Let’s start with a little 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 needs to be listed electronically using Structured Product Labeling (SPL) 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 needs to be certified every year as being up-to-date, either by being submitted at least once during the year or by 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.
This paper focuses on compliance with the requirements.
The FDA regards the manufacturer as responsible for all drug listings, including listings done for private label distributors (PLDs) using the PLD’s NDC labeler code. But, the actual listings may be done by private label distributors, U.S. agents for the manufacturers, importers of the manufacturers, regulatory consultants, and drug sponsors acting on behalf of the manufacturers or distributors.
The FDA’s placing the requirement on the manufacturers just 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.
Knowing Who Is Handling the Listings
Let’s now discuss the new requirements in terms of two types of listings, those made using manufacturers’ labeler codes and those made using distributors’ labeler codes.
First, there are Manufacturers Listings. These are listings done where the product’s marketing category is 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), or manufactured under contract (product is ready for distribution a separate distributor). The NDCs in the drug product information use the manufacturer’s labeler code.
There’s also Distributors Listings, which are listings done where the marketing category is OTC Monograph Final/Not Final, any one of the “unapproved” marketing categories such as unapproved medical gas, any of application type marketing categories such as NDA, or any of the other marketing categories other than a bulk ingredient, drug for further processing, or manufacturer under contract.
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. (For reasons outside the scope of this paper, 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 it contracts with.
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, U.S. agents, and distributors) need to know who is handling the listings.
As indicated earlier, there are Manufacturer’s and Distributor’s listings handled by a party other than the manufacturer. In other cases the Distributor’s 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.
Detailing How to Meet the Latest FDA Drug Listing Regulations
To catch up, we recommend contacting the FDA’s Electronic Drug Registration and Listing System (EDRLS; [email protected]) group for the setId and version numbers for the listing(s) for a particular NDC, product code, or labeler code, to verify what was the last listing.
In some cases, the last listing was done using a paper form (before June 2009) so they will need to prepare and submit SPL. In other cases they may find products that are in the FDA’s records as currently active but are no longer being manufactured. Those will need to be de-listed.
If the company cannot track down existing SPL files they either need to re-create them, download them from NLM’s DailyMed (https://dailymed.nlm.nih.gov/dailymed/index.cfm) or FDA’s Online Label repository (https://labels.fda.gov), or contact EDRLS and ask if the file can be provided.
Going forward, after all products have either been confirmed as being unchanged or been updated a company should prepare a BNCC with all the product codes they are handling and submit it (before January 1). For 2018 and later years the company needs to establish an ongoing procedure 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.
During the fourth quarter period ending December 31, they should submit the BNCC after removing any product codes that have been de-listed, expired, or have a data deficiency not yet rectified (BNCCs with any of those product codes will not pass validation).
Meeting the latest FDA drug listing regulations has been, for 2017, a major task for many companies. But, moving forward with a disciplined approach it will be much simpler and ensure that the FDA has the latest information to ensure the safety of our nation’s drug supply.
About the Author
Howard Shatz is SPL Project Manager at Data Conversion Laboratory (DCL, www.dclab.com). DCL offers content conversion and regulatory and compliance services such as SPL & ACA6004.