[Federal Register Volume 91, Number 43 (Thursday, March 5, 2026)]
[Rules and Regulations]
[Pages 10749-10771]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-04368]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 201 and 207
[Docket No. FDA-2021-N-1351]
RIN 0910-AI52
Revising the National Drug Code Format and Drug Label Barcode
Requirements
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
issuing a final rule to standardize the format of the National Drug
Code (NDC). Under this final rule, all FDA-assigned NDCs will be
required to be 12 digits in length with 3 distinct segments and 1
uniform format. The first segment is a 6-digit labeler code, the second
segment is a 4-digit product code, and the third segment is a 2-digit
package code. Additionally, we are revising the drug product barcode
label requirements to permit the use of other data carriers that meet
the standards of this final rule.
DATES: This rule is effective March 7, 2033.
ADDRESSES: For access to the docket to read background documents or
comments received, go to https://www.regulations.gov and insert the
docket number found in brackets in the heading of this final rule into
the ``Search'' box and follow the prompts, and/or go to the Dockets
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852-
0001, 240-402-7500.
FOR FURTHER INFORMATION CONTACT:
With regard to the aspects of the final rule pertaining to human
drug products: Leyla Rahjou-Esfandiary, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 2262, Silver Spring, MD 20993-0002, 301-796-3185, [email protected].
With regard to the aspects of the final rule pertaining to human
biological products: Phillip Kurs, Center for Biologics Evaluation and
Research, Food and Drug Administration, 240-402-7911,
[email protected].
With regard to the aspects of the final rule pertaining to animal
drug products: Charise Kasser, Center for Veterinary Medicine, Food and
Drug Administration, 240-402-6816, [email protected].
With regard to the information collection: Domini Bean, Office of
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852-2766, 301-796-5733,
[email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose of the Final Rule
B. Summary of the Major Provisions of the Final Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
A. Need for the Rulemaking
B. History of the Rulemaking
C. Summary of Comments to the Proposed Rule
IV. Legal Authority
V. Comments on the Proposed Rule and FDA Response
A. Introduction
B. Description of General Comments and FDA Response
C. NDC Format
D. Barcode Format Requirement
E. Delayed Effective Date and Transition Period
F. Technical Amendments
VI. Effective Date
VII. Final Economic Analysis of Impacts
A. Introduction
B. Overview of Benefits, Costs, and Transfers
C. Comments on the Preliminary Economic Analysis of Impacts and
Our Responses
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Consultation and Coordination With Indian Tribal Governments
XII. References
I. Executive Summary
A. Purpose of the Final Rule
FDA is modifying our regulations to establish a uniform, 12-digit
format for the NDC (21 CFR 207.33). FDA's transition to a uniform
format for FDA-assigned NDCs is intended to facilitate the adoption of
a single NDC format across the entire healthcare industry, eliminating
the need to convert NDCs from one of FDA's prescribed formats to a
different standardized format used by other sectors of the healthcare
industry (e.g., healthcare providers and payors). FDA is also revising
the drug product barcode label requirements (21 CFR 201.25) to allow
the use of either linear or nonlinear barcodes, so long as the barcode
format conforms to certain standards and is recognized by FDA.
B. Summary of the Major Provisions of the Final Rule
Under this final rule, FDA is amending its regulations to adopt a
uniform, 12-digit format for the NDC. Under the revised format, NDCs
will continue to consist of three segments: the labeler code, the
product code, and the package code. However, the labeler code will be 6
digits, the product code will be 4 digits, and the package code will be
2 digits. To provide maximum flexibility on the type of barcode used on
the label of a drug product, this final rule allows the use of either
linear or nonlinear barcodes, so long as the barcode format conforms to
certain standards and is recognized by FDA.
On the effective date of this final rule, FDA will begin assigning
new NDCs in the uniform, 12-digit format, and existing 10-digit NDCs
assigned by FDA prior to the effective date will be required to convert
to the uniform 12-digit NDC format.\1\ As a result, all
[[Page 10750]]
parties that use FDA-assigned NDCs will need to have systems capable of
handling the new, uniform, 12-digit NDC format on the effective date of
the final rule. Therefore, FDA is delaying the effective date of the
final rule for a period of 7 years following its publication to allow
interested parties time to develop and implement such systems.
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\1\ FDA considers the conversion of a 10-digit NDC assigned by
FDA prior to the effective date to the new, uniform 12-digit NDC
format to be a ministerial, administrative change and not the
assignment of a ``new'' NDC. Furthermore, FDA considers such an NDC
in its original 10-digit format and in its converted 12-digit format
to be the same NDC with different formats. A drug product that was
originally assigned a 10-digit NDC prior to the effective date would
be considered to have a new NDC only if it were assigned a new NDC
by FDA after the effective date (e.g., pursuant to a request for a
new NDC because there was change to any of the information
identified in 21 CFR 207.35(b) or (c)).
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Additionally, this final rule allows for a 3-year transition period
following the effective date of the final rule. During this 3-year
transition period, firms that use 10-digit NDCs assigned prior to the
effective date on drug product labeling should begin updating their
labeling to replace the 10-digit NDC format with the new 12-digit NDC
format by adding leading zeros to the labeler code, product code, and/
or package code segments as needed, as soon as possible. However, to
aid with the transition, FDA does not intend to object to continued use
of such 10-digit NDCs on the labeling of products remaining in
interstate commerce after the effective date during the 3-year
transition period. The purpose of the transition period is to mitigate
the potential costs associated with reprinting labels for these
products. Therefore, during this transition period, interested parties
should ensure that their systems are capable of handling both the 10-
digit and 12-digit NDC formats.
C. Legal Authority
FDA is amending our regulations on foreign and domestic
establishment registration and listing for drugs, including biological
products and animal drugs. FDA's authority for this rule derives from
the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 321, et
seq.) applicable to drugs, including biological products, and the
biological product provisions of the Public Health Service Act (PHS
Act) (42 U.S.C. 262, et seq.). In particular, the rule will standardize
the format of NDCs assigned under section 510(e) of the FD&C Act (21
U.S.C. 360(e)) and will aid in efficient enforcement of the FD&C Act
pursuant to section 701(a) of the FD&C Act (21 U.S.C. 371(a)) and
section 351(j) of the PHS Act (42 U.S.C. 262(j)).
D. Costs and Benefits
This final rule requires that all NDCs, including any 10-digit NDCs
issued by FDA prior to the effective date, be 12 digits in length with
a uniform format: a 6-digit labeler code, a 4-digit product code, and a
2-digit package code. As a result, drug product labeling that includes
a 10-digit NDC will need to be updated to convert to the standard 12-
digit format.
FDA's transition to a uniform format for native NDCs is intended to
facilitate the adoption of a single NDC format across the entire
healthcare industry. Such an adoption will eliminate the need to
convert NDCs from one of the FDA-assigned formats to a different
standardized format used by other sectors of the healthcare industry
(e.g., healthcare providers and payors). Eliminating the need to
convert NDCs should reduce potential errors caused by converting the
FDA-assigned NDC to a different NDC format used by other sectors of the
healthcare industry. Standardization and adoption of a single format
will also eliminate the need for additional quality control and
validation by certain stakeholders, such as payors and prescribers, to
ensure a drug product and its respective NDC are accurate; this is
particularly important for insurance coverage and reimbursement claims.
Another benefit of the rule will be to avoid any potential risks to the
public health from medication errors and the risk of confusion. We do
not have enough information to quantify these potential benefits.
The costs to industry of converting current NDCs to the
standardized format will include one-time costs of updating software
systems, other transition costs, coordinating labeling updates, and
reading and understanding the rule. We estimate annualized costs will
be about $14.64 million ranging from $7.64 million to $22.79 million
using a 7-percent discount rate over a ten-year horizon. Similarly, we
estimate annualized costs will be about $14.90 million ranging from
$7.79 million to $23.18 million using a 3-percent discount rate over a
10-year horizon.
II. Table of Abbreviations/Commonly Used Acronyms in This Document
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Abbreviation/acronym What it means
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2D................................. Two-dimensional.
AI................................. Application Identifier.
ANDA............................... Abbreviated New Drug Application.
BLA................................ Biologics License Application.
DSCSA.............................. Drug Supply Chain Security Act.
EAN/UCC............................ European Article Number/Uniform
Code Council.
EHR................................ Electronic Health Record.
FDA................................ Food and Drug Administration.
FD&C Act........................... Federal Food, Drug, and Cosmetic
Act.
FRIA............................... Final Regulatory Impact Analysis.
GTIN............................... Global Trade Item Number.
HCT/P.............................. Human Cells, Tissues, and Cellular
and Tissue-Based Product.
HIBCC.............................. Health Industry Business
Communications Council.
HHS................................ Department of Health and Human
Services.
HIPAA.............................. Health Insurance Portability and
Accountability Act.
ICD................................ International Classification of
Diseases.
IT................................. Information Technology.
NDA................................ New Drug Application.
NDC................................ National Drug Code.
OMB................................ Office of Management and Budget.
PHS Act............................ Public Health Service Act.
PRA................................ Paperwork Reduction Act of 1995.
PRIA............................... Preliminary Regulatory Impact
Analysis.
UPC................................ Universal Product Code.
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III. Background
A. Need for the Rulemaking
The NDC is an FDA standard for uniquely identifying drugs marketed
in the United States. Section 510(j) of the FD&C Act requires each
person who registers an establishment under section 510(b), (c), (d),
or (i) to provide FDA with a current list of all drugs manufactured,
prepared, propagated, compounded, or processed by the establishment for
commercial distribution. Drug products are identified and listed using
the NDC (21 CFR 207.49).
Currently, the NDC assigned by FDA (a ``native'' NDC) for each
listed drug marketed in the United States is a unique 10-digit,\2\ 3-
segment number (Sec. 207.33(b)). The three segments of the NDC include
the labeler code, product code, and package code (Sec. 207.33(b)). The
first segment, the labeler code, is a unique 4-, 5-, or (in the future)
6-digit number assigned by FDA that identifies the manufacturer,
repacker, relabeler, or private label distributor of the drug (Sec.
207.33(b)(1)). The second segment, the product code, is a 3- or 4-digit
number that identifies a specific active ingredient, strength, dosage
form, and other distinguishing characteristics of a drug manufactured,
repackaged, relabeled, or distributed by the labeler (id.; Sec.
207.35(b)). The third segment, the package code, is a 1- or 2-digit
number that identifies package sizes and types (Sec. 207.33(b)(1)).
Different package codes differentiate between different quantitative
and qualitative attributes of the product packaging (Sec.
207.33(b)(iii)). The NDC for a given drug is currently in one of the
following configurations (with each numeral representing the number of
digits in that segment): 4-4-2, 5-3-2, or 5-4-1.
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\2\ Under 21 CFR 207.33(b), an NDC must consist of 10 or 11
digits, divided into three segments. This FDA 11-digit NDC refers to
the NDC length once the Agency starts assigning 6-digit labeler
codes.
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Currently, only 5-digit labeler codes are being assigned by FDA. A
5-digit labeler code format provides FDA with 90,000 labeler codes that
could be
[[Page 10751]]
assigned to drug manufacturers and private label distributors ranging
from 10,000 to 99,999. Based on current assignment rates, FDA
anticipates that it will run out of 5-digit labeler codes in
approximately 10 to 15 years. At that point in the future, FDA will
begin assigning 6-digit labeler codes due to exhaustion of 5-digit
labeler codes. Under the current regulations, moving to 6-digit labeler
codes will expand the entire NDC to 11 digits and, per regulation,
allow for two additional NDC configurations: 6-3-2 and 6-4-1, for a
total of 5 possible NDC configurations (including the three 10-digit
NDC configurations) (see Sec. 207.33(b)(2)).
The Health Insurance Portability and Accountability Act of 1996
(HIPAA) (Pub. L. 104-191) contains administrative simplification
provisions that require the Department of Health and Human Services
(HHS) to adopt ``national standards for electronic health care
transactions and code sets, unique health identifiers, and security.''
\3\ In its implementation of these rules, on August 17, 2000, HHS
published the final rule, ``Health Insurance Reform: Standards for
Electronic Transactions'' which addressed standards for electronic
transactions that established NDCs as the standard medical data code
set for reporting drugs and biological products in all standard
transactions under HIPAA (65 FR 50312 at 50313). If a HIPAA-covered
transaction includes a drug, the NDC is required to be part of the
medical code data set (see 45 CFR 162.1002(c)(1)). However, in the
preamble to the HIPAA regulations, HHS stated that it was adopting a
uniform 11-digit format to conform with customary practice used in
computer systems (65 FR 50312 at 50329). The HIPAA standard 11-digit
NDC format is standardized such that the labeler code is always 5
digits, the product code is always 4 digits, and the package code
always 2 digits (i.e., 5-4-2 configuration). To convert a 10-digit NDC
to an 11-digit HIPAA standard NDC, a leading zero is added to the
appropriate segment to create the 11-digit configuration as defined
above.
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\3\ See https://www.hhs.gov/hipaa/for-professionals/index.html
(accessed November 7, 2025).
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If, in the absence of this final rule, FDA were to begin issuing 6-
digit labeler codes under Sec. 207.33(b), the resulting 11-digit
native NDC configurations would have the same number of digits as
required by the HIPAA standards, but they will not be in the same
format. Specifically, an 11-digit native NDC would have an extra
labeler code digit but will be short a digit in either the product code
or package code. Additionally, some of the systems that utilize HIPAA
standard 11-digit NDCs \4\ do not use hyphens to separate the segments
which, as illustrated in Table 1, would result in some 11-digit native
NDCs being indistinguishable from HIPAA standard 11-digit NDCs.
Therefore, to ensure that native and HIPAA standard unhyphenated 11-
digit NDCs would be distinguishable, FDA anticipated that the HIPAA
standards, and other code sets that currently require 10-digit native
NDCs to be converted to 11-digit NDCs, would likely need to be updated
in some manner. We note that such updates are outside the scope of FDA
authority.
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\4\ NDCs that contain additional digits necessary to comply with
HIPAA standards are referred to as ``converted'' NDCs.
Table 1--NDC Conversion Example
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Converted NDC format
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Native NDC format 11-Digit converted 11-Digit converted
10-Digit hyphenated (hyphenated) (unhyphenated)
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Native 10-digit (5-3-2)....................... 10010-001-01 10010-0001-01 10010000101
Native 11-digit (6-3-2)....................... .................... 100100-001-01 10010000101
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B. History of the Rulemaking
1. 2016 Final Rule
In 2016, FDA published the final rule ``Requirements for Foreign
and Domestic Establishment Registration and Listing for Human Drugs,
Including Drugs That Are Regulated Under a Biologics License
Application, and Animal Drugs'' (the Registration and Listing Final
Rule). Recognizing that FDA would run out of 5-digit labeler codes in
the near future, the Registration and Listing Final Rule established
two additional NDC configurations: 6-3-2 and 6-4-1, for a total of five
possible NDC configurations (including the three 10-digit NDC
configurations) (Sec. 207.33(b)(2)). At the same time, FDA
acknowledged in the preamble to the Registration and Listing Final Rule
that some interested parties recommended that FDA adopt a single,
standard format for NDCs and announced that it planned to initiate a
public discussion of future formatting options (81 FR 60170 at 60187).
2. 2018 Public Hearing
On November 5, 2018, FDA began these public discussions by holding
a public hearing.\5\ At the public hearing, FDA outlined several
proposed formatting options that FDA could adopt once it begins issuing
6-digit labeler codes. Specifically, FDA outlined the following four
formatting options:
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\5\ See https://www.regulations.gov/document/FDA-2018-N-2610-0001 (accessed November 7, 2025).
