0045 SS Revision in support of Aug 2016 Final Rule

Establishment Registration of Producers of Drugs and
Listing of Drugs in Commercial Distribution
OMB Control No. 0910-0045; RIN 0910-AA49
SUPPORTING STATEMENT

A. Justification
1. Circumstances Making the Collection of Information Necessary
Requirements for drug establishment registration and drug listing are set forth in section 510 of
the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360), and section 351 of
the Public Health Service Act (42 U.S.C. 262). Section 224 of Food and Drug Administration
Amendments Act (FDAAA) amended section 510(p) of the FD&C Act to require electronic
drug establishment registration and drug listing. Before the enactment of FDAAA, the FD&C
Act provided for electronic submission of drug establishment registration information upon a
finding that electronic receipt was feasible, and section 510(j) provided that drug listing
information was to be prepared in the form and manner prescribed by FDA.
Under a proposed rule issued August 29, 2006 (71 FR 51276), FDA began to implement
electronic submission of drug establishment registration and drug listing information consistent
with statutory requirements. In 2009, we issued guidance entitled, “Guidance for Industry;
Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration
and Drug Listing” describing the information to include for drug establishment registration and
drug listing and providing instruction on how to prepare and submit the information in an
electronic format (Structured Product Labeling (SPL) files) that FDA can process, review, and
archive.
In the Federal Register of August 31, 2016 (81 FR 60170), we finalized the 2006 proposed rule
setting forth drug establishment registration and listing requirements at 21 CFR part 207. The
final rule entitled, “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,” codifies the statutory requirement for electronic submissions,
adopting most of the provisions found in the proposed rule and discussed in the guidance.
Specifically, the final rule describes how and when owners or operators of establishments at
which drugs are manufactured or processed must register their establishments with FDA and
list the drugs they manufacture or process. In addition, the rule makes certain changes to the
National Drug Code (NDC) system. The final rule is intended to improve management of drug
establishment registration and drug listing requirements and make these processes more
efficient and effective for industry and FDA. Specific provisions of the rule and associated
information collection are discussed below and may be found in the final rule at Table 1 –
Substantive Changes from the Proposed Rule to the Final Rule on p. 60172 (81 FR 60172).

Forms FDA 2656, Registration of Drug Establishment/Labeler Code Assignment, Form FDA
2657, Drug Product Listing, and Form FDA 2658, Registered Establishments' Report of
Private Label Distributors are retained for use in cases when a waiver has been granted.
2. Purpose and Use of the Information Collection
The information collection is used in support of FDA’s mission to protect the public health
through post-marketing surveillance for serious adverse drug reactions, inspection of drug
manufacturing and processing facilities, and monitoring of drug products imported into the
United States. The information collection also implements the electronic prescribing
provisions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2013
(MMA) and the availability of current drug labeling information through DailyMed, a
computerized repository of drug information maintained by the National Library of Medicine.
3. Use of Improved Information Technology and Burden Reduction
The information collection establishes mandatory electronic reporting, however waivers may
be issued in individual cases. Registration of establishments takes place annually during the
period beginning on October 1 and ending on December 31. We estimate all respondents will
submit the information electronically, unless exempted.
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection.
5. Impact on Small Businesses or Other Small Entities
As explained in the Final Regulatory Flexibility Analysis (FRIA), the rulemaking does not
impose a significant burden on a substantial number of small entities, and FDA certifies that
the final rule will not have a significant economic impact on a substantial number of small
entities.
6. Consequences of Collecting the Information Less Frequently
Information collection schedule is consistent with statutory requirements.
7. Special Circumstances Relating to the Guidelines in 5 CFR 1320.5
There are no special circumstances related to the information collection.

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8. Comments in Response to the Proposed Rule and Efforts to Consult Outside the Agency
In the Federal Register of August 29, 2006 (71 FR 51276) FDA published a proposed rule
entitled, “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,” including a PRA analysis and invited public comment. While several
comments were received, none addressed the four information collection topics solicited in the
proposal. Substantive comments are addressed in the agency’s final rule that published August
31, 2016 (81 FR 60170) at Section III and may be found under Docket No. FDA–2005–N–0464
(formerly Docket No. 2005N–0403). FDA finalized the rule in the Federal Register of August
31, 2016 (81 FR 60170) and again invited public comment. None were received regarding the
information collection.
9. Explanation of Any Payment or Gift to Respondents
No payment or gift is provided to respondents.
10. Assurance of Confidentiality Provided to Respondents
Confidentiality of drug listing information is safeguarded by 21 CFR 207.37.
11. Justification for Sensitive Questions
There are no questions of a sensitive nature.
12. Estimates of Annualized Hour Burden and Costs
12a. Annualized Hour Burden Estimates
The agency estimates the annual burden as follows:
TABLE 1. Estimated Annual Reporting Burden1
Activity; 21 CFR Citation

