[Federal Register Volume 87, Number 141 (Monday, July 25, 2022)]
[Proposed Rules]
[Pages 44038-44048]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-15414]
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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, Department of Health and Human
Services (HHS).
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
proposing to amend our regulations governing the format of the National
Drug Code (NDC). The NDC is an FDA standard for uniquely identifying
drug products marketed in the United States. This action, if finalized,
will standardize the format of all NDCs. Specifically, all NDCs will be
required to be 12 digits in length with 3 distinct segments and 1
uniform format. The first segment is the labeler code and will be 6
digits, the second segment is the product code and will be 4 digits,
and the third segment is the package code and will be 2 digits.
Additionally, we are proposing to revise the drug product barcode label
requirements to permit the use of other data carriers that meet certain
standards.
DATES: Either electronic or written comments on the proposed rule must
be submitted by November 22, 2022. Submit comments on information
collection issues under the Paperwork Reduction Act of 1995 (PRA) by
August 24, 2022.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of November 22, 2022. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
[[Page 44039]]
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2021-N-1351 for ``Revising the National Drug Code Format and Drug
Label Requirements.'' Received comments, those filed in a timely manner
(see ADDRESSES), will be placed in the docket and, except for those
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, 240-402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
Submit comments on information collection issues under the PRA:
Submit comments on the information collection under the PRA to the
Office of Management and Budget (OMB) at https://www.reginfo.gov/public/do/PRAMain. Find this particular information collection by
selecting ``Currently under Review--Open for Public Comments'' or by
using the search function. The title of this proposed collection is
``Revising the National Drug Code Format and Drug Label Requirements.''
FOR FURTHER INFORMATION CONTACT: With regard to the aspects of the
proposed 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, 301-796-3185, [email protected].
With regard to the aspects of the proposed rule pertaining to human
biological drug products: Stephen Ripley, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm.7301, Silver Spring, MD 20993, 240-402-
7911, [email protected].
With regard to the aspects of the proposed rule pertaining to
animal drug products: Charise Kasser, Center for Veterinary Medicine,
Food and Drug Administration, 7519 Standish Pl., Rm. 2626, Rockville,
MD 20855, 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, 301-796-5733,
[email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose of the Proposed Rule
B. Summary of the Major Provisions of the Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
A. Current Regulatory Framework and the Need for the Regulation
B. History of the Rulemaking
IV. Legal Authority
V. Description of the Proposed Rule
A. Adoption of a Uniform 12-Digit NDC
B. Scope/Applicability
C. Implementation of New, Uniform, 12-Digit NDC
D. Proposed Delayed Effective Date
E. Proposed Transition Period
VI. Proposed Effective Date(s)
VII. Preliminary Economic Analysis of Impacts
A. Introduction
B. Summary of Costs and Benefits
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 Proposed Rule
FDA is proposing to modify our regulations to establish a uniform,
12-digit format for the NDC (21 CFR 207.33) that can accommodate longer
NDCs once FDA begins issuing 6-digit labeler codes. FDA estimates that
it will exhaust its inventory of available 5-digit labeler codes and
begin assigning 6-digit labeler codes in 10-15 years. The use of a
consistent, uniform format is intended to eliminate 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 proposing to revise the
drug barcode label requirements to allow the use of either linear or
nonlinear barcodes, so long as the barcode meets the prescribed
standards.
B. Summary of the Major Provisions of the Proposed Rule
Under the proposed rule, FDA would amend its regulations to adopt a
uniform, 12-digit format for the NDC. As proposed, NDCs will continue
to consist of three segments: the labeler code, the product code, and
the package code. However, we are proposing that the labeler code be 6
digits, the product code be 4 digits, and the package code be 2 digits.
To provide maximum flexibility on the type of barcode used on the label
of a drug product, we are proposing to allow the use of either linear
or nonlinear barcodes, so long as the barcode meets one of the
prescribed standards in Sec. 201.25 (21 CFR 201.25).
On the effective date of the final rule, FDA would begin assigning
new NDCs in the uniform, 12-digit format, and existing 10-digit NDCs
assigned by FDA prior to the effective date would be required to
convert to the new, uniform, 12-digit NDC format. As a result, all
stakeholders that use FDA-assigned NDCs would need to have systems
[[Page 44040]]
capable of handling the new, uniform, 12-digit NDC on the effective
date of the final rule. Therefore, FDA is proposing to delay the
effective date of the final rule for a period of 5 years following its
publication to allow stakeholders time to develop and implement such
systems.
Additionally, FDA is proposing to allow for a 3-year transition
period following the effective date of the final rule. During this
proposed 3-year transition period, firms that use 10-digit NDCs
assigned prior to the effective date on product labeling should begin
updating their labeling to replace the 10-digit NDCs with the new 12-
digit NDCs by adding leading zeros to the labeler code, product code,
and/or package code segments as needed, 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 proposed transition period,
stakeholders should ensure that their systems are capable of handling
both 10-digit NDCs and 12-digit NDCs.
C. Legal Authority
FDA is proposing to amend our regulations on foreign and domestic
establishment registration and listing for drugs, including biological
products and animal drugs. FDA's authority for this proposed 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
proposed 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) (21
U.S.C. 371(a)) and section 351(j) of the PHS Act.
