2021-08-23
1. Who must list, when, and how?
Registrants not exempt under 21 CFR 207.10 must submit the initial listing information for all drugs in commercial distribution at the time of their initial registration of their establishment(s) (21 CFR 207.21(a)).
Failure to provide any listing information required by section 510(j) of the Act is a prohibited act under section 301(p). Also, under section 502(o) of the Act, a drug is misbranded if it was not included in a list required by section 510(j) of the Act.
Although FDA does not accept drug establishment registration information from private label distributors (PLDs), PLDs may request their own NDC Labeler Code and elect to submit drug listing information to FDA. (21 CFR 207.20(b)). By submitting drug listing information, the PLD assumes full responsibility for compliance with the listing requirements. (21 CFR 207.20(b)) In such instances, at the time of submitting or updating drug listing information, private label distributors must certify to the registered establishment(s) that manufactured, prepared, propagated, compounded or processed (which includes, among other things, repackaging and relabeling) the listed drug(s) that the drug listing submission was made (21 CFR 207.20(b)). The certification to the registered establishment by the private label distributor may be satisfied using paper format. If a drug product is listed by the PLD, it should not also be listed by the owner(s) of the registered establishment(s) that manufactured, prepared, propagated, compounded or processed (which includes, among other things, repackaging and relabeling) the listed drug(s).
Registrants (and, if applicable, private label distributors) must update their drug listing information, and include drugs that have been introduced for commercial distribution and have not previously been listed (Section 510(j)(2) of the Act; 21 CFR 207.21(b); 21 CFR 20720(b)). Any updates must be submitted every June and December (Section 510(j)(2) of the Act; 21 CFR 207.21(b)). However, registrants (and, if applicable, private label distributors) are encouraged to submit updates through the registration and listing system more frequently as changes occur, including labeling updates required to be submitted under listing requirements (21 CFR 207.21(b); 21 CFR 207.22(b); 21 CFR 207.25; 21 CFR 207.30), or labeling submission needed to fulfill obligations for electronic submission of content of labeling in connection with approval applications. (See section II of this document and footnote 12.) As previously discussed in section II of this document, because the drug listing system is a key repository for labeling, it is particularly important to keep this information up to date.
Section 510(p) of the Act, as amended by FDAAA, now requires drug listing, including updates, to be submitted electronically unless a waiver is granted. Therefore, listing information should now be submitted electronically using SPL files with coded data fields.
The electronic drug establishment registration and drug listing system will permit FDA to electronically populate the Agency’s listing databases and the NDC Directory and will, therefore, improve the inclusiveness and accuracy of these databases.
2. What information is submitted for drug listing?
Section 510 of the Act and 21 CFR Part 207 set forth the drug listing information required to be submitted by domestic and foreign drug establishments. (Section 510(j) of the Act; 21 CFR 207.25(b) and (c); 21 CFR 207.30; 21 CFR 207.31; 21 CFR 207.40). For representative samples of advertising and labeling required under 21 CFR 207.25(b)(4) and (b)(5), only one need be submitted of each sample type, as described in 21 CFR 207.3(a)(9) and (a)(10).
Historically, registrants have also submitted additional drug listing information on Form FDA 2657 and Form FDA 2658. Likewise, for electronic submission, registrants should submit the following additional information in their SPL file:
1) Name of establishment(s) manufacturing or processing the listed drug and the type of operation(s) performed;
2) DEA schedule;
3) Route(s) of administration;
4) Inactive ingredients;
5) Marketing information (e.g., category, start/stop date)20;
6) Information related to the application (e.g., type and year of approval) or OTC
monograph citation number; and
7) Package size and type.
In addition to information that was previously submitted on Forms FDA 2657 and FDA 2658, the registrant should also submit:
8) NDC Product Code for a Source Drug Repacked or Relabeled
Repackers and relabelers should submit the NDC Product Code for the source drug that is repacked or relabeled, in order to reference manufacturing establishment information submitted in the listing entry for the source drug.
9) Unique Ingredient Identifiers (UNII) and other code sets
An explanation of UNII codes and other code sets and where they may be found is described in section IV.B of this document.
10) Confidentiality Flag
Registrants (and, if applicable, private label distributor) may identify an inactive ingredient or the registrant’s business relationship with an establishment that they view as confidential when submitting registration and listing information. Pursuant to a Freedom of Information Act request or on our own initiative, FDA will ultimately make determinations as to whether drug establishment registration and drug listing information can be disclosed to the public pursuant to the Trade Secrets Act, the Freedom of Information Act, and other applicable law (e.g., section 510(f) of the Act and 21 CFR 207.37).
11) Distinctive Characteristics of Certain Listed Drugs
Registrants (and, if applicable, private label distributors) should provide the following
characteristics for the listed drug, when applicable. Registrants (or private label distributors) have previously provided these characteristics voluntarily as helpful information for the safe and effective use of their products.
o Flavor
When applicable, the registrant (and, if applicable, private label distributor) should provide the flavor as a unique distinguishing characteristic of the listed drug. (Registrants have previously provided this information on Form FDA 2657 as an ingredient.)
o Color
For liquid dosage forms, the registrant (and, if applicable, private label distributor) should provide the color as a unique distinguishing characteristic. This may be useful to assist in judging whether a change in color may indicate contamination or to avoid confusion of the intended color of a solution with contamination.
o Image
For solid oral dosage forms, the registrant (and, if applicable, private label distributor) may submit an image of the actual dosage form. This information is helpful in identifying the drug, for example in order to help determine that the correct drug has been dispensed. The registrant can obtain instructions on obtaining the image and the proper format in the SPL file by following the instructions for technical assistance in section IV.D of this document.
