as “PV” and “drug safety” will bring interesting news, press releases, blog addresses, and sites (https://www.google.com/alerts).
It is easy to spend one’s entire day just reading blogs and news on the Internet. A good compromise would be to find one or two sources that provide the updates the reader needs for his or her work. Attending a conference on drug safety once or twice a year is also valuable for both updates and networking.
CHAPTER
8
The United States Food and Drug Administration
The “grand daddy” of drug safety “regulatory agencies” dates back to 18th century Japan, when the eighth shogun, Yoshimune Tokugawa (1716–1745), upon recovering from an illness, awarded 124 medicinal traders in Osaka special privileges to examine medicines throughout the country. However, the safety of the medicines was difficult to guarantee despite these efforts. A shrine in Osaka, called Shinno-san, was created and dedicated to Shinno, the guardian of the pharmaceutical industry and the divine founder of medicine from China. This information was found at the Osaka tourism website.
Introduction
Since the time of the shoguns, multiple other government authorities have become involved in drug safety. Very often governments have responded to misbehavior or tragedies by strengthening laws intended to address perceived shortcomings in protecting patient safety. In the past 30 or so years, the number of organizations devoted to drug safety has increased markedly, in particular, outside the United States. This chapter is focused on key activities of the US Food and Drug Administration (FDA), which regulates biopharmaceutical products and medical devices for human use. FDA also regulates certain foods and veterinary products, for a total of more than US$ 2.4 trillion worth of products each year. The latter topics are outside the scope of this chapter.
The FDA is a complex organization with over 15,000 employees strategically posted at US domestic locations and overseas stations. Several distinct parts of FDA handle safety matters. The largest areas touching drug safety reside within the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). In addition, within CDER and CBER, functions are generally split between pre- and post-marketing regulatory activities.
The FDA has undergone and continues to undergo major changes following various scientific, public, and political controversies, drug withdrawals, investigations, and changes in the law. This chapter will summarize the key functions that deal with medical product safety and will outline some of the initiatives that will undoubtedly lead to further advances in “regulatory science” in the coming years.
Center for Drug Evaluation and Research
This is the prime (and largest) center in the FDA for handling the safety of biopharmaceutical products in the US. The Center for Drug Evaluation and Research (CDER) handles new drugs from the IND stage (when a product first moves into human study) to the evaluation of the NDA/ANDA or BLA for approval or rejection of the request to market the product in the United States. A separate group within CDER then evaluates the post-marketing safety of the product on a continuous basis. Although simple in theory, the actual practice is complex and has evolved over time. It continues to change, often in response to Congressional mandate, and should be viewed as a work in progress.
The FDA organization chart is posted online and is quite useful. It gives names, addresses, and contact information on the FDA organization and key personnel (www.fda.gov). The chart is updated regularly with changes (see below). When this chapter was written, there were 45 “offices” in CDER covering many areas, including biotechnology, new medical product evaluation, counterterrorism, pediatric drug development, generic drugs (including biosimilars), compliance, biostatistics, prescription drug promotion, translational sciences, and, of course, product safety.
See CDER’ s website (www.fda.gov/cder). In 2017, there were 33 advisory committees made up of external members, who provide consultation and give expert and consumer advice to the FDA. The FDA generally follows an advisory committee’s recommendation, but is not bound to do so. There is an advisory committee on Drug Safety and Risk Management that evaluates new products and safety concerns across the product lifecycle continuum.
The FDA reorganizes periodically. As of mid-2018, the structure was as follows: the Office of the CDER Center Director has under it approximately 32 offices, including the Office of Surveillance and Epidemiology (OSE). OSE is considered a safety “SuperOffice”, available for consultation on safety concerns across all of FDA, not only CDER-regulated products. In 2018, were two Offices and six divisions in OSE:
Division of Epidemiology I & II (two divisions): The staff conducts active surveillance using the Sentinel System and also conducts epidemiologic studies using observational data sources. An increasingly important activity is the review of epidemiologic study protocols, which are conducted by applicants as post-marketing commitments or post-marketing requirements. The Division evaluates various post-marketing surveillance tools that may be incorporated into non-routine risk minimization strategies, such as patient registries and restricted distribution systems. They estimate the public health impact of safety signals by evaluating digital claims databases, healthcare datasets, and the published literature, etc.
Division of Risk Management: The staff handles data resources, risk communication, and outcomes and effectiveness research components of drug safety risk management programs (i.e., Risk Evaluation and Mitigation Strategies (REMS)). This division oversees MedWatch, risk communication research, and activities such as Medication Guides, Patient Packet Inserts, and pharmacy information surveys, and international regulatory liaison activities (such as videoconferencing) for all drug and post-marketing safety issues for therapeutic biologics.
In 2005, the FDA created a new Drug Safety Oversight Board (DSB), which advises the CDER Center Director on handling and communicating important and emerging drug safety issues. The board meets monthly and is composed of representatives from three FDA Centers and six other federal government agencies: the Agency for Healthcare Research and Quality (AHRQ), Centers for Disease Control and Prevention (CDC), Department of Defense (DOD), Indian Health Service (IHS), National Institutes of Health (NIH), and Department of Veterans Affairs (VA). The DSB provides scientific and regulatory recommendations on drug safety and communication issues and policies to the senior FDA management on the following: