Study Points

Expanding the Options: The Drug-Approval Process in the United States

Course #95000 - $25 • 5 Hours/Credits

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  • Participation Instructions
    • Review the course material online or in print.
    • Complete the course evaluation.
    • Review your Transcript to view and print your Certificate of Completion. Your date of completion will be the date (Pacific Time) the course was electronically submitted for credit, with no exceptions. Partial credit is not available.
  1. The Center for Drug Evaluation and Research (CDER) has oversight responsibilities for

    CENTER FOR DRUG EVALUATION AND RESEARCH

    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

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  2. The Federal Food, Drug, and Cosmetic (FD&C) Act requiring that drugs be proven safe before marketing was signed into law in

    DEFINING SAFE AND EFFECTIVE

    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.

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  3. New drug application safety data must be presented by each of the following subgroups, EXCEPT:

    DEFINING SAFE AND EFFECTIVE

    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].

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  4. All of the following are main goals of adequate and well-controlled studies, EXCEPT:

    DEFINING SAFE AND EFFECTIVE

    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

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  5. The first step in the drug-development process is

    THE DRUG DEVELOPMENT AND APPROVAL PROCESS

    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.

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  6. Preclinical studies

    THE DRUG DEVELOPMENT AND APPROVAL PROCESS

    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

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  7. Which of the following is NOT a type of research investigational new drug (IND) application?

    THE DRUG DEVELOPMENT AND APPROVAL PROCESS

    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.

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  8. All IND applications must include

    THE DRUG DEVELOPMENT AND APPROVAL PROCESS

    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

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  9. Phase 3 clinical trials typically consist of

    THE DRUG DEVELOPMENT AND APPROVAL PROCESS

    Phase 3

    Study Participants : Typically 300 to 3,000 volunteers who have the disease or condition [18]

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  10. Approximately what proportion of novel drugs approved in 2019 benefitted from one of the FDA's expedited review programs?

    EXPEDITED REVIEW PROGRAMS

    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 benefited from one of the FDA's expedited review programs (Table 1) [22,23]:

    • Accelerated approval

    • Fast track

    • Breakthrough therapy

    • Priority review

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  11. A qualified infectious disease product may be eligible for

    EXPEDITED REVIEW PROGRAMS

    SUMMARY DESCRIPTIONS OF DRUGS ELIGIBLE FOR EXPEDITED REVIEW

    Expedited ProgramCharacteristics of Eligible Drugs
    Fast track
    A qualified infectious disease product
    A drug intended to treat a serious condition and clinical or nonclinical data demonstrate it has the potential to address an unmet medical need
    Breakthrough therapy
    A drug intended to treat a serious condition
    Preliminary clinical evidence shows the drug may demonstrate substantial improvement on a clinically significant endpoint over available therapies
    Accelerated approvalA drug that treats a serious medical condition and generally provides a meaningful advantage over available therapies. The drug demonstrates an effect on:
    • A surrogate endpoint that is reasonably likely to predict clinical benefit, or

    • A clinical endpoint that can be measured before irreversible morbidity or mortality, or

    • Reasonable likelihood of predicting an effect on irreversible morbidity or mortality or on an intermediate clinical endpoint

    Priority review
    An application (original or efficacy supplement) for a drug that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness
    Any supplement that proposes a labeling change related to pediatric studies
    An application for a drug that has been designated as a qualified infectious disease product
    Any application or supplement for a drug submitted with a priority review voucher
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  12. In order to be considered a breakthrough therapy, a drug must

    EXPEDITED REVIEW PROGRAMS

    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.

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  13. Breakthrough therapy designation requests are submitted

    EXPEDITED REVIEW PROGRAMS

    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].

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  14. If a drug qualifies for priority review, the drug review process is completed within

    EXPEDITED REVIEW PROGRAMS

    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

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  15. Risk Evaluation and Management Strategy (REMS)

    POST-APPROVAL RESPONSIBILITIES

    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].

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  16. The MedWatch program

    POST-APPROVAL RESPONSIBILITIES

    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.

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  17. Reports in FAERS are evaluated by

    POST-APPROVAL RESPONSIBILITIES

    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.

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  18. A rare disease is defined as one that affects

    RARE DISEASES DRUG DEVELOPMENT

    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.

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  19. Expanded drug access is reserved for patients

    EXPANDED ACCESS

    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].

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  20. All of the following are categories of expanded drug access, EXCEPT:

    EXPANDED ACCESS

    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

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  • Back to Course Home
  • Participation Instructions
    • Review the course material online or in print.
    • Complete the course evaluation.
    • Review your Transcript to view and print your Certificate of Completion. Your date of completion will be the date (Pacific Time) the course was electronically submitted for credit, with no exceptions. Partial credit is not available.