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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

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Food and Drug Administration, HHS.




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).


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


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 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.

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FDA PRA Staff, Office of Operations, Food and Drug Administration, Three White Flint North, 10A63, 11601 Landsdown St., North Bethesda, MD 20852,

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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 Start Printed Page 79505reportable 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, § 1271.350(b) (21 CFR 1271.350(b)), in brief, 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. 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 § 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 § 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 § 606.171. CBER estimates that 5 percent of the total BPD reports submitted to CBER under § 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

21 CFR section; activityFDA Form No.Number of respondentsNumber of responses per respondentTotal annual responsesAverage burden per responseTotal hours
600.14; Reporting of BPDs by licensed manufacturers34861025.9961121,222
606.171; Reporting of product deviations by licensed manufacturers, unlicensed registered blood establishments, and transfusion services34861,73826.3445,774291,548
1271.350(b); HCT/P deviations3486972.642562512
Web-based Addendum2 3486A8726.312,2890.25 (15 minutes)572
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 × 0.05 = 87) and total annual responses to CBER (45,774 × 0.05 = 2,289).
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Dated: November 7, 2016.

Leslie Kux,

Associate Commissioner for Policy.

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[FR Doc. 2016-27259 Filed 11-10-16; 8:45 am]