Reg and Listing Supporting Statement for Final Rule 2016

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
RIN 0910-AA49
OMB Control No. 0910-NEW
SUPPORTING STATEMENT
A. Justification
1. Circumstances Making the Collection of Information Necessary
This information collection supports agency rulemaking that amends regulations governing drug
establishment registration and drug listing. The rulemaking describes when and how to register
and list, what information must be submitted for registration and listing, clarifies the National
Drug Code (NDC) system for drugs, and requires that each drug product subject to the listing
requirements of this final rule have a unique NDC. The rulemaking codifies the current statutory
requirement that registration and listing information be submitted to FDA electronically instead
of using paper forms unless a waiver is obtained. Historically, drug establishment registration
and drug listing information was submitted using Form 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). Before the
enactment of the Food and Drug Administration Amendments Act (FDAAA), section 510(p) of
the Federal Food, Drug, and Cosmetic Act (FD&C Act) expressly provided for electronic
submission of drug establishment registration information upon a finding that electronic receipt
was feasible, and section 510(j) of the FD&C Act specified that drug listing information was to
be prepared in the form and manner prescribed by FDA. Section 224 of FDAAA, which
amended section 510(p) of the FD&C Act, now requires electronic drug listing in addition to
electronic drug establishment registration. In certain cases, as discussed below, if it is
unreasonable to expect a person to submit registration and listing information electronically,
FDA may grant a waiver from the electronic submission requirement.
In June 2009, FDA made available the electronic registration and listing guidance (74 FR 26248)
to provide recommendations on fulfilling the statutory requirement to submit electronically drug
establishment registration and drug listing information. The guidance describes the types of
information to include for purposes of drug establishment registration and drug listing and how
to prepare and submit the information in an electronic format (Structured Product Labeling
(SPL) files) that FDA can process, review, and archive. In June 2009, FDA began accepting
submissions required under the part 207 regulations into our electronic drug registration and
listing system. The format for these electronic submissions employs Extensible Markup
Language (XML) and uses the SPL standard to organize the data within the file. This electronic
registration and listing enables FDA to employ a number of automated validations to ensure the
quality of the data received.

In addition to the information that previously was collected on the FDA Forms, the electronic
registration and listing guidance addresses, with respect to part 207, the electronic submission of
other statutorily required information as follows:
● The name of each importer that is known to the establishment (the U.S. company or
individual in the United States that is an owner, consignee, or recipient of the foreign
establishment's drug that is imported into the United States) (section 510(i)(1)(A) of the FD&C
Act);
● The name of each person who imports or offers the foreign establishment’s drug for
import (the name of each agent, broker, or other entity, other than a carrier, that the foreign drug
establishment uses to facilitate the import of its drug into the United States) (section 510(i)(1)(A)
of the FD&C Act); and
● For a registered foreign drug establishment, the name, address, and telephone number
of its U.S. agent (§ 207.40(c)).
The electronic registration and listing guidance also recommends the voluntary
submission of the following additional information, when applicable:
● The email address for the U.S. agent, and the telephone number(s) and email address
for the importer and person who imports or offers for import their drug;
● A site-specific Data Universal Numbering System (DUNS) number for each entity (in
November 2014, we issued the “guidance for industry entitled “Specification of the Unique
Facility Identifier System for Drug Establishment Registration” (79 FR 65977, November 6,
2014) and obtained OMB approval to broaden the entity identification number covered in OMB
Control Number 0910-0045 (discussed below));
● The NDC product code for the source drug that is repacked or relabeled;
● Distinctive characteristics of certain listed drugs (i.e., the flavor, the color, and image
of the actual solid dosage form); and
● Registrants may indicate that they view as confidential an inactive ingredient or the
registrant's business relationship with an establishment.
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 is also intended to improve management of drug
establishment registration and drug listing requirements and make these processes more efficient
and effective for industry and for FDA. Finally, the information collection implements the
electronic prescribing provisions of the Medicare Prescription Drug, Improvement, and
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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 that most all respondents will
submit the information electronically. Finally, FDA has issued guidance for industry entitled,
Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration and
Drug Listing (currently approved under OMB Control No. 0910-0045), and sponsors online
Webinars to help respondents with drug establishment registration and listing requirements.
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.
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 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).

