0458 SS 2017 Extension

Biological Products: Reporting of Biological Product Deviations & Human Cells, Tissues, &
Cellular and Tissue-Based Product Deviations; Form FDA 3486 and Addendum 3486A
OMB Control No. 0910-0458
SUPPORTING STATEMENT
Justification
1. Circumstances Making the Collection of Information Necessary
Under section 351 of the Public Health Service Act (PHS Act)(42 U.S.C. 262), all biological
products, including human blood and blood components, offered for sale in interstate
commerce must be licensed and meet standards, including those prescribed in the FDA
regulations, designed to ensure the continued safety, purity, and potency of such products. In
addition under section 361 of the PHS Act (42 U.S.C. 264), FDA may issue and enforce
regulations necessary to prevent the introduction, transmission, or spread of communicable
diseases between the States or possessions or from foreign countries into the States or
possessions. Further, section 501 of the Federal Food, Drug, and Cosmetic Act (the FD&C
Act) (21 U.S.C. 351) provides that drugs and devices, including human blood and blood
components, are adulterated if they do not conform with Current Good Manufacturing Practice
(CGMP). Accordingly, establishments manufacturing biological products including human
blood and blood components must comply with the applicable CGMP regulations (Parts 211,
606, and 820 (21 CFR Parts 211, 606, and 820)) and CGTP regulations (21 CFR Part 1271) as
appropriate. FDA regards BPD reporting and HCT/P deviation reporting to be an essential tool
in its directive to protect public health by establishing and maintaining surveillance programs
that provide timely and useful information. The agency is, therefore, requesting approval for
the following provisions:
21 CFR 600.14; Reporting
Requires the licensed manufacturer who holds the biological product license, for other than
human blood and blood components, and who had control over a distributed product when the
deviation occurred, to report to the Center for Biologics Evaluation and Research (CBER) or to
the Center for Drugs Evaluation and Research (CDER) as soon as possible but at a date not to
exceed 45 calendar days after acquiring information reasonably suggesting that a reportable
event has occurred.
21 CFR 600.171; Reporting
Requires licensed manufacturers of human blood and blood components, including Source
Plasma, unlicensed registered blood establishments, or transfusion services who had control
over the product when the deviation occurred, to report to CBER as soon as possible but at a
date not to exceed 45 calendar days after acquiring information reasonably suggesting that a
reportable event has occurred.

21 CFR 1271.350(b); Reporting
Requires human cells, tissues, and cellular and tissue-based product (HCT/P) establishments
that manufacture non-reproductive HCT/Ps described in § 1271.10 to investigate and report to
CBER all HCT/P deviations relating to a distributed HCT/P that relates to the core current
good tissue practice (CGTP) requirements, if the deviation occurred in the establishment’s
facility or in a facility that performed a manufacturing step for the establishment under
contract, agreement, or other arrangement; and to report such HCT/P deviations within 45 days
of the discovery of the event.
Forms FDA 3486 and 3486A (Biological Product Deviation Report and Web-based
Addendum); Reporting
Form FDA 3486 is used to submit biological product deviation (BPD) and HCT/P deviation
reports. CBER also developed a Web-based addendum to Form FDA 3486 (Form FDA
3486A) to provide additional information when a BPD report submitted under § 606.171 has
been reviewed by FDA and evaluated as a possible recall.
2. Purpose and Use of the Information Collection
The objectives of the BPD reporting and HCT/P deviation reporting requirements are to: (1)
enable FDA to respond when public health may be at risk; (2) expedite reporting of BPD and
HCT/P deviations in manufacturing; (3) provide FDA with uniform data to track trends that
may indicate broader threats to the public health; (4) create a uniform reporting requirement
that can be enforced against non-complying entities; and (5) help ensure that licensed
manufacturers and unlicensed blood establishments as well as manufacturers of HCT/Ps are
taking appropriate actions to investigate and correct biological product deviations. The
reporting system builds on quality assurance (QA) programs to assure better protection of the
public health. Reporting of BPDs and HCT/P deviations also enables FDA to identify areas in
which further regulation or guidance is needed to assist licensed manufacturers and unlicensed
blood establishments as well as non-reproductive HCT/P establishments in decreasing the
occurrence of these events.
3. Use of Improved Information Technology and Burden Reduction
FDA has implemented a standardized form FDA 3486 for reporting deviations in the
manufacturing of a biological product. After completion, the form is submitted pursuant to §§
600.14(e), 606.171(e), or 1271.350(b)(3). Respondents may also submit the information
electronically using web-based form FDA 3486A.
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection.

