On July 25, 2022, the Food and Drug Administration (FDA or Agency) issued a proposed rule to amend the Agency's drug establishment registration and listing regulations as it pertains to national drug code (NDC) requirements.1 Specifically, FDA is proposing to establish a uniform 12-digit format for the NDC, comprised of a 6-digit labeler code segment, a 4-digit product code segment, and a 2-digit package code segment. Currently, FDA-assigned NDCs are 10-digits in length with 5-digit labeler codes, and can be in multiple formats (5-4-1, 5-3-2). FDA's proposal to implement a uniform 12-digit NDC format is in part due to Agency concerns about the potential for confusion and medication errors with the co-existence of 10-digit and 11-digit NDCs when the Agency runs out of 5-digit labeler codes and begins issuing 6-digit labeler codes in the coming years. If finalized as proposed, on the effective date of the final rule, FDA would begin issuing only 6-digit labeler codes and 12-digit NDCs, and existing 10-digit NDCs would be converted to 12-digits with the addition of leading zeroes. To allow stakeholders sufficient time to implement system changes for handling 12-digit NDCs, FDA proposes to delay the effective date of the rule to 5 years from the date of issuance of a final rule. The Agency also proposes to allow for an additional 3-year transition period from the effective date for updating of NDCs on drug labeling for products assigned 10-digit NDCs prior to the effective date of the final rule.
An NDC is an FDA standard for uniquely identifying drug products marketed in the US that is assigned during the drug listing process. Section 510(k) of the Federal Food, Drug, and Cosmetic Act (FDCA) and FDA's implementing regulations (21 C.F.R. Part 207) require registered drug establishments to provide FDA with a current list of all drugs manufactured by the establishment for commercial distribution unless an exemption applies. Drug products are identified and listed using an NDC number. An NDC number consists of 3 distinct segments. The first segment, which is assigned by FDA, is known as the labeler code and identifies the labeler (e.g., manufacturer, repacker, relabeler, private label distributor). The second segment, known as the product code, identifies the distinguishing characteristics of the drug (e.g., active ingredient, strength, dosage form). The third segment, known as the package code, identifies the package size and type of the drug. In contrast to the labeler code, both the product and package codes are proposed for assignment by persons submitting drug listing information rather than being assigned by FDA in the first instance.
Under the current Part 207 regulations as updated in 2016, a labeler code can consist of 4, 5, or 6 digits, the product code can consist of 3 or 4 digits, and the package code can consist of 1 or 2 digits. Under the current regulations, if a labeler code is either 5 or 6 digits in length, it may be combined with a product code and package code in a manner that results in a 10 or 11 digit NDC (either 5-4-1, 6-4-1, 5-3-2, or 6-3-2 configuration). If a labeler code is 4 digits in length, it may be combined only with a product code consisting of 4 digits and a package code of 2 digits for a total NDC length of 10 digits (4-4-2). A registrant with a given labeler code must use only one product-package code configuration for all NDCs under that labeler code.2
Although the current regulations provide that labeler codes may consist of 4, 5, or 6 digits, FDA currently only assigns 5-digit labeler codes, resulting in 10-digit NDCs (5-4-1 or 5-3-2 configuration). A 5-digit labeler code format provides FDA with 90,000 labeler codes that could be assigned to drug manufacturers and private label distributors.3 FDA anticipates that it will run out of 5-digit labeler codes in approximately 10 to 15 years, at which point FDA would begin assigning 6-digit labeler codes. Under the current regulations, moving to 6-digit labeler codes would expand the entire NDC to 11 digits. This would, per regulation, result in two additional NDC configurations (6-3-2 and 6-4-1) for a total of 5 possible NDC configurations (5-3-2, 5-4-1, 4-4-2 being the others).4
The future switch to the issuance of 6-digit labeler codes would thus result in some drugs having 11-digit NDCs, while others continue to have 10-digit NDCs. Consequently, when FDA last updated the Part 207 regulations in 2016, some stakeholders had expressed an interest in FDA moving to a single, standard format for NDCs. In response, FDA initiated public discussions of future formatting options, beginning with a November 2018 public hearing where the Agency outlined several proposed formatting options that FDA could adopt once it began issuing 6-digit labeler codes. Per FDA, most of the comments received by the Agency during and after the meeting were in favor of FDA's adoption of a single standardized format that could be used by all stakeholders.5
Under the new proposed rule, NDCs would continue to consist of the same three segments (labeler code, product code, and package code). However, the existing NDC formats would be replaced with a uniform 12-digit format. The labeler code would be 6 digits, the product code 4 digits, and the package code 2 digits (a 6-4-2 format). As explained in the preamble to the proposed rule, on the effective date of the final rule, FDA would begin assigning new NDCs in the uniform, 12-digit format utilizing only 6-digit labeler codes. As of the effective date, FDA would no longer assign 5-digit labeler codes or 10-digit NDCs. Therefore, all drug listing files submitted on or after the effective date proposing a new NDC would be required to use the 12 digit (6-4-2) NDC format.