D. Costs and Benefits
The proposed rule, if finalized, would require 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. Specifically, the NDC
will consist of three segments: a 6-digit labeler code, a 4-digit
product code, and a 2-digit package code. As a result, product labeling
that includes a product's 10-digit NDC would need to be updated to
convert the 10-digit NDC to the standard 12-digit format.
One expected benefit of the proposed rule, if finalized, is that
the proposed standardized format would facilitate the adoption of a
single NDC format by all stakeholders. Such an adoption would eliminate
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). Eliminating the need
to convert NDCs should reduce potential errors caused by converting
from the FDA-assigned NDC format to a different format used by other
sectors of the healthcare industry. Standardization and adoption of a
single format would 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 proposed rule would be to
avoid any potential risks to the public health from potential
reductions in medication errors and risk of confusion. We do not have
data to quantify these potential benefits and request comments.
The costs to industry of converting current NDC codes to the
proposed format would include one-time costs of updating software
systems, new training for employees, coordinating labeling updates, and
reading and understanding the proposed rule. Industry, however, can
incorporate any changes to existing labeling due to this proposed rule
into their recurring labeling updates and avoid any relabeling costs.
Some software and training costs would occur even without the proposed
rule because FDA will begin issuing 6-digit labeler codes, and the
current 10-digit NDC formats are not capable of accommodating 6-digit
labeler codes. Our estimates, therefore, are conservative. We estimate
annualized costs would be about $12.4 million ranging from $6.1 million
to $19.4 million using a 7-percent discount rate over a 10-year
horizon. Similarly, we estimate annualized costs would be about $10.2
million ranging from $5.1 million to $16.0 million using a 3-percent
discount rate over a 10-year horizon. The present-value of the
estimated costs would be $87.1 million ranging from $43.1 million to
$136.3 million at both the 7-percent and 3-percent discount rates.
II. Table of Abbreviations/Commonly Used Acronyms in This Document
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Abbreviation/ acronym What it means
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ANDA............................... Abbreviated New Drug Application.
BLA................................ Biologics License Application.
EAN/UCC............................ European Article Number/Uniform
Code Council.
FDA................................ Food and Drug Administration.
FD&C Act........................... Federal Food, Drug, and Cosmetic
Act.
GTIN-14............................ Global Trade Identification Number
14.
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.
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.
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III. Background
A. Current Regulatory Framework and the Need for the Regulation
The NDC is an FDA standard for uniquely identifying drugs marketed
in the United States. Currently, NDCs assigned by FDA contain 10
digits. As currently described in Sec. 207.33(b) (21 CFR 207.33(b)),
NDCs consist of three segments: the labeler code, the product code, and
the package code. At some point in the next 10 to 15 years, NDC
formatting will need to be updated to accommodate longer NDCs because
new labelers are continually entering the U.S. market. In 2016, when
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), the Agency stated
that when it runs out of 5-digit labeler codes, it will begin assigning
6-digit labeler codes (81 FR 60169 at 60187, August 31, 2016). As a
result, under existing regulations, FDA would add 2 new 11-digit NDC
formats (6-3-2 and 6-4-1) to accommodate the longer labeler codes.
However, FDA acknowledged that some stakeholders expressed an interest
in FDA moving to a single, standard format for NDCs and announced that
it planned to initiate a public discussion of future formatting options
(See id.). FDA initiated the public discussion by holding a public
hearing on November 5, 2018, requesting comments from stakeholders
[[Page 44041]]
on the impact of the transition to 6-digit labeler codes (83 FR
38666).\1\
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\1\ https://www.regulations.gov/document/FDA-2018-N-2610-0001.
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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).
The NDC for each listed drug marketed in the United States is a
unique 10-digit,\2\ 3-segment number (Sec. 207.33(b) (21 CFR
207.33(b)). The 3 segments of the NDC include the labeler code, product
code, and package code (id.). 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 (id.). The second segment, the product code, is
a 3- or 4-digit number that identifies a specific active ingredient,
strength, and dosage form of a drug manufactured, repackaged,
relabeled, or distributed by the labeler (id.; Sec. 207.35(b) (21 CFR
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)).
Different package codes differentiate between different quantitative
and qualitative attributes of the product packaging (Sec. 207.35).
Both the product and package codes are proposed by persons submitting
drug listing information (see Sec. 207.33(d)(1)). The Agency will
assign a proposed NDC if it has not been used previously, is not
currently in use, and has not been reserved for future assignment to a
different drug (Sec. 207.33(d)(2)). The NDC for a given drug is
currently in one of the following configurations (with each number
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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According to current regulations, labeler codes may consist of 4,
5, or 6 digits (Sec. 207.33(b)(1)). Currently, 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 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 (HIPAA)
(Pub. L. 104-191) contains provisions calling for the administrative
simplification ``of the national standards for electronic health care
transactions and code sets, unique health identifiers, and security''
\3\ and specifically references the NDC. In its implementation of these
rules, on August 17, 2000, the Department of Health and Human Services
(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 biologics 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(a)(3)). 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. 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/ocr/privacy/hipaa/administrative/index.html (last accessed March 22, 2017).
