The Implications of FDA Drug Listing Requirements
Structured Product Labeling (SPL): History and Background
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:
A drug last listed using paper forms must be listed electronically using SPL, which is an XML format. Electronic listings began in June 2009 for listing new drugs and revising existing listings; drug listings that hadn’t changed since they were last listed using paper forms previously did not need to be listed using SPL.
A drug listing is considered certified either by
being submitted at least once during the year
including its product code in a new type of SPL file, Blanket No Change Certification (BNCC).
Previously, if the last SPL listing was still accurate, nothing needed to be done.
How to Comply With FDA Requirements?
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.
Manufacturers’ Labeler Codes vs Distributors’ Labeler Codes
These are listings done where the product’s marketing category is
a bulk ingredient (used for APIs (Active Product Ingredients))
drug for further processing (product needs additional work such as packaging and/or labeling by another manufacturer before being commercially distributed)
manufactured under contract (product is ready for commercial distribution by a private label distributor; note that:
a private label distributor in this context can be a drug manufacturer that distributes a drug manufactured for them under contract by a different drug manufacturer)
The manufacturer in this case is not necessarily the manufacturer of the drug, it can be the company that bought the drug either in bulk from the drug manufacturer and packaged and labeled it, or in packages from the packager of the drug and placed labels on the packages; the FDA includes manufacturing, packaging, and labeling in the overall manufacturing process for drugs.
The NDCs in the drug product information use the manufacturer’s labeler code.
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 contract (OTC Monograph Final/Not Final, any of the application type marketing categories such as NDA, or any one of the “unapproved” marketing categories such as unapproved medical gas).
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. They are having a relatively easy time of making any updates or submissions this year. In practice, though, we are finding that many companies have not been doing that tracking.
Meeting the Latest FDA Drug Listing Regulations
Companies first need to make sure their drugs are currently considered active by searching the NDC Directory (for drugs not listed under Drug Manufactured under Contract) or by contacting the FDA's Electronic Drug Registration and Listing System (EDRLS, firstname.lastname@example.org) for drugs listed under marketing category Drug Manufactured under Contract.
The FDA is classifying as inactive all drug listings not certified in the prior year, and, if all drug listings for a labeler code are inactive, the FDA marks the labeler code itself as inactive. To re-activate an inactive labeler code you need to ask the FDA to re-activate the labeler code by contacting email@example.com; a drug listing is made active again by resubmitting it, but only if the labeler code is active.
To check the status of any drug listing other than those listed under marketing category Manufactured Under Contract, use the NDC Directory's searchable database at https://www.accessdata.fda.gov/scripts/cder/ndc/index.cfm, or the new NDC Express Mobile Application (download from either Apple's App Store or Google Play). Search by:
Clicking on Finished Products for listings under marketing categories other than Bulk Ingredient, Drug For Further Processing, or Manufactured Under Contract (i.e. Distributor Listing) or clicking on Unfinished Products for listings under marketing category Bulk Ingredient and/or Drug for Further Processing
Selecting from pull-down list to Select Type. We recommend NDC Code if known.
Entering text in the "Enter at least three characters" window; we recommend entering the NDC code with either the first 2 parts or all 3 parts for specific product code, or only 1st part to see all product codes for the labeler
If the results show all the information for an NDC then the product is active, if only limited information than the product is inactive and should not be distributed.
If a listing is inactive, reactivate by re-submitting the last successful listing after, at a minimum, updating the document id and version number; other changes may be needed in order to meet current SPL validation rules. If you don't have the last listing you need to either download it from the DailyMed if it is there, or re-create it. To re-create it you need to contact the FDA’s Electronic Drug Registration and Listing System (EDRLS; firstname.lastname@example.org) group for the setId and version number used in the last listing.
In searching the NDC Directory, products may be found that are no longer being manufactured. Whether those products are considered active or inactive by the FDA, they should be de-listed. De-listing means taking the last listing or re-creating the listing and changing the marketing status to "completed" and adding an end marketing date for the product, the expiration date of the last lot manufactured; de-listing should be done so the FDA's database are up-to-date.
Once a company determines that its listings are all active, nothing needs to be done until the last calendar quarter of the year. In the last quarter the company needs to either re-submit its labels that were not submitted earlier in the year, or include all product codes in a Blanket No-Change Certification (BNCC) file all product codes that were not submitted during the year; we recommend the BNCC; do not include in a BNCC product codes that have been de-listed, a de-listed product code in a BNCC will cause a validation error.
Pharma and manufacturing companies need to establish ongoing procedures to review listings and update them by the following June or December after a change is made.
On an ongoing basis the FDA is reviewing drug listings and if they find issues they will issue a data deficiency notice to the manufacturer and require that the deficiency be rectified by a certain date in a revised listing submission. That listing certifies the label for that year and the product code(s) in the label do not need to be included in a BNCC for that year.
Meeting the latest FDA drug listing regulations can be a major task for many companies. However, this disciplined approach guarantees that the FDA has the latest information to ensure the safety of our nation’s drug supply.
DCL Can Create and Submit Your SPL
DCL helps many large pharma companies, small biotech startups, and manufacturers transition workflows to meet all FDA requirements. We continue to support organizations with the creation of SPL and the submission of that content to the FDA. Our team is active in the SPL working group. Our SPL conversion services include prescription drugs, OTC products, veterinary medicine, homeopathic products, and bulk ingredients.
Contact us today if you would like to learn more about how we can support your SPL creation and submission process.