CDER Compounding GFI NEW

Guidance for Industry on Electronic Drug Product Reporting for Human Drug Compounding
Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act
OMB Control No. 0910-[NEW]
Supporting Statement Part A

A. Justification
1. Circumstances Making the Collection of Information Necessary
On November 27, 2013, the President signed the Drug Quality and Security Act (DQSA) into
law. The DQSA added a new section 503B to the Federal Food, Drug, and Cosmetic Act
(FD&C Act) creating a category of entities called “outsourcing facilities.” Outsourcing facilities,
as defined in section 503B(d)(4) of the FD&C Act, are facilities that meet all of the requirements
described in section 503B. These conditions include registering with FDA as an outsourcing
facility and submitting regular reports identifying the drugs compounded by the outsourcing
facility during the previous 6-month period.
The first of these reports must be submitted upon initial registration as an outsourcing facility.
Thereafter, product reports must be submitted once during the month of June and once during the
month of December each year, for as long as an establishment remains registered as an
outsourcing facility.
Drug products compounded in an outsourcing facility can qualify for exemptions from the FDA
approval requirements in section 505 of the FD&C Act (21 U.S.C. 355) and the requirement to
label products with adequate directions for use under section 502(f)(1) of the FD&C Act (21
U.S.C. 352(f)(1)) if the requirements in section 503B are met.
The guidance is intended for entities that compound human drugs and elect to register as
outsourcing facilities under section 503B of the FD&C Act. Once an entity has elected to
register as an outsourcing facility, it must submit reports identifying the drugs compounded by
the outsourcing facility. The guidance describes who must report, the format of the report, the
content that should be included in each report, when to report, and how outsourcing facilities
may submit reports to FDA.
The guidance contains the following collections of information, as specified by the DQSA:
Upon initial registration as an outsourcing facility, each outsourcing facility that registers shall
submit a report identifying the drugs compounded by such outsourcing facility during the
previous 6-month period, and, with respect to each drug reported, provide the active ingredient,
the source of the active ingredient, the National Drug Code (NDC) number of the source drug or
bulk drug ingredient, if available, the strength of the active ingredient per unit, the dosage form
and route of administration, the package description, the number of individual units produced,
and the NDC number of the final products, if assigned.

Once during the month of June each year and once during the month of December each year,
each outsourcing facility shall submit a report identifying the drugs compounded by such
outsourcing facility during the previous 6-month period, and, with respect to each drug reported,
provide the active ingredient, the source of the active ingredient, the National Drug Code
Number of the source drug or bulk drug ingredient, if available, the strength of the active
ingredient per unit, the dosage form and route of administration, the package description, the
number of individual units produced, and the NDC number of the final products, if assigned.
2. Purpose and Use of the Information Collection
After an entity has elected to register as an outsourcing facility, it must submit regular reports
identifying the drugs compounded by the outsourcing facility during the previous 6-month
period. The guidance describes who must report, the format of the report, the content that should
be included in each report, when to report, and how outsourcing facilities may submit reports to
FDA.
3. Use of Improved Information Technology and Burden Reduction
Section 503B(b)(3) of the FD&C Act requires outsourcing facilities to register and report by
electronic means unless FDA grants a request for a waiver of this requirement because the use of
electronic means is not reasonable for the person requesting the waiver. Compounded product
information must be submitted to FDA electronically using the Structured Product Labeling
(SPL) format and in accordance with section IV of the FDA guidance entitled “Providing
Regulatory Submissions in Electronic Format--Drug Establishment Registration and Drug
Listing” (available at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064994.h
tm)
4. Efforts to Identify Duplication and Use of Similar Information
The requirements do not duplicate nor are they similar to any current requirements for these
outsourcing facilities.
5. Impact on Small Businesses or Other Small Entities
FDA estimates that approximately 32% of outsourcing facilities would be considered small
businesses. The information being requested in the final guidance has been held to the absolute
minimum required for the intended use of the data. Most of the information requested in this
guidance is specifically required by section 503B of the FD&C Act.