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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
In the tables below, we estimate burden we believe is being introduced by the
rulemaking. Because the rulemaking revises regulations currently supported by approved ICRs,
we have organized the tables accordingly. As FDA revises the affected collections, we will
discontinue this information collection in support of the rulemaking.
Description of Respondents: Manufacturers, repackers, relabelers, drug product
salvagers, and private label distributors as described in the final rule.
I. Burden to be incorporated into OMB Control No. 0910-0045
TABLE 1. Estimated Annual Reporting Burden Under Part 207
Reporting Requirement; 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
June and December review and
update (or certification) of listing;
207.35, 207.57
Waiver requests; 207.65

Number of
Respondents

No. of
Responses
Per
Respondent

Total
Annual
Responses

Hours Per
Response

Total
Hours

1,400

2

2,800

1

2,800

10,000

1

10,000

.50

5,000

1,713

7.28

12,470

1.5

18,705

5,300

20

106,000

.75

79,500

1

1

1

.50

1

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Public disclosure exemption
requests; 207.81(c)
TOTAL

100

1

100

18,514

1

100

131,371

106,106

TABLE 2. Estimated Annual Recordkeeping Burden Under Part 207
SOP for creating
and uploading the
SPL file
One-time
preparation of SOP
SOP maintenance
Total

Number of
Recordkeepers
1,000

Number of
Records per
Recordkeeper
1

3,295

1

Total
Average Burden
Annual
per
Records
Recordkeeping
1,000
40
3,295

Total
Hours
40,000

1

3,295
43,295

II. Burden to be incorporated into OMB Control No. 0910-0052
TABLE 3. Estimated Annual Reporting Burden Under Part 607
21 CFR Sections

Initial Establishment
Registration and Product
Listing
(607.22(a) and
607.25(a) and (b)(3))
Annual Review and
Update of Establishment
Registration and Blood
Product Listing
(607.22(a) and
607.25(a) and (b)(3))
Waiver requests
(607.22(b))
TOTAL

Number of
Respondents

Number of
Responses
Per
Respondent

Total Annual
Responses

Average Burden
per Response

Total
Hours

68

1

68

1

68

2,615

1

2,615

0.5

1,308

25

1

25

1

25

2,708

2,708

5

1,401

III. Burden to be incorporated into OMB Control No. 0910-0543
TABLE 4. ESTIMATED ANNUAL REPORTING BURDEN UNDER PART 1271
21 CFR Sections

Initial
Establishment
Registration and
Listing
(1271.25)
Annual Review
and Update of
Establishment
Registration and
Listing
(1271.25)
Waiver requests
(1271.23)
Amend
Establishment
Registration
(1271.26)
Total

No. of
Respondents

No. of
Responses
per
Respondent

Total Annual
Responses

Average
Burden per
Response

Total
Hours

225

1

225

0.75

168.75

2,700

1

2,700

0.5

1,350

100

1

100

1

100

1,200

1

1,200

0.25

300

4,225

4,225

1,918.75

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 $20,311,726.75.
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
Registration and listing responsibilities are currently funded out of allocated resources. The
burden from the information collection revise and thus will be incorporated into three existing
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ICRs wherein the cost of collection is discussed. Therefore we estimate no cost to the Federal
government for this collection of information.
15. Explanation for Program Changes or Adjustments
This is a new information collection reflecting burden introduced by rulemaking. Because the
rulemaking revises regulations currently supported by three currently approved ICRs: 09100045 Registration of Producers of Drugs and Listing of Drugs in Commercial Distribution; 09100052, Blood Establishment Registration and Product Listing; and 0910-0543, Eligibility
Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products
(HCT/Ps). FDA will revise these collections accordingly and upon doing so will discontinue this
collection.
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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