updated as needed, the FDA strengthened that requirement by making two changes to the regulations:
Making it clear that a manufacturer, domestic or foreign, had to list the drugs they manufacturer using their labeler code, even if they shipped it for distribution by another company.
Requiring that a drug listing be certified annually, either by 1) being submitted at least once during the year, or 2) including its product code in a Blanket No Change Certification (BNCC) file; previously, if the last SPL listing was still accurate, nothing needed to be done.
Companies may encounter validation errors when they submit their listings, and, during the course of the year they may receive letters from the FDA, notifying them that their listings will be inactivated if they do not update their listings.
The most common type of validation issue when submitting a revised listing for an existing drug is because they changed the drug product information that requires a change to the product code (such as the active moiety), or the package code (such as the package type). If the actual product or package did change, that requires a change to the appropriate code, but, if you are correcting the previously submitted information, you can request an override, explaining that you are correcting the information.
FDA inactivates listings in February if either the listing was not certified the prior year (the listing itself was not submitted the prior year and its product code was not included in a BNCC in the last quarter of the prior year), or an establishment in the listing did not renew its registration in the prior year. In July a listing will be inactivated if an establishment in the listing de-registered.