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When FDA moves to a 6-digit labeler code, FDA's new 11-digit native
NDC \4\ configurations will have the same number of digits as required
by the HIPAA standards, but they will not be in the same format. An 11-
digit native NDC will 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 \5\ do
not use hyphens to separate the segments which, as illustrated below,
will result in some 11-digit native NDCs being indistinguishable from
HIPAA standard 11-digit NDCs. Therefore, to ensure unhyphenated NDCs
are distinguishable, FDA anticipates that the HIPAA standards, and
other code sets that currently require 10-digit native NDCs to be
converted to 11-digit NDCs, will likely need to be updated in some
manner.
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\4\ NDCs in the format and with the digits assigned by FDA are
referred to as native NDCs.
\5\ 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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FDA is proposing 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 and the HIPAA
standards, and other code sets, that require 10-digit native NDCs to be
converted to 11-digit NDCs are not updated. Specifically, standardizing
the NDC to one format should eliminate the need for stakeholders to
constantly convert a drug's FDA-assigned NDC to a different
standardized format because those stakeholders seeking a standardized
format will be able to adopt FDA's new, uniform, 12-digit format. This
should reduce errors caused by converting from FDA's current
nonstandardized NDC format to a standardized format. Additionally,
standardization should
[[Page 44042]]
eliminate the need for stakeholders to use multiple versions of an NDC
(e.g., the FDA-assigned 10-digit NDC and the converted HIPAA standard
11-digit NDC).
Finally, using 12-digits will allow FDA to adopt a uniform NDC
format without requiring extensive changes to existing 10-digit NDCs.
Instead, stakeholders 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.
B. History of the Rulemaking
1. 2016 Final Rule
In 2016, FDA published 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 stakeholders recommended that FDA adopt a single, standard
format for NDCs instead and announced that it planned to initiate a
public discussion of future formatting options (81 FR 60169 at 60187).
2. 2018 Public Hearing
On November 5, 2018, FDA began these public discussions by holding
a public hearing.\6\ 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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\6\ https://www.regulations.gov/document/FDA-2018-N-2610-0001.
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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 stakeholders 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 payer 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 NDC codes, there would still be multiple formats.
Additionally, there is 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
stakeholders 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 stakeholders 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 and for industry to adopt this as the single NDC format.
Therefore, under this option, 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 stakeholders, government payers, 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
stakeholders. The majority of the commenters were also in favor of FDA
establishing a certain date when stakeholders 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 proposed rule.
IV. Legal Authority
FDA is proposing to amend our regulations on foreign and domestic
establishment registration and listing for drugs, including biological
products and animal drugs. FDA's authority for this proposed rule
derives from the FD&C Act applicable to drugs, including biological
products and the biological product provisions of the PHS Act. In
particular, this proposed rule will standardize the format of NDCs
assigned under section 510(e) of the FD&C Act and will aid in efficient
enforcement of the FD&C Act pursuant to sections 701(a) and 351(j) of
the PHS Act.
V. Description of the Proposed Rule
A. Adoption of a Uniform 12-Digit NDC
We are proposing to replace the existing NDC formats with a
uniform, 12-digit format (see proposed amendments to Sec. 207.33(b)).
Under the proposed rule, the NDC would remain a 3-segment numerical
code consisting of the labeler code, the product code, and the package
code. However, we are proposing to establish a uniform length for each
segment to create a uniform format. Specifically, we are proposing that
the labeler code would be 6 digits in length, the product code would be
4 digits in length, and the package code would be 2 digits in length (a
6-4-2 format).
The new format requirements we are proposing would not apply only
to NDCs assigned after the effective date of the final rule. Instead,
if finalized as proposed, all existing 10-digit NDCs would be converted
to the new, uniform, 12-digit format by the addition of leading zeros
to the labeler code, the product code, and/or package code segments as
needed to produce the 6-4-2 format.
Before deciding to propose the new, uniform, 12-digit NDC, FDA
considered not only the four options outlined above, but also several
proposals submitted as comments to the public hearing docket. Although
many of the comments were supportive of the uniform, 12-digit NDC,
others raised concerns that this could impact the ability to use
barcodes that utilize GS1's Global Trade Identification Number 14
(GTIN-14) because GTIN-14 is only capable of encoding NDCs up to 10
digits.\7\ Those raising this concern suggested that FDA no longer be
responsible for assigning NDCs and, instead, delegate assignment of
NDCs to
[[Page 44043]]
third parties, similar to unique device identifiers. However, we chose
not to adopt this alternative because, unlike the implementation of the
unique device identifier requirements, FDA is already deeply involved
in the assignment of NDCs and changing this system has the potential to
cause significant disruption, particularly with the handling of a
transition from FDA-assigned NDCs to a new, third-party-assigned NDC.
Although there may be some disruption resulting from the implementation
of a new, uniform, 12-digit NDC, FDA will be in the best position to
minimize and mitigate the disruption because it would continue to be
involved in the process for assigning the new 12-digit NDCs. If this
responsibility were handed over to a third party, FDA would have less
ability to minimize and mitigate the disruption.
---------------------------------------------------------------------------
\7\ The GTIN-14 is a global numerical data structure containing
14 numbers.
