By Susan Crane, EAS Independent Consultant
It’s now been 5 years since FDA updated the regulations for establishment registrations and drug listings. Despite numerous on-line reference materials and tutorials available, it appears that some companies still have difficulties understanding and meeting these two regulatory requirements in a compliant manner. For those who struggle with the concept and practice of creating or updating these submissions, this article will aim to clarify some misconceptions.
There are two numbers that are often confused; the Unique Facility Identifier (UFI) and the Establishment Registration Number (EIN). The UFI is the DUNS number that is included with the initial registration of the establishment and must also be included with any labeler code request submission and drug listing. As such, any entity that does business with FDA must obtain a DUNS number specific to their business location from Dun and Bradstreet. The EIN on the other hand, is a number assigned by the FDA to registered establishments AFTER the facility has been duly registered for the first time. In neither case does the FDA issue any type of certificate but the information can be accessed / viewed in applicable, publicly available, databases should verification of registration be needed.
Another common misconception relates to who (i.e., what type of facility/business) is required to register. Only those companies engaged in actual product manufacturing, repacking, relabeling or salvaging (unless otherwise exempt as provided for in the regulation) are required to register. Note that the term “manufacture” includes each step in the manufacture, preparation, propagation, compounding, or processing of a drug. The regulations specifically state “Manufacture includes the making by chemical, physical, biological, or other procedures or manipulations of a drug, or an animal feed bearing or containing a new animal drug, including control procedures applied to the final product or to any part of the process. Manufacture includes manipulation, sampling, testing, or control procedures applied to the final product or to any part of the process, including, for example, analytical testing of drugs for another registered establishment’s drug.”
This does NOT include private label distributors (defined as a “person who did not manufacture, repack, relabel, or salvage the drug but under whose label or trade name the drug is commercially distributed.”) However, private label distributors must have their own labeler code under which any product marketed in their name is duly listed.
One important change made more recently to establishment registrations concerns those companies that manufacturer over-the-counter (OTC) drugs. As a result of the CARES Act signed into law in 2020, facilities that manufacture OTC monograph drugs must now pay an annual user fee, the amount of which is determined each year based on the number of registered facilities. Companies that are affected by this law should ensure that their facility registration is both kept up-to-date and more importantly, de-registered if no longer manufacturing product (to avoid both being included in the fee calculation and assessed the eventual amount.)
Drug listings also have their own set of issues that many find confusing. In a presentation to interested parties last year, the FDA highlighted some of the more common errors in drug listings, with the most significant being an incorrect declaration of the strength of the active ingredient. It’s not difficult to find examples of this when comparing product labels to the SPL data found on Daily Med. Those responsible for listing submissions should ensure that they understand how active ingredient strength is both calculated and expressed. Other common errors cited were incorrect NDC, incorrect or missing active ingredients, and incorrect or missing Establishment information. It’s very important that listing information submitted is complete and correct; FDA has been issuing warning letters to companies for both failing to list AND for incorrect listings.
Another common misconception concerns those products that are manufactured for private label distribution. Such products must be listed under an NDC using the labeler code of the private label distributor AS WELL AS an NDC using the labeler code of the manufacturer, even if the manufacturer does not commercially market that product under its own trade name. For example, Company ABC manufactures a fluoride toothpaste for 3 different retail chains. The same formula is used in all; only the labeling differs. In this case, Company ABC would list the product once under their own NDC (with a marketing category indicating the product is manufactured under contract) and also list that same product under an NDC for each of the retailers, using their assigned labeler codes.
Drug listings should be updated whenever there is a change to the product or its label but must, at a minimum, be updated or otherwise certified that no changes occurred during a given calendar year. This coincides with the annual Establishment Registration renewal period between October 1 – December 31. Failure to update listings will result in the product being removed from FDA’s NDC Directory or unfinished drug download file. The FDA considers these products expired and their continued marketing is in breach of regulations. Even if the product is no longer being marketed, listings should be updated to reflect that fact so they can be correctly removed from FDA’s databases.
Finally, the issue of National Drug Code numbers should be mentioned. While the labeler code portion (first 4 or 5 digits) is straightforward, many companies struggle with the concept of the product code and package code and how these should be assigned.
The middle digits of the NDC comprise the product code and should reflect the unique characteristics of the product itself – active ingredient/strength, dosage form, physical characteristics (color, shape, flavor, scoring, imprint, etc.) There is no set procedure or pattern for assigning this number but it will be unique to each firm based on their choosing. Different formulations, or different strengths of the same formulation, should have different product codes. Likewise, products that share the same formulation but have different characteristics (e.g., shape, color) should also have different product codes.
The final digit(s) of the NDC is the package code which differentiates between the quantitative and qualitative attributes of the product packaging, like the number of pills a bottle, or the weight or volume of a product, or the type of package like bottle, blister pack or tube. The same product marketed in more than one package configuration would all be included in the same drug listing, even if new package sizes are added subsequent to the initial listing.
Unfortunately, many companies just randomly assign NDC numbers with no consideration given to what each part represents. While this may not present an issue if there are only a few products involved, as a company grows and products get added, failure to have a uniform system for assigning NDCs (and documented in a procedure) will make listings more difficult; not to mention they do not meet the requirement set forth in the regulations.
The information provided above is not all-inclusive with regard to the establishment registration and drug listing requirements as new regulations and laws get enacted over time. Companies should keep abreast of these developments to ensure that their submissions and procedures are compliant with FDA’s expectations. As always, EAS Consulting Group is available to answer your questions or assist with these activities.
Posted in Issue of the Month, Medical Devices.