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Option A: Do not revise the regulations and continue with the
status quo. Under this option, FDA would continue assigning the
remainder of the 5-digit labeler codes and whenever the Agency runs out
of 5-digit labeler codes, start assigning 6-digit labeler codes. This
would expand FDA's NDC inventory to 10 and 11 digits, resulting in 5
different configurations. FDA would use 10- and 11-digit NDCs.
Option B: Same as Option A, except that FDA would stop issuing 5-
digit labeler codes and start issuing 6-digit labeler codes on a
specified date in the future, before FDA anticipated running out of 5-
digit labeler codes. This option was intended to provide more certainty
to interested parties by establishing a designated future date on which
they would need to have systems in place to handle 11-digit NDCs in
either 6-4-1 or 6-3-2 format.
Option C: Adopt the hyphenated NDC 11-digit format (5-4-2 format)
currently used by the payor industry and convert all current 10-digit
NDCs to the hyphenated 11-digit format by adding a leading zero to the
short segment of the NDC. When the supply of 5-digit labeler codes is
exhausted, FDA would begin assigning 6-digit labeler codes for use in
6-3-2 and 6-4-1 formats. Although this would establish a uniform total
length for all NDCs, there would still be multiple formats.
Additionally, there is
[[Page 10752]]
the potential for an 11-digit format with a 6-digit labeler code and an
11-digit format with a 5-digit labeler code to be identical when the
hyphens separating the various segments are removed.
Option D: Allow for the harmonization of NDCs between FDA and other
interested parties by adopting 12-digit NDCs in a single, uniform 6-4-2
format. Once FDA starts assigning 6-digit labeler codes, all NDCs (new
and existing) would be required to be presented in a 6-4-2 format.
Existing NDCs would be converted from their existing format by adding
leading zeros to the short segments. This would create one standard
configuration for all NDCs that can be used by all interested parties
without conversion. As an added benefit, it would provide the industry
with more product or package codes.
An appropriate number of years would be necessary to adapt existing
databases and structures to be able to handle the new, uniform, 12-
digit NDC format and for industry to adopt this as the single NDC
format. Therefore, under Option D, FDA would implement this change on a
prespecified date that would occur before the current pool of 5-digit
labeler codes is exhausted, to provide certainty and predictability to
industry parties, government payors, and other interested parties.
FDA received oral comments during the hearing, and written comments
were submitted afterwards. Most of the comments were in favor of FDA's
adoption of a single standardized format that could be used by all
interested parties. The majority of the commenters were also in favor
of FDA establishing a certain date when interested parties would be
required to have systems capable of handling the new format, with many
advocating for a 10-year delay. For the most part, the commenters were
not in favor of Options A, B, or C. Instead, in general, the commenters
either favored Option D or advocated for FDA to no longer be
responsible for assigning NDCs and, instead, allow for a third party to
take over that role. FDA considered these comments in developing this
rulemaking.
3. The Proposed Rule
We proposed to adopt a single, uniform, 12-digit NDC format to
avoid confusion and reduce medication errors that could result if, as
described above, FDA were to begin issuing 11-digit NDCs when the HIPAA
standards and other code sets that require 10-digit native NDCs to be
converted to 11-digit NDCs are not updated. We noted that standardizing
the FDA-assigned NDC to one format should eliminate the need for
interested parties to constantly convert a drug's FDA-assigned NDC to a
different standardized format if the HIPAA and other code sets are
modified to adopt FDA's new, uniform, 12-digit format. This should
reduce errors caused by converting from FDA's current nonstandardized
NDC format to a standardized NDC format. Additionally, standardization
should eliminate the need for interested parties to use multiple
versions of an NDC (e.g., the FDA-assigned 10-digit NDC and the
converted HIPAA standard 11-digit NDC). Finally, we noted that using
12-digits would allow FDA to adopt a uniform NDC format without
requiring extensive changes to existing 10-digit NDCs. Instead,
interested parties would only need to add leading zeros to certain
segments of the existing 10-digit NDC to convert it to the new 12-digit
NDC format.
C. Summary of Comments to the Proposed Rule
We received approximately 50 comments on the proposed rule. The
comments were submitted by a variety of interested parties, including
healthcare professionals, consumers, drug manufacturers, wholesale
distributors, trade associations, health information technology (IT)
developers and vendors, and other organizations. The comments addressed
a variety of topics, including (i) general support for or opposition to
a uniform 12-digit NDC format; (ii) the proposal's intersection with
Drug Supply Chain Security Act (DSCSA) requirements; (iii)
implementation timeframe; (iv) FDA coordination with external parties;
and (v) implementation costs.
IV. Legal Authority
FDA is amending our regulations on foreign and domestic
establishment registration and listing for drugs, including biological
products and animal drugs. FDA's authority for this rule derives from
the FD&C Act (21 U.S.C. 321, et seq.) applicable to drugs, including
biological products, and the biological product provisions of the PHS
Act (42 U.S.C. 262, et seq.). In particular, the rule will standardize
the format of NDCs assigned under section 510(e) of the FD&C Act (21
U.S.C. 360(e)) and will aid in efficient enforcement of the FD&C Act
pursuant to section 701(a) of the FD&C Act (21 U.S.C. 371(a)) and
section 351(j) of the PHS Act (42 U.S.C. 262(j)).
V. Comments on the Proposed Rule and FDA Response
A. Introduction
We describe and respond to the comments on the proposed changes in
sections V.B. through V.E. of this document. Comments on the economic
analysis are addressed in section VII.C. of this document and in the
Final Regulatory Impact Analysis (FRIA). We have numbered each comment
to help distinguish between different comments. We have grouped similar
comments together under the same number, and in some cases, we have
separated different issues discussed in the same comment and designated
them as distinct comments for purposes of our responses. The number
assigned to each comment or comment topic is purely for organizational
purposes and does not signify the comment's value or importance or the
order in which comments were received.
B. Description of General Comments and FDA Response
Some comments made general remarks regarding the proposed rule
without focusing on a particular proposed provision. In the following
paragraphs, we discuss and respond to such general comments.
(Comment 1) Many commenters agree that the NDC format must change
and want assurance that this final rule would fully satisfy future
needs without requiring another expansion or modification to the NDC
format. One commenter requests that we disclose the number of NDCs that
have been assigned and how many are currently in use.
(Response 1) We recognize that any revision to the NDC format is a
complex and costly effort and that this final rule should be as future-
proof as possible. FDA typically assigns an average of 1,000 new
labeler codes each year. By expanding the labeler code from 5 to 6
digits, this final rule will add approximately 900,000 labeler codes.
At our current labeler code assignment rate, this final rule should
provide a 900-year supply of labeler codes and constitutes a
sufficiently future-proof solution. The number of NDCs assigned and
currently in use can be determined by reviewing the FDA NDC
Directory.\6\
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\6\ For human drug NDCs, see https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory and https://www.accessdata.fda.gov/scripts/cder/ndc/index.cfm; for animal drug
NDCs, see https://www.fda.gov/industry/structured-product-labeling-resources/electronic-animal-drug-product-listing-directory.
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(Comment 2) Some commenters are concerned that the conversion of a
10-
[[Page 10753]]
digit NDC to the uniform 12-digit NDC format would result in a ``new''
NDC, which could trigger renegotiation of pricing and rebates for the
drug at issue. The commenters request that FDA differentiate between a
``new'' NDC and a ``reformatted'' NDC in the regulation text and
clarify the circumstances that would trigger the need for a ``new'' NDC
instead of a ``converted'' NDC. One commenter asks whether the
proposal, if finalized, would increase the number of products for which
a sponsor would be required to pay user fees under the FD&C Act.
(Response 2) FDA considers the conversion of a 10-digit NDC to a
12-digit NDC format to be a ministerial, administrative change and not
the assignment of a ``new'' NDC for purposes of drug registration and
listing or FD&C Act user fees. Furthermore, FDA considers such an NDC
in its original 10-digit format and in its converted 12-digit format to
be the same NDC with different formats. We do not believe it is
necessary to modify the codified regulation text to clarify this point.
Our regulations address both the initial assignment of a new NDC (Sec.
207.33(c) and (d)) and the circumstances under which a new NDC must be
obtained for a drug that has already been assigned an NDC (Sec.
207.35). None of those provisions requires that NDC formatting changes
such as those required by this final rule would result in a ``new''
NDC.
(Comment 3) One commenter notes that the proposed rule refers to
NDCs being ``assigned by FDA.'' The commenter asserts that because the
product and package codes are selected by the manufacturer, this final
rule should clarify that an NDC ``assigned by FDA'' refers to the
Agency's assignment of the labeler code in accordance with our existing
regulation at Sec. 207.33(b)(1)(i).
(Response 3) Under Sec. 207.33(d)(1), a manufacturer, repacker, or
relabeler merely ``propose[s] an NDC for assignment by FDA'' when it
submits the product's listing information for the first time.
Specifically, the registrant proposes the product and package codes
together with the applicable labeler code already assigned by FDA. FDA
will assign the proposed NDC to the drug identified by the registrant
only if the proposed NDC is in the correct format, is not reserved for
a different drug, and has not previously been assigned to a different
listed drug (Sec. 207.33(d)(2)). Thus, FDA ultimately assigns each
NDC, including each component of an NDC. Accordingly, we decline to
adopt the commenter's recommendation.
(Comment 4) One commenter advocates that FDA relinquish
responsibility for assigning NDCs and permit a third party to assume
that role.
(Response 4) In the proposed rule, we considered and rejected
similar comments that were submitted to the 2018 public hearing docket
(see 87 FR 44038 at 44042-44043). Specifically, the proposed rule noted
that FDA is deeply involved in the assignment of NDCs and that changing
the existing system would have the potential to cause significant
disruption, particularly in transitioning the assignment of NDCs from
FDA to a third party. We also recognized that although there would be
disruption in transitioning to a 12-digit NDC, FDA would be in the best
position to minimize and mitigate the disruption because it would
continue to be involved in the process for assigning the reformatted
12-digit NDCs. In the proposed rule, we stated that if the
responsibility for assigning the reformatted 12-digit NDCs were handed
over to a third party, FDA would have less ability to minimize and
mitigate the disruption. Accordingly, we did not propose to revise
Sec. 207.33 and other regulations to remove references to the
assignment of NDCs by FDA. The commenter does not offer any reason why
FDA should change course on this policy in this final rule, and we
decline to make such a significant and potentially disruptive revision
to our regulations in this final rule.
(Comment 5) Numerous commenters advocate that FDA should implement
an extensive communication and outreach strategy to engage, coordinate,
and inform all interested parties, including Federal and State
agencies; manufacturers, repackagers, and distributors; drug compendial
services; insurers and pharmacy benefit managers; healthcare providers;
software vendors; retailers; and other entities. The commenters believe
that a comprehensive communication plan will increase awareness of the
new NDC format and promote timely implementation among all interested
parties, thereby minimizing or preventing disruption in drug
purchasing, reimbursement, and delivery of patient care.
(Response 5) To help ensure industry readiness for the transition
to a 12-digit NDC, FDA intends to broadly engage with relevant
government and private parties during the 7-year period preceding the
effective date of this rule.
(Comment 6) One commenter urges FDA and other Federal agencies to
pursue a national synchronization effort to link 12-digit NDCs to 10-
digit NDCs in every historical table and document.
(Response 6) This rule operates on a prospective basis only and
does not mandate changes to historical government records. However, we
intend to publish a database that will map each 10-digit NDC appearing
in the NDC Directory to the corresponding 12-digit NDC at least until
the end of the transition period.
(Comment 7) We received numerous miscellaneous comments. Most of
these commenters seek clarification or changes to DSCSA requirements or
labeling or registration and listing provisions that the proposed rule
did not propose to modify. Two commenters advocate for the availability
of investment credits or other types of government funding for the
costs of implementing the transition to a 12-digit NDC.
(Response 7) These comments are outside the scope of the rule. In
addition, the comments advocating for government funding of efforts to
transition to a 12-digit NDC are outside the scope of FDA authority.
C. NDC Format
Currently, under Sec. 207.33(b)(1), an NDC consists of either 10
or 11 digits, divided into the following three segments: (1) a labeler
code of 4, 5, or 6 digits; (2) a product code of 3 or 4 digits; and (3)
a package code consisting of 1 or 2 digits. Section 207.33(b)(2)
specifies five different permitted NDC formats that differ based on the
number of digits in each of the three segments: 4-4-2; 5-3-2; 5-4-1; 6-
3-2; and 6-4-1. Section 207.33(b)(3) requires a registrant or private
label distributor with a given labeler code to use a single product and
package code configuration in all NDCs that include the given labeler
code and are reserved or listed in accordance with applicable
regulations. Finally, existing Sec. 207.33(b)(4) permits FDA to
approve an alternatively formatted NDC for certain human cells,
tissues, and cellular and tissue-based products (HCT/Ps).
We proposed to amend Sec. 207.33(b) to establish a uniform, 12-
digit format for the NDC for all drug products that are required to be
listed under section 510 of the FD&C Act and 21 CFR part 207.
Specifically, we proposed to modify Sec. 207.33(b)(1) to state that
the NDC must consist of 12 digits, divided into three segments as
follows: (i) a 6-digit labeler code; (ii) a 4-digit product code; and
(iii) a 2-digit package code. We proposed to remove existing Sec.
207.33(b)(2) and (3) as inapplicable to a uniform, 12-digit NDC format.
We proposed to retain at new Sec. 207.33(b)(2) the existing language
of Sec. 207.33(b)(4) regarding the permissibility of an alternatively
[[Page 10754]]
formatted NDC for HCT/Ps. The proposed rule related only to FDA's
assignment of NDCs; it did not propose any revisions to the HIPAA
standard code set, which is outside the scope of FDA authority.
In the following paragraphs, we discuss comments on our proposed
revisions of Sec. 207.33(b). We are finalizing the proposal without
change.
(Comment 8) A number of commenters support our proposal to require
a single, uniform NDC format for FDA-assigned NDCs. In general, these
commenters support a uniform FDA-assigned NDC format for reasons
related to patient safety, efficiency, and/or reduced burden. One
commenter asserts that it is very burdensome to transmit and accept
NDCs in multiple formats. Some commenters note that the coexistence of
multiple NDC lengths and formats, with and without hyphens, can lead to
incorrect drug inventory data, data loss, and transaction errors. Some
commenters claim that a single, uniform NDC format could be used for
all purposes and would eliminate the need to convert NDCs to a
different format depending on the nature of the transaction, thereby
reducing the potential for patient harm caused by errors in
transmitting drug information. One commenter indicates that a uniform
NDC format would eliminate the need for multiple layers of quality
control. Another commenter notes that a single, uniform format is
needed because the NDC is used for so many purposes other than drug
identification, such as payment, controlled substance monitoring and
reporting, and more. A trade association representing wholesale
distributors of drugs strongly supports a uniform format for the NDC,
arguing that, once the relevant parties are educated and acclimated to
the new format, it will provide enormous efficiencies. This commenter
notes that a uniform NDC format will eventually eliminate the need to
cross-reference indexes and conversion tables, remove existing
uncertainties regarding the lengths of the three NDC segments, and
reduce errors.
(Response 8) We appreciate the support of the commenters. We agree
that the various NDC formats (whether FDA-assigned or converted to
another format) have created data quality and integrity issues. For
example, as illustrated in Table 2, if hyphens are removed from an FDA-
assigned NDC in an electronic system, there is no reliable way to know
where the hyphens were in the original NDC. We believe that moving to a
single, uniform format for the FDA-assigned NDC is an important and
necessary improvement that will improve efficiency and reduce errors.
Although we recognize that FDA's adoption of a single, uniform, 12-
digit NDC format may require the NDC format currently used under HIPAA
or other code sets to change, this final rule does not change the NDC
format currently used under HIPAA and other code sets because that is
outside the scope of FDA's authority. However, the Agency's adoption of
a uniform NDC format may facilitate adoption of a uniform format
industry-wide.