---------------------------------------------------------------------------
One commenter suggested that FDA could retain its 10-digit NDC
format after it ran out of the current lot of 5-digit labeler codes by
starting to assign 5-digit, alphanumeric labeler codes. Although this
would allow firms to continue using their existing 10-digit NDCs, it
would not accomplish the goal of uniformity advocated by many
commenters. Additionally, except for systems used for certain minimally
manipulated human cells, tissues, and cellular and tissue-based
products (HCT/P) under Sec. 207.33(b)(4), it would not likely relieve
many stakeholders of the requirement to update their systems to be
capable of handling the new NDC format, as many current systems are
unlikely to be able to handle alphanumeric NDCs. Finally, we had some
concerns that the introduction of alphabetic characters into the
labeler code could increase the risk of medication errors because some
may misread a letter as a number. Some examples include similarity
between lowercase letter ``o'' and uppercase letter ``O'' with numeral
0 (zero), or uppercase letter ``B'' with numeral 8 (eight).
After taking these and other suggestions into consideration, FDA
chose to propose the uniform, 12-digit NDC format because it could be
adopted by all stakeholders seeking uniformity and would not require
conversion between formats in perpetuity. We recognize that during the
transition period described in section V.E. below, there will still
need to be some conversion between the existing 10-digit NDC formats
and the new, uniform, 12-digit format. However, as noted further below,
this would be temporary, and FDA intends to publish, on our website,
NDCs in both formats to facilitate these conversions. We also recognize
that the establishment of a new, uniform, 12-digit NDC may require
changes to other standards in order for stakeholders to adopt the 12-
digit NDC as a universal standard. However, it is likely that any
change from the 10-digit NDC format would have required such changes,
and, as FDA is running out of 5-digit labeler codes, a change is
necessary.
B. Scope/Applicability
This proposed rule will affect all drug products that are required
to be listed under section 510 of the FD&C Act and 21 CFR part 207.
Specifically, once effective, all existing 10-digit NDCs will be
required to convert to the new uniform 12-digit NDC format, and all new
NDCs will be assigned in the 12-digit format.
However, FDA will still allow the following HCT/Ps, if they are
minimally manipulated, to use an alternatively formatted NDC that is
approved for use by the relevant Center Director: Hematopoietic stem/
progenitor cells derived from peripheral and cord blood, and
lymphocytes collected from peripheral blood (Sec. 207.33(b)(4)). HCT/
Ps that do not fall within the exception set forth in Sec.
207.33(b)(4) would be required to use the new 12-digit NDC format. This
proposed rule only relates to FDA's assignment of NDCs; it does not
propose any revisions to the HIPAA standard code set.
C. Implementation of New, Uniform, 12-Digit NDC
1. Issuance of New, Uniform, 12-Digit NDCs
On the effective date of the final rule (which we propose would be
5 years from publication of the final rule), FDA would no longer assign
5-digit labeler codes or 10-digit NDCs. Instead, FDA would begin only
issuing 6-digit labeler codes and NDCs in the new, uniform, 12-digit
format. Therefore, all drug listing files submitted on or after the
effective date proposing a new NDC would be required to use the
uniform, 12-digit (6-4-2) NDC format. For example, if such a proposal
is submitted by a firm with a 4- or 5-digit labeler code, the firm
would need to convert its labeler code to a 6-digit labeler code by
adding one or two leading zeros, as appropriate, and request the new
NDC in the 6-4-2 format. If the submission involves a drug that is
being listed for the first time or a change to an already listed drug
that requires the use of a new product code under Sec. 207.35(b), the
firm must ensure that it is requesting a unique, 12-digit NDC,
including a unique, 4-digit product code. If the submission involves a
request to assign a new package code for a product already listed with
a 10-digit NDC, the firm would need to convert its 4- or 5-digit
labeler code to a 6-digit labeler code by adding one or two leading
zeros.
If the firm currently uses the 5-3-2 format, it would additionally
need to convert the existing product code from a 3-digit code to a 4-
digit code by adding a leading zero to achieve the 6-4-2 format. If the
firm currently uses the 5-4-1 format, it would not need to convert the
existing product code because it is already four digits. However, it
still would need to convert its labeler code to six digits and would
need to request a unique package code.
As all new NDCs will only be assigned using the new, uniform, 12-
digit format starting on the effective date of the final rule, all
stakeholders will need to have systems in place that are capable of
handling the new, uniform, 12-digit NDCs. However, as described in more
detail below in section V.E., during the 3-year transition period, FDA
does not intend to object to continued use of 10-digit NDCs assigned
prior to the effective date on product labels. Therefore, during this
proposed transition period, stakeholders should ensure that their
systems are capable of handling both 10-digit and 12-digit NDCs.
2. Converting Existing 10-Digit NDCs
To reduce the burden on registrants, FDA does not intend to require
them to resubmit all of their existing drug listing files to convert
the NDCs from one of the discontinued 10-digit formats to the new,
uniform, 12-digit, 6-4-2 format. Instead, FDA intends to convert
existing NDCs on its own, on the effective date, by adding leading
zeros to the appropriate segments. Additionally, for the reasons
described in more detail below regarding the transition period, FDA
intends to begin publishing, on the effective date, both the 10-digit
and 12-digit NDCs for those drugs with NDCs assigned prior to the
effective date.