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6. Consequences of Collecting the Information Less Frequently
The frequencies related to the submission of drug product reports under this guidance are
specified by the DQSA. Under section 503B(b)(2)(A) of the FD&C Act, facilities that elect to
register with FDA must submit product reports upon registration and in June and December of
each year. The drug reporting requirement and the frequency which reports shall be submitted is
specified by statute; therefore, any less frequent collection of reports would be in conflict with
the statutory requirements. In order to be recognized as an “outsourcing facility” as defined in
the FD&C Act, an entity must report as specified; if an entity does not report, that entity is not
eligible for the exemptions from the FDA approval requirements in section 505 of the FD&C Act
(21 U.S.C. 355) and the requirement to label products with adequate directions for use under
section 502(f)(1) of the FD&C Act (21 U.S.C. 352(f)(1)).
7. Special Circumstances Relating to the Guidelines in 5 CFR 1320.5
There are no special circumstances relating to this information collection. (The submission of
proprietary, trade secret, or other confidential information is addressed under section 10 below).
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency
In response to the November 24, 2014, Federal Register (81 FR 69857) notice, FDA received 3
comments on the revised draft guidance that raised issues pertaining to the information
collection. The issues raised are addressed below.
Issue One: Several comments said that the guidance should clarify FDA’s definition of
the source of the active ingredient used to compound the final product and the information the
outsourcing facility should submit to FDA. One commenter requested clarification with regard to
the source of active ingredient and whether the Agency will require solely the name of the
registered supplier for the bulk and finished drug product or will outsourcing facilities be
expected to provide other information.
FDA Response to Issue One: FDA thanks the commenter for raising this issue, which is
beyond the scope of the present guidance. FDA intends to address this issue in future guidance or
regulations.
Issue Two: One commenter expressed concern about being unable to submit a product
report within the required 30-day reporting period because of the extensive amount of time to
create a product report, especially for facilities with large product portfolios. The comment noted
that FDA failed to recognize that each outsourcing facility will have numerous SPL entries into
the electronic reporting system to make up a product report.
FDA Response to Issue Two: FDA agrees that the estimated total burden hours in the
tables should be increased, and we have changed our estimate below. A facility’s product report
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is comprised of individual product SPL submissions, identified as responses in the table. FDA
has also clarified in the final guidance, however, that there are ways to simplify the submission
of product reporting information and reduce the number of responses and total burden of
submitting product reporting information. Initially, the creation of product report submissions
can be time consuming, but submissions can be saved, updated, and resubmitted for subsequent
reporting periods instead of creating a new submission each time. In addition, multiple strengths
of the same drug, package sizes, and source NDC numbers can be consolidated into a single
product submission in SPL. FDA has changed the estimates that were provided in the November
24, 2014, Federal Register notice to account for the fact that each product report will consist of
multiple SPL responses per facility.
9. Explanation of Any Payment or Gift to Respondents
There is no payment or gift to respondents associated with this guidance.
10. Assurance of Confidentiality Provided to Respondents
Information submitted to the FDA under these requirements will be handled consistent with
applicable disclosure laws and regulations, including but not limited to the Freedom of
Information Act (5 U.S.C. 552) and FDA’s disclosure regulations in 21 CFR part 20.
As explained in the guidance, FDA intends to make proactive disclosures of some of the
information provided by respondents. Section 503B(b)(1)(B)(i) provides that outsourcing
facility registrations are available for inspection to any person so requesting and section
503B(b)(2)(C) specifies that product reports are exempt from inspection under section
503B(b)(1)(B)(i) unless the Secretary finds that such an exemption would be inconsistent with
the protection of the public health. FDA finds that exempting from disclosure some of the
information submitted in product reports would be inconsistent with the protection of the public
health, specifically, for each marketed product: the name of the outsourcing facility, address of
the outsourcing facility, name of the active ingredient, strength of the active ingredient per unit,
dosage form, package description, and NDC of the final product (if assigned). This information
is generally required on product labels or publicly available, but publication of this information
will facilitate product recalls when they are necessary, and assist the public in finding
outsourcing facilities that have compounded certain drug products, particularly drugs in shortage.
FDA intends to publish this information on our Web site. FDA does not intend to publish
information about a drug submitted in a product report if an outsourcing facility notes in the
report that it has not distributed the drug and has not advised any person of its intent or ability to
compound the drug.
11. Justification for Sensitive Questions
There are no sensitive questions associated with this guidance.

