Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Providing Waiver-Related Materials in Accordance With the Guidance for Industry on Providing Post-Market Periodic Safety Reports in the International Conference on Harmonisation E2C(R2) Format

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) 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.

DATES:

Fax written comments on the collection of information by September 7, 2017.

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 0910-0771. Also include the FDA docket number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT:

Domini Bean, Office of Operations, Food and Drug Administration, Three White Flint North, 10A63, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-5733, 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.

Providing Waiver-Related Materials in Accordance With the Guidance for Industry on Providing Post-Market Periodic Safety Reports in the International Conference on Harmonisation E2C(R2) Format (Periodic Benefit-Risk Evaluation Report); OMB Control Number 0910-0771—Extension

The International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use issued, on November 15, 2012, the ICH harmonized tripartite guideline entitled “Periodic Benefit-Risk Evaluation Report (PBRER) E2C(R2)” (the PBRER guideline) (available at https://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html ). The PBRER guideline is intended to promote a consistent approach to periodic post-marketing safety reporting among the ICH regions, to enhance efficiency and reduce burden by reducing the number of reports generated for submission to the regulatory authorities. The PBRER is intended to provide a common standard for periodic reporting on approved drugs or biologics among the ICH regions.

FDA currently has OMB approval for the required submission of periodic adverse drug experience reports (PADER) for drugs subject to a new drug application (NDA) or an abbreviated new drug application (ANDA) (§ 314.80(c)(2) (21 CFR 314.80(c)(2)) (OMB control number 0910-0230), and for the required submission of periodic adverse experience reports (PAER) for drugs subject to a biologics license application (BLA) (§ 600.80(c)(2) (21 CFR 600.80(c)(2)) (OMB control number 0910-0308).

There is considerable overlap in the information required under §§ 314.80(c)(2) and 600.80(c)(2) and the information requested in a periodic safety report using the ICH E2C(R2) PBRER format. Applicants subject to periodic safety reporting requirements under FDA regulations could choose to continue to submit the reports as specified in those regulations, and would be permitted to submit reports in the PBRER format and submit reports as specified in FDA regulations with an approved waiver. Companies who submit periodic reports on the same drug to multiple regulators, including not only the United States, but, also the European Union, Japan, and regulators in other countries who have elected to adopt the ICH standards, may find it in their interest to prepare a single PBRER, rather than preparing multiple types of reports for multiple regulators. As a result, FDA, in the Federal Register of November 29, 2016 (81 FR 85976), announced the availability of the guidance for industry entitled “Providing Post-marketing Periodic Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report)” to indicate its willingness to accept post-market periodic safety reports using the ICH PBRER format in lieu of the specific reports described in FDA regulations.

Because FDA regulations in §§ 314.80(c)(2) and 600.80(c)(2) include specific requirements for periodic safety reports, in order for an applicant to submit an alternative report, such as the PBRER, for a given product, FDA must grant a waiver. Existing regulations permit applicants to request waivers of any post-marketing safety reporting requirement, and the information collections associated with such waiver requests generally are approved under existing control numbers. (See § 314.90(a), waivers for drugs subject to NDAs and ANDAs, approved under OMB control number 0910-0001, and § 600.90(a), waivers for products subject to BLAs, approved under OMB control number 0910-0308.) The November 29, 2016, guidance both explains conditions under which applicants that have previously received waivers to submit reporting information in the format of the previous ICH guidance would be permitted to apply those existing waivers to the submission of PBRERs, and also advises how applicants that have not previously obtained a waiver may submit waiver requests to submit the PBRER.

There are information collections proposed in the November 29, 2016, guidance that are related to waivers specifically to enable the submission of PBRERs, and these information collections are not already addressed under the approved control numbers covering waiver submissions and periodic safety reports generally. FDA has previously granted waiver requests, submitted under §§ 314.90(a) and 600.90(a), that allow applicants to prepare and submit reports using the periodic safety update report (PSUR) format described in FDA's 1996 and 2004 ICH E2C guidance. In accordance with the recommendations of the November 29, 2016, guidance, if an applicant already has a PSUR waiver in place for a given approved application, FDA will consider the existing PSUR waiver to allow the applicant to submit a PBRER instead of a PSUR because the PBRER replaces the PSUR for post-marketing periodic safety reporting for that application. The applicant would not need to submit a new waiver request unless the applicant wishes to change the frequency of reporting. FDA will consider requests to be waived of the quarterly reporting requirement but will not waive applicants of the annual reporting requirement.

If an applicant submits a PBRER in place of the PSUR and uses a different data lock point, the applicant should submit overlapping reports or submit a one-time PADER/PAER in order to cover the gap in reporting intervals. The applicant should submit notification to the application(s), indicating the change in data lock point and should include a description of the measures taken to ensure that there are no resulting gaps in reporting.

If an applicant submits a PBRER in place of the PSUR and uses a different reporting frequency for the PBRER than was used for the PSUR, the continued validity of the waiver will be conditioned on the submission of a PADER/PAER as needed to fulfill the reporting frequency requirement under FDA regulations. The applicant should submit a notification to the application(s), describing this change and the measures taken to ensure that the periodicity requirements are being met.

FDA expects approximately 187 waiver requests and notifications to include the additional information described previously in this document for using a different data lock point and/or for using a different reporting frequency when submitting a PBRER. FDA expects approximately 55 applicants to make these submissions, and we estimate that the time for submitting the additional information described previously would be on average approximately 1 hour for each waiver request or notification.

If an applicant does not have a PSUR waiver in place for an approved application, the applicant may submit a waiver request under § 314.90(a) or § 600.90(a) to submit a PBRER instead of the PADER/PAER. The applicant should submit a request to FDA for each approved application for which a waiver is requested, and a single waiver request letter can include multiple applications. Waiver requests should be submitted to each of the application(s) in the request, and may be submitted electronically or by paper as described in the November 29, 2016, guidance. Each PBRER waiver request should include the following information:

• The product name(s) and application number(s);
• a brief description of the justification for the request;
• the U.S. approval date for the product(s) and current reporting interval used;
• the reporting interval of the last PADER/PAER submitted for the product(s); and
• the data lock point that will be used for each PBRER. If a data lock point other than one aligned to the U.S. approval date is proposed, the applicant should describe how he/she will ensure that there are no gaps in reporting intervals (e.g., by submitting overlapping reports; submitting a one-time PADER/PAER to cover the gap period; or, if the gap is less than 2 months, extending the reporting interval of the final PADER/PAER to close the gap).
• The frequency for submitting the PBRER, as described in section IV.C of the April 8, 2013, draft guidance.
• The email address and telephone number for the individual who can provide additional information regarding the waiver request.

As explained earlier, existing regulations at § 314.90(a) or 600.90(a) permit applicants to request waivers of any post-marketing safety reporting requirement, and the information collections associated with such waiver requests generally are approved under OMB control numbers 0910-0001 and 0910-0308. FDA believes that the information submitted under numbers 1-4 and number 7 in the list in the previous paragraph is information that is typical of any waiver request regarding post-marketing safety reporting and is accounted for in the existing approved collections of information for waiver requests and reports. Concerning numbers 5 and 6, FDA expects approximately 67 waiver requests to include the additional information for using a different data lock point and/or for using a different reporting frequency when submitting a PBRER. FDA expects approximately 29 applicants to make these submissions, and we estimate that the time for submitting the additional information described in the previous paragraph would be on average approximately 2 hours for each waiver request.

In the Federal Register of May 23, 2017 (82 FR 23578), we published a 60-day notice requesting public comment on the proposed extension of this collection of information. No comments were received.

We therefore estimate the burden of this collection of information as follows: