0458 Biologics deviations reports SSA 2019 Ext

UNITED STATES FOOD & DRUG ADMINISTRATION
Biological Products:
Reporting of Biological Product Deviations and Human Cells,
Tissues, and Cellular and Tissue-Based Product Deviations
Form FDA 3486 and Addendum 3486A
OMB Control No. 0910-0458
SUPPORTING STATEMENT – Part A: 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 Food and Drug
Administration (FDA, the agency, us or we) 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, 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) assuring that they meet the requirements
of the FD&C Act. Accordingly, establishments manufacturing biological products including
human blood and blood components must comply with the applicable CGMP regulations in
21 CFR Parts 211, 606, and 820, and current good tissue practice (CGTP) regulations (21
CFR Part 1271) as appropriate. We regard Biological Product Deviations (BPD) reporting
and human cells, tissues, and cellular and tissue-based product (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.
FDA is, therefore, requesting an extension of Office of Management and Budget (OMB)
approval for the information collection associated with the reporting of biological product
deviations found in the applicable regulations:
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 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 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.
We are also requesting an extension of OMB approval for associated Form FDA 3486 and
Form FDA 3486A (Biological Product Deviation Report and web-based addendum), as
discussed in more detail at Question 3 in this supporting statement.
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 developed the following forms to assist respondents to the information collection:
Forms FDA 3486 and 3486A (Biological Product Deviation Report and Web-based
Addendum) – Form FDA 3486 is used to submit 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 21 CFR 606.171 has been
reviewed by FDA and evaluated as a possible recall. After completion, the form is submitted
pursuant to 21 CFR 600.14(e), 606.171(e), or 1271.350(b)(3). Form FDA 3486 can be
submitted electronically to CBER, but CDER does not currently accept electronic filings.
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Respondents may also submit the information for the web-based Form FDA 3486A
electronically.
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection. Although FDA has established
information collection requests supporting regulations in part 211 (21 CFR 211, currently
approved under OMB Control No. 0910-0139); part 600 (21 CFR 600, currently approved under
OMB Control No. 0910-0302); and part 1271 (21 CFR 1271, currently approved under OMB
Control No. 0910-0543); this information collection specifically supports reporting associated
with biological product deviations as described in the applicable regulations and included in our
burden analysis at Question 12.
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: https://www.fda.gov/industry/small-businessassistance and through the Center for Biologics Evaluation and Research (CBER)’s Office of
Communication, Outreach, and Development, Division of Manufacturer’s Assistance and
Training or Center for Drug Evaluation and Research (CDER)’s Office of Communication.
6. Consequences of Collecting the Information Less Frequently
The information collection schedule is consistent with statutory and regulatory requirements.
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 July 31, 2019 (84 FR 37321). One comment offering general support for
the information collection was received in response to the notice.

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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
This Information Collection Request collects personally identifiable information (PII) or other
data of a personal nature. PII is collected in the context of the subject individuals’ professional
capacity and the FDA-related work they perform for their employer (e.g., point of contact at a
regulated entity). The PII submitted for FDA Form 3486 (Biological Product Deviation Report)
is name, telephone number, and email address. The PII submitted for FDA Form 3486A
(Addendum) is name, address, telephone number, and email address.
FDA further determined this collection is not subject to the Privacy Act of 1974 and the
particular notice and other requirements of the Act do not apply. Specifically, FDA does not use
name or any other personal identifier to routinely retrieve records from the information
collected.
In preparing this Supporting Statement, FDA staff consulted with the FDA Privacy Office to
ensure appropriate handling of information collected. FDA minimized the PII to be collected to
protect the privacy of the individuals.
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 94,592.5 hours and 49,328
responses, itemized as follows:

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Table 1—Estimate Annual Reporting Burden
21 CFR Section;
Activity

FDA
Form

No. of
Respondents

600.14; Reporting of
product deviations by
licensed manufacturers

3486

93

606.171; Reporting of
product deviations by
licensed manufacturers,
unlicensed registered blood
establishments, and
transfusion services

3486

1,937

1271.350(b); HCT/P
3486
deviations
Form; Web-based Addendum 3486A1

No. of
Responses per
Respondent

Total
Annual
Responses

6.14

23.847

93

2.61

102

22.76

Total
Hours

571

Avg.
Burden
per
Response
2.0

46,192

2.0

92,384

243

2.0

486

2,322

1,142

0.25

580.5

Total
49,328
1
Five percent of the number of respondents (1,937+93 x 0.05 = 102) and total annual responses to CBER
(46,192+243 x 0.05 = 2,322).

94,592.5

Activities such as investigating, changing standard operating procedures or processes, and
followup are currently required under 21 CFR parts 211 (approved under OMB control
number 0910-0139), 606 (approved under OMB control number 0910-0116), 820 (approved
under OMB control number 0910-0073). and 1271 (approved under OMB control number
0910-0543) and, therefore, are not included in the burden calculation for the separate
requirement of submitting a deviation report to FDA.
12b. Annualized Cost Burden Estimate
The estimated annualized cost to the respondents is $4,256,662.50, as reflected below:
Activity
Reporting

Total Burden Hours
94,592.5

Hourly Wage Rate
$45

Total Cost
$4,256,662.50

This estimated cost is based on a pay rate of $45 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. As stated previously, we estimate no additional
costs for 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.
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14. Annualized Cost to the Federal Government
The estimated annualized cost to FDA is $879,024.96, as reflected below:
Activity
Report Review

No. of
Reports
49,328

Time per
Report
20 minutes
(0.33 hours)

Average Cost
per Hour
$54.00

Total Cost
$879,024.96

This estimate was reached by multiplying the number of total annual responses by the time
spent reviewing and assessing the information. We then multiplied that figure (16,278.24)
by the average pay rate of $54.00 (GS/13-5 Washington DC/Metro Area) of one Full-Time
Equivalent.
15. Explanation for Program Changes or Adjustments
The information collection reflects an overall increase of 738 hours and 398 responses. We
attribute the adjustment to an increase in the number of submissions of BPDs over the last
few years. We have also uploaded respondent cost-information to appear at
www.reginfo.gov.
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.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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