Table 2--Illustration of Ambiguity With Unhyphenated NDC
------------------------------------------------------------------------
FDA-assigned NDC
FDA-assigned NDC (unhyphenated) possibilities
------------------------------------------------------------------------
9999912345.......................................... 9999-9123-45
99999-123-45
99999-1234-5
------------------------------------------------------------------------
(Comment 9) A number of commenters support our proposal to require
a 12-digit NDC in 6-4-2 format. These commenters prefer a 12-digit NDC
over an 11-digit NDC because it would not lead to overlapping NDCs (as
illustrated in Table 1 of the proposed rule). In addition, these
commenters believe that a uniform NDC length and format would minimize
risk of error in a variety of processes (e.g., prescription processing,
medication history analysis, drug utilization reviews, and more). One
commenter notes that the proposed NDC format is the most concise and
consistent data structure for the NDC, with the most uniform
methodology for updating the NDC on current products and assigning new
NDCs to new products. This commenter also believes that our proposal is
the most efficient option because it would minimize mapping and
programming costs. Another commenter notes that the proposed 12-digit
format (6-4-2) would allow continued use of legacy labeler codes by
adding leading zeros and would solve the scarcity of labeler codes for
a longer period of time than an 11-digit NDC. Several commenters are
concerned that errors in converting existing NDCs to a 12-digit NDC
would cause ordering and medication administration errors.
(Response 9) We agree with the commenters that support FDA's
adoption of a uniform, 12-digit NDC in the 6-4-2 format. Although we
agree that there is potential for error in converting NDCs from the 10-
digit format to the 12-digit format, a uniform format for FDA-assigned
NDCs will result in greater efficiency over time and be less
susceptible to error. Moreover, to minimize any potential for error,
FDA intends to publish a database that will map each 10-digit NDC
appearing in the NDC Directory to the corresponding 12-digit NDC at
least until the end of the transition period.
(Comment 10) Several commenters advocate for an expanded labeler
code of 7 or 8 digits, because they are concerned that a 6-digit
labeler code would not be sufficient to satisfy future demand. One
commenter suggests that we increase the product code from 4 digits to 5
digits because it would increase the lifespan of labeler codes. This
commenter reasons that an expanded product code could increase the
lifespan of labeler codes since manufacturers cannot reuse codes.
According to the commenter, NDCs get consumed faster than expected due
to the requirement to assign NDCs to bulk active pharmaceutical
ingredient, bulk intermediate, and finished products that are imported
into the U.S. market. One commenter suggests that we eliminate the
package code in an effort to reduce the number of NDCs assigned to each
manufacturer.
(Response 10) We decline the suggestions to expand the labeler
codes to more than 6 digits because, as explained in Response 1, a 6-
digit labeler code will satisfy demand for hundreds of years. We also
decline the suggestion to expand the product code to 5 digits. A 4-
digit product code accommodates up to 10,000 different product codes
(0000 to 9999). Because only a very small number of manufacturers and
private label distributors need more than 10,000 product codes, it
would be more efficient and less burdensome to assign those
manufacturers an additional labeler code when they use up all of the
product codes under an existing labeler code rather than expand the
product code. We disagree with the suggestion to eliminate the package
code. The package code is a useful segment of the NDC because it
identifies a drug's package size and type and distinguishes different
quantitative and qualitative attributes of the product packaging (21
CFR 207.33(b)(1)(iii)). For example, the package code is used to
distinguish bottles of 30, 100, and 500 tablets of the same drug and
whether the tablets are packaged in a bottle or blisterpack. Thus, the
package code allows FDA, manufacturers, and other interested parties to
more precisely identify and trace a drug throughout the supply chain.
Eliminating the package code would hinder FDA efforts to ensure a
secure drug supply chain and cause disruption in reimbursement, order
fulfillment, inventory and supply chain management, and other matters.
We are finalizing without change our proposal
[[Page 10755]]
to standardize the package code as a 2-digit, final segment of the NDC.
(Comment 11) A large number of commenters advocate that we continue
to allow 10-digit NDCs in the currently permitted formats (4-4-2, 5-3-
2, 5-4-1) and that we address the need for additional labeler codes by
issuing 5-character alphanumeric labeler codes only for new labelers
after exhausting the supply of 5-digit numerical labeler codes. To
eliminate the potential for medication errors that could occur when
certain letters are misread as numerals, these commenters suggest that
the alphanumeric labeler code should be limited to only 21 letters (all
letters except B, D, I, O, and Q) or 20 letters (all letters except B,
D, I, O, Q, and S).
According to the commenters, this approach has numerous advantages.
First, the commenters assert that a limited 5-character alphanumeric
labeler code would provide an abundant supply of labeler codes, thereby
resolving the problem that prompted this rulemaking. A few commenters
assert that such a limited 5-character alphanumeric labeler code would
expand the supply of labeler codes to over 26 million codes.
Second, the commenters advocate for an alphanumeric labeler code on
the grounds that it would be far less costly and disruptive and much
easier and faster to implement because it would preserve much of the
status quo. Under this approach, there would be no change for existing
labelers. Only new labelers would be issued an alphanumeric labeler
code after the supply of numeric labeler codes has been exhausted. The
commenters note that the transition to an alphanumeric labeler code
would be less costly because many entities, including pharmacy system
vendors, already store NDCs in alphanumeric fields that would not
require any software adjustments. In addition, commenters note that
this approach would preserve the HIPAA-mandated 11-character format (5-
4-2) already in use for many transactions, eliminating the need to
modify the NDC format used under HIPAA. These commenters also believe
that an alphanumeric labeler code would allow historical records to be
preserved without change, thereby reducing change management costs.
Third, numerous commenters favor an alphanumeric labeler code
because it would cause less confusion and minimize risks to patient
safety. Many of these commenters disagree with our statement in the
proposed rule that a uniform, 12-digit NDC format would reduce
medication errors by eliminating the need to convert the various
nonstandardized 10-digit NDCs to the HIPAA 11-digit NDC format. These
commenters note that there is already little risk of error in such
conversions because conversions are executed by drug data vendors
(compendia) that publish the standardized National Council for
Prescription Drug Programs (NCPDP) 11-digit product identifier NDC, and
most affected parties use the compendium-published NDC. These
commenters believe that the risk of medication errors and patient harm
would be greater if every existing 10-digit NDC is converted to a 12-
digit NDC and both NDCs appear on the product during the transition
period. A number of commenters assert that an alphanumeric labeler code
would be less disruptive to industry and patient care because it avoids
impact to other identifiers, such as the Universal Product Code (UPC),
that are currently reformatted into an NCPDP 11-digit product
identifier NDC for use in the pharmacy industry. In addition, one
commenter notes that a numeric labeler code that begins with a zero may
be misread by those systems that treat the Product Service ID as a
numeric field (that is, leading zeros would be dropped, resulting in
errors). Some commenters argue that there is precedent for use of an
alphabetic code to reduce confusion; they cite FDA's implementation of
a four-character alphabetic code for biological products to reduce
confusion in identifying biosimilar products.
Finally, a small number of commenters assert that an alphanumeric
labeler code would make it easier for State Medicaid programs and their
vendors to invoice and dispute claims. Specifically, these commenters
argue that it would be very burdensome to pursue historical claims from
as far back as 1991 for drugs bearing a 10-digit NDC.
In contrast, our decision not to propose an alphanumeric labeler
code is supported by a trade association representing wholesale
distributors and a healthcare services company with operations
throughout the drug delivery and supply chain. In addition, comments
from an organization responsible for implementation of global standards
in the U.S. healthcare industry (GS1 US) identify some important
disadvantages of an alphanumeric labeler code after engaging a
workgroup comprised of nearly 40 organizations from throughout the
supply chain, including manufacturers, wholesale distributors,
providers, technology solutions companies, and industry associations.
These commenters recognize that the transition to an alphanumeric
labeler code would never achieve the goal of a uniform NDC sought by
many in the industry. They assert that a single, standardized, and
uniform NDC format will reduce errors and inefficiencies, particularly
if it does not include letters. Two of the commenters note that it may
be even more difficult to transition to an alphanumeric NDC compared to
a 12-digit NDC and could require additional time to make the
transition.
According to the three commenters, many IT systems currently in use
cannot accommodate alphabetic characters (``alpha characters''), and an
alphanumeric NDC would not relieve many interested parties from the
requirement to update their systems. One of these commenters states
that the addition of an alpha character to the NDC would increase the
difficulty and expense of developing, mapping, and testing the new NDC
format, possibly requiring additional transition time. Another of these
commenters, the global standards organization, expresses its concern
that an alphanumeric NDC would not be compatible with the global supply
system because alphanumeric codes are not used in all countries and
organizations. Moreover, the organization states that an NDC of uniform
length and structure would help eliminate some of the variability that
undermines the integrity of the standardized numerical identifier,
which uses the NDC combined with a serial number to uniquely identify
each package or homogenous case in the supply chain, as required by the
DSCSA. All three of these commenters also share concern that, unlike
numeric barcodes, barcodes that include letters cannot be compressed to
conserve space on drug packages and labels, which is particularly
critical for small drug packages. In addition, the commenters note that
the transition to an alphanumeric NDC would require all barcode formats
and scanners to be updated, which could potentially require additional
transition time and create potential patient safety risks.
(Response 11) We appreciate the thoughtful and comprehensive
comments advocating for a 5-digit alphanumeric labeler code, and we
seriously considered adopting an alphanumeric labeler code. Ultimately,
we believe that the safer, more efficient approach is to finalize
without change our proposal to institute a uniform, 12-digit NDC.
According to the Institute for Safe Medication Practices (ISMP),
information that contains both numerals and letters is particularly
prone to errors, and even typed, computer-
[[Page 10756]]
generated, or electronic prescription orders and transcriptions may not
prevent confusion among certain alphanumeric symbols (Ref. 1).
Moreover, the alpha characters that the commenters suggested should be
excluded from the NDC to minimize confusion is likely underinclusive.
In addition to the uppercase letters suggested by the commenters, ISMP
has identified the following uppercase and lowercase letters as
commonly confused for another letter or a numeral (Table 3).
Table 3--Commonly Confused Letters and Numerals
----------------------------------------------------------------------------------------------------------------
Lowercase letter for
Uppercase letter for another Uppercase letter for a another lowercase Lowercase letter for a
uppercase letter numeral letter numeral
----------------------------------------------------------------------------------------------------------------
T and I.............................. G and 6................ g and q................ l and 1.
C and G.............................. F and 7................ p and n................ b and 6.
L and I.............................. Z and 2................ m and n................ o and 0.
M and N.............................. Q and 2................ y and z................ g and 9.
P and B.............................. Y and 5................ u and v................ q and 9.
F and R.............................. Z and 7................ c and e................
U and O.............................. T and 7................
U and V.............................. U and 4................
E and F.............................. U and 0................
V and W..............................
X and Y..............................
----------------------------------------------------------------------------------------------------------------
We believe that a numeric-only NDC has less potential to generate
medication errors compared to an alphanumeric NDC. Simply put, there is
less opportunity for confusion when a human user must input only
numerals instead of numerals and letters. In retail and hospital
pharmacy practice, the printed patient prescription label placed on the
dispensed bottle identifies the NDC of the source bottle from which the
drug was dispensed. When visually comparing the NDC on the printed
patient prescription label to the NDC on the source bottle, a person
may mistake a letter for a numeral and vice versa. It is less taxing
and less error prone for the human brain to consider only 10 possible
digits as potential options for each character in a 6-digit labeler
code. In contrast, under the approach desired by the commenters, there
would be a total of 50 possible characters (10 numerals, 20 uppercase
letters, and 20 lowercase letters) for each character in an
alphanumeric 6-digit labeler code. Moreover, this plethora of
possibilities would not be limited only to newly issued alphanumeric
labeler codes. The knowledge that some NDCs are alphanumeric may cause
a human to misread a numeral as a letter even when trying to process an
entirely numeric labeler code. This is likely to generate medication
errors when the NDC must be manually typed into an electronic health
record (EHR) or pharmacy information system. We note that phonetic
factors can also contribute to medication errors with the use of
alphanumeric NDCs. For example, if an NDC is confirmed by reading it
aloud, the letter ``A'' may be mistaken for the numeral ``8.''
Alphanumeric NDCs may also contribute to confusion with other required
label information, such as alphanumeric lot numbers, suffixes used for
biosimilar and biological nonproprietary names, salt abbreviations
(e.g., HCl (hydrogen chloride) or NaCl (sodium chloride)), and product
identifiers used for investigational drug products.
Limiting the alpha characters as suggested by some commenters would
not eliminate the potential for medication and inventory errors.
Although we suspect that some of the additional letters identified in
Table 3 above may be more susceptible to confusion only when
handwritten (e.g., the letter ``U'' being confused with the numeral
``4''), it appears that an alphanumeric NDC should be limited to fewer
alpha characters than suggested by the commenters. Regardless of
whether FDA were to further limit the scope of alpha characters beyond
that advocated by the commenters, the mere existence of an alphanumeric
code is likely to increase the possibility that a letter is confused
for a different letter or for a numeral (e.g., an ``F'' could be
misread as an ``R'' or as the numeral ``7'') or that a numeral is
misread as a letter (e.g., the numeral ``6'' may be confused for the
letter ``G''). This is particularly true because not all people who
will be interacting with the NDC will know that the letters assigned by
FDA do not include all letters in the English alphabet. Thus, the
commenters' approach does not eliminate the possibility that a letter
or a numeral will be misread as a letter that FDA would never assign to
a labeler code (e.g., an ``L'' could still be misread as the capital
letter ``I'' and a zero could still be misread as the letter ``O''). In
addition, a numeric-only NDC is more efficient to work with because the
use of alphanumeric characters slows down human verification.
Specifically, it may be natural to read strings of letters and numbers
together as a word (Refs. 2, 3, 4). Therefore, it may take cognitive
effort to reject that interpretation and re-read the string as separate
alphanumeric characters.
We disagree with the suggestion made by some commenters that an
alphanumeric labeler code is similar to the alphabetic suffixes used by
FDA in assigning a nonproprietary name for certain biological products
licensed under section 351(a) or 351(k) of the PHS Act. Under FDA's
current naming convention for such biological products, the Agency
designates a nonproprietary name that is a combination of the core name
and a distinguishing suffix that is composed of four lowercase letters.
In contrast to the use of an alphabetical suffix as part of a product
name, the commenters propose to add alphabetic characters to the
numeric NDC, which for the reasons discussed above risks confusion.
Finally, we disagree that the concerns raised about claiming and
disputing historical Medicaid drug rebates should outweigh the
advantages of promulgating a uniform, 12-digit NDC format that contains
a numeric labeler code. As noted above, FDA does not view conversion of
a 10-digit NDC to a 12-digit NDC as resulting in a ``new'' NDC.
Moreover, nothing in this final rule requires a change to the NDC
format used for purposes of claiming or disputing historical claims for
Medicaid drug rebates.
In summary, although a limited 5-digit alphanumeric labeler code
would result in additional labeler codes that would extend the use of
10-digit NDCs, FDA must consider not just sheer numbers, but also
safety and useability.
[[Page 10757]]
As noted above, adding an alpha character to the numeric NDC entails a
greater potential for confusion and medication errors. Moreover, it
would not result in an NDC of uniform length because, under the
commenters' approach, some FDA-assigned NDCs will remain 10-digits in
length, while other FDA-assigned NDCs will have 11 characters. In
addition, the commenters' approach would not achieve a uniform NDC
configuration because each segment of the NDC would vary in length.
Even if an alphanumeric labeler code might be an easier solution to
implement in the short term, we believe a standardized, numeric 12-
digit NDC eliminates the potential for medication errors that could
occur with an alphanumeric labeler code and will be more efficient to
work with in the long term. We note that because the linear barcode
cannot accommodate alpha characters, adopting an alphanumeric NDC would
require barcode formats and scanners to be updated.