Initial establishment registration;
§§207.17, 207.21, 207.25
Annual review and update of
registration information (including
expedited updates); § 207.29
Initial listing (including NDC);
207.33, 207.41, 207.45, 207.49,
207.53, 207.54, 207.55

No. of
Respondents

1,480

2

2,960

Hours
Per
Respons
e
1

10,000

1

10,000

.50

5,000

1,713

7.28

12,470

1.5

18,705

3

No. of
Responses
Per
Respondent

Total
Annual
Responses

Total
Hours

2,960

Activity; 21 CFR Citation

No. of
Respondents

June and December review and
update (or certification) of listing;
207.35, 207.57
Waiver requests; 207.65
Public disclosure exemption
requests; 207.81(c)
TOTAL
1

Total
Annual
Responses

5,300

No. of
Responses
Per
Respondent
20

106,000

Hours
Per
Respons
e
.75

1
100

1
1

1
100

.50
1

18,514

131,371

Total
Hours

79,500

1
100
106,266

There are no capital or operating and maintenance costs associated with the information collection.

TABLE 2. Estimated Annual Recordkeeping Burden1
SOP for creating and
uploading the SPL file

No. of
Recordkeepers

One-time preparation
of SOP
SOP maintenance
TOTAL
1

No. of Records
per
Recordkeeper

Total
Annual
Records

Avg. Burden
per
Recordkeepin
g

Total
Hours

1,000

1

1,000

40

40,000

3,295

1

3,295

1

3,295
43,295

There are no capital or operating and maintenance costs associated with the information collection.

A. Registration Under Part 207
Under § 207.17, manufacturers, repackers, relabelers, and drug product salvagers must register
their establishments. This is consistent with current registration information collection, except
that PET drug producers are not exempt from registration under the final rule, and the final rule
states that FDA will accept registration information from a private label distributor if it is
acting as an authorized agent for and submitting information that pertains to an establishment
that manufactures, repacks, relabels, or salvages drugs.
Under § 207.21, domestic manufacturers, domestic repackers, domestic relabelers, and
domestic drug product salvagers must complete initial registration of each establishment no
later than 5 calendar days after beginning to manufacture, repack, relabel, or salvage a drug. In
addition, foreign manufacturers, foreign repackers, foreign relabelers, and foreign drug product
salvagers must register each establishment before the drug is imported or offered for import
into the United States.
The information that must be provided to FDA for registration is described in § 207.25 and
includes the following:

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(a) Name of the owner or operator of each establishment; if a partnership, the name of
each partner; if a corporation, the name of each corporate officer and director, and the
place of incorporation;
(b) Each establishment's name, physical address, and telephone number(s);
(c) All name(s) of the establishment, including names under which the establishment
conducts business or names by which the establishment is known;
(d) Registration number of each establishment, if previously assigned by FDA;
(e) A Unique Facility Identifier in accordance with the system specified under section 510
of the Federal Food, Drug, and Cosmetic Act;
(f) All types of operations performed at each establishment;
(g) Name, mailing address, telephone number, and email address of the official contact for
the establishment, as provided in §207.69(a); and
(h) Additionally, with respect to foreign establishments subject to registration, the name,
mailing address, telephone number, and email address must be provided for:\
(1) The United States agent, as provided in §207.69(b);
(2) Each importer in the United States of drugs manufactured, repacked, relabeled, or
salvaged at the establishment that is known to the establishment; and
(3) Each person who imports or offers for import such drug to the United States.
Also, the final rule lengthens the current time period for reporting changes to registration
information from 5 days (10 business days for a change in U.S. agent information) to 30
calendar days. The final rule revokes the current requirement to report a change in individual
ownership and corporate or partnership structure and the current requirement to submit a
signed statement for a change in a registered establishment's firm name. Finally, new
registration information collected under the final rule includes the certification that no changes
have occurred and reporting certain changes as expedited updates within 30 calendar days.
Based on the number of new establishments that currently register each year, we estimate that
approximately 1,400 registrants will submit electronically approximately 2,800 new
establishment registrations annually. Based on the number of registered establishments in our
database, we estimate that approximately 10,000 registrants will provide approximately 10,000
annual reviews and updates of registration information (including expedited updates) or
reviews and certifications that no changes have occurred. The estimates include the
registration of establishments for both domestic and foreign manufacturers, repackers,
relabelers, and drug product salvagers, and registration information submitted by anyone acting
as an authorized agent for an establishment that manufactures, repacks, relabels, or salvages
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drugs. The estimates include an additional 80 PET drug producers who are not exempt from
registration under the final rule and approximately 30 manufacturers of plasma derivatives.
We estimate that it will take approximately 1 hour for registrants to submit initial registration
information electronically for each new establishment. We also estimate that it will take
approximately 30 minutes for each annual review and update of registration information
(including any expedited updates) or each review and certification that no changes have
occurred. The burden hour estimates above are based on our familiarity with the amount of
time it takes registrants to input registration information electronically since June 2009. The
estimates are an average of the time it would take to register a domestic or foreign
establishment and an average of the time it would take to review registration information and
update several registration items in the database or review registration information and only
certify that no changes have occurred.
B. Listing Under Part 207
Under § 207.41, registrants must list drugs they manufacture, repack, relabel, or salvage for
commercial distribution. This requirement includes drug product salvagers not previously
included. Also, the final rule revises NDC-related listing submissions as follows:


A registrant must list each drug it manufactures, repacks, or relabels using an NDC that
includes the registrant’s own labeler code, regardless of whether the drug is
commercially distributed under the registrant’s own label or trade name or under the
label or trade name of a private label distributor.



Each registrant must list each drug it manufactures, repacks or relabels for commercial
distribution under the trade name or label of a private label distributor using an NDC
that includes such private label distributor’s labeler code.
During listing, each manufacturer, repacker, or relabeler must propose for assignment
by FDA an NDC that includes its own labeler code for each package size and type of
drug that it manufactures, repacks, or relabels for commercial distribution.





If a drug is distributed under the trade name or label of a private label distributor, the
manufacturer, repacker, or relabeler must also propose for assignment by FDA an NDC
that includes the labeler code of the private label distributor under whose trade name or
label the drug is distributed, for each package size and type so distributed.



A manufacturer, repacker, relabeler, or private label distributor may also reserve a
proposed NDC for a drug, before the drug is listed, by submitting certain information.

Under § 207.45, registrants must list, no later than 3 days after the initial registration of each
establishment, any drug being manufactured, repacked, relabeled, or salvaged for commercial
distribution at that establishment.

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Under the final rule, the information the registrants must submit to list a drug, including the
information that must be submitted (by a registrant or a private label distributor) to receive a
labeler code, is described in §§ 207.33, 207.49, 207.53, 207.54, 207.55, and 207.61. Under
part 207, we assign a labeler code to each registrant and the registrant assigns the product code
and the package code for each drug product’s NDC.
The listing and NDC information collections required by the final rule adds the following
elements:
(1) The name of each inactive ingredient in a listed drug (assertions of confidentiality
associated with individual inactive ingredients are covered in the electronic registration
and listing guidance);
(2) Additional information, such as email address, to identify a domestic registrant
(identifying information for foreign registrants is part of the electronic registration and
listing guidance information collection and in current § 207.40(c));
(3) The drug master file or veterinary master file number, if one exists, must be submitted
by the manufacturer for an unfinished drug;
(4) Drug product salvagers (who do not repack or relabel) must submit the lot number and
expiration date and NDC assigned to the drug immediately before the drug is received by
the drug product salvager;
(5) All new labeling for a repacked or relabeled drug must be submitted, and not only the
changed labeling;
(6) Package type and volume information corresponding to the package code segment of
the NDC must be submitted;
(7) A drug’s OTC monograph reference (if any) and the date on which the drug was or will
be introduced into commercial distribution are both requested for voluntary submission;
and
(8) The name and UFI of the establishment where the registrant who lists the drug
manufactures it and the type of operation performed on the drug at that establishment, and,
if an immediate source NDC is not provided, the name and UFI of every other
establishment where manufacturing is performed for the drug and the type of operation
performed at each such establishment must be provided.
Under § 207.57, registrants must update drug listing information submitted previously (either
when the change is made or, at a minimum, each June and December). Registrants must also
notify FDA if any listed drug has been discontinued from marketing or if any discontinued drug
has been reintroduced and provide listing information for any drug not yet listed (at the time of
annual establishment registration if not sooner).
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Under § 207.35, registrants must notify us of a change in any of the drug characteristics (except
certain identifying information) for an NDC in § 207.33, and assign a new product code and
package code for that drug.
Burden Estimates
Based on the number of drugs listed annually since June 2009, we estimate that approximately
1,713 registrants will submit electronically approximately 12,469 new listings annually
(including the information submitted to obtain a labeler code and to reserve an NDC for future
use).
Based on the number of drugs in our listing database and the current number of changes to
listing information submitted, we estimate that approximately 5,300 registrants will provide
approximately 10,000 June and 10,000 December reviews and updates of listing information--a
total of approximately 20,000 submissions annually (including the information submitted to
revise an NDC).
The estimates for the number of drug listings include both domestic and foreign listings,
listings submitted by registrants for products sold under their own names as well as products
intended for private label distribution, and information submitted related to an NDC and to
obtain a labeler code. The estimate for the number of drugs subject to the listing requirements
includes PET drugs and approximately 30 plasma derivatives. The estimates for the number of
June and December reviews and updates of listing information include the number of changes
to drug characteristics pertaining to the drug product code to obtain a new NDC and the reports
of the withdrawal of an approved drug from sale under § 314.81(b)(3)(iii).
Based on our familiarity with the time required to input listing information electronically since
June 2009, we estimate that it will take registrants approximately 1 hour and 30 minutes to
submit information electronically for each drug they list for the first time (for both foreign and
domestic registrant listings). These estimates are an average of the time it will take
manufacturers, repackers, relabelers, and drug product salvagers, with drug product salvagers
taking considerably less time than manufacturers. The estimates include the time for
submitting the content of labeling and other labeling in electronic format. (For drugs subject to
an approved marketing application, the electronic submission of the content of labeling under
§ 314.50(l)(1)(i) is approved under OMB Control Number 0910-0001). We also estimate that
it will take approximately 45 minutes for each June and December review and update. These
estimates represent the average amount of time it would take to review and update listing
information or to review and certify that no changes have occurred. The estimates include the
time for submitting any labeling for each drug, changes to the drug's characteristics submitted
for a new NDC, and reports of the withdrawal of an approved drug from sale under
§ 314.81(b)(3)(iii).