3. The Effect on Other Non-FDA NDC Formats
As mentioned above, FDA decided to propose replacing the multiple
10- and possibly 11-digit NDC formats with a new, uniform, 12-digit
format, in part, because of concerns that an FDA-assigned 11-digit NDC
could be identical to a HIPAA converted 11-digit NDC for a different
drug if the hyphens are removed. FDA could have chosen to avoid this by
replacing its 11-digit formats with a 12-digit format, while still
keeping the 10-digit formats. However, this would still have required
[[Page 44044]]
an update to the HIPAA standard format so that it could accommodate the
new FDA-assigned 12-digit format and likely still would have required
at least the FDA-assigned 10-digit NDCs to be converted to a new HIPAA
standard format. Although this may have reduced some of the initial
burden of converting existing 10-digit NDCs to the new, uniform, 12-
digit format, this approach would likely have required stakeholders to
update their systems a second time and would have required ongoing
conversion from FDA's NDC formats to the HIPAA standard format(s).
Thus, this option would require a conversion and would also create
costs, while not reducing the overall risk of medication errors.
Therefore, FDA is proposing to adopt a single, uniform, 12-digit NDC
format in hopes that it will be adopted as the new HIPAA standard
format for NDCs, and no conversions will be necessary from FDA's NDC
format to the HIPAA standard format.
In addition to impacting the HIPAA standard format, we recognize
that a 12-digit NDC may impact some stakeholders who use the GTIN-14
data standard to encode FDA's 10-digit NDC in the barcode on their
label because the GTIN-14 cannot accommodate a 12-digit NDC. We
acknowledge that FDA's establishment of a uniform, 12-digit NDC may
require the development of new data standard(s) that can enable an NDC
of this length to be encoded in a data carrier such as barcodes. That
is one of the considerations that went into FDA's proposal to delay the
effective date of the final rule, as this would provide time for the
development of new data standard(s) and any respective changes to data
carriers to accommodate an NDC of this length.
Recognizing that new data standard(s) may be necessary to encode
the new, uniform, 12-digit NDC into a data carrier, we propose to
revise Sec. 201.25(c) to allow the use of linear or nonlinear barcodes
that meet specified standards. FDA is considering whether to further
revise Sec. 201.25(c) to accommodate potential advances in
technologies and standards development by allowing the use of
unspecified automatic identification and data capture formats other
than linear or nonlinear barcodes in the future without the need to
revise the regulation again. Therefore, we are asking stakeholders to
provide comments on whether to include such flexibility.
D. Proposed Delayed Effective Date
We propose to delay the effective date of the final rule for a
period of 5 years following its publication. Delaying the effective
date of the final rule is intended to provide stakeholders sufficient
time to update their systems to be able to handle the new, uniform 12-
digit NDC format, and plan on updating their labeling during the
transition period, in a way that reduces burden to them. The delay is
also intended to provide sufficient time to implement the necessary
corresponding changes to the HIPAA standards and data standards that
can enable an NDC of this length to be encoded in a data carrier such
as barcodes, as discussed above. FDA is proposing a fixed effective
date relative to the publication of the final rule to provide
stakeholders with certainty as to when they would need to implement
systems capable of handling the new, uniform 12-digit NDC format.
However, in establishing the specific effective date, FDA will need to
ensure that it occurs before FDA runs out of 5-digit labeler codes.
Therefore, this 5-year effective date may result in stakeholders having
less time to update their systems to be able to handle the new, uniform
12-digit NDC format than if the effective date were established based
on when FDA runs out of 5-digit labeler codes.
The proposed 5-year delay balances the need to give stakeholders
sufficient time to update their systems and make other necessary
changes to be able to handle the new, uniform 12-digit NDC format, with
the need to ensure that the final rule is effective before FDA runs out
of 5-digit labeler codes and needs to start issuing 6-digit labeler
codes. At this time, FDA believes there are sufficient 5-digit labeler
codes remaining such that FDA can delay the effective date of the final
rule for a period of 5 years following its publication. However, since
the time FDA began developing this proposed rule, the rate at which
labeler codes are assigned has increased significantly, particularly
due to an influx of requests during the COVID-19 pandemic. Therefore,
recognizing the importance of providing certainty to all stakeholders
regarding the date on which they will all be expected to have systems
in place capable of handling the new 12-digit NDC, FDA intends to
reevaluate, prior to publishing the final rule, whether sufficient 5-
digit labeler codes remain to allow for a 5-year delay in the effective
date. FDA may finalize a shorter delay in the effective date based on
our estimation of when we anticipate running out of 5-digit labeler
codes. FDA believes this approach to ensuring FDA does not run out of
5-digit labeler codes before the effective date is a better approach
than either of the two following alternatives: (1) accelerating the
effective date after publication of the final rule by promulgating a
new rule with a shorter effective date or (2) beginning to issue 6-
digit labeler codes and 11-digit NDCs before the effective date.
E. Proposed Transition Period
FDA is proposing a 3-year transition period following the effective
date of the final rule during which FDA does not intend to object if
drugs that were assigned a 10-digit NDC prior to the effective date
continue to be labeled with the 10-digit NDC. However, if a firm
includes an NDC in its labeling, we would request that the firm start
labeling drugs that were assigned a 10-digit NDC with the new 12-digit
NDC as soon as possible, but no later than when a firm runs out of its
existing labeling inventory for the drug and orders or begins printing
new labeling. At the end of the transition period (i.e., 8 years after
the publication of the final rule), all firms will be required to use a
12-digit NDC in listing files, and FDA will no longer exercise
enforcement discretion with respect to the 12-digit NDC format
requirement for all products that include the NDC on their labeling
that are introduced or offered for introduction into interstate
commerce. As noted above, during this transition period, FDA will
continue to maintain and publish 10-digit NDCs for listed drugs,
simultaneously with the converted 12-digit NDCs. However, FDA does not
intend to continue publishing and maintaining the 10-digit NDCs after
the end of this transition period. Therefore, FDA encourages firms to
begin labeling these products with the 12-digit NDC as soon as possible
after the effective date to ensure that, at the end of the transition
period, there are no products labeled with an old, 10-digit NDC
remaining in interstate commerce.
