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8 BioPharm International eBook September 2019 www.biopharminternational.com Regulatory Sourcebook Regulatory Guidance Update "This series of guidance docu- ments is intended to facilitate the advancement and use of systematic approaches to collect and use robust and meaningful patient and care- giver input that can better inform medical product development and regulatory decision making," FDA said in the announcement. On July 30, 2019, FDA issued draft guidance that answers questions regarding priority review vouch- ers for certain rare pediatric disease treatments that meet criteria of the Food, Drug, & Cosmetic Act (FD&C Act) (2). As part of the FD&C Act, FDA may give special incentives to companies for the development of treatments for rare pediatric dis- eases. This draft guidance revises a previous draft guidance and clari- fies the qualifications and process for requesting priority review vouchers. Specifically, the guidance gives detailed answers to questions regard- ing the definition of a rare pediat- ric disease, eligibility requirements, a sponsor's responsibilities after approval of an application, desig- nation information requests, the submission process, marketing appli- cations, and use and transfer of a rare pediatric disease priority review voucher. REGULATORY SUBMISSIONS Guidance released on July 16, 2019 describes how applicants should organize the content they submit to the agency electronically (3). The guidance applies to all submission types under section 745A(a) of the FD&C Act. The guidance also refer- ences technical specification docu- ments and the Electronic Common Technical Document Conformance (eCTD) Guide. Specifically, the guid- ance implements the electronic submission of content submitted in new drug applications (NDAs), abbreviated new drug applications (ANDAs), certain biologics license applications (BLAs), and certain investigational new drug applica- tions (INDs) to the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). A previous version of this guid- ance, published in May 2015, indi- cated that NDAs, BLAs, ANDAs, and master files were to be submitted electronically in eCTD format start- ing on May 5, 2017 (May 5, 2018, for commercial INDs). In response to industry concerns, however, FDA extended the implementation date for drug master files (DMFs) to May 5, 2020. This new revision modi- fies previous versions by including exemptions for Type III DMFs. The guidance has also been updated to include the criteria identifying those types of submissions that may qualify for a long-term or short-term waiver from the eCTD submission requirement and instructions on how to submit a waiver request. FDA published draft guidance on July 11, 2019 for sponsors of new drug applications and biologics license applications on how to apply population pharmacokinetic (popu- lation PK) analysis, which is used in therapeutic individualization such as tailored dosing. Population PK data collection and analysis may alleviate the need for postmarketing require- ments or postmarketing commit- ments, according to FDA (4). The guidance lists common appli- cations of population PK analysis to provide sponsors with illustrative examples. FDA provides data and model requirements, recommen- dations on drug labeling based on population PK analysis, and the format and content of popu- lation PK reports. Specifically, the guidance discusses selecting dos- ing regimens, sample sizing and scheme requirements, exposure metrics, pediatric study designs, and drug–drug interactions. Data topics discussed include study sub- jects, sampling schedules, prelim- inary examination of data, model development and validation, and simulations based on population PK models. FDA published the final version of its REMS guidance document, Risk Evaluation and Mitigation Strategies: Modifications and Revisions Guidance for Industry, on July 9, 2019 (5). The guidance provides information on types of approved risk evaluation and mitigation strategies (REMS) and how applicants should submit changes to an approved REMS. The guidance also clarifies the differ- ences between modifications of a REMS and revisions of a REMS. FDA timeframes for assessing R EMS changes—including rev i- sions, minor modifications, major modifications, modifications due to safety labeling changes, and mul- tiple types of REMS changes—are also included in the document. An appendix provides detailed submis- sion procedures. The guidance applies to all types of REMS but does not address addi- tional submission procedures that may apply to application holders proposing changes to a shared sys- tem and that use a DMF for their REMS submission. In July, FDA published guidance on the content development and format of Instructions-for-Use docu- ments (IFUs) to be submitted with a NDA or a BLA (6). The guidance was written to help applicants develop consistent content and formats across IFUs that will make patient information regarding complicated or detailed use instructions easy to understand. The guidance applies to human prescription drugs, biological prod- ucts, and drug–device or biologic– device combination products. It does not apply to labeling for standalone medical devices legally marketed