
[Federal Register Volume 81, Number 219 (Monday, November 14, 2016)]
[Notices]
[Pages 79504-79506]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-27259]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0579]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Biological Products: 
Reporting of Biological Product Deviations and Human Cells, Tissues, 
and Cellular and Tissue-Based Deviations in Manufacturing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or we) is announcing 
that a proposed collection of information has been submitted to the 
Office of Management and Budget (OMB) for review and clearance under 
the Paperwork Reduction Act of 1995 (the PRA).

DATES: Fax written comments on the collection of information by 
December 14, 2016.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-0458. 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A63, 11601 
Landsdown St., North Bethesda, MD 20852, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.
    Biological Products: Reporting of Biological Product Deviations and 
Human Cells, Tissues, and Cellular and Tissue-Based Product Deviations 
in Manufacturing; Forms FDA 3486 and 3486A.

OMB Control Number 0910-0458--Extension

    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 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) 
assuring that they meet the requirements of the FD&C Act. 
Establishments manufacturing biological products, including human blood 
and blood components, must comply with the applicable CGMP regulations 
(21 CFR parts 211, 606, and 820)) and current good tissue practice 
(CGTP) regulations (part 1271 (21 CFR part 1271)) as appropriate. FDA 
regards biological product deviation (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.
    Section 600.14 (21 CFR 600.14), in brief, requires the 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

[[Page 79505]]

reportable event has occurred. Section 606.171 (21 CFR 606.171), in 
brief, requires licensed manufacturers of human blood and blood 
components, including Source Plasma, unlicensed registered blood 
establishments, and transfusion services, who had control over a 
distributed 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. Similarly, Sec.  1271.350(b) (21 CFR 1271.350(b)), in brief, 
requires HCT/P establishments that manufacture non-reproductive HCT/Ps 
described in Sec.  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. Form FDA 
3486 is used to submit BPD reports and HCT/P deviation reports.
    Respondents to this collection of information are (1) licensed 
manufacturers of biological products other than human blood and blood 
components, (2) licensed manufacturers of blood and blood components 
including Source Plasma, (3) unlicensed registered blood 
establishments, (4) transfusion services, and (5) establishments that 
manufacture non-reproductive HCT/Ps regulated solely under section 361 
of the PHS Act as described in Sec.  1271.10. The number of respondents 
and total annual responses are based on the BPD reports and HCT/P 
deviation reports FDA received in fiscal year 2015. The number of 
licensed manufacturers and total annual responses under Sec.  600.14 
include the estimates for BPD reports submitted to both CBER and CDER. 
Based on the information from industry, the estimated average time to 
complete a deviation report is 2 hours, which includes a minimal one-
time burden to create a user account for those reports submitted 
electronically. The availability of the standardized report form, Form 
FDA 3486, and the ability to submit this report electronically to CBER 
(CDER does not currently accept electronic filings) further streamlines 
the report submission process.
    CBER has developed a Web-based addendum to Form FDA 3486 (Form FDA 
3486A) to provide additional information when a BPD report has been 
reviewed by FDA and evaluated as a possible recall. The additional 
information requested includes information not contained in the Form 
FDA 3486 such as: (1) Distribution pattern; (2) method of consignee 
notification; (3) consignee(s) of products for further manufacture; (4) 
additional product information; (5) updated product disposition; and 
(6) industry recall contacts. This information is requested by CBER 
through email notification to the submitter of the BPD report. This 
information is used by CBER for recall classification purposes. At this 
time, Form FDA 3486A is being used only for those BPD reports submitted 
under Sec.  606.171. CBER estimates that 5 percent of the total BPD 
reports submitted to CBER under Sec.  606.171 would need additional 
information submitted in Form FDA 3486A. CBER further estimates that it 
would take between 10 to 20 minutes to complete Form FDA 3486A. For 
calculation purposes, CBER is using 15 minutes.
    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.
    In the Federal Register of June 7, 2016 (81 FR 36550), we published 
a 60-day notice requesting public comment on the proposed extension of 
this collection of information. 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.
    FDA is appreciative of this feedback. At this time, however, 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 
integrate barcode or other technologies that facilitate or otherwise 
improve reporting, we must ensure that upgrades are compatible with our 
existing system.
    FDA estimates the burden of this collection of information as 
follows:

                                                      Table 1--Estimate Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                         Number of
      21 CFR section; activity         FDA Form No.      Number of     responses per   Total annual       Average burden per response       Total hours
                                                        respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
600.14; Reporting of BPDs by                    3486             102            5.99             611  2.................................           1,222
 licensed manufacturers.
606.171; Reporting of product                   3486           1,738           26.34          45,774  2.................................          91,548
 deviations by licensed
 manufacturers, unlicensed
 registered blood establishments,
 and transfusion services.
1271.350(b); HCT/P deviations.......            3486              97            2.64             256  2.................................             512
Web-based Addendum..................       \2\ 3486A              87           26.31           2,289  0.25 (15 minutes).................             572
                                     ----------------------------------------------------------------                                    ---------------
    Total...........................  ..............  ..............  ..............  ..............  ..................................          93,854
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ 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).



[[Page 79506]]

    Dated: November 7, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-27259 Filed 11-10-16; 8:45 am]
 BILLING CODE 4164-01-P


