2021-13968. Agency Information Collection Activities; Proposed Collection; Comment Request; Postmarketing Adverse Experience Reporting and Recordkeeping for Drug and Biological Products

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA, Agency, or we) is announcing an opportunity for public comment on the proposed collection of certain information by the Agency. Under the Paperwork Reduction Act of 1995 (PRA), Federal Agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on postmarketing reporting and recordkeeping of adverse experiences for drug and biological products.

DATES:

Submit either electronic or written comments on the collection of information by August 30, 2021.

ADDRESSES:

You may submit comments as follows. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before August 30, 2021. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of August 30, 2021. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date.

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2021-N-0515 for “Postmarketing Adverse Experience Reporting and Recordkeeping for Drug and Biological Products.” Received comments, those filed in a timely manner (see ADDRESSES), will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/​content/​pkg/​FR-2015-09-18/​pdf/​2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT:

Domini Bean, Office of Operations, Food and Drug Administration, Three White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-5733, [e-mail].

SUPPLEMENTARY INFORMATION:

Under the PRA (44 U.S.C. 3501-3521), Federal Agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. “Collection of information” is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document.

With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

Postmarketing Adverse Experience Reporting and Recordkeeping for Drug and Biologics Products

OMB Control Number 0910-0230—Extension

This information collection supports statutory provisions set forth in the Federal Food, Drug, and Cosmetic Act (FD&C Act) regarding the monitoring of FDA-regulated products. Specifically, FDA must be promptly informed of adverse experiences associated with the use of marketed drugs, including human drugs and biological products. Regulations in §§ 310.305 and 314.80 (21 CFR 310.305 and 314.80) implement reporting and recordkeeping requirements that enable FDA to take action to protect the public health from adverse drug experiences. All applicants who have received marketing approval for drug products are required to report serious, unexpected adverse drug experiences (15-day “Alert reports”), as well as followup reports (§ 314.80(c)(1)) to FDA. This includes reports of all foreign or domestic adverse experiences as well as those based on information from applicable scientific literature and certain reports from postmarketing studies. Section 314.80(c)(1)(iii) pertains to such reports submitted by nonapplicants.

Under § 314.80(c)(2), applicants must provide periodic reports of adverse drug experiences. For the reporting interval, a periodic report includes reports of serious, expected adverse drug experiences, all nonserious adverse drug experiences, and an index of these reports; a narrative summary and analysis of adverse drug experiences; an analysis of the 15-day Alert reports submitted during the reporting interval; and a history of actions taken because of adverse drug experiences. Under § 314.80(j), applicants must keep for 10 years records of all adverse drug experience reports known to the applicant.

For marketed prescription drug products without approved new drug applications (NDAs) or abbreviated new drug applications (ANDAs), manufacturers, packers, and distributors are required to report to FDA serious, unexpected adverse drug experiences as well as followup reports (§ 310.305(c)). Section 310.305(c)(5) pertains to the submission of followup reports to reports forwarded to the manufacturers, packers, and distributors by FDA. Under § 310.305(g), each manufacturer, packer, and distributor shall maintain for 10 years records of all adverse drug experiences required to be reported.

Section 760 of the FD&C Act (21 U.S.C. 379aa) also provides for mandatory safety reporting for over-the-counter (OTC) human drug products not subject to applications approved under section 505 of the FD&C Act (21 U.S.C. 355) (NDAs or ANDAs). These requirements apply to all OTC drug products marketed without an approved application, including those marketed under the OTC Drug Monograph Review process (whether or not subject to a final monograph), those marketed outside the monograph system, and including those that have been discontinued from marketing but for which a report of an adverse event was received. Under 21 CFR 329.100, respondents must submit reports according to section 760 of the FD&C Act in an electronic format.

To assist respondents with implementation of section 760 of the FD&C Act, FDA developed the guidance for industry entitled “Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed Without an Approved Application,” available at https://www.fda.gov/​media/​77193/​download. The guidance document discusses what should be included in a serious adverse drug event report submitted under section 760(b)(1) of the FD&C Act, including how to submit these reports and followup reports under section 760(c)(2) of the FD&C Act.

Section 760(e) of the FD&C Act also requires that responsible persons maintain records of nonprescription drug adverse event reports, whether the event is serious or not, for a period of 6 years. FDA's guidance recommends that respondents maintain records of efforts to obtain the minimum data elements for a report of a serious adverse drug event and any followup reports.