(Comment 12) Some commenters advocate for a uniform, 11-character
NDC in the HIPAA-mandated 5-4-2 format, except that it would eventually
incorporate an alphanumeric labeler code for new labelers. These
commenters note that this approach would provide an adequate supply of
labeler codes, achieve the goal of an NDC of uniform length and
configuration, and be less costly and safer to implement for the
reasons summarized in Comment 11. Under this approach, there would be
very little change for the existing labelers because their native 10-
digit NDCs would simply be converted to an 11-digit NDC format in the
same manner that such NDCs are currently converted to the 11-digit
HIPAA NDC format.
(Response 12) We decline to adopt an 11-character NDC with an
alphanumeric labeler code for the reasons discussed in Response 11. We
note that for firms that currently have FDA-assigned 10-digit NDCs, the
adoption of an 11-character NDC would not reduce the costs of updating
labeling to include the new 11-digit NDC.
(Comment 13) A number of commenters request that FDA permit the
elimination of dashes in the NDC format when the NDC is communicated
and stored electronically. The commenters reason that dashes increase
the amount of data that must be exchanged and stored and can be
misread, which interferes with interoperable data exchange and may
result in errors. They note that electronic messaging and electronic
data interchange standards do not include dashes and that dashes will
not be necessary with a uniform NDC format. In contrast, one commenter
asserts that dashes should not be eliminated because it is difficult to
know where to place leading zeros when NDCs are transmitted without
dashes. This commenter states that FDA should ensure interoperable data
communication by providing clear guidance regarding the use of dash
separators.
(Response 13) We appreciate the concerns of the commenters, but the
electronic storage and exchange of NDCs is outside the scope of this
rulemaking. Nothing in this final rule governs the use of dashes in the
NDC when the NDC is communicated and stored electronically. We note
that the new uniform format (6-4-2) should eliminate any existing
uncertainty regarding placement of dashes for human-readable formats of
the NDC.
(Comment 14) A comment from a pharmacy benefit manager (PBM)
asserts that the proposed rule does not address the format for the
product and package codes in a 12-digit NDC. The PBM advocates that
leading zeros be added to existing 3-digit product codes and existing
1-digit package codes, noting that it would be consistent with the
current NCPDP product identifier standard.
(Response 14) We addressed the format for product and package codes
in the proposed rule. Specifically, we proposed that all existing 10-
digit NDCs would be converted to the uniform, 12-digit format by the
addition of leading zeros to the labeler code, the product code, and/or
the package code segments as needed to produce the 6-4-2 format (87 FR
44038 at 44042-, 44043). We are finalizing this proposal without
change.
(Comment 15) One commenter notes concern that leading zeros are
often truncated and requests clarification that truncation of leading
zeros would not be permitted. Another commenter notes that the addition
of leading zeros to existing NDCs could lead to medication errors if
software systems are not programmed to read NDCs correctly.
(Response 15) Leading zeros are part of the NDC, whether they exist
under the current regulations or will be added in accordance with this
final rule. FDA believes that leading zeros should not be truncated,
and both existing and future electronic systems will need to be
designed accordingly.
(Comment 16) One commenter requests confirmation that FDA would not
assign a labeler code consisting entirely of a single repeating numeral
(e.g., 000000, 111111). The commenter asserts that such a policy would
preserve existing industry use of these values.
(Response 16) We decline to accept the commenter's request. The
commenter does not provide any context for how industry may use such
values and the likelihood that industry's use of these values would be
confused with an NDC. We note that there are no 4- or 5-digit labeler
codes that consist entirely of zeros, but FDA has assigned labeler
codes consisting entirely of other repeating numerals. We are not
persuaded to change the current practice.
(Comment 17) One commenter seeks confirmation that 6-digit labeler
codes for new labelers would be assigned starting at 100000.
(Response 17) The commenter is correct. Because leading zeros will
be added to existing labeler codes of less than 6 digits, new 6-digit
labeler codes that begin with a zero will not be issued.
(Comment 18) Several commenters ask how historical patient records
containing NDCs should be handled. These commenters query whether it
will be necessary to convert to the new format any NDCs that appear in
patient records regarding medication history and drug allergy
information. The commenters note that there could be drug-drug
interactions or a drug allergy that must be considered in the patient's
ongoing treatment. They also believe that it will be very burdensome to
convert NDCs in patient records, especially if the conversions cannot
be safely automated and would require clinician review.
(Response 18) These comments are beyond the scope of this
rulemaking. This final rule does not set forth any requirements with
respect to historical paper or electronic patient records that include
an NDC.
(Comment 19) Comments from a health IT vendor and an association
representing EHR software developers appreciate our statement in the
proposed rule indicating that FDA will continue to maintain and publish
10-digit NDCs for listed drugs simultaneously with their converted 12-
digit NDC equivalents during the transition period (87 FR 44038 at
44044). Both commenters request that FDA make this information
available in perpetuity to avoid potential confusion after the
effective date of the final rule.
(Response 19) We intend to publish a database that will map each
10-digit NDC appearing in the NDC Directory to the corresponding 12-
digit NDC at least until the end of the transition period. We may
consider the matter further as the end of the transition period
approaches. We note that if FDA
[[Page 10758]]
discontinues publication of this database, a similar database could be
made available by a third party.
(Comment 20) Two commenters representing health IT vendors advocate
that the final rule should require health IT vendors to include only
the converted 12-digit NDC in interoperable outbound messages that
occur on or after the effective date of the final rule. The commenters
suggest that such a policy would support interoperability in the
exchange of patient data.
(Response 20) Although FDA agrees that the interoperable exchange
of patient health data is important and necessary, the commenters'
suggestion is outside the scope of this rulemaking. This final rule
does not set forth any requirements with respect to the electronic
exchange of patient data containing NDCs. As we indicated in the
proposed rule (87 FR 44038 at 44044), one of the purposes of the
delayed effective date is to allow sufficient time for the HIPAA
standards to be updated to accommodate the uniform, 12-digit format for
NDCs and for all interested parties to update their systems and make
other changes necessary for handling the uniform, 12-digit NDC upon the
effective date of this final rule. To the extent that any messages
transmitted after the end of the transition period are required by the
FD&C Act to include the NDC, the NDC set forth in such message must be
in the uniform 12-digit format.
(Comment 21) A comment from an association representing pharmacists
requests additional guidance regarding how FDA intends to handle the
practice of converting 10-digit NDCs to 11-digit NDCs during the
transition to 12-digit NDCs. The commenter states that once the 12-
digit NDC is introduced, the use of all three formats at the same time
may introduce confusion and increase the likelihood of errors.
(Response 21) The commenter is mistaken; NDCs of 10, 11, and 12
digits will not all be used at the same time. As explained in section
I.B. of this document, FDA will continue to assign new 10-digit NDCs
until the effective date of this final rule. Upon the effective date of
this final rule, all existing FDA-assigned 10-digit NDCs will be
converted to 12-digit NDCs, and FDA will begin assigning new NDCs in
the uniform, 12-digit format. As explained in section V.E. of this
document, this final rule has a 7-year delayed effective date. Because
the current HIPAA standards cannot accommodate a 12-digit NDC, we
expect that the current HIPAA 11-digit standard will be discontinued,
and a new HIPAA standard that can accommodate a 12-digit NDC will be
implemented on or before the effective date of this rule. To minimize
any potential for confusion during the 3-year transition period that
begins on the effective date, FDA will publish both the 10-digit and
12-digit NDCs for all listed drugs that had been assigned a 10-digit
NDC.
D. Barcode Format Requirement
The FDA regulation at 21 CFR 201.25 specifies when, where, and in
what format a barcode must appear on the label of a human prescription
drug product, a biological product, and an over-the-counter drug
product. Currently, Sec. 201.25(c) provides that each drug product
subject to the barcode label requirements must have a barcode that
contains, at a minimum, the appropriate NDC in a linear barcode that
meets European Article Number/Uniform Code Council (EAN/UCC) or Health
Industry Business Communications Council (HIBCC) standards or another
standard or format that has been approved by the relevant FDA Center
Director. Section 201.25(c)(1) further states that the barcode must be
surrounded by sufficient blank space so that it can be scanned
correctly, and it must remain intact under normal conditions of use.
We proposed to revise Sec. 201.25(c) to allow use of barcodes in a
linear or nonlinear format that is approved by the relevant FDA Center
Director. We also proposed that approved standards would include those
that meet EAN/UCC or HIBCC standards. In the proposed rule, we
recognized that the current barcode standards that utilize GS1's Global
Trade Item Number (GTIN)-14 cannot accommodate the embedding of a 12-
digit NDC (87 FR 44038 at 44042, 44044). Therefore, we stated that the
delayed effective date of the rule would allow time for the development
of new data standards, data carriers, and systems and processes to
accommodate a 12-digit NDC.
In the following paragraphs, we discuss comments on proposed Sec.
201.25(c)(1). We are finalizing the proposal with modification.
Specifically, we are amending Sec. 201.25(c)(1) to allow the use of a
barcode in a linear or nonlinear format if it ``conforms to the
standards developed by a widely recognized international standards
development organization and that format and standard is recognized by
the relevant Food and Drug Administration Center Director.'' We have
removed references to specific standard-setting organizations, two of
which became outdated (according to comments submitted by GS1 US, EAN
and UCC merged in 2005 and are now known as GS1 and GS1 US,
respectively). The more general term ``widely recognized international
standards development organization'' is understood throughout industry,
unlikely to become obsolete, and does not constitute a change in the
status quo because GS1, GS1 US (a member of GS1), and HIBCC are
``widely recognized international standards development
organizations.'' In addition, this change has the benefit of
characterizing the nature of the organizations whose barcode formats
and standards FDA may recognize in the future.
Although the proposed rule and the existing regulation text refer
to barcode formats and standards ``approved'' by FDA, this final rule
requires that barcode standards and formats be ``recognized'' by FDA.
The purpose of this change is to clarify FDA's role with regard to
industry's adoption of barcode formats and standards that can comply
with all requirements of Sec. 201.25(c). Specifically, FDA is not a
standards development organization; it does not develop, prescribe, or
officially ``approve'' highly technical barcode standards and formats.
Rather, FDA relies on the expertise and activities of widely recognized
international standards development organizations to develop barcode
formats and standards for drug labels that will satisfy the
requirements of Sec. 201.25(c) while accommodating industry needs and
leveraging technological innovations. The Agency will ensure that
industry is notified if an FDA Center Director recognizes a new barcode
format and standard or revokes the recognition of a barcode format and
standard. In the meantime, FDA recognizes those barcode formats and
standards developed by GS1, GS1 US, and HIBCC that comply with the
requirements of Sec. 201.25(c).
(Comment 22) A number of commenters support our proposal to permit
the use of nonlinear barcodes. Some drug products must include on their
labels both the linear barcode currently required under existing Sec.
201.25(c) as well as a two-dimensional (2D) data matrix barcode that is
required for certain prescription drug packages under the DSCSA (Title
II of Pub. L. 113-54).\7\ One commenter advocates
[[Page 10759]]
eliminating linear barcodes for any drug label that bears a 2D data
matrix barcode encoding a product identifier. The commenter reasons
that space constraints make it difficult to fit both types of barcodes
on a single product package, and barcodes can be difficult to scan when
placed too close together. Two commenters assert that the GS1 UPC-A
linear barcode, which is commonly used to implement the current barcode
labeling requirement, is already of limited future utility because it
cannot accommodate the 11-digit NDC authorized under existing Sec.
207.33(b)(1). A different commenter encourages FDA to continue
supporting the use of linear barcodes.
---------------------------------------------------------------------------
\7\ The DSCSA was enacted to help secure the integrity of the
drug supply chain by, among other things, requiring serialization
and tracing of prescription drugs. For certain prescription drugs,
under sections 582(b)(2) and (e)(2) of the FD&C Act (21 U.S.C.
360eee-1(b)(2) and (e)(2)), manufacturers and repackagers are
required to affix or imprint a ``product identifier'' on each
package and homogenous case of product intended to be introduced in
a transaction into commerce (see section 581(24)(B) of the FD&C Act
(21 U.S.C. 360eee(24)(B)) for exemptions to the definition of
``transaction''). A ``product identifier'' is a standardized graphic
that includes the product's NDC and serial number (collectively, the
``standardized numerical identifier''), lot number, and expiration
date (sections 581(14) and (20) of the FD&C Act). The product
identifier must be in human-readable form and on a machine-readable
data carrier that conforms to standards developed by a widely
recognized international standards development organization (section
581(14) of the FD&C Act). For packages of product, the data carrier
is a 2D data matrix barcode (section 582(a)(9) of the FD&C Act).
---------------------------------------------------------------------------
(Response 22) We appreciate the commenters' support and believe
that allowing the use of nonlinear barcodes will accommodate
advancements in technology and industry needs by providing more options
for labeling compliance. After the effective date of this final rule,
if a product is required under Sec. 201.25 to include on its label a
barcode that encodes the drug's NDC, the manufacturer or repackager
will be able to encode the NDC into either a linear or nonlinear
barcode that complies with the requirements of Sec. 201.25. If the
same drug label is also required under the DSCSA to include a product
identifier, the 2D data matrix barcode could satisfy both sets of
barcode requirements (Sec. 201.25 and DSCSA) because the 2D data
matrix barcode includes encoding of the NDC. Accordingly, this final
rule should reduce scanning failures due to close placement of multiple
barcodes and avoid potential errors from manual entry of drug
information, thereby improving patient care and increasing efficiency
across the supply chain. This final rule does not prohibit the use of
both linear and nonlinear barcodes on the same label, as long as
applicable requirements under Sec. 201.25 and the DSCSA are met.
(Comment 23) Many commenters are concerned that the proposed
changes to the NDC format would require modifications to how the NDC is
encoded within a barcode. Commenters seek additional guidance regarding
the impact of a 12-digit NDC on barcode standards, such as a UPC
barcode or a 2D data matrix barcode used for the product identifier
required under the DSCSA.
(Response 23) We understand from comments submitted by GS1 US that
a 12-digit NDC would be incompatible with the current barcode standards
that utilize GS1's GTIN-12 or GTIN-14 (e.g., GS1's UPC-A and 2D data
matrix barcode) because a 12-digit NDC is too long to be embedded into
the current GTIN structure. GS1 US indicated that industry will no
longer be able to use the UPC-A barcode. To continue to support
industry in its NDC-based requirements, GS1 US states that it has
created an application identifier (AI) for the NDC, referred to as ``AI
(715).'' GS1's AI (715) is an additional data element that enables the
NDC to be encoded in barcodes that can manage multiple AIs and an
increased number of characters. According to GS1 US, the following
barcodes can encode AI (715) for the 12-digit NDC: (i) the GS1 2D
DataMatrix barcode (nonlinear); (ii) the GS1-128 barcode (linear); and
(iii) the GS1 DataBar barcode (linear). Therefore, for purposes of
Sec. 201.25(c) requirements, linear barcodes (e.g., GS1-128 or GS1
DataBar barcode) or nonlinear barcodes (e.g., GS1 2D DataMatrix
barcode) can transition to encoding the 12-digit NDC through the use of
GS1's AI (715). In addition, for DSCSA product identifier requirements,
the 2D data matrix barcode can encode the 12-digit NDC through the use
of GS1's AI (715), along with other required data elements (e.g.,
serial number, lot number, expiration date). According to GS1 US,
barcodes that encode the NDC using the AI (715) can be read only with
camera-based scanners. Affected parties should consider this to ensure
they have equipment and systems capable of handling the new, uniform,
12-digit NDC format on the effective date of the final rule.
(Comment 24) One commenter requests that FDA provide examples of
barcodes that would comply with this final rule. Several commenters
note the need for consistency between the FDA barcode rule and DSCSA
requirements.