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12b. Annualized Cost Burden Estimates
The FRIA uses an hourly wage of $66.50 from the Bureau of Labor Statistics
corresponding to management occupations in pharmaceutical and medicine manufacturing.
This base wage is multiplied by a factor of two to adjust for benefits and overhead. The result
is an adjusted wage of $133. By multiplying $133 times the total hours in the tables above,
FDA estimates an annual cost burden of $19,891,613.
13. Estimates of Other Total Annual Cost Burden to Respondents and Recordkeepers
There are no start-up, operating, or maintenance costs associated with this information
collection.
14. Annualized Cost to the Federal Government
FDA currently devotes approximately 13 FTEs to maintaining the registration and listing
database for human and veterinary drugs and biologics. If each FTE equals approximately
$250,000 (fully-burdened), the total cost to government is approximately $3,250,000.
15. Explanation for Program Changes or Adjustments
This information collection is being revised by rulemaking (see Q8 for public notice and
comment discussion). Individual collection provisions are discussed previously under Q12 of
this supporting statement and more fully in the agency’s final rule (81 FR 60170). Data
elements of the collection have been modified to add, remove, expand, reduce, and clarify
specific requirements, however we believe these changes are marginal and thus we have
increased our estimated number of annual responses by just 292. At the same time, and as
explained in our proposed rule of August 29, 2006 (71 FR 51276, at 51341), having now
allowed respondents time to become experienced with the electronic system, we have reduced
our estimate of the time necessary for the respective reporting elements themselves. Thus,
there is a cumulative reduction in the annual hourly burden by 484,307.
Individual ICs have been modified as reflected in the table below. Specifically, IC 1 (Initial
Registration) has been modified to include an estimated 80 additional respondents that
represent producers of PET drugs who were not previously required to register under the
proposed rule. Although discussed in the final rule publication (81 FR at 60207), the additional
80 respondents were inadvertently omitted from the burden table but are included at Q12 of this
supporting statement.
IC 3, “Initial Listing” consolidates two previously itemized ICs (new listings and new listings
for private label distributor) but, as discussed above, reduces time per reporting activity. IC 4
reflects new burden associated with § 207.81(c) – requests for exemptions from public
disclosure of certain information, but eliminates burden now consolidated at IC 3.
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IC 5 (updates) reflects no new reporting burden but, again as discussed above, we have reduced
the associated time burden. The remaining ICs are unchanged and are associated with waiver
requests and recordkeeping responsibilities.

IC 1
IC 2
IC 3
IC 4
IC 5,
IC 6, 7, 8
TOTAL

Responses
Hours
160
-9,640
0
-40,000
1,501
-30,656
-1,369
-6,511
0
-397,500
0
0
292
-484,307

16. Plans for Tabulation and Publication and Project Time Schedule
Information collected under this rulemaking will not be tabulated or published.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display of OMB Expiration date is appropriate.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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