Department of Health and Human Services May 12, 2021 – Federal Register Recent Federal Regulation Documents

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled ``E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials.'' The guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The guidance clarifies, updates, and extends the guidance for industry ``E9 Statistical Principles for Clinical Trials'' issued in September 1998 in two main areas. Concerning estimands, it provides a framework for discussion of how the aims of a trial relate to the proposed statistical analysis. Concerning sensitivity analysis, it discusses how to use additional analyses to address concerns about the validity of assumptions underlying the main analysis. The guidance is intended to better align the choice of statistical methods with questions of regulatory importance and so to improve the reliability of decisions about and representations of the effects of medical products. The guidance replaces the draft guidance issued on October 31, 2017.

On May 28, 2010, the Office of Management and Budget (OMB) issued Paperwork Reduction Act (PRA) guidance \1\ related to the ``generic'' clearance process. Generally, this is an expedited process by which agencies may obtain OMB's approval of collection of information requests that are ``usually voluntary, low-burden, and uncontroversial collections,'' do not raise any substantive or policy issues, and do not require policy or methodological review. The process requires the submission of an overarching plan that defines the scope of the individual collections that would fall under its umbrella. On October 23, 2011, OMB approved our initial request to use the generic clearance process under control number 0938-1148 (CMS-10398). It was last approved on April 26, 2021, via the standard PRA process which included the publication of 60- and 30-day Federal Register notices. The scope of the April 2021 umbrella accounts for Medicaid and CHIP State plan amendments, waivers, demonstrations, and reporting. This Federal Register notice seeks public comment on one or more of our collection of information requests that we believe are generic and fall within the scope of the umbrella. Interested persons are invited to submit comments regarding our burden estimates or any other aspect of this collection of information, including: The necessity and utility of the proposed information collection for the proper performance of the agency's functions, the accuracy of the estimated burden, ways to enhance the quality, utility and clarity of the information to be collected, and the use of automated collection techniques or other forms of information technology to minimize the information collection burden.

As stipulated by the Federal Advisory Committee Act, the Department of Health and Human Services (HHS) is hereby giving notice that a meeting is scheduled to be held for the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB). The meeting will be open to the public via WebEx and teleconference; a pre- registered public comment session will be held during the meeting. Pre- registration is required for members of the public who wish to attend the meeting via WebEx/teleconference. Individuals who wish to send in their written public comment should send an email to CARB@hhs.gov. Registration information is available on the website https:// www.hhs.gov/paccarb and must be completed by June 25, 2021. Additional information about registering for the meeting and providing public comment can be obtained at https://www.hhs.gov/paccarb on the Meetings page.

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled ``Qualified Infectious Disease Product DesignationQuestions and Answers.'' The Food and Drug Administration Safety and Innovation Act (FDASIA) created incentives for the development of antibacterial and antifungal drug products that treat serious or life-threatening infections. The purpose of this final guidance is to provide a resource for information on FDA's policies and procedures related to the designation of a qualified infectious disease product (QIDP). This guidance finalizes the draft guidance of the same name issued on January 30, 2018.

This notice announces the intention of the Agency for Healthcare Research and Quality (AHRQ) to request that the Office of Management and Budget (OMB) approve the proposed information collection project ``Patient Safety Organization Certification for Initial Listing and Related Forms, Patient Safety Confidentiality Complaint Form, and Common Formats.''

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled ``S11 Nonclinical Safety Testing in Support of Development of Pediatric Pharmaceuticals.'' The guidance was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), formerly the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. The guidance recommends international standards for the nonclinical safety studies recommended to support the development of pediatric medicines. The guidance provides a weight of evidence approach to determine when nonclinical toxicity studies may be recommended in juvenile animals. If such studies are recommended, the guidance provides appropriate study designs. The guidance is intended to promote harmonization of recommendations for such studies and should facilitate the timely conduct of pediatric clinical trials and reduce the use of animals in accordance with the 3R (replace/reduce/refine) principles. Tissue engineered products, gene and cellular therapies, and vaccines are excluded from the scope of this guidance. The guidance replaces the draft guidance issued on February 1, 2019.

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled ``M9 Biopharmaceutics Classification System-Based Biowaivers.'' The guidance was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), formerly the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. The guidance provides recommendations to support the biopharmaceutics classification of drug substances and the Biopharmaceutics Classification System (BCS)-based waiver of the in vivo bioequivalence (BE) study requirement for certain drug products. The guidance is intended to avoid or reduce the need for human BE trials based on extensive in vitro characterization of the drug substance and drug product properties. The guidance replaces the existing FDA guidance issued December 26, 2017, entitled ``Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System.'' The guidance also finalizes the draft ICH guidance, ``M9 Biopharmaceutics Classification System-Based Biowaivers,'' issued on October 26, 2018.