(Response 24) The barcode labeling requirements of this final rule
would be satisfied by any barcode that encodes the appropriate NDC and
conforms to a standard developed by GS1, GS1 US, HIBCC, or another
organization whose linear or nonlinear barcode format is recognized by
FDA. We cannot provide examples of barcodes that will satisfy the
requirements of this final rule because GS1, GS1 US, and HIBCC may
change barcode formats and standards over time. We note, as summarized
in Comment 23, that GS1 has made it possible for linear and nonlinear
barcodes to encode the new 12-digit NDC on the effective date of this
final rule. Although the UPC-A linear barcode may not be used to encode
a 12-digit NDC, it would not have been able to encode the 11-digit NDC
that would have been issued under existing Sec. 207.33(b)(1) had this
rule not been finalized.
We presume that the commenters advocate for consistency between the
barcode labeling requirements of this final rule and the DSCSA product
identifier requirements to ensure that, when appropriate, a single
barcode could be used to satisfy both sets of requirements. We agree
that regulatory consistency on requirements related to barcodes is
desirable whenever possible, and based on comments received from GS1,
the addition of AI (715) will allow the 12-digit NDC to be incorporated
into one or more types of barcodes that could satisfy the requirements
of this final rule as well as DSCSA requirements. We anticipate that
standards organizations will continue to support industry's efforts to
integrate NDCs into barcodes for supply chain security purposes in a
manner that ensures consistency with the barcode labeling requirements
in this final rule.
(Comment 25) Some commenters seek guidance regarding how the new
NDC format would affect the use of GTINs, particularly for purposes of
DSCSA compliance. One commenter asks FDA to confirm that manufacturers
may continue to use the GTIN in barcodes where feasible (for example,
when package size is sufficient to accommodate the relevant barcode).
Another commenter asks FDA to recognize the GTIN-14 as an optional data
element of the unique product identifier required under section
582(b)(2) of the FD&C Act so that GTIN-14 can continue to be used for
global supply chain harmonization efforts; it could then be voluntarily
included within a 2D data matrix barcode and provided in human-readable
format on the package.
(Response 25) The direct relationship between GS1's GTIN-12 or -14
and NDC will no longer exist once the new 12-digit NDC format is fully
adopted because the use of 10- and 11-digit NDCs will be phased out and
the GTIN-12 and GTIN-14 cannot accommodate the embedding of a 12-digit
NDC. Regarding prescription drugs subject to DSCSA requirements,
manufacturers
[[Page 10760]]
and repackagers may continue to voluntarily include their associated
GTIN as part of the product identifier, as long as the product package
remains compliant with applicable DSCSA product identifier requirements
and inclusion of the GTIN-12 or -14 does not violate the barcode
requirements under Sec. 201.25.
(Comment 26) One commenter asks whether the current GS1 GTIN
without leading zeros would be accepted.
(Response 26) This final rule sets forth how 10- and 11-digit NDCs
will be converted to 12-digit NDCs. While this conversion will include
the addition of leading zeros in some segments of the NDC, FDA cannot
speak to how this would affect GS1 GTINs and general GS1 requirements
beyond the information that the Agency has received from GS1 through
this notice and comment process. FDA has addressed GTIN-related
comments in Responses 23 and 25.
(Comment 27) One commenter states that this final rule should
define a common barcode symbol and specify how it should be encoded.
The commenter suggests a specific encoding format and believes that
allowing GS1 to establish the barcode and encoding standards would
involve too much delay and would not result in uniform standards across
industry.
(Response 27) We decline to accept the commenter's suggestion. We
are concerned that promulgating a single barcode symbol and encoding
format could impede innovation in barcode technology for drug products
subject to the barcode label requirements. We note that given the
delayed effective date and GS1's development of AI (715) as an option
for encoding the 12-digit NDC in certain linear and nonlinear barcodes,
the commenter's concerns regarding delay have been addressed.
(Comment 28) In response to our solicitation of comment in section
V.C.3 of the proposed rule, an association of biopharmaceutical
research and manufacturing companies urges FDA not to further revise
Sec. 201.25(c) to accommodate potential advances in technologies by
allowing the use of unspecified automatic identification and data
capture formats other than linear or nonlinear barcodes. The
association notes that such a generic standard should not be
implemented without providing an opportunity for public notice and
comment. In addition, the association notes that any additional changes
to the regulation should be specific in nature to ensure alignment and
interoperability among all supply chain partners.
(Response 28) We understand the commenter's concern and will not
permit the use of unspecified automatic identification and data capture
formats at this time. We may consider the matter in future rulemaking.
E. Delayed Effective Date and Transition Period
In the following paragraphs, we discuss comments on our proposal to
delay the effective date of the final rule for 5 years after its
publication and to provide a 3-year transition period during which FDA
would exercise enforcement discretion with respect to drugs labeled
with a 10-digit NDC. In light of the public comments and the current
rate at which labeler codes are assigned, we are delaying the effective
date of this final rule for a period of 7 years after the date of its
publication. We are finalizing without change our proposal for a 3-year
transition period.
(Comment 29) Some commenters support the proposal to set a specific
effective date for the use of 12-digit NDCs, rather than implement the
new NDC format only after the supply of 5-digit labeler codes is
exhausted. These commenters note that a specific effective date would
mitigate disruption, patient risk, and the cost of the transition. In
particular, the commenters support a definitive effective date because
it allows for adequate planning and budgeting and is less likely to
result in a chaotic and inconsistent implementation.
(Response 29) We agree with the commenters and appreciate their
support.
(Comment 30) Several commenters believe that the proposed 5-year
delayed effective date and 3-year transition period are sufficient to
accomplish an orderly transition to the uniform, 12-digit NDC format
while minimizing the potential for drug shortages and patient harm.
Many other commenters, however, urge FDA to further delay the effective
date of the final rule or to adopt a longer transition period, or both.
Although most commenters do not suggest a specific alternative
implementation timeframe, several commenters suggest that full
implementation of the final rule (delayed effective date and transition
period) should occur over at least a 10-year period. One commenter
advocates for a 7-year delayed effective date, and another commenter
urges FDA to adopt a 10-year delayed effective date. A third commenter
asserts that the transition period should end at least 10 years from
the close of the comment period on the proposed rule (i.e., November
2032). Drug manufacturers and associations representing manufacturers
advocate for a 5-year transition period.
Commenters supporting a longer implementation timeframe assert that
the complexity and burden of migrating to a new NDC format warrants a
longer period of time for full implementation. Those supporting a
longer delayed effective date argue that pharmacies, payors, and other
parties throughout the healthcare supply chain and delivery system
would need more time to develop, test, and upgrade software systems to
handle both 10- and 12-digit NDCs; invest in new hardware for barcode
scanning; implement new internal processes; and train personnel. These
commenters assert that without more time, there would be significant
data exchange errors that would affect product delivery and impede
patient access.
Commenters representing the drug manufacturing sector assert that
the proposed 3-year transition period is too short to accommodate the
required labeling, barcode, and packaging changes, especially for
generic drug manufacturers with large numbers of labeler codes, drug
products, and packaging that must be updated. These commenters note
their belief that FDA's proposed 3-year transition period is based on a
flawed premise that most drug products have a 2-year expiration date
and most drug product labeling is updated at least once every 3 years.
The commenters note that many older generic drugs with stable safety
profiles expire after 3 or more years, and a few expire after 10 years.
One large generic drug manufacturer notes that it markets over 500
products with expiration dates longer than 2 years. In addition,
commenters argue that generic drug companies may have dozens or
hundreds of products for which labeling changes are not needed as
frequently as every 3 years, and carton and container labeling is
changed far less frequently. Moreover, commenters assert that, because
12-digit NDCs will not be assigned before the effective date of the
final rule, manufacturers cannot use the 7-year period before the
effective date to begin transitioning all labeling and packaging to the
new NDC format. According to the commenters, it will not be possible
for some manufacturers with large product portfolios to update all drug
product labeling and packaging within 3 years, and there will be a
substantial amount of product labeled with 10-digit NDCs on the market
at the end of the transition period. The commenters further note that,
as a practical matter, even drugs with a 2-year expiration date would
need to have their labeling updated by the end of the
[[Page 10761]]
first year of the transition period to avoid having unexpired inventory
on the market after 3 years. According to the commenters, a transition
period of at least 5 years is necessary to ensure that there is
sufficient time to make labeling changes for all products (including
barcode changes), minimize the amount of inventory that will need to be
taken off the market at the end of the transition period, and avoid
drug shortages. The commenters also believe that a longer transition
period would minimize the need to expedite a large volume of labeling
changes, thereby imposing a lower economic burden.
Two commenters, including a trade association of EHR developers,
advocate for a transition period shorter than 3 years, arguing that the
coexistence of 10- and 12-digit NDCs during the transition period would
pose a risk to public health that would not be outweighed by the
challenges manufacturers will face in updating their labeling to
conform to the final rule. The commenters suggest that the potential
for public health and safety risks would be reduced if the final rule
minimizes the amount of time during which health information systems
must accommodate multiple NDC formats. Another commenter is concerned
about the potential for confusion and medication errors during the
transition period.
(Response 30) In response to the comments we received asking for a
longer time period between the publication of the final rule and the
effective date, we are revising the proposed 5-year delayed effective
date to a 7-year delayed effective date. We reevaluated the supply of
5-digit labeler codes. Based on that reevaluation, we determined that
we could delay the effective date for 2 additional years without
significantly increasing the risk of running out of 5-digit labeler
codes prior to the effective date. Accordingly, we are delaying the
effective date of this final rule for 7 years. We have chosen a 7-year
delayed effective date because it responds to the needs of the
commenters, will help ensure an orderly and safe transition to the new
NDC format, and is not likely to occur before the supply of 5-digit
labeler codes is exhausted. Further delaying the effective date could
jeopardize the supply of 5-digit labeler codes.
We decline to extend the transition period beyond 3 years. We
continue to believe that the coexistence of drug labeling with either
the 10- or 12-digit NDC poses risks to public health. Simultaneously
accommodating 10- and 12-digit NDCs raises the risk of confusion, which
in turn could increase medication errors and the potential for
illegitimate product to be introduced into the market. We disagree with
the commenters' assertion that manufacturers cannot use the 7-year
period before the effective date of this final rule to begin the work
of transitioning all labeling and packaging to the new NDC format.
Although the new labeling cannot be used before the effective date,
manufacturers will know how each existing 10-digit NDC will be
converted to the new format. Thus, they can begin preparing new labels
and packaging before the start of the transition period. Accordingly,
we do not believe the need for a transition period longer than 3 years
outweighs the risks of extending the time period during which both 10-
digit and 12-digit NDCs will be used. Nevertheless, given the
challenges cited by these commenters, we are concerned that a
transition period shorter than 3 years would not be feasible. We are
finalizing a 3-year transition period to support a smooth transition
that minimizes the potential for confusion and medication errors.
(Comment 31) In lieu of a longer transition period, some commenters
advocate for a more flexible approach that would alleviate some of the
challenges they perceive with a 3-year transition period. These
commenters suggest that FDA implement a waiver process pursuant to
which manufacturers could apply for an extension of the transition
period upon a demonstration of need. Under this approach, manufacturers
would still use the new NDC format, but would have more time to
transition products with 10-digit NDC labeling from the market.
Alternatively, commenters suggest a staggered or phased implementation
approach that would permit companies with large numbers of NDCs to have
a longer transition period. Finally, commenters suggest that FDA treat
products that bear a 10-digit NDC as exempt from the requirements of
this final rule as long as the products entered interstate commerce
(i.e., were packaged) or were actually distributed (i.e., changed
ownership) prior to the end of the transition period. According to one
commenter, this approach would give manufacturers more time to deplete
stock of remaining product with the 10-digit NDC while introducing
little additional risk into the market.
(Response 31) No enforcement action would be taken against any
unexpired product for being labeled with a 10-digit NDC (rather than a
12-digit NDC) if it remains in interstate commerce after the transition
period ends, so long as it was introduced or delivered for introduction
into interstate commerce prior to the effective date of this final
rule. We decline, however, to extend the transition period in the
manner suggested by the commenters for the reasons noted in Response
30. Accordingly, any products that are introduced into interstate
commerce with a 10-digit NDC after the effective date and before the
end of the transition period are subject to enforcement action if they
remain in interstate commerce after the end of the transition period.
We believe this approach will encourage prompt transitioning of
labeling while decreasing compliance costs and the potential for drug
shortages.
(Comment 32) One commenter representing allergen manufacturers
requests that its members be exempt from the requirement to identify
their drug products with a 12-digit NDC. The commenter reasons that
converting allergen extract products to a 12-digit NDC format after
they have been identified by 10-digit NDCs for over 50 years may cause
confusion and is too burdensome.
(Response 32) We see no reason to treat allergen manufacturers any
differently than manufacturers of other drugs. For the reasons
explained in Responses 8 and 9, we believe that using the uniform, 12-
digit format NDC for all drugs is ultimately safer, less confusing, and
less expensive. Moreover, FDA considers an NDC in its original 10-digit
format and in its converted 12-digit format to be the same NDC with
different formats.
(Comment 33) Some commenters advocate for FDA to exercise
flexibility regarding the implementation of the final rule if
unanticipated events arise that interfere with industry's ability to
implement the necessary system changes by the effective date.
(Response 33) We are extending the effective date of this final
rule to 7 years after publication, which provides additional
flexibility. Although FDA has provided some flexibility with respect to
other effective dates, affected parties should not expect or anticipate
any extensions in the effective date of this final rule given the
limited supply of labeler codes. Affected parties should be prepared to
accommodate the 12-digit NDC no later than 7 years after the
publication of this final rule. Once the Agency begins issuing 12-digit
NDCs, affected parties must be ready to handle that NDC; the inability
to do so could jeopardize patient care and access to medication.
(Comment 34) A commenter representing wholesale distributors seeks
clarity on the legal status of drug products that bear only a 10-digit
NDC and enter the supply chain before the
[[Page 10762]]
effective date of this final rule. The commenter urges FDA to clarify
that such products may remain in the supply chain indefinitely after
the effective date. Similarly, another comment from an association of
wholesale distributors advocates that products packaged prior to the
effective date should be permitted to remain on the market until the
expiration date of those products. The comment reasons that this
approach would allow patient access to products already in the market.
(Response 34) Products that are introduced into interstate commerce
or delivered for introduction into interstate commerce before the
effective date can remain on the market and accessible to patients
after the 3-year transition period, as long as they have not expired.
We note that most products introduced or delivered for introduction
into interstate commerce before the effective date of this final rule
will expire before the end of the transition period. Products that are
packaged before the effective date but are introduced into interstate
commerce or delivered for introduction into interstate commerce with a
10-digit NDC (rather than a 12-digit NDC) after the effective date are
subject to enforcement action if they remain in interstate commerce
after the end of the transition period.
(Comment 35) One commenter suggests that FDA conduct a study to
determine if the proposed delayed effective date and transition period
allow sufficient time for all interested parties to implement the final
rule.
(Response 35) We decline to conduct a study as suggested by the
commenter. Such a study is unnecessary because the public comments have
provided sufficient feedback on our proposed implementation timeframe.
Moreover, a study would further delay the final rule and jeopardize
FDA's ability to transition to 6-digit labeler codes before exhausting
the supply of 5-digit labeler codes.
(Comment 36) Several commenters urge FDA to provide periodic
updates identifying the remaining number of 5-digit labeler codes or
estimating how much longer FDA can continue to issue 5-digit labeler
codes. The commenters note that this information would be useful in
determining when to begin or accelerate efforts to comply with the
final rule.
(Response 36) We decline to provide the requested updates because
the volume of remaining 5-digit labeler codes will not impact the
effective date of the final rule, and FDA does not intend to extend the
effective date even if the number of 5-digit labeler codes may allow
for such an extension. Therefore, interested parties should work with
all diligence to ensure that, as of the effective date of this final
rule, they have systems in place to handle the new 12-digit NDC format.