The primary purpose of FDA's adverse drug experience reporting system is to enable identification of signals for potentially serious safety problems with marketed drugs. Although premarket testing discloses a general safety profile of a new drug's comparatively common adverse effects, the larger and more diverse patient populations exposed to the marketed drug provide the opportunity to collect information on rare, latent, and long-term effects. Signals are obtained from a variety of sources, including reports from patients, treating physicians, foreign regulatory agencies, and clinical investigators. Information derived from the adverse drug experience reporting system contributes directly to increased public health protection because the information enables FDA to make important changes to the product's labeling (such as adding a new warning), to make decisions about risk evaluation and mitigation strategies or the need for postmarketing studies or clinical trials and, when necessary, to initiate removal of a product from the market.

In addition, this information collection includes an International Council for Harmonisation (ICH) guidance for industry entitled “Providing Postmarketing Periodic Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report),” available at https://www.fda.gov/​media/​85520/​download. The guidance describes the conditions under which applicants may use the ICH3 E2C(R2) Periodic Benefit-Risk Evaluation Report format for certain types of adverse event reporting. FDA regulations in §§ 314.80(c)(2) and 600.80(c)(2) (21 CFR 600.80(c)(2)) require applicants to submit postmarketing periodic safety reports for each approved application. The reports must be submitted quarterly for the first 3 years following the U.S. approval date and annually thereafter and must contain the information described in §§ 314.80(c)(2)(ii) and 600.80(c)(2)(ii) (the information collection associated with 21 CFR part 600—Biological Products, is approved under OMB control number 0910-0308). The Agency guidance assists respondents with satisfying the regulatory requirements in an alternative format, noting that the process differs depending on whether an applicable periodic safety update report (PSUR) waiver is in place. The information collection burden for waivers of a PSUR are currently approved in OMB control number 0910-0771; however, it is being consolidated with this information collection for administrative efficiency.

Similarly, the information collection accounts for burden that may be applicable to the guidance document, “Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic,” available at https://www.fda.gov/​media/​72498/​download. In response to the Coronavirus Disease 2019 public health emergency, we revised the Agency guidance document, “, to provide recommendations for recordkeeping applicable to any pandemic, not just influenza, including recommendations for planning, notification, and documentation for continuity of operations for firms that report postmarketing adverse events during any pandemic.

Respondents to this collection of information are (1) manufacturers, packers, distributors, and applicants of FDA-regulated drug and biologic products; (2) manufacturers, packers, and distributors of marketed prescription drug products without an FDA-approved application; and (3) manufacturers, packers, and distributors of marketed nonprescription drug products, including OTC drug products marketed without an approved application, OTC drug products marketed under the OTC Drug Monograph Review process (whether subject to a final monograph or not), and drug products marketed outside the monograph system.

FDA estimates the burden of this collection of information as follows:

Table 1—Estimated Annual Reporting Burden ¹

21 CFR section or type of respondent and activity	Number of respondents	Number of responses per respondent	Total annual responses	Average burden per response	Total hours
310.305(c)(5)	3	1	3	1	3
314.80(c)(1)(iii)	5	1	5	1	5
314.80(c)(2)	820	17.32	14,202	60	852,120
Reports of serious adverse drug events (§ 329.100)	285	690	196,650	6	1,179,900
Applicants that have a PSUR waiver for an approved application	55	3.4	187	1	187
Applicants that do not have a PSUR waiver for an approved application	29	2.3	67	2	134
Notifying FDA when normal reporting is not feasible	350	1	350	8	2,800
Total 2			211,464		2,035,149
1 The reporting burden for §§ 310.305(c)(1), (2), and (3), and 314.80(c)(1)(i) and (ii) is covered under OMB control number 0910-0645.
2 The capital costs or operating and maintenance costs associated with this collection of information are approximately $25,000 annually.

Table 2—Estimated Annual Recordkeeping Burden ¹

21 CFR section or FD&C Act section and activity	Number of recordkeepers	Number of records per recordkeeper	Total annual records	Average burden per recordkeeping	Total hours
310.305	25	1	25	16	400
314.80(j)	325	2,025	658,240	16	10,531,840
Recordkeeping of nonprescription drug adverse event reports (Section 760(e)(1) of the FD&C Act)	300	885.6667	265,700	8	2,125,600
Adding Adverse Event report planning to Continuity of Operations Plans	100	1	100	50	5,000
Maintaining documentation of pandemic conditions and resultant high absenteeism	350	1	350	8	2,800
Maintaining records to identify what reports have been stored and when the reporting process was restored	350	1	350	8	2,800
Total 2			924,765		12,668,440
1 There are no capital costs or operating costs associated with this collection of information.
2 There are maintenance costs of approximately $22,000 annually.

The information collection reflects adjustments resulting in an overall decrease in burden hours and an increase in annual responses. We believe these adjustments reflect expected fluctuations in burden and invite comment on our assumptions.

Dated: June 25, 2021.

Lauren K. Roth,

Acting Principal Associate Commissioner for Policy.