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12. Estimates of Annualized Hour Burden and Costs
12a. Annualized Hour Burden Estimate
Based on current data for outsourcing facilities, we estimate a total of approximately 55
outsourcing facilities (“Number of Respondents” in table 1, row 1) will submit to FDA an initial
report identifying all drugs compounded in the facility in the previous 6 months. For the
purposes of this calculation, each product’s SPL submission is considered a separate response,
and therefore each facility’s product report will include multiple responses.
Taking into account that a particular product that is compounded into different strengths from
different sources of active ingredient can be reported in a single SPL response, we estimate that
the number of products reported per facility will average 220 products per facility (“Number of
responses per respondent” in tables 1 and 2, row 1). This estimate is based on current data in
product reports.
Concerning the comment that each outsourcing facility will have numerous SPL entries, FDA
agrees and has changed the estimates that were provided in the November 24, 2014, Federal
Register notice to account for the fact that each product report will consist of multiple SPL
responses per facility. We estimate that preparing and submitting this information electronically
could take up to approximately 2 hours for each initial SPL response (“Average burden per
response” in table 1, row 1).
We also estimate that a total of approximately 55 outsourcing facilities (“Number of
Respondents” in table 2, rows 1 and 2) will submit to FDA a report twice each year identifying
all drugs compounded at the facility in the previous six months. As described above, we estimate
on average 220 SPL responses per facility. We estimate that preparing and submitting this
information electronically will take approximately .5 hours per response (“Average burden per
response” in table 2, rows 1 and 2). We have reduced the burden for semiannual product
submissions due to the fact that outsourcing facilities can save each SPL response once initially
created and submitted. For subsequent reports, an outsourcing facility may resubmit the same
file(s) after changing only the following data elements to appropriate values for the reporting
period (along with other data as appropriate): RootID and version number (both SPL metadata);
effective date (to identify the reporting period); and the number of units produced. Furthermore,
if a product was not compounded during a particular reporting period, no SPL response needs be
sent for that product during that reporting period.
We expect to receive no more than one waiver request from the electronic submission process
for initial product reports and semi-annual reports, and each request should take approximately 1
hour to prepare and submit to FDA.
Therefore, FDA estimates the burden of this collection of information as follows:

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Table 1.—Estimated Initial Reporting Burden1
Product Reporting for
Compounding Outsourcing
Facilities

Submission of Initial
Product Report
Waiver Request From
Electronic Submission of
Initial Product Report
Total
1

Number of
Respondents

Number of
Responses
per
Respondent

Total Annual
Responses

Average
burden per
response
(hours)

Total
Hours

55

220

12,100

2

24,200

1

1

1

1

1

24,201

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

Table 2 - Estimated Annual Reporting Burden1
Total Annual
Responses

Average
burden per
response
(hours)

Total
Hours

Product Reporting for
Compounding Outsourcing
Facilities

Number of
Respondents

Number of
Responses
per
Respondent

Submission for June
Product Report
Submission for
December Product
Report
Waiver Request From
Electronic Submission of
Product Reports
Total

55

220

12,100

.5

6,050

55

220

12,100

.5

6,050

1

1

1

1

1

1

12,101

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

12b.

Annualized Cost Burden Estimate

The industry burden estimate calculated above would result in labor costs. FDA estimates that
registrations are generally submitted by a regulatory affairs manager, and that labor hours are
valued using the mean hourly wage of $63.89 as reported by the U.S. Department of Labor,
Bureau of Labor Statistics, 2013 Employment Occupational Statistics for Management
Occupations (SOC 11-0000) in Pharmaceutical and Medicine Manufacturing (North American
Industry Notification, NAICS, code 325400). Wages are further adjusted for benefits and
overhead, for an average hourly labor cost of $127.78 ($63.89 x 2). Using this wage rate, times
36,302 hours calculated above for this information collection, equals approximately
$4,638,541.78 in labor costs.

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13. Estimates of Other Total Annual Cost Burden to Respondents and/or Recordkeepers/Capital
Costs
There are no capital, start-up, operating, or maintenance costs associated with this information
collection.
14. Annualized Cost to the Federal Government.
We estimate approximately 0.5 FTE ($142,500; each FTE equals $285,000) annually to do the
following: Receive, review, acknowledge, and confirm outsourcing facility product reporting
submissions; respond to inquiries regarding outsourcing facility product reporting, including
interpretation of section 503B product reporting provisions. This does not include IT
development and maintenance costs. Development of IT solution cost is $107,000 via the Drug
Quality Compliance Portal contract. Annual maintenance costs are included in the Operations
and Maintenance portion of that contract.
15. Explanation for Program Changes or Adjustments
Because human drug compounders have not been required to register and list under section 510
of the FD&C Act and 21 CFR 207, it has been difficult to anticipate the number of outsourcing
facilities that will participate in the process and the burden hours that they will incur.
Consequently, we estimated a total of 302 hours in the PRA section of the November 24, 2014,
Federal Register notice. As a result of the public comments, we have re-evaluated and increased
the total burden hours to 36,302.
16. Plans for Tabulation and Publication and Project Time Schedule
There are no plans for tabulation and publication and project time scheduling.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
The OMB expiration data will be displayed where required.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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