FDA has carefully established the effective date of this final rule to
occur before the supply of 5-digit labeler codes is exhausted.
(Comment 37) One commenter requests clarification on when FDA will
begin issuing 6-digit labeler codes and converting 10-digit NDCs to 12-
digit NDCs. The commenter also seeks clarification on when repackagers
must begin labeling products using the 12-digit NDC format.
(Response 37) Starting on the effective date of this final rule,
FDA will issue only 6-digit labeler codes and all new NDCs will be
assigned in the uniform, 12-digit format (except in the case of certain
HCT/Ps for which an alternatively formatted NDC is approved by FDA
pursuant to Sec. 207.33(b)(2) of this final rule). In addition, on the
effective date, FDA will convert all existing 10-digit NDCs in all
product listing structured product labeling (SPL) and NDC labeler code
request SPLs (hereinafter ``drug listing files'') to the 12-digit
format by adding leading zeros to the labeler code, product code, and/
or package code segment of the NDC, as needed to produce the uniform 6-
4-2 format. All drug listing files submitted after the effective date
must identify the NDC using the 12-digit NDC format. Manufacturers and
repackagers should start labeling drugs that were assigned a 10-digit
NDC with the 12-digit NDC as soon as possible after the effective date
of this final rule.
(Comment 38) A comment from an association representing a variety
of parties in the pharmaceutical distribution system urges FDA to
retain the proposed policy under which FDA would automatically convert
NDCs to the 12-digit format on the effective date of the final rule.
This comment notes that requiring registrants to resubmit existing drug
listing files to reflect a reformatted NDC would be unmanageable and
impose an enormous burden. Several commenters representing the
manufacturing sector oppose the proposed automatic conversion policy on
the grounds that it will result in confusion and could render product
immediately unsellable. One commenter notes that distributors could put
a 10-digit NDC product into a non-sellable status and eventually return
the product to the manufacturer for destruction, which would be
wasteful. This commenter also notes that current purchasing systems
would require significant changes to allow for the same drug product to
be sold with different NDCs. Commenters opposed to the automatic
conversion policy advocate that FDA should not activate new 12-digit
NDCs until the manufacturer has introduced product with that NDC into
the market after submitting an SPL file with updated labeling
reflecting the 12-digit NDC. According to the commenters, their
proposed approach would ensure that the NDC that appears on a drug
label will match the NDC that appears for that product in the NDC
Directory and the DailyMed searchable database. The commenters also
note that their approach would reduce confusion and the potential for
medication errors and would avoid the need to discard labeling stock
and usable product.
(Response 38) We agree that it would be unduly burdensome for
manufacturers to resubmit all existing drug listing files merely to
reflect a reformatted NDC that is not a ``new'' NDC. The commenters
opposed to the automatic conversion policy appear to have misunderstood
the nature of the proposed NDC conversion. As explained in Response 2,
FDA considers the conversion of a 10-digit NDC assigned by FDA to the
new, uniform 12-digit NDC format to be a ministerial, administrative
change and not the assignment of a ``new'' NDC. Furthermore, FDA
considers such an NDC in its original 10-digit format and in its
converted 12-digit format to be the same NDC with different formats.
Because the converted NDC is not a ``new'' NDC, the commenters'
concerns that the labeling update renders product immediately
unsaleable are unfounded. Moreover, by publishing both the 10-digit and
12-digit NDCs for all listed drugs that had been assigned a 10-digit
NDC, FDA would minimize the potential for confusion that may occur
during the transition period before a drug's labeling is updated. We
recognize that electronic systems will require significant changes to
process transactions involving NDCs under both formats after the
effective date and for this reason have delayed the effective date for
7 years. We note that the alternative approach suggested by the
opposing comments would not ensure that the NDC that appears on a drug
label will match the NDC that appears for that product in the NDC
Directory and DailyMed, except in the unlikely event that all stock of
the product labeled with a 10-digit NDC has been removed from the
market at the time the manufacturer has submitted a new SPL file and
introduced into interstate
[[Page 10763]]
commerce product labeled with the 12-digit NDC.
Accordingly, upon the effective date, FDA will update existing SPL
files to reflect the 12-digit NDC by linking or otherwise associating
both NDC formats. For those products that are required to include an
NDC on their labeling, a manufacturer must report that it has updated a
product label to reflect the 12-digit NDC by using the annual reporting
process under 21 CFR 314.81(b)(2)(iii) for drugs subject to a new drug
application (NDA) or abbreviated new drug application (ANDA) or 21 CFR
601.12(f)(3) for biological products subject to a biologics license
application (BLA). Manufacturers that voluntarily include the NDC on
the label of an animal drug must make a similar report in accordance
with 21 CFR 514.80(b)(4)(ii). In addition, in accordance with Sec.
207.49(a)(15), the manufacturer must update the relevant SPL file with
the new labels and packaging that includes the 12-digit NDC format.
(Comment 39) A comment from a generic drug manufacturer asserts
that, in the case of a labeling update required under section 505(o)(4)
of the FD&C Act (21 U.S.C. 355(o)(4)), FDA should not require the
revised labeling to update the NDC to the new 12-digit format. The
commenter notes that, under section 505(o)(4)(B)(i) of the FD&C Act, a
manufacturer has only 30 days to propose labeling changes to reflect
new safety, effectiveness, or other information regarding a reference
listed drug (RLD). The commenter conveys concern that RLD sponsors
could ``force'' generic drug manufacturers to update labeling with
respect to the NDC before the manufacturer has prepared new packaging
and other materials featuring the reformatted NDC, thereby disrupting
complex internal systems and processes.
(Response 39) As stated in the proposed rule, if a firm includes an
NDC in its labeling, it should start labeling drugs that were assigned
a 10-digit NDC with the 12-digit NDC as soon as possible after the
effective date, but no later than when it runs out of its existing
labeling for the drug and orders or begins printing new labeling (87 FR
44038 at 44044). We recognize that the speed with which labeling
changes must be made pursuant to section 505(o)(4)(B)(i) of the FD&C
Act may be challenging, particularly if they are unexpected. However,
firms can take advantage of the 7-year delayed effective date to plan
and prepare for timely implementation of labeling updates after the
effective date of this final rule. Such preparation will minimize the
challenges posed by labeling changes that must be made to reflect new
safety, effectiveness, or other information under section 505(o)(4) of
the FD&C Act. We note that FDA cannot approve new labeling that is not
in compliance with applicable requirements. Therefore, in the case of a
drug whose labeling must include the NDC, the 12-digit NDC format must
be used in any new labeling that includes the NDC that is submitted for
FDA approval after the effective date of this rule.\8\
---------------------------------------------------------------------------
\8\ We note that FDA only assigns an NDC in accordance with 21
CFR 207.33(d). Approval of a drug's labeling that includes an NDC
that has yet to be assigned by FDA in accordance with Sec.
207.33(d) should not be interpreted as FDA's assignment of such NDC.
---------------------------------------------------------------------------
(Comment 40) Several commenters seek more detailed information
regarding the revision and submission of drug listing files.
Specifically, the commenters seek clarification on when manufacturers
should begin incorporating the 12-digit NDC format into drug listing
files, whether such updates would be accomplished by amending existing
drug listing files or if manufacturers would need to submit new drug
listing files, and whether FDA would accept an updated drug listing if
the data elements in the drug listing file reflect the 12-digit NDC,
but the drug's labeling has not yet been updated to reflect the 12-
digit NDC format.
(Response 40) Upon the effective date of this final rule, FDA will
update all drug listing files to reflect the 12-digit NDC format.
Accordingly, manufacturers will not need to submit new or updated drug
listing files solely to effectuate the NDC format change. If a drug
listing file must be updated for other reasons after the effective
date, the manufacturer should follow the usual procedures for such
updates. During the transition period, FDA will accept an updated drug
listing file that includes the NDC in a 12-digit format, even if the
drug's labeling still reflects a 10-digit NDC.
(Comment 41) A commenter seeks clarity on whether it could begin to
initiate conversion of 10-digit NDCs to the 12-digit NDC format on
product labeling after the effective date of the final rule. Another
commenter notes concern that some manufacturers would wait until after
the transition period to begin labeling updates to reflect the 12-digit
NDC.
(Response 41) Firms should not delay their labeling compliance
efforts until the end of the transition period. Rather, they should use
the 7-year period before the effective date to plan and prepare for
updating their labeling during the transition period. For products
whose labels must include the NDC, firms should start labeling products
with the 12-digit NDC format as soon as possible after the effective
date and no later than when existing labeling stock is depleted.
(Comment 42) A few commenters inquire whether the NDC Directory and
DailyMed would be updated and searchable on both the 10-digit and 12-
digit NDCs.
(Response 42) For products previously assigned a 10-digit NDC, the
NDC Directory will be updated on the effective date to reflect NDCs in
the 12-digit format, and we anticipate that it will be searchable using
either the 10-digit or 12-digit format. Although the DailyMed database
is maintained by the National Institutes for Health (NIH), not FDA, the
Agency will coordinate with NIH to help ensure that DailyMed is
similarly updated and searchable on both NDC formats as of the
effective date.
(Comment 43) One commenter seeks confirmation that the NDC format
appearing on certain prescription drug packages is expected to match
the NDC included in the transaction information required to be
exchanged to satisfy DSCSA requirements. The commenter notes that the
product identifier for DSCSA purposes should match what appears on the
physical label and packaging.
(Response 43) This comment is outside the scope of this final rule
and will be addressed through DSCSA implementation efforts. Detailed
information on DSCSA implementation can be found at https://www.fda.gov/drugs/drug-supply-chain-integrity/drug-supply-chain-security-act-dscsa.
(Comment 44) A commenter seeks clarification regarding compliance
obligations at the end of the transition period. Specifically, the
commenter questions whether all drug products in the supply chain at
the end of the transition period must be labeled with a 12-digit NDC or
if only those drug products manufactured after expiration of the
transition period must bear a 12-digit NDC.
(Response 44) Most drug products in the supply chain at the end of
the transition period must be labeled with a 12-digit NDC. Drug
products labeled with a 10-digit NDC that are introduced into
interstate commerce or delivered for introduction into interstate
commerce after the effective date and that remain on the market after
the end of the transition period are subject to enforcement action. In
contrast, drug products labeled with a 10-digit NDC that are introduced
into interstate commerce or delivered for introduction into interstate
commerce before the
[[Page 10764]]
effective date of this rule can remain on the market after expiration
of the 3-year transition period, as long as they have not expired.
Because many drug products expire within 3 years, we do not expect a
large supply of drug products labeled with 10-digit NDCs to remain on
the market after expiration of the transition period.
As stated above, drug products manufactured after the effective
date should be labeled with the new NDC format no later than when new
labels need to be printed. We recognize that drug products labeled with
a 10-digit NDC will likely be introduced into the market during the
first year after the effective date, as firms attempt to deplete their
labeling inventory. By the second year after the effective date, we
expect most firms to be using new labeling that conforms to the 12-
digit NDC format. Firms still using old labeling during the third year
after the effective date will be at risk for enforcement action if drug
products with such labeling remain on the market after the transition
period ends.
F. Technical Amendments
After the proposed rule was published, FDA modified the authority
citation for 21 CFR part 201 to include the following additional
statutory provisions: 21 U.S.C. 343, 360ccc, 360ccc-1, and 360ee. The
authority citation set forth in this final rule repeats the current
authority citation without change.
VI. Effective Date
This rule will become effective 7 years after the date of its
publication in the Federal Register. In addition, as discussed in
section V.E. of this document, this rule provides for a 3-year
transition period following the effective date. We expect the
transition period to minimize possible disruption to the distribution
of products subject to this rule and to minimize the burden on
manufacturers and labelers. During the transition period, firms with
products that were assigned 10-digit NDCs prior to the effective date
of the final rule must use a 12-digit NDC for all drug listings
submitted to FDA and should transition to using a 12-digit NDC on
labeling.
VII. Final Economic Analysis of Impacts
A. Introduction
We have examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, Executive Order 14192, the
Regulatory Flexibility Act (5 U.S.C. 601-612), the Congressional Review
Act/Small Business Regulatory Enforcement Fairness Act (5 U.S.C. 801,
Pub. L. 104-121), and the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4).
Executive Orders 12866 and 13563 direct us to assess all benefits
and costs of available regulatory alternatives and, when regulation is
necessary, to select regulatory approaches that maximize net benefits.
Rules are economically significant under Executive Order 12866 if they
have an annual effect on the economy of $100 million or more; or
adversely affect in a material way the economy, a sector of the
economy, productivity, competition, jobs, the environment, public
health or safety, or State, local, or tribal governments or
communities. The Office of Information and Regulatory Affairs (OIRA)
has determined that this final rule is not a significant regulatory
action under Executive Order 12866.
Executive Order 14192 requires that any new incremental costs
associated with certain significant new regulations ``shall, to the
extent permitted by law, be offset by the elimination of existing costs
associated with at least 10 prior regulations.'' This final rule is not
considered an Executive Order 14192 regulatory action because this rule
is not significant under Executive Order 12866.
Because this rule is not likely to result in an annual effect on
the economy of $100 million or more or to meet other criteria specified
in the Congressional Review Act/Small Business Regulatory Enforcement
Fairness Act, OIRA has determined that this rule does not fall within
the scope of 5 U.S.C. 804(2).
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because the one-time costs could be as much as 0.59 percent
of average annual revenue for some very small entities in the
pharmaceutical industry, 0.33 percent of average annual revenue for
some very small entities in the insurance industry, and 0.40 percent of
average annual revenue for some very small entities in the healthcare
industry, we certify that the final rule will not have a significant
economic impact on a substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes estimates of
anticipated impacts, before issuing ``any rule that includes any
Federal mandate that may result in the expenditure by State, local, and
tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation) in any 1 year.''
The current threshold after adjustment for inflation is $187 million,
using the most current (2024) Implicit Price Deflator for the Gross
Domestic Product. This final rule will not result in an expenditure in
any year that meets or exceeds this amount.
B. Overview of Benefits, Costs, and Transfers
The final rule amends regulations governing the format of the NDC
by standardizing it to 12 digits in length. Currently, the NDC assigned
by FDA is 10-digits and can be in multiple formats. The NDC for each
listed drug in the United States is a unique 3-segment number, where
the three segments are the labeler code, product code, and package
code. Under this final rule, the standardized NDC will consist of three
segments: a 6-digit labeler code, a 4-digit product code, and a 2-digit
package code. When the rule becomes effective, FDA-assigned 10-digit
NDCs will be converted to the uniform 12-digit format by adding leading
zeros to the labeler code, product code, or package code segment of the
NDC, as needed to produce the uniform 6-4-2 format.
FDA's transition to a uniform format for FDA-assigned NDCs is
intended to facilitate the adoption of a single NDC format across the
entire healthcare industry. Such an adoption will eliminate the need to
convert NDCs from one of the FDA-assigned formats to a different
standardized format used by other sectors of the healthcare industry
(e.g., healthcare providers and payors). Eliminating the need to
convert NDCs should reduce potential errors caused by converting the
FDA-assigned NDC format to a different NDC format used by other sectors
of the healthcare industry. Standardization and adoption of a single
format will also eliminate the need for additional quality control and
validation by certain interested parties, such as payors and
prescribers, to ensure a drug product and its respective NDC are
accurate; this is particularly important for insurance coverage and
reimbursement claims. Another benefit of the rule will be to avoid any
potential risks to the public health from medication errors and the
risk of confusion. We do not have enough information to quantify these
potential benefits, so we only qualify them in this analysis.