FDA is proposing this 3-year transition period to facilitate a
smooth transition from the current 10-digit NDC formats to the new,
uniform 12-digit NDC format. In light of the nature of the drug supply
chain, FDA recognizes that it would be difficult for firms to
immediately transition from a 10-digit NDC to a 12-digit NDC without a
transition period. Specifically, if on the effective date, all drugs
were required to be labeled with a 12-digit NDC and there was no
enforcement discretion regarding 10-digit NDC-labeled products
remaining in interstate commerce, then firms would be required to
remove products labeled with the 10-digit NDC from interstate commerce
and either destroy them or relabel them. As the cost to the firms would
be based on the volume of product remaining on the
[[Page 44045]]
market with the 10-digit NDC, this could incentivize firms to minimize
how much product remains on the market at the time of the transition.
This could increase the risk of a drug shortage which could harm the
public health.
At the same time, the coexistence of drug labeling with either the
10- or 12-digit NDC for a period of time poses its own risks to the
public health. Specifically, it raises the risk of confusion,
medication errors, and possibly, the risk of the introduction of
illegitimate product into the market because of the confusion. In an
effort to balance these risks, FDA is proposing to limit the transition
period to 3 years following the effective date. FDA is proposing a 3-
year transition period for two reasons. First, the expiration date of
many drugs is no more than 2 years. Therefore, there should not be many
drugs remaining in interstate commerce labeled with NDCs in the 10-
digit format at the end of the transition period so long as firms start
labeling their products with the 12-digit NDC within the first year
after the effective date. Second, most firms make changes to the
labeling of a human prescription drugs at least once every 3 years.\8\
Therefore, even if a firm wanted to wait until the next time it
implemented a labeling change before transitioning from the 10-digit to
a 12-digit NDC, most firms would be able to do so within the transition
period.
---------------------------------------------------------------------------
\8\ For rates of labeling revisions for prescription drug
products, see Ref. 2. For nonprescription products, see Ref. 3.
---------------------------------------------------------------------------
Additionally, FDA intends to mitigate the risk of medication error
and confusion during the transition period by maintaining and
publishing both the 10-digit and 12-digit NDC formats for products
assigned a 10-digit NDC prior to the effective date. This will provide
stakeholders with a resource to confirm the identity of the drug in the
event of any confusion.
VI. Proposed Effective Date(s)
We are proposing to delay the effective date of the final rule
until 5 years after its publication in the Federal Register. However,
as discussed in section V.D above, FDA may finalize the rule with a
shorter effective date to ensure it is effective before FDA runs out of
5-digit labeler codes and is required to start issuing 6-digit labeler
codes.
In addition, as discussed in section V.E above, to minimize
possible disruption to the distribution of products subject to this
proposed rule and to minimize the burden on manufacturers and labelers,
FDA is proposing to provide for a 3-year transition period following
the effective date. During this transition period, firms with products
that were assigned 10-digit NDCs prior to the effective date of the
final rule will need to use a 12-digit NDC for all drug listings
submitted to FDA and should transition to using a 12-digit NDC on
labeling.
VII. Preliminary Economic Analysis of Impacts
A. Introduction
We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4). Executive Orders 12866 and 13563 direct us to assess all costs
and benefits of available regulatory alternatives and, when regulation
is necessary, to select regulatory approaches that maximize net
benefits (including potential economic, environmental, public health
and safety, and other advantages; distributive impacts; and equity). We
believe that this proposed rule is not a significant regulatory action
as defined by Executive Order 12866.
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 cost could be as much as 0.56 percent of
average annual revenue for some very small stakeholders in the
insurance industry, 0.45 percent of average annual revenue for some
very small stakeholders in the pharmaceutical industry, and 0.02
percent of average annual revenue for some very small stakeholders in
the healthcare industry, we propose to certify that the proposed rule,
if finalized, would 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 an assessment of
anticipated costs and benefits, before proposing ``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 one year.'' The current threshold after adjustment
for inflation is $158 million, using the most current (2020) Implicit
Price Deflator for the Gross Domestic Product. This proposed rule would
not result in an expenditure in any year that meets or exceeds this
amount.
B. Summary of Costs and Benefits
This proposed rule, if finalized, would amend regulations governing
the format of the NDC by standardizing the format of NDCs to be 12
digits in length. Currently FDA-assigned NDCs are 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 3 segments are the labeler
code, product code, and package code. The proposed standardized NDC
would consist of three segments: a 6-digit labeler code, a 4-digit
product code, and a 2-digit package code. If the proposed rule is
finalized, FDA-assigned 10-digit NDCs would need to be updated to
convert to the uniform 12-digit format by adding leading zeros to the
respective segments.
One expected benefit of the proposed rule, if finalized, is that
the proposed standardized format would facilitate the adoption of a
single NDC format by all stakeholders. Such an adoption would eliminate
the need to convert NDCs from one of the FDA-prescribed 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
from the FDA-assigned NDC format to a different format used by other
sectors of the healthcare industry. Standardization and adoption of a
single format would 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 proposed rule would be to
avoid any potential risks to the public health from potential
reductions in medication errors and risk of confusion. We do not have
data to quantify these potential benefits and request comments.