Significantly, the new format requirements would apply not only to NDCs assigned after the effective date of the final rule, but also to existing 10-digit NDCs. FDA proposes that existing NDCs would be converted to the new, uniform, 12-digit format by the addition of leading zeros to the labeler code, the product code, and/or the package code segment as needed to produce the 6-4-2 format. However, for existing NDCs, to reduce the burden on registrants, FDA does not intend to require them to resubmit all of their existing drug listing files to convert the NDCs from one of the discontinued 10-digit formats to the new, uniform, 12-digit, 6-4-2 format.6 Instead, FDA intends to convert existing NDCs on its own, on the effective date, by adding leading zeros to the appropriate segments.
As noted by FDA, due to the proposed NDC format changes, stakeholders that use FDA-assigned NDCs would need to have systems capable of handling the new, 12-digit NDC on the effective date of the final rule.7 Therefore, FDA is proposing to delay the effective date of the final rule for a period of 5 years following its publication to allow stakeholders time to develop and implement such systems and to plan to update their drug labels during the transition period in a way that reduces burden. The delay is also intended to provide sufficient time to implement the necessary corresponding changes to the Health Insurance Portability and Accountability Act (HIPAA) standards and data standards that can enable a 12-digit NDC to be encoded in a data carrier such as barcodes.8 Notably, in implementing HIPAA rules, the Department of Health and Human Services previously adopted an 11-digit NDC format, with conversion of NDCs from 10-digit "native" FDA NDCs to HIPAA standard NDCs requiring addition of a leading zero in the appropriate segment. Such converted 11-digit NDCs are also utilized by various payers.
In addition to a delayed effective date, FDA is proposing to allow for a 3-year transition period following the effective date of the final rule to provide firms that use 10-digit NDCs time to update their labeling to replace the 10-digit NDCs with the new 12-digit NDCs (by adding leading zeros to the labeler code, product code, and/or package code segments as needed). During this 3-year transition period, FDA does not intend to object to continued use of 10-digit NDCs on the labeling of products remaining in interstate commerce. The purpose of the transition period is to mitigate the potential costs associated with reprinting labels for these products.9 FDA explains that during this proposed transition period, stakeholders should ensure that their systems are capable of handling both 10-digit NDCs and 12-digit NDCs.10 At the end of the transition period (i.e., 8 years after the publication of the final rule), all firms would be required to use a 12-digit NDC in listing files.11
In addition to the NDC format changes described above, the proposed rule would also revise FDA's 21 C.F.R. Part 201 drug product barcode label requirements to permit the use of other data carriers that meet certain standards. Specifically, FDA is proposing to revise the drug barcode label requirements to allow use of either linear or nonlinear barcodes, so long as the barcode meets one of the prescribed standards. This change is intended to help provide flexibility of the type of barcodes used on drug labels.
Because NDCs are currently used across the healthcare system, the proposed NDC format changes would impact a range of stakeholders, including but not limited to drug manufacturers, insurers and payers, wholesale distributors, pharmacies, hospitals, healthcare providers, federal agencies, and state and local governments that utilize FDA-assigned NDCs. If finalized, the proposed NDC standardized format would facilitate the adoption of a single NDC format by all stakeholders. FDA believes that standardizing the NDC to one format will eliminate the need for stakeholders to constantly convert a drug's FDA-assigned NDC to a different standardized format because those stakeholders seeking a standardized format will be able to adopt FDA's new, uniform, 12-digit format. For example, adoption of a single 12-digit NDC format would avoid confusion and reduce medication errors that could result if FDA were to begin issuing 11-digit NDCs and the HIPAA standards, and other code sets, that require 10-digit native NDCs to be converted to 11-digit NDCs are not updated.12
Comments on the proposed rule are due by November 22, 2022.
Footnotes
1. 87 Fed. Reg. 44038 (July 25, 2022).
2. See 21 C.F.R. 207.33(b)(2).
3. 87 Fed. Reg. 44041.
4. See § 207.33(b)(2).
5. 87 Fed. Reg. 44042.
6. Id. at 44043.
7. Id. at 44040.
8. Id. at 44044.
9. Id. at 44040.
10. Id.
11. Id. at 44044.
12. Id. at 40441.
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