The costs to industry of converting current NDCs to the
standardized format will include one-time costs of updating software
systems, other transition costs, coordinating labeling updates, and
reading and understanding the rule. Table 4 shows a summary of the
[[Page 10765]]
quantified costs of the rule. We estimate annualized costs will be
about $14.64 million ranging from $7.64 million to $22.79 million using
a 7-percent discount rate over a 10-year horizon. Similarly, we
estimate annualized costs will be about $14.90 million ranging from
$7.79 million to $23.18 million using a 3-percent discount rate over a
10-year horizon.
Table 4--Summary of Benefits, Costs, and Distributional Effects of the Final Rule
[$millions, 2024]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Units
-----------------------------------
Category Primary Low High Period Notes
estimate estimate estimate Year Discount covered
dollars rate (%) (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
Annualized Monetized ($millions/ .......... .......... .......... ......... 7 ..........
year). 3
Annualized Quantified.............. .......... .......... .......... ......... 7 ..........
3
----------------------------------------------------------------------------------------------------------------
Qualitative........................ Potential cost savings by eliminating different formats of the NDCs. Reductions in annual audits, billing
issues, cost of software, and potential medication errors.
----------------------------------------------------------------------------------------------------------------
Costs:
Annualized Monetized ($millions/ $14.64 $7.64 $22.79 2024 7 10 Costs to labelers increase with the
year). 14.90 7.79 23.18 2024 3 10 quantity of NDCs they handle.
Annualized Quantified.............. .......... .......... .......... ......... 7 ..........
3
----------------------------------------------------------------------------------------------------------------
Qualitative........................ The net monetized costs are likely overestimated because they do not account for cost-savings.
----------------------------------------------------------------------------------------------------------------
Transfers:
Federal Annualized Monetized .......... .......... .......... ......... 7 ..........
($millions/year). 3
-----------------------------------------------------------------------
From/To............................ From:
To:
-----------------------------------------------------------------------
Other Annualized Monetized .......... .......... .......... ......... 7 ..........
($millions/year). 3
----------------------------------------------------------------------------------------------------------------
From/To............................ From:
To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
State, Local, or Tribal Government: No estimated effect.............................................................................................
Small Business: One-time costs will be no more than 1 percent of average revenue for some very small stakeholders in the pharmaceutical, insurance,
and healthcare industries. We certify that the final rule will not have a significant economic impact on a substantial number of small entities..
Wages: No estimated effect..........................................................................................................................
Growth: No estimated effect.........................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
The total present value, in 2024 millions of dollars, across all
three industries ranges from $53.65 million to $160.08 million with a
primary estimate of $102.85 million using a 7-percent discount rate. By
contrast, using a 3-percent discount rate, the total present value of
estimated costs ranges from $66.42 million to $197.76 million with a
primary estimate of $127.08 million. These costs are likely to be
spread out over the 7-year period between publication of the rule and
its effective date. Thus, we assume that one-seventh of these costs
occur each year of this period and that the first year of the rule is
2026. We assume the reading and understanding costs, however, will
occur the first year after the rule is published.
In line with Executive Order 14192, in Table 5 we estimate present
and annualized values of costs, cost savings, and net costs over a
perpetual time horizon. We estimate that this rule will generate $7.90
million in annualized costs at a 7-percent discount rate, discounted
relative to year 2024, over a perpetual time horizon.
Table 5--E.O. 14192 Summary Table of Costs and Cost Savings
[$millions, 2024]
----------------------------------------------------------------------------------------------------------------
Primary estimate
7% Low estimate 7% High estimate 7%
----------------------------------------------------------------------------------------------------------------
Present Value of Costs................................. $112.90 $53.65 $160.08
Present Value of Cost Savings.......................... ................. ................. .................
Present Value of Net Costs............................. 112.90 53.65 160.08
Annualized Costs....................................... 7.90 3.76 11.21
Annualized Cost Savings................................ ................. ................. .................
Annualized Net Costs................................... 7.90 3.76 11.21
----------------------------------------------------------------------------------------------------------------
Note: Values discounted over an infinite time horizon and year one is assumed to be 2026.
[[Page 10766]]
C. Comments on the Preliminary Economic Analysis of Impacts and Our
Responses
On July 25, 2022, we published the proposed rule ``Revising the
National Drug Code Format and Drug Label Barcode Requirements'' (87 FR
44038). We received several comments on the Preliminary Regulatory
Impact Analysis (PRIA) of the proposed rule (Ref. 5). Below, we group
the comments by topic and offer a brief description of each and our
responses. The order of comments and responses is not a reflection of
importance.
1. Cost Estimates
(Comment 45) Some commenters express that the cost estimates of
transitioning 10-digit NDCs to a 12-digit format are underestimated and
that they should be three to ten times the International Classification
of Diseases (ICD) conversion reference cited in the PRIA.
(Response 45) We disagree. We clarify that the ICD-9 to ICD-10
conversion is only a reference to assess the burden of updating
information systems. We agree that the NDC and the ICD conversion do
not involve the same amount of effort. The mapping of ICD-9 to ICD-10
codes involved the mapping of 57 ICD-10 codes per each ICD-9 code on
average (according to the RAND Corporation (RAND) 2004 report we use,
Ref. 6). In the PRIA, we use an effort relative to the ICD conversion
of 10 percent because the mapping of NDCs is 1-to-1 instead. This is a
conservative approach because estimates are likely higher than what the
costs will be. However, in section II.F.2 of the FRIA, we are updating
estimates in the cost category entitled ``Other Transition Costs,''
previously named ``Learning and Training.'' In addition, in the
sensitivity analysis in section II.I.1 of the FRIA, we include a range
of 1 percent to 50 percent relative to the ICD-conversion estimates.
(Comment 46) Some commenters express that the cost estimates do not
represent the cost burden some large companies will experience.
(Response 46) Feedback from industry helps us with estimates. We
note that larger companies may refer to the upper bound costs rather
than the average estimates for reference. This feedback, however, may
only represent a few companies.
(Comment 47) Commenters express that estimating costs based on the
ICD-9 to ICD-10 transition is not appropriate because ICD codes are not
used by as many interested parties as NDCs.
(Response 47) We disagree. We do not use the ICD estimates to
calculate that the NDC transition will cost the same amount. We
emphasize that the estimates that use the ICD conversion only apply to
some elements in the calculation of software updates and to other
transition costs. Other categories of costs, such as coordination of
label updates, are estimated using other additional inputs. We also
clarify that we use the ICD estimates to assess certain cost inputs
rather than to claim that an entire industry group will have a fixed
amount of costs; that is, we use the breakdown of cost items and not
the aggregate ICD cost per interested party.
(Comment 48) Some commenters express that the cost estimates do not
account for the need to update the physical packaging in addition to
the labeling.
(Response 48) The labeling cost model that we use from RTI
International accounts for the coordinated and uncoordinated relabeling
costs, which include packaging updates (Ref. 7). In the PRIA, however,
we opted not to include the cost element of disposing old inventory or
updating it with new labels over the old ones because we stated that
during the 3-year transition period, we do not intend to object to
products being introduced into interstate commerce with the 10-digit
NDC that they were previously assigned. That is, in general, we will
allow old labels to be exhausted and thus minimize the need to discard
old inventory.
In addition, we note that we are increasing the delay in effective
date of the rule to 7 years instead of 5 years to allow interested
parties sufficient time to update their systems and make other changes
necessary to ensure a safe and orderly transition to the new NDC format
occurs on the effective date. This way, labelers can better assess the
inventory of labels with 10-digit NDCs that will be needed.
Furthermore, the 3-year transition period provides time to perform
updates to the affected packaging.
(Comment 49) Commenters express that the costs are underestimated
because the rule will have a greater impact on products subject to
DSCSA requirements. For example, under DSCSA, firms must include the
NDC in transaction information.
(Response 49) We acknowledge that the NDC is to be included in the
transaction information under the DSCSA. We do not, however, ignore
this cost or other transaction costs that may arise with the new NDC
format. This FRIA provides higher estimates in the cost category
entitled ``Other Transition Costs,'' previously named ``Learning and
Training,'' and makes it more explicit that the costs of transitioning
to the uniform, 12-digit NDC format, including the transaction
information required under the DSCSA, are included in this category, as
well as meetings for pre-planning, execution, additional quality
controls, adjustments to the reformatted NDCs, and correction of any
discrepancies that arise.
(Comment 50) Commenters convey that the costs are underestimated
for pharmacies as there are more changes needed beyond software
updates, such as updates to purchase orders and controlled substances
reporting requirements.
(Response 50) We agree that these costs are not included in the
cost category entitled ``Software and Updates of NDC Records'' in the
PRIA. We cover these potential costs, and some others, in section
II.F.2 of the FRIA, entitled ``Other Transition Costs,'' previously
named ``Learning and Training.'' We update the costs in this category
to nearly double the previous estimates to account for potential
underestimates in the PRIA.
(Comment 51) Commenters express that the PRIA fails to recognize
that many systems cannot handle two codes for the same product and
there will be costs to update those systems.
(Response 51) We include estimated costs for such system updates,
and some other costs, in a general category we call ``Software and
Updates of NDC Records'' in the FRIA (see section II.F.1 of the FRIA).
(Comment 52) Some commenters express that the estimated costs were
based on an accurate but incomplete list of interested parties. The
commenters identify additional interested parties, including state
prescription drug monitoring programs; State Medicaid agencies; drug
compendia; drug distributors; pharmacy benefit managers; pharmacy
claims processors; other payors beyond insurers, such as employers'
health plans and claim sponsors; rebate processors; software vendors;
auditors; intermediate and clearing houses; data aggregators; other
government agencies; health information exchanges; and regulatory
agencies.
(Response 52) We disagree with this interpretation of the PRIA. We
classify interested parties into aggregate categories. Listing all the
different disaggregated interested parties is not feasible as
exemplified in the comment submitted. For example, the commenters
express that the interested parties affected ``include, but are not
limited to,'' the entities listed. By acknowledging that the interested
parties are ``not limited to'' the list
[[Page 10767]]
submitted, commenters show how difficult it is to list all of them.
More importantly, many parties identified by the commenters can be
grouped into more general and useful categories. For example, other
government agencies and Medicaid agencies can be grouped together with
other payors that perform that function. Pharmacy benefit managers,
pharmacy claims processors, and any other intermediary in processing
claims, rebates, audits, or any activity related to a drug product
transaction can be grouped into the larger insurance component, as we
do by referring to them as other involved intermediaries. Note that
software vendors are included in the pharmaceutical industry category
we use because the former will bill the latter when they perform system
updates; separating these two groups and adding costs for each would
double count the costs. Our analysis also acknowledges interested
parties that process information but do not perform distribution or
transactions. In sum, further dividing interested parties into
subgroups beyond what we describe in the economic analysis does not add
any accuracy or completeness to the analysis.
(Comment 53) Some commenters offered different cost estimates than
what we presented in the PRIA. For example, some commenters express an
amount of $100 million per wholesale distributor due to the many
databases to update and systems to modify. Others express costs of $5
million for manufacturers and costs of up to $50 million for the
largest generic companies.
(Response 53) We appreciate this kind of feedback. The more
information we have, the better our estimates become. We have adjusted
some of our estimates. However, we also note that these comments offer
cost figures as an opinion and do not offer details about how these
costs are estimated. We used the RAND 2004 report (Ref. 6) for these
types of costs and the report dissects the different parts, which make
our estimates trackable as compared to the ones offered by the
commenters. We also note that the NDC updates, unlike the ICD updates,
can be programmed as the update only needs a leading digit added to the
respective sequence of digits. We agree that the communication for
multiple systems may add a layer of quality control. We do account for
this layer, and we have updated our ``Other Transition Costs,''
previously named ``Learning and Training,'' estimates to represent a
higher burden.
(Comment 54) Some commenters express support for the Agency's
proposal to convert 10-digit NDCs to the uniform, 12-digit format by
adding a leading zero to the appropriate NDC segment. According to the
commenters, this is the most efficient conversion option because it
minimizes mapping and programming costs, and the standardization
eliminates the use of multiple NDC formats.
(Response 54) We agree. This comment highlights that the effort to
update systems can be automated to greatly reduce the burden.
2. Long-Term Cost Savings
(Comment 55) Some commenters highlight that current processing of
NDCs between providers of drug products and payors is substantial and
costly due to the lack of a standard format. These commenters highlight
the potential for cost savings in the long term despite some transition
costs in the short term.
(Response 55) We agree with these comments.
(Comment 56) Some commenters highlight that the standardization
will mitigate the potential for disruption, patient risk, and high
costs by ensuring there will be a single NDC format and predetermined
date for implementation. The comments also highlight that having
multiple NDC formats can lead to incorrect drug inventory and errors in
sending and receiving drugs.
(Response 56) We agree with these comments. Although we are not
able to quantify the cost savings, we agree that in the medium-to-long
term, cost savings will be realized as the multiple formats for FDA-
assigned NDCs are eliminated and multiple related quality control steps
become unnecessary. In the short term, industry will experience a
transition process and eliminate inefficiencies caused by multiple
formats for the FDA-assigned NDC.
3. Misunderstanding Incremental Cost
(Comment 57) Some commenters express that maintaining the 10-digit
NDC and adopting a limited alphanumeric labeler code for new labelers
would be less costly than adopting a 12-digit NDC format. Commenters
argue that fewer entities would have major conversions to perform and
that any needed conversions would be less expensive than under this
rule because they would be performed faster. These commenters also
express that preserving the 10-digit NDC format and using an
alphanumeric format would avoid any changes to the HIPAA 11-digit NDC
format.
(Response 57) We disagree. As explained in Response 11, the
alphanumeric option may lead to some confusion. In addition, the
alphanumeric option may be costlier than commenters expect because
systems that currently can process only numeric NDCs would need to be
updated to handle both alphanumeric NDCs as well as the existing
numeric NDCs that would be retained under the alphanumeric option.
Thus, the alphanumeric option would also add to the use of multiple
formats and the perpetual additional quality control costs associated
with this.
As for permitting continued use of existing 10-digit NDCs, we agree
that in the short term, this would be less costly to labelers who use
them than to reformat them because it would not require them to update
their drug labels to reflect a reformatted NDC. However, this option
would not result in a uniform NDC format for all FDA-assigned NDCs.
Even without this final rule, the 6-digit labeler code would roll out
after the supply of 5-digit labeler codes is exhausted, thereby
creating 11-digit NDCs that affected parties would have to process
along with all the other different formats in perpetuity. Any quality
assurance costs involved in handling multiple formats would likely
negate any cost savings from continued use of existing 10-digit NDCs.
(Comment 58) Several commenters express that the rule will be
overly burdensome and that it would cost billions of dollars to update
IT systems across multiple interested parties beyond labelers such as
pharmacies as well as government and private payors.
(Response 58) We disagree that the rule will cost billions of
dollars. We note that under current Sec. 207.33, industry will
eventually need to accommodate 11-digit NDCs, which will entail some
implementation costs. The cost estimates for this final rule need only
consider the incremental costs that this final rule will generate over
and above the costs associated with transitioning to 11-digit NDCs. We
also disagree that the cost estimates do not incorporate other
interested parties beyond labelers. The economic analysis considers the
overall healthcare sector (hospitals, physician establishments, nursing
care facilities, pharmacies, dentists, residential health, home
healthcare, outpatient care centers, medical and diagnostic centers,
medical equipment suppliers, other health practitioners, etc.) and the
insurance sector (administrators of claims for commercial and public-
sponsored insurance plans, and other involved intermediaries).
(Comment 59) Some commenters express that it would be very
burdensome to convert historical
[[Page 10768]]
medication information in patient records.
(Response 59) These comments are outside the scope of the final
rule. This final rule does not mandate that historical patient records
be updated to reflect a 12-digit NDC.
(Comment 60) A commenter expresses that any changes to the NDC will
require changing the automatic process by which GTINs are generated.
The commenter believes that coordinating NDC and GTIN formatting and
implementing the requisite system changes would increase costs and
create opportunities for error.
