From aspirin to cancer treatments, CDER has oversight responsibilities for prescription, over-the-counter, and generic drugs. The products differ in significant ways:

Before President Roosevelt signed the Federal Food, Drug, and Cosmetic (FD&C) Act of 1938 into law, manufacturers did not have to show that a drug was safe before it could be marketed. There were no scientific requirements for testing or approval nor were there any data submission requirements for companies marketing drugs. The FD&C Act of 1938 established the "safety" standards still in use today and subjected new drugs to premarket safety evaluation for the first time with two key changes:

The applicant must submit an integrated summary of all available information about the safety of the drug product, including pertinent animal data, demonstrated or potential adverse effects of the drug, clinically significant drug-drug interactions, and other safety considerations, such as data from epidemiologic studies of related drugs. The safety data must be presented by gender, age, and racial subgroups. When appropriate, safety data from other subgroups of the population of patients treated also must be presented, such as for patients with renal failure or patients with different levels of severity of the disease. A description of any statistical analyses performed in evaluating safety data should also be included [9].

Since 1962, the FDA has overseen substantial refinements to the broad legal requirement that post-1962 new drugs be approved on the basis of "adequate and well-controlled" studies [11]. With regard to quantity, it has been the FDA's position that Congress generally intended to require at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness. The FDA's position is based on the language in the statute and the legislative history of the 1962 amendments. Section 505(d) of the Act uses the plural form in defining "substantial evidence" as "adequate and well-controlled investigations, including clinical investigation." Section 505(b) of the Act, which lists the contents of an NDA, also uses the plural "investigations." Language in a Senate report suggested that the phrase "adequate and well-controlled investigations" was designed not only to describe the quality of the required data but also the "quantum" of required evidence [12]. The three main goals of "adequate and well-controlled investigations" are to ensure:

The development process for drugs involves five basic steps:

During a new drug's early development process, the sponsor's primary goal is to determine if the drug is reasonably safe for human use and if its course of action, or pharmacologic activity, justifies commercial development. Preclinical studies are typically not very large but must provide detailed information on dosing and toxicity levels of IND products. The sponsor has three options for fulfilling this requirement [16]:

INDs can fall into either a commercial or research (non-commercial) category. Commercial INDs are typically submitted by companies that hope to gain marketing approval for a new pharmaceutical product. There are three types of research INDs [17]:

All IND applications must include:

Phase 3

Study Participants: Typically, 300 to 3,000 volunteers who have the disease or condition

Expedited review means the FDA can hasten its review process to help the product reach patients sooner if the new drug addresses an unmet medical need and treats a serious or life-threatening condition[21]. Expediting the availability of life-changing drugs benefits everyone. This is especially true if a drug becomes the first available treatment for a particular condition or has advantages over existing treatments[6]. In 2016, for example, CDER approved the first ever treatments for spinal muscular atrophy and Duchenne muscular dystrophy. An estimated 60% of novel drugs approved in 2019–2022 benefited from one of the FDA's expedited review programs (Table 1)[22,23]:

The authority to designate a breakthrough product was created in a 2009 statute. A "breakthrough" therapy may sound like a ground-breaking medical discovery or advancement, but only preliminary clinical evidence is necessary to show that a breakthrough drug may substantially improve existing therapies on at least one endpoint. The breakthrough therapy designation aims to speed the development and review of drugs intended to treat a serious or life-threatening disease alone or with other drugs.

Because the breakthrough-therapy designation intends to develop evidence supporting drug approval as efficiently as possible, the FDA does not anticipate that designation requests will be made after submission of the original biologic license application, NDA, or supplement. Designation requests should be received by the FDA before the end of phase of Phase 2 meetings. FDA will respond to these requests within 60 days [15].

Every drug marketed in the United States goes through the FDA's detailed review process. In 1992, however, FDA created a new two-tiered system aimed to improve drug review times: standard review (10 months) and priority review (6 months). A drug can earn priority review designation if it treats a serious or life-threatening condition and would significantly improve the safety or effectiveness of the treatment, diagnosis, or prevention of that condition if approved. Significant improvement may be demonstrated by [30]:

The FDAAA also gave the FDA new authorities and responsibilities to enhance drug safety. One of its provisions gave the FDA the authority to require a Risk Evaluation and Mitigation Strategy (REMS) from sponsors to ensure that the benefits of a drug or biologic product outweigh its risks. REMS are required risk management plans that use risk minimization strategies beyond the professional labeling to ensure that the benefits of certain prescription drugs outweigh their risks [33].

The MedWatch program is for health professionals and the public to voluntarily report serious reactions and problems with medical products, such as drugs and medical devices. MedWatch also ensures that new safety information is rapidly communicated to the medical community to improve patient care. All data contained on the MedWatch form will be entered into the FDA Adverse Event Reporting System (FAERS) database. The MedWatch page includes sections on how to report an adverse event, safety information, and publications.

The FAERS is a computerized information database designed to support the FDA's post-marketing safety surveillance program for all approved drug and therapeutic biologic products. The ultimate goal of FAERS is to improve the public health by providing the best available tools for storing and analyzing safety reports. The reports in FAERS are evaluated by a multidisciplinary staff of safety evaluators, epidemiologists, and other scientists in the CDER Office of Surveillance and Epidemiology to detect safety signals and to monitor drug safety. If a potential safety concern is identified in FAERS, further evaluation is performed, such as conducting studies using other large databases. Based on an evaluation of the potential safety concern, the FDA may take regulatory action to improve product safety and protect the public health, such as requiring changes to the drug's labeling. Drug safety labeling changes are published online.

A rare disease is defined as one that affects a limited number of people, specifically fewer than 200,000 people in the United States [38]. However, it is important to note that the term can be deceptive. There are approximately 7,000 different rare diseases, collectively affecting as many as 30 million people, or about 10% of the U.S. population. So, while the number of patients with any given rare disease may be small, the cumulative impact on public health is large.

Some patients may be eligible for use of an investigational medical product outside of a clinical trial. Expanded access is reserved for patients with serious or immediately life-threatening diseases or conditions who have no comparable or satisfactory alternative therapy and who seek access to potentially life-saving investigational drugs [32].

Under the FDA's current regulations for investigational drugs and biologics, there are three categories of expanded access [13]: