William Gregory

Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition)


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with the applicant that usually last no more than 30 days, after which time the FDA may force the applicant to make labeling changes that the agency “deems appropriate”. The FDA has used this new authority on several occasions, including the addition of a black box regarding an increased risk of death in elderly patients treated with antipsychotics for dementia, the addition of a black box regarding an increased risk of tendon injury with fluoroquinolone antibiotics, and the addition of a black box regarding the risk of histoplasmosis and other fungal infections with TNF alpha-blockers.

      Other sections deal with the following:

      ImagesPre-approval review of proprietary names;

      ImagesModernization of information technology;

      ImagesMedical devices, including enhancements in the device review program, inspections by third parties, new requirements for certain single-use devices, and user fees;

      ImagesMore studies in the pediatric population;

      ImagesDevelopment of products for tropical diseases, rare diseases, and other “neglected” diseases;

      ImagesThe Reagan–Udall Foundation, made up of senior advisers from outside the federal government, to advise FDA on innovation and enhanced food and drug safety. (the foundation was not initially funded by Congress, but sustainability models are evolving):

      ImagesMore transparency regarding possible conflicts of interest is required for potential Advisory Committee participation; and

      ImagesThe clinical trials database was expanded.

      The 21st Century Cures Act was passed by Congress and then signed into law on December 13, 2016. The stated intent of this legislation was to accelerate innovative medical product development and get advances to patients who need these products more efficiently.

      The law encourages FDA to consider the perspectives of patients in FDA’ s decision-making process in medical product development. This encompasses innovation in drugs, therapeutic biologics, vaccines, and medical devices. The legislation encourages new approaches to scientifically-sound clinical trial designs and clinical outcome assessments.

      The law also provides new authority to facilitate recruitment and retention of a broad base of highly qualified personnel to execute these innovative programs. The legislation contemplates new approaches to expedite innovation, including the following:

      ImagesRegenerative Medicine Advanced Therapy (RMAT): This describes an expedited option for certain eligible biologics products;

      ImagesThe Breakthrough Devices Program: This is intended to speed the review of certain innovative medical devices.

      In addition, this legislation directs FDA to create cross-center initiatives to coordinate activities in strategic areas, e.g., diseases with a major public health impact. These activities cascade to the regulation of combination products. It also establishes an FDA Oncology Center of Excellence (OCE), which supports patient-centered decision-making and an integrated approach to the evaluation of drugs, biologics, and devices medical products for the treatment of cancer. The OCE works with centers and offices across the FDA.

      This Act authorized an additional US$ 500 million for FDA over 9 years to implement the legal requirements.

      FDA Reauthorization Act (FDARA) was signed into law on August 18, 2017 and it extended the user fee programs for drugs, medical devices, generic drugs, and biosimilar biological products through FY 2022 (and added other obligations). It reauthorized PDUFA for the fifth time. In addition, the Medical Device User Fee Amendments (MDUFA) was reauthorized for the third time, and included both the Generic Drug User Fee Amendments (GDUFA) and the Biosimilar User Fee Act (BsUFA) for the first time.

      Selected provisions of FDARA include the following:

      ImagesAn enhanced ability to capture patient preferences in drug development;

      ImagesFlexibility to inspect medical device facilities based on risk, while encouraging predictability and transparency in the inspection process;

      ImagesA focus on treatment of rare diseases (especially in pediatrics);

      ImagesAdditional resources for review of breakthrough therapies;

      Images“Real world evidence” to inform decision-making (including use of the Sentinel System);

      ImagesEnhanced partnerships with patients;

      ImagesMore flexibility in the regulatory pathway for certain medical device accessories;

      ImagesNew opportunities for scientific advice on surrogate endpoints;

      ImagesCross-center coordination of combination product review;

      ImagesEnhanced hiring and retention of well-qualified staff.

      Bottom line: The reauthorization of PDUFA, MDUFA, GDUFA, and BsUFA support FDA’s organizational ability to focus on improved health outcomes while promoting biomedical innovation.

      Launched by FDA in 2008 as a result of 2007 legislation, the Sentinel System is a US National medical product safety monitoring system that taps into electronic medical records across the country. It is an active electronic safety surveillance system that strengthens FDA’s ability to monitor the safety of marketed medical products. The program began as a pilot, which reached a milestone of 100 million covered lives by 2011. As of June 2018, the Agency had 17 distributed data partners with 178 million covered members, each of whom had pharmacy and medical coverage. It is a large system with longitudinal medical records and an analytic center in Boston which handles coordination among the data partners. Data partners retain control of the medical records to protect privacy and maintain security; FDA prepares analytic queries to explore questions, but they do not have a centralized data repository for this system. Queries can be developed by FDA and anonymized results from more than 178 million covered lives can be obtained from