The costs to industry of converting current NDC codes to the
proposed format would include one-time costs of updating software
systems, new training for employees, coordinating labeling updates, and
reading and understanding the proposed rule. Table 2 shows a summary of
the quantified costs of the proposed rule. We estimate annualized costs
would be about $12.4 million ranging from $6.1 million to $19.4 million
using a 7-percent discount rate over a 10-year horizon. Similarly, we
estimate annualized costs would be about $10.2 million ranging from
$5.1 million to $16.0 million using a 3-percent discount rate over a
10-year
[[Page 44046]]
horizon. The present-value of the estimated costs would be $87.1
million ranging from $43.1 million to $136.3 million at both the 7-
percent and 3-percent discount rates.
Table 2--Summary of Benefits, Costs, and Distributional Effects of Proposed Rule
--------------------------------------------------------------------------------------------------------------------------------------------------------
Units
Primary Low High --------------------------------------------------
Category estimate estimate estimate Year Discount Notes
dollars rate (%) Period covered (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
Annualized Monetized millions/year.. .......... .......... .......... .......... 7 ........................ ........................
3
Annualized Quantified............... .......... .......... .......... .......... 7 ........................ ........................
3
--------------------------------------------------------------------------------------
Qualitative......................... Potential reductions in annual
audits, billing issues, cost of
software, and medication error.
..........
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
Annualized Monetized millions/year.. $12.4 $6.1 $19.4 7 ........................ ........................
10.2 5.1 16.0 3
Annualized Quantified............... .......... .......... .......... .......... 7 ........................ ........................
3
--------------------------------------------------------------------------------------
Qualitative.........................
..........
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
Federal Annualized Monetized .......... .......... .......... .......... 7 ........................ ........................
millions/year. 3
--------------------------------------------------------------------------------------
From/To............................. From:
To: ..........
--------------------------------------------------------------------------------------------------------------------------------------------------------
Other Annualized Monetized millions/ .......... .......... .......... .......... 7 ........................ ........................
year. 3
--------------------------------------------------------------------------------------
From/To............................. From:
To: ..........
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
State, Local or Tribal Government: No estimated effect..............................................................................................
Small Business: One-time cost could be no more than 0.56 percent of annual revenue for some very small stakeholders with fewer than 5 employees in
the insurance industry, 0.45 percent in the pharmaceutical industry, and 0.02 percent also for some very small stakeholders in the healthcare
industry..
Wages: No estimated effect..........................................................................................................................
Growth: No estimated effect.........................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
We have developed a comprehensive Preliminary Economic Analysis of
Impacts that assesses the impacts of the proposed rule. The full
preliminary analysis of economic impacts is available in the docket for
this proposed rule (Ref. 4) and at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.
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 proposed rule contains information collection provisions that
are subject to review by OMB under the PRA (44 U.S.C. 3501-3521). A
description of these provisions is given in the Description section of
this document with an estimate of the 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.
FDA invites comments on these topics: (1) whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Title: Format of National Drug Code.
Description: The proposed rule would require that the respondents
identified below revise the format of their NDCs and would require that
some of these respondents update any of their product labeling that
include the NDC to incorporate the new NDC format. For drugs subject to
a new drug application (NDA) or abbreviated new drug application
(ANDA), the respondent would be required to report these labeling
changes through an annual report; therefore, this proposed rule affects
the reporting burden associated with Sec. 314.81(b)(2)(iii) (21 CFR
314.81(b)(2)(iii)). For biological products subject to a biologics
license application (BLA), the respondents will be required to report
these labeling changes through an annual report; therefore, this
proposed rule affects the reporting burden associated with Sec.
601.12(f)(3) (21 CFR 601.12(f)(3)).
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)
[[Page 44047]]
since the previous report. Under this proposed rule, the change in the
NDC format would result in a labeling change. We have previously
estimated the reporting burden for submitting labels as currently
required under Sec. 314.81(b)(2)(iii), and OMB has approved the
collection of information under OMB control number 0910-0001. We are
not re-estimating these approved burdens in this rulemaking. We are
only estimating the additional reporting burden associated with the
submission of labeling changes associated with the 12-digit NDC format
under Sec. 314.81(b)(2)(iii). We have previously estimated the
reporting burden for submitting labels as currently required under
Sec. 601.12(f)(3), and OMB has approved the collection of information
under OMB control number 0910-0338. We are not re-estimating the
approved burden in this proposed rule. We are only estimating the
additional reporting burden associated with the submission of labeling
changes associated with the 12-digit NDC format under Sec.
601.12(f)(3).
One-time costs and annual operating and maintenance costs
associated with the proposed rule are discussed in Section II.F--Costs
of the Proposed Rule of the Preliminary Regulatory Impact Analysis
(PRIA). 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 PRIA are incurred by firms other
than the respondents described below.
To minimize recordkeeping burden that would result from
implementing the proposed changes to the NDC format, we provide for 5-
year delay in the effective date and a 3-year implementation period.