2

5. Impact on Small Businesses or Other Small Entities
The information collection supports agency regulations protecting the public health and
provides for no exemptions to small businesses. FDA provides assistance to small businesses
through guidance available on our website at:
http://www.fda.gov/ForIndustry/SmallBusinessAssistance/SmallBusinessRepresentatives/guida
nce and through the Center for Biologics Evaluation and Research’s (CBER) Office of
Communication, Outreach, and Development, Division of Manufacturer’s Assistance and
Training.
6. Consequences of Collecting the Information Less Frequently
Less frequent information collection would not provide the information necessary for FDA to
monitor the safety, purity, and potency of distributed biological products. BPD reports and
HCT/P deviation reports, in conjunction with inspections and other surveillance activities, give
FDA a continuing overview of the biological product industry. Less frequent collection of
information would inhibit FDA’s oversight. There are no technical or legal obstacles to
reducing the burden.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
The information may be reported to FDA more frequently than quarterly based on the
frequency of BPD reports and HCT/P deviation reports that may occur during manufacturing.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
Agency
In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice for public comment in the
Federal Register of June 7, 2016 (81 FR 36550). One comment was submitted in response to
the notice concerning potential ways to minimize the burden associated with the information
collection. The commenter encouraged FDA to permit the use of attachments to Forms FDA
3486 and 3486A when reporting multiple biological product deviations from a single starting
source rather than retype the information. The comment suggested, alternatively, that
respondents’ burden might be reduced by “capping the forms at a much lower number of
products/lots than the current maximum of 100.” Finally, the comment suggested Forms FDA
3486 and 3486A incorporate technology that would permit barcode scanning for relevant fields.
In our 30-day notice we expressed appreciation of the comment but explained that we are
unable to make the suggested revisions to the information collection. Currently, product
information can readily be imported from a Microsoft Excel file (in XLS format) into the eBPD
report without having to be retyped (up to 100 units/lots). In addition, the product information
entered on Form FDA 3486 automatically populates Form FDA 3486A minimizing the need to
manually reenter required information. While we will consider future enhancements that allow
for attachments and integrates barcode or other technologies that facilitate or otherwise
improve reporting, we must ensure that upgrades are compatible with our existing system.
3

9. Explanation of Any Payment or Gift to Respondents
No payment or gift is provided to respondents.
10. Assurance of Confidentiality Provided to Respondents
The confidentiality of information received by FDA would be consistent with the Freedom of
Information Act (FOIA) and the FDA’s published regulations of “Public Information” under 21
CFR Part 20.
11. Justification for Sensitive Questions
No questions of a sensitive nature are included in the information collection.
12. Estimates of Annualized Burden Hours and Costs
12a. Annualized Hour Burden Estimate
The estimated annual burden for this information collection is 93,854 hours and 48,930
responses, itemized as follows:
Table 1—Estimate Annual Reporting Burden1
21 CFR Section;
Activity

FDA
Form

600.14; Reporting of
BPDs by licensed
manufacturers
606.171; Reporting
of product deviations
by licensed
manufacturers,
unlicensed registered
blood establishments,
and transfusion
services
1271.350(b); HCT/P
deviations
Web-based
Addendum
Total

3486

No. of
Respondents

No. of
Total
Avg.
Total
Responses per Annual
Burden per Hours
Respondent
Responses Response
102
5.99
611
2.0
1,222

3486

1,738

26.34

45,774

2.0

91,548

3486

97

2.64

256

2.0

512

3486A2

87

26.31

2,289

0.25

572

48,930

1

93,854

There are no capital costs or operating and maintenance costs associated with this collection of information.
2
Five percent of the number of respondents (1,738 x 0.05 = 87) and total annual responses to CBER (45,774 x
0.05 = 2,289).

4

12b. Annualized Cost Burden Estimate
The estimated annualized cost to the respondents is $4,035,722, as reflected below:
Activity
Reporting

Total Burden Hours
93,854

Hourly Wage Rate
$43

Total Cost
$4,035,722

This estimated cost is based on a pay rate of $43 per hour for a mid-level professional who has
the training and skills to handle the various reporting requirements. This salary estimate
includes benefits but no overhead costs. There should not be any additional costs of
investigating BPDs and HCT/P deviations or keeping records of them, since these activities are
already required under other sections in 21 CFR Parts 211, 606, 820, and 1271.
13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs
There are no capital costs or operating and maintenance costs associated with this collection of
information.
14. Annualized Cost to the Federal Government
The estimated annualized cost to FDA is $831,565.35, as reflected below:
Activity
Report Review

No. of
Reports
48,930

Time per
Report
~20 minutes
(0.33 hours)

Average Cost
per Hour
$51.50

Total Cost
$831,565.35

This estimate was reached by multiplying the number of annual submissions by the time spent
reviewing, assessing, and recording/inputting the information. We then multiplied that figure
(161,469) by the average pay rate of $51.50 (GS/13-5 Washington DC/Metro Area) of one
FTE.
15. Explanation for Program Changes or Adjustments
The information collection reflects an overall decrease of 18,645 hours and 9,723 responses.
We attribute the reduction to a normal variation in submissions of BPDs.
16. Plans for Tabulation and Publication and Project Time Schedule
Information collected will not be tabulated or published.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display of OMB Expiration date is appropriate.
5

18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

6