|
| A) | generic drugs. | ||
| B) | prescription drugs. | ||
| C) | over-the-counter drugs. | ||
| D) | All of the above |
From aspirin to cancer treatments, CDER has oversight responsibilities for prescription, over-the-counter, and generic drugs. The products differ in significant ways:
Prescription drugs: Any drug products that require a prescriber's authorization to purchase
Generic drugs: A drug product that is equivalent to brand name products in terms of quality and performance
Over-the-counter drugs: Products available to consumers without a physician's prescription
| A) | 1908. | ||
| B) | 1938. | ||
| C) | 1962. | ||
| D) | 1983. |
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:
Premarket notification to the FDA: Any new drug must have submitted an NDA, which came into effect (essentially approved) after six months of submission, unless objected by the FDA.
Demonstration of safety: The FDA could refuse to approve the NDA due to safety or labeling issues.
| A) | Age | ||
| B) | Race | ||
| C) | Gender | ||
| D) | Sexual orientation |
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].
| A) | Bias minimization | ||
| B) | Ensuring a valid control group | ||
| C) | Limiting participation to specific populations | ||
| D) | Documentation of sufficient details to allow critical evaluation |
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:
A valid control group, whereby the control group is very similar to the test group so one can isolate the difference due to drug given
Bias minimization of the clinical trial (in how test and control group are selected, treated, observed, assessed, and analyzed)
Documentation of sufficient study details to allow a critical evaluation of whether the characteristics of an adequate and well-controlled study are present
| A) | clinical research. | ||
| B) | preclinical research. | ||
| C) | post-market safety monitoring. | ||
| D) | drug discovery and development. |
The development process for drugs involves five basic steps:
Drug discovery and development: Research for a new drug begins in the laboratory.
Preclinical research: Drugs undergo laboratory and animal testing to answer basic questions about safety.
Clinical research: Drugs are tested on people to make sure they are safe and effective.
FDA review: FDA teams thoroughly review all of the submitted data related to the drug and make a decision to approve or not to approve it.
FDA post-market safety monitoring: FDA monitors drug safety after products are available for use by the public.
| A) | are typically very large. | ||
| B) | should include all potential patient populations. | ||
| C) | cannot rely on data from previous clinical testing. | ||
| D) | must provide detailed information on dosing and toxicity levels. |
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]:
Compiling existing nonclinical data on past laboratory or animal studies on the compound
Compiling data from previous clinical testing or marketing of the drug in the United States or countries with similar populations
Conducting new preclinical studies designed to provide the necessary evidence to support the safety of administering the compound to humans
| A) | Treatment | ||
| B) | Investigator | ||
| C) | Experimental | ||
| D) | Emergency use |
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]:
Investigator IND: Submitted by a physician who initiates and conducts an investigation. The investigational drug is administered or dispensed under the physician's immediate direction. A physician might submit a research IND to propose studying an unapproved drug or to study an approved product for a new indication or in a new patient population.
Emergency use IND: Allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with federal regulations (21CFR, Sec. 312.23 or Sec. 312.20). It is also used for patients who do not meet the criteria of an existing study protocol or if no approved study protocol exists.
Treatment IND: Submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and FDA review occurs.
| A) | manufacturing information. | ||
| B) | clinical protocols and investigator information. | ||
| C) | preclinical data from animal pharmacology and toxicity studies. | ||
| D) | All of the above |
All IND applications must include:
Preclinical data from animal pharmacology and toxicity studies, including prior experience with the drug in humans, if possible
Manufacturing information ensuring the drug company can produce and supply consistent batches of the drug
Clinical protocols and investigator information, such as informed consent and institutional review board sign-off, detailing how clinical trials on humans would be designed to prevent exposure to unnecessary risks
| A) | 20 to 100 healthy volunteers. | ||
| B) | up to 200 people with the disease/condition. | ||
| C) | 300 to 3,000 volunteers who have the disease/condition. | ||
| D) | at least 10,000 healthy volunteers. |
| A) | 6% | ||
| B) | 30% | ||
| C) | 60% | ||
| D) | 90% |
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]:
Accelerated approval
Fast track
Breakthrough therapy
Priority review
| A) | priority review. | ||
| B) | accelerated approval. | ||
| C) | fast track designation. | ||
| D) | breakthrough therapy designation. |
SUMMARY DESCRIPTIONS OF DRUGS ELIGIBLE FOR EXPEDITED REVIEW
| Expedited Program | Characteristics of Eligible Drugs | ||||
|---|---|---|---|---|---|
| Fast track |
| ||||
| Breakthrough therapy |
| ||||
| Accelerated approval | A drug that treats a serious medical condition and generally provides a
meaningful advantage over available therapies. The drug demonstrates an effect on:
| ||||
| Priority review |
|
| A) | treat a condition for which there are no other approved treatments. | ||
| B) | be more effective than any other treatment approved for the disease/condition. | ||
| C) | exhibit high-quality evidence indicating it is safer than a currently approved treatment. | ||
| D) | exhibit preliminary clinical evidence that it may substantially improve existing therapies on at least one endpoint. |
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.
| A) | before Phase 1 trials begin. | ||
| B) | before the end of Phase 2 meetings. | ||
| C) | upon completion of Phase 3 trials. | ||
| D) | at any point in the drug-development process. |
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].
| A) | 1 month. | ||
| B) | 6 months. | ||
| C) | 10 months. | ||
| D) | 18 months. |
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]:
Evidence of increased effectiveness in treatment, prevention, or diagnosis of condition
Elimination or substantial reduction of a drug reaction that may limit treatment
Documented enhancement of patient compliance that is expected to lead to an improvement in serious outcomes
Evidence of safety and effectiveness in a new subpopulation
| A) | is a voluntary program. | ||
| B) | was introduced in 1938. | ||
| C) | must be mandated by Congress rather than the FDA. | ||
| D) | is used to ensure that the benefits of a drug or biologic product outweigh its risks. |
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].
| A) | is for health professionals only. | ||
| B) | must be used by all licensed prescribers. | ||
| C) | data is entered into the FDA Adverse Event Reporting System (FAERS). | ||
| D) | All of the above |
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.
| A) | an appointed epidemiologist. | ||
| B) | the general public and media. | ||
| C) | a team of physicians who are members of an Advisory Committee. | ||
| D) | multidisciplinary staff of the CDER Office of Surveillance and Epidemiology. |
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) | less than 15% of a given population. | ||
| B) | fewer than 200,000 people in the world. | ||
| C) | fewer than 200,000 people in the United States. | ||
| D) | 200,000 to 500,000 people in the United States. |
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.
| A) | with limited financial means. | ||
| B) | with serious or immediately life-threatening diseases or conditions. | ||
| C) | with conditions for which there is no comparable or satisfactory alternative therapy. | ||
| D) | Both B and C |
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].
| A) | Pandemic | ||
| B) | Widespread use | ||
| C) | Individual patients | ||
| D) | Intermediate-size patient populations |
Under the FDA's current regulations for investigational drugs and biologics, there are three categories of expanded access [13]:
Expanded access for individual patients, including for emergency use
Expanded access for intermediate-size patient populations
Expanded access for widespread use