FDA Warning Letters focus on inaccurate drug product listings.
Over the last year, the US Food and Drug Administration (FDA or Agency) has increased its enforcement efforts concerning drug product listing requirements, resulting in a number of Warning Letters for what appear to be simple errors in electronic submissions of drug product listings.
The Federal Food, Drug and Cosmetic Act (FFDCA) and FDA’s implementing regulations require the listing of all commercially distributed drugs (including active pharmaceutical ingredients). In August 2016, FDA finally completed its rulemaking to adopt the 2007 amendment to the FFDCA that requires all drug establishment registration and drug product listing information to be submitted to FDA electronically in the absence of an Agency waiver.
While FDA has required electronic submission of this information via the electronic drug registration and listing service (eDRLS) for many years, enforcement activity for alleged violations of the listing requirements is fairly recent. Since March 2016, the Agency has issued five Warning Letters based solely on listing violations, two of which were issued in the last month. For example, FDA issued Warning Letters for the following submission errors:
- Failure to update drug listing files to reflect discontinuance of drug products
- Missing active ingredient and incorrect information
- Missing copy of the product label
- Incorrect spelling of the active ingredient
- Incorrect application number referenced
- Incorrect proprietary name included in the listing
- Incorrect quantity for the package size
- Incorrect strength of active ingredient
- Failure to include the drug product’s Drug Enforcement Agency (DEA) schedule
In all cases, FDA expressed concern that incorrect drug product listings are accessible to the public, including consumers. In most cases, asserting the need to “protect and promote the public health” by “maintain[ing] a correct and accurate database,” and citing misbranding and drug product listing violations under the FFDCA, the Agency immediately removed only the incorrect listings from FDA’s National Drug Code (NDC) Directory such that they would not be publicly viewable. In one case, however, FDA did not limit removal to just those listings that were incorrect—instead, stating that “FDA’s Drug Registration and Listing Staff does not have sufficient resources to check each of [the] drug listing files before the data is published,” the Agency refused to make any of the firm’s listing files public.
In addition to mandating correction of the inaccurate information in the drug product listings, FDA required each Warning Letter recipient to provide a plan to prevent a recurrence of the violations. In the case of the firm where FDA refused to make any of the firm’s listings public, the Agency required, at a minimum, that the response include the following:
- How the firm reviewed, or plans to review, all current drug listings to identify those listings that need to be updated
- How the firm corrected, or plans to correct, the identified errors (e.g., submit corrected Structured Product Labeling files for existing listings, delist NDCs no longer in use by submitting end marketing dates and changing marketing status to complete)
- The plan or process the firm has implemented, or plans to implement, in order to prevent the recurrence of the violations
While FDA occasionally cites noncompliance with the drug listing requirements in its enforcement letters, such observations frequently accompany other, more significant alleged regulatory violations. In these instances, however, the listing violations were the sole focus of FDA’s enforcement letters. Moreover, based on the text of the enforcement letters, in some cases, the FDA Warning Letter may have been the first time that the Agency notified the recipient of an issue with its drug listings. Many of the cited violations likely were administrative or clerical oversights that occurred when entering the drug information into the eDRLS.
While listing drugs is perceived as merely an administrative task, failure to list drug products or incorrectly listing products is a violation of the FFDCA, as the Warning Letters reflect. Failure to fulfill listing obligations misbrands the applicable product under the FFDCA, and the FFDCA further prohibits the introduction of misbranded products into interstate commerce.
Taken together, this round of Warning Letters indicates that FDA may be more apt to take public enforcement action based solely on a company’s failure to properly list drug products, even in the absence of any other violations, rather than sending private communications regarding errors through the eDRLS staff. The immediate removal of a product from FDA’s NDC Directory raises questions about ongoing distribution of the product pending FDA’s acceptance of the corrective measures. This situation is more complicated for imported drug products if they are subject to this type of enforcement action, as they may be refused entry into the United States until FDA accepts the corrective action.
It would appear that FDA is sending a public message to regulated firms regarding the importance of accurate and completed drug product listing submissions. As a result, firms should refamiliarize themselves with FDA’s listing requirements, consider reviewing prior electronic drug product listing submissions for accuracy and compliance with FDA regulations, and assess the need for an internal procedure to ensure current listings are appropriately updated and new listings are accurate and complete before submission.