The purpose of this phased-in implementation is to allow respondents to
make the labeling change that would result from the proposed change in
NDC format at the time of any periodic update that may be made during
the 3-year implementation period. Based on the frequency at which drug
labeling is updated, we anticipate that nearly all firms will be able
to incorporate the labeling change required by this proposed rule as
part of a labeling change that they intend to make unrelated to this
proposed rule. Therefore, we believe that the incremental information
collection burden associated with this proposed rule is likely to be de
minimis. However, for purposes of this burden estimate, we have
estimated the one-time burden associated with this proposed rule,
assuming conservatively that all finished prescription drug products
and all finished over-the-counter drug products include the NDC on the
label and their label would be updated solely for the purposes of
modifying the format of the NDC on their label.
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. 314.81, and
license holders are subject to the regulatory requirements of Sec.
601.12.
We estimate the burden of the information collection as follows:
Table 3--Estimated One-Time Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
Format of National Drug Code; Number of responses per Total annual Average burden per response Total hours
implementing new requirements respondents respondent responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Section 201.25 (barcode labeling 12,800 22.5 288,000 1............................................ 288,000
requirements); and part 207, subpart D
(requirements for the NDC).
Section 314.81(b)(2)(iii) (other 2,000 6 12,000 10 minutes (0.167 hours)..................... 2,000
postmarketing reports) or Sec.
601.12(f)(3) (changes to an approved
BLA).
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 none of the respondents would be able to
include these labeling changes into other labeling changes they were
making during the transition period. As the change should not require a
substantial redesign, but would only require a slight change to the
existing NDC format already included on the label, we assumed that each
label change would take a respondent 1 hour. Based on the drug listing
database, we understand that there are approximately 12,800 respondents
and 288,000 listed drug packages, resulting in an estimated burden of
288,000 or 22.5 hours per respondent to change the labels for these
products.
For prescription drugs whose label changes would be
reported in an annual report pursuant to Sec. 314.81 or Sec.
601.12(f)(3) for biological products, there are approximately 2,000
respondents that would submit reports and there are approximately
12,000 active approved applications. This means that on average each
application holder will need to submit 6 annual reports (12,000 active
approved applications x 1 annual report per active approved
application/2000 unique application holders). Information on listed
drugs indicates there are approximately 120,000 separate, identifiable
product packages that that are subject to an approved ANDA, BLA, or
NDA. This means that on average each separate and distinct approved
application includes approximately 10 separate and distinct product
packages (120,000 unique distinct product packages/12,000 unique
approved applications). Section 314.81(b)(2)(iii) requires firms to
submit an annual report that includes a summary of any changes in
labeling since the last annual report. Similarly, Sec.
601.12(f)(3)(i)(A) requires manufacturers of biologics to include in
their annual reports editorial or similar minor labeling changes. 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 will include 10 such
declarations (one for
[[Page 44048]]
each unique product package), we estimate the burden to report these
changes to be approximately 10 minutes per annual report. Thus, the
total reporting burden would be 2,000 hours (2,000 respondents x 6
annual reports per respondent x 10 minutes per annual report/60 minutes
= 2,000 hours).
To ensure that comments on information collection are received, OMB
recommends that written comments be submitted through https://www.reginfo.gov (see ADDRESSES). All comments should be identified with
the title of the information collection.
In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3507(d)), we have submitted the information collection provisions of
this proposed rule to OMB for review. These information collection
requirements will not be effective until FDA publishes a final rule,
OMB approves the information collection requirements, and the rule goes
into effect. FDA will announce OMB approval of these requirements in
the Federal Register.
X. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
this proposed 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 summary impact statement is not required.
XI. Consultation and Coordination With Indian Tribal Governments
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the proposed rule does not contain policies that would
have a substantial direct effect 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. The Agency solicits comments from tribal
officials on any potential impact on Indian Tribes from this proposed
action.
XII. References
The following references 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 are also
available electronically at https://www.regulations.gov. FDA has
verified the website addresses, as of the date this document publishes
in the Federal Register, but websites are subject to change over time.
1. HIPAA for Professionals, available at https://www.hhs.gov/ocr/privacy/hipaa/administrative/index.html (last accessed March 22,
2021).
2. Eastern Research Group, Inc. (2003), ``The Pharmaceutical
Labeling Revisions Cost Model,'' January 2, 2003, Contract No. 223-
94-8031, Task Order No. 8.
3. RTI International (2015), ``2014 FDA Labeling Cost Model.''
4. FDA, Preliminary Regulatory Impact Analysis, ``Format of National
Drug Code,'' available at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.
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, the Food and Drug Administration
proposes to amend 21 CFR parts 201 and 207 as follows:
PART 201--LABELING
0
1. The authority citation for part 201 is revised to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360,
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.
0
2. In Sec. 201.25:
0
a. Revise the section heading;
0
b. Remove the word ``bar code'' and add the word ``barcode'' in its
place; and
0
c. Revise paragraph (c)(1) introductory text.
The revisions 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
approved by the relevant Food and Drug Administration Center Director.
Approved standards include those that meet European Article Number/
Uniform Code Council (EAN/UCC) or Health Industry Business
Communications Council (HIBCC) standards. 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 and cord blood, and lymphocytes collected from
peripheral blood.
* * * * *
Dated: July 11, 2022.
Robert M. Califf,
Commissioner of Food and Drugs.
[FR Doc. 2022-15414 Filed 7-22-22; 8:45 am]
BILLING CODE 4164-01-P