(Response 60) We understand that a 12-digit NDC would be
incompatible with the current barcode standards that utilize GS1's UPC-
A and 2D data matrix barcodes because the GTIN cannot embed an NDC
longer than 10 digits. We acknowledge that there are transition costs
associated with reformatting 10-digit NDCs to 12-digit NDCs, and our
final economic analysis includes such costs. We note that even without
the rule, under existing Sec. 207.33(b)(1), industry would incur costs
to transition away from the GTIN, which cannot accommodate the 11-digit
NDCs that would have been assigned absent this rule.
We have developed a comprehensive Economic Analysis of Impacts that
assesses the impacts of the final rule. The full analysis of economic
impacts is available in the docket for this final rule (Ref. 8) and at
https://www.fda.gov/about-fda/economics-staff/regulatory-impact-analyses-ria.
VIII. Analysis of Environmental Impact
We have determined under 21 CFR 25.30(k) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
IX. Paperwork Reduction Act of 1995
This final rule contains information collection provisions that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521). The
title, description, and respondent description of the information
collection provisions are shown in the following paragraphs with an
estimate of the annual recordkeeping burden. Included in the estimate
is the time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and
reviewing each collection of information.
Title: Format of National Drug Code.
Description: This rulemaking requires the respondents identified
below to revise the format of their NDCs and to update any of their
product labeling that includes the NDC to incorporate the new NDC
format.
For drugs subject to an NDA or ANDA, the respondents must report
these labeling changes through an annual report in accordance with
Sec. 314.81(b)(2)(iii). For biological products subject to a BLA, the
respondents must report these labeling changes through an annual report
in accordance with Sec. 601.12(f)(3). Including the NDC on the label
of an animal drug is voluntary. Manufacturers that voluntarily include
the NDC on the label of an animal drug must report the labeling change
in accordance with Sec. 514.80(b)(4)(ii).
Section 314.81(b)(2)(iii) requires the submission of an annual
report containing a representative sample of the package labels,
currently used professional labeling, patient brochures, package
inserts, and a summary of labeling changes (or if no changes have been
made, a statement to that effect) since the previous report. The change
in the NDC format required by this rule will result in a labeling
change.
One-time costs and annual operating and maintenance costs
associated with this rule are discussed in section VII.B. of this
document and in the FRIA. However, many of these costs are not
associated with the information collections subject to OMB review under
the PRA but, instead, are associated with changes in their usual and
customary business operations as a result of the new NDC format.
Additionally, many of the costs discussed in the FRIA are incurred by
firms other than the respondents described below.
To minimize recordkeeping burden resulting from changes to the NDC
format, this final rule has a 7-year delay in the effective date
followed by a 3-year transition period. The purpose of the transition
period is to mitigate potential labeling costs by allowing respondents
to deplete labeling inventory and update labels with the new NDC format
at the time of a periodic labeling update that may be made during the
3-year transition period. Based on the frequency at which drug labeling
is typically updated, we anticipate that nearly all firms will be able
to incorporate the labeling change required by the final rule as part
of a periodic labeling change that they intend to make unrelated to
this rule. Therefore, we believe that the incremental information
collection burden associated with this rule is likely to be de minimis.
As a result of the extension in the delayed effective date, which
allows for more precise timing of labeling changes, and for consistency
with the FRIA, we have modified our estimate of the one-time burden
associated with the final rule, assuming that all finished prescription
drug products and all finished over-the-counter drug products include
the NDC on the label and that 95 percentof the label updates with the
new NDC format will be made in coordination with a periodic labeling
change that they intend to make unrelated to this rule.
In the proposed rule, we sought comments on our burden analysis. We
did not receive any comments that were specific to our numeric hour
burden estimates. However, on our own initiative, we modified our
estimates to include burden hours related to animal drug label changes,
which were inadvertently not included in the analysis of the proposed
rule. We received numerous comments on the provisions of the proposed
rule having to do with the proposed NDC format, the barcode format
requirement, and the effective date. This final rule contains comment
summaries and responses for these comments in sections V.C. through E.
Additionally, we received comments about our cost estimates in the
PRIA. This final rule contains comment summaries and responses for
these comments in section VII.C.
Description of Respondents: Manufacturers, repackers, relabelers,
drug product salvagers, and private label distributors are subject to
the regulatory requirements in 21 CFR parts 201 and 207; application
holders are subject to the regulatory requirements of Sec. Sec. 314.81
and 514.80; and license holders are subject to the regulatory
requirements of Sec. 601.12.
We estimate the burden of the information collection as follows:
Recordkeeping burden related to labeling updates:
[[Page 10769]]
Table 6--Estimated One-Time Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of Total
21 CFR section; activity Number of records per annual Average burden per Total
recordkeepers recordkeeper records recordkeeping hours
----------------------------------------------------------------------------------------------------------------
Section 201.25 (barcode labeling 13,583 1 13,583 1..................... 13,583
requirements); and part 207,
subpart D (requirements for the
NDC).
Section 314.81(b)(2)(iii) (other 1,324 9 11,916 10 minutes (0.167 1,990
postmarketing reports). hours).
Section 601.12(f)(3) (changes to an 104 6 624 10 minutes (0.167 104
approved BLA). hours).
Section 514.80(b)(4)(ii) (periodic 79 20 1,580 20 minutes (0.333 526
reports; labeling). hours).
---------------------------------------------------------------------------
Total........................... .............. .............. 27,703 ...................... 16,203
----------------------------------------------------------------------------------------------------------------
\1\ Figures have been rounded.
We have characterized the information collection as a recordkeeping
burden consistent with 44 U.S.C. 3502(13)(C), which defines the term
``recordkeeping requirement'' to include records disclosed to third
parties, the Federal government, or the public. Our estimates are based
on the following assumptions:
We assumed that all listed drug packages include the NDC
format on their label and that 95 percent of the label updates with the
new NDC format will be made in coordination with a periodic labeling
change that respondents intend to make unrelated to this rule during
the transition period.
We assumed that each label change would take a respondent
1 hour because only a slight change and not a substantial redesign
would be needed to modify the existing NDC format and barcode already
included on the label.
Based on the drug listing database maintained by FDA, we
understand that there are approximately 271,655 listed drug packages.
We estimate that 5 percent of the 271,655 label updates (13,583 labels)
will not be made in coordination with a periodic labeling change,
resulting in an estimated one-time burden of 13,583 hours.
Section 314.81(b)(2)(iii)(c) requires firms to submit an annual
report that includes a summary of any changes in labeling since the
last annual report. For prescription drugs whose label changes would be
reported in an annual report pursuant to Sec. 314.81, there are
approximately 1,324 respondents that would submit reports, and there
are approximately 11,593 active approved applications. This means that,
on average, each application holder subject to Sec. 314.81 will need
to submit 8.76 annual reports (rounded to 9). Information on listed
drugs indicates there are approximately 117,367 separate, identifiable
product packages that that are subject to an approved ANDA or NDA. This
means that, on average, each separate and distinct approved application
includes approximately 10 separate and distinct product packages
(117,367 unique distinct product packages / 11,593 unique approved
applications). We expect that the updating of the NDC format on a label
would necessitate a simple statement in the annual report declaring
that the NDC format has been updated, so we have assigned an estimate
of 1 minute for such statements per label. As each annual report under
Sec. 314.81(b)(2)(iii)(c) will include 10 such declarations (one for
each unique product package), we estimate the burden to report these
changes to be approximately 10 minutes (0.167 hours) per annual report.
Thus, we estimate the total burden under Sec. 314.81(b)(2)(iii)(c) to
be 1,990 hours (1,324 respondents x 9 annual reports per respondent x
0.167 hours = 1,990 hours).
Similarly, Sec. 601.12(f)(3)(i)(A) requires manufacturers of
biologics to include in their annual reports editorial or similar minor
labeling changes. For drug products whose label changes would be
reported in an annual report pursuant to Sec. 601.12(f)(3) for
biological products, there are approximately 104 respondents that would
submit reports and there are approximately 588 active approved
applications. This means that, on average, each application holder will
need to submit 5.65 annual reports (rounded to 6). There are
approximately 5,940 separate, identifiable product packages that that
are subject to an approved BLA. This means that, on average, each
separate and distinct approved application includes approximately 10
separate and distinct product packages (5,940 unique distinct product
packages / 588 unique approved applications). Thus, we estimate the
total burden under Sec. 601.12(f)(3)(i)(A) to be 104 hours (104
respondents x 6 annual reports per respondent x (0.167 hours) = 104
hours).
For animal drugs whose label changes would be reported in an annual
report pursuant to Sec. 514.80(b)(4)(ii), we estimate there are 79
respondents that would submit reports and there are approximately 1,582
active approved applications. On average, each respondent will submit
20 annual reports (1,582 active approved applications x 1 annual report
per active approved application / 79 unique application holders). We
expect that the updating of the NDC format on a label would necessitate
a simple statement in the annual report declaring that the NDC format
has been updated. We estimate 1 minute for such statements per label.
As each annual report will include 20 such declarations (1 for each
unique product package), we estimate the burden to report these changes
to be approximately 20 minutes per annual report (0.333 hours). Thus,
we estimate the total burden to be 526 hours (79 respondents x 20
annual reports per respondent x 0.333 hours = 526 hours).
The information collection provisions in this final rule have been
submitted to OMB for review as required by section 3507(d) of the
Paperwork Reduction Act of 1995.
Before the effective date of this final rule, FDA will publish a
notice in the Federal Register announcing OMB's decision to approve,
modify, or disapprove the information collection provisions in this
final rule. An Agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays
a currently valid OMB control number.
X. Federalism
We have analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
does not contain policies that have substantial direct effects on the
States, on the relationship between the National Government and the
States, or on the distribution of power and responsibilities among the
various levels of government. Accordingly, we conclude that the rule
does not contain policies that have federalism implications as defined
in the Executive Order and, consequently, a federalism
[[Page 10770]]
summary impact statement is not required.
XI. Consultation and Coordination With Indian Tribal Governments
We have analyzed this rule in accordance with the principles set
forth in Executive Order 13175. We have determined that the rule does
not contain policies that have substantial direct effects on one or
more Indian Tribes, on the relationship between the Federal Government
and Indian Tribes, or on the distribution of power and responsibilities
between the Federal Government and Indian Tribes. Accordingly, we
conclude that the rule does not contain policies that have tribal
implications as defined in the Executive Order and, consequently, a
tribal summary impact statement is not required.
XII. References
The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. Although FDA verified the website addresses
in this document, please note that websites are subject to change over
time.
1. Grissinger M, 2017, Misidentification of Alphanumeric Symbols
Plays a Role in Errors, P T, 42(10):604-606, available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614409/ (accessed January 2,
2026).
2. Molinaro N, Du[ntilde]abeitia JA, Mar[igrave]n-Guti[egrave]rrez
A, and Carreiras M, 2010, From Numbers to Letters: Feedback
Regularization in Visual Word Recognition, Neuropsychologia,
48(5):1343-1355, available at https://pubmed.ncbi.nlm.nih.gov/20038435/ (accessed January 2, 2026).
3. Carreiras M, Monahan PJ, Lizarazu M, Du[ntilde]abeitia JA, and
Molinaro N, 2015, Numbers Are Not Like Words: Different Pathways for
Literacy and Numeracy, Neuroimage, 118:79-89, available at https://pubmed.ncbi.nlm.nih.gov/26067344/ (accessed January 2, 2026).
4. Nara S, Raza H, Carreiras M, and Molinaro N, 2023, Decoding
Numeracy and Literacy in the Human Brain: Insights From MEG and
MVPA, Sci Rep, 13(1):10979, available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326015/ (accessed January 2,
2026).
5. *FDA, 2022, Preliminary Regulatory Impact Analysis, Initial
Regulatory Flexibility Analysis, and Unfunded Mandates Reform Act
Analysis, Revising the National Drug Code Format and Drug Label
Barcode Requirements, available at https://www.fda.gov/about-fda/economics-staff/regulatory-impact-analyses-ria (accessed January 2,
2026).
6. RAND Corporation, 2004, The Costs and Benefits of Moving to the
ICD-10 Code Sets, prepared by Martin Libcki and Irene Brahmakulam,
Contract No. ENG-9812731, 2004, available at https://www.rand.org/pubs/technical_reports/TR132.html#citation (accessed January 2,
2026).
7. *RTI International, 2015, 2014 FDA Labeling Cost Model, prepared
by Mary K. Muth, Samantha Bradley, Jenna Brophy, Kristen Capogrossi,
Michaela C. Coglaiti, and Shawn A. Karns, Contract No. HHSF-223-
2011-10005B, Task Order 20, available at https://www.regulations.gov/document/FDA-2021-N-1351-0006 (accessed January
2, 2026).
8. *FDA, 2025, Final Regulatory Impact Analysis, Final Regulatory
Flexibility Analysis, and Unfunded Mandates Reform Act Analysis,
Revising the National Drug Code Format and Drug Label Barcode
Requirements, available at https://www.fda.gov/about-fda/economics-staff/regulatory-impact-analyses-ria.
List of Subjects
21 CFR Part 201
Drugs, Labeling, Reporting and recordkeeping requirements.
21 CFR Part 207
Drugs, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR parts 201 and 207 are amended as
follows:
PART 201--LABELING
0
1. The authority citation for part 201 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 343, 351, 352, 353, 355, 358,
360, 360b, 360ccc, 360ccc-1, 360ddd, 360ddd-1, 360ee, 360gg-360ss,
371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.
0
2. In Sec. 201.25:
0
a. Remove the word ``bar code'' wherever it appears and add the word
``barcode'' in its place; and
0
b. Revise the section heading and paragraph (c)(1) introductory text to
read as follows:
Sec. 201.25 Barcode label requirements.
* * * * *
(c) * * *
(1) Each drug product described in paragraph (b) of this section
must have a barcode that contains, at a minimum, the appropriate
National Drug Code (NDC) number in a linear or nonlinear format that
conforms to the standards developed by a widely recognized
international standards development organization and that format and
standard is recognized by the relevant Food and Drug Administration
Center Director. Additionally, the barcode must:
* * * * *
PART 207--REQUIREMENTS FOR FOREIGN AND DOMESTIC ESTABLISHMENT
REGISTRATION AND LISTING FOR HUMAN DRUGS, INCLUDING DRUGS THAT ARE
REGULATED UNDER A BIOLOGICS LICENSE APPLICATION, AND ANIMAL DRUGS,
AND THE NATIONAL DRUG CODE
0
3. The authority citation for part 207 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360b, 371,
374, 381, 393; 42 U.S.C. 262, 264, 271.
0
4. In Sec. 207.33, revise paragraph (b) to read as follows:
Sec. 207.33 What is the National Drug Code (NDC), how is it assigned,
and what are its requirements?
* * * * *
(b) What is the format of an NDC? (1) Except as described in
paragraph (b)(2) of this section, the NDC must consist of 12 digits,
divided into three segments as follows:
(i) The first segment of the NDC is the labeler code and consists
of 6 digits. The labeler code is assigned by FDA.
(ii) The second segment of the NDC is the product code and consists
of 4 digits.
(iii) The third segment of the NDC is the package code and consists
of 2 digits. The package code identifies the package size and type of
the drug and differentiates between different quantitative and
qualitative attributes of the product packaging.
(2) An alternatively formatted NDC that is approved for use by the
relevant Center Director may be used for the following HCT/Ps if they
are minimally manipulated: Hematopoietic stem/progenitor cells derived
from peripheral
[[Page 10771]]
and cord blood, and lymphocytes collected from peripheral blood.
* * * * *
Robert F. Kennedy, Jr.,
Secretary, Department of Health and Human Services.
[FR Doc. 2026-04368 Filed 3-4-26; 8:45 am]
BILLING CODE 4164-01-P