The process to get a drug, vaccine, or medical device approved in the US may at first seem labyrinthine, but there is a method to the complexity. Understanding the steps and actions is important to foster consumer trust, and to encourage people to participate in pre-clinical and clinical research.
How drugs are normally approved
When Americans shop for medicines, or are given a prescription by their doctor, they can be assured that they benefit from the world’s safest and most advanced pharmaceutical system.
The Center for Drug Evaluation and Research (CDER) within the Food and Drug Administration (FDA) plays a big role by evaluating new drugs before they go to market. The center makes sure drugs work as they should, and that their benefits outweigh any risks.1
Pharmaceutical companies first test the drugs they wish to sell. They do this through pre-clinical and clinical trials, and then they submit the data from these studies to the FDA. Physicians, statisticians, chemists, pharmacologists, and other scientists at CDER then review this data and any associated proposed labeling.1
Companies can choose from 5 different application types when they wish to submit a drug for FDA approval: investigational new drug, new drug application, abbreviated new drug application, over-the-counter drugs, or a biologic license application.2 (Go here for more information about each of these applications.)
CDER uses a structured framework that scrutinizes 3 key areas when it is evaluating an application:1
- Analysis of the target condition and available treatment,
- Assessment of benefits and risks from clinical data
- Strategies for managing risks.
If CDER determines that the benefits outweigh the risks, the drug receives FDA.1 The biggest hidden cost to this process, for consumers, may be time: the drug approval process can take 12 to 15 years.3
How vaccines are normally approved
The process to get a vaccine approved is similar, but is overseen by a different center at the FDA, the Center for Biologics Evaluation and Research (CBER). Vaccine developers typically begin their research and discovery in a lab, just like drug developers, then proceed to testing in animals in the pre-clinical phase, then testing in people for clinical development.4
While clinical testing is on-going, it’s common for the FDA to assess how and where the vaccine is manufactured. After the manufacturing process is vetted for reliability and consistency, and after the pre-clinical and clinical development phases are complete, vaccine companies submit a Biologics License Application to the FDA. This is how the company informs the FDA of its pre-clinical and clinical data, and manufacturing process.4
A team at CBER of physicians, statisticians, chemists, pharmacologists, toxicologists, microbiologists, and inspectors specializing in manufacturing and facilities then evaluates the BLA application with an eye on safety and efficacy. After a vaccine receives FDA approval, post-market monitoring continues to surveil consumers for adverse events and long term complications.4
What can be authorized for emergency use?
When certain kinds of public health emergencies occur, the FDA’s normal approval timelines and processes may hamper the government’s ability to get what’s called medical countermeasures (MCMs) to the people who need them.5
MCMs are FDA-regulated products that can be used in public health emergencies to diagnose and treat, or prevent and protect people from, health conditions associated with national threats. MCMs include medicines (such as anti-infectives or antidotes), devices (diagnostic tests or personal protective equipment), and biologics (vaccines, blood products, and antibody or cellular treatments).5
The FDA has the authority to allow both the use of an unapproved medical product, or the previously unapproved use of an approved medical product. This means they can accelerate the approval of a product that has not gone through the normal review process, or they can approve a new use of a product that has already been approved for different applications (this would be akin to approving off-label uses).5
The FDA supports MCM development by working with partners at all levels of government, along with non-governmental organizations, and researchers from academic institutions or industry.5
When can emergency authorization be used?
Public health emergencies that trigger an EUA may originate from a wide variety of sources including chemical, biological, radiological, or nuclear attacks or events—and emerging infectious diseases.5,6
For the FDA to authorize drugs, vaccines, or other medical countermeasures under an (EUA designation, the Secretary of the US Department of Health and Human Services must first declare that a threat or potential threat to public health exists. This requirement is spelled out under section 564 of the Federal Food, Drug, and Cosmetic Act.6
What does the emergency use authorization process involve?
Depending upon the specific national threat, MCMs may be obtained from the strategic national stockpile (such as patient ventilators and health care provider personal protective equipment), or they may be accessed through special FDA approvals, such as the Emergency Use Authorization.7
The FDAs guidelines for the Emergency Use Authorization of Medical Products and Related Authorities defines the conditions under which EUAs may be issued, and for what type of products.8
The FDA will only issue an EUA if the following 4 conditions have been met:8
- The health threat must be a serious or-life threatening disease or condition.
- There must be evidence that the medical product “may be effective” to mitigate a disease or condition — language that presents a slightly lower bar for evidence than the effectiveness standards used by the FDA for typical approvals.
- The benefits of the medical product at diagnosing, preventing, or treating the disease or condition outweigh the risks.
- There are no other adequate, approved, or available alternatives.
To start the EUA process, an industry or government sponsor engages with the FDA about medical products that could be used with EUA before submitting an application. These are called “pre-EUA activities” and are meant to help guide the submission process.8
EUA submissions should include:8
- Information about the product and its use,
- A description of the products FDA-approval status (if there is one),
- The need for the product,
- All available safety and efficacy data,
- A discussion of its risks and benefits,
- Information on its chemistry,
- Information about how much of the product is on hand and how quickly more can be made in the event of a surge for demand,
- Information similar to a package insert
The FDA will then review the EUA submissions based on priority which include factors ranging from the immediacy of the threat, to the urgency of the treatment, and the pharmaceutical company’s ability to manufacture it.8
Companies can initiate a full approval submission under the normal process at the same time that their product is being used under an EUA. When EUAs are no longer needed, they are terminated or revoked and a public record is preserved.9
EUAs have the potential to play an important role in bringing vaccines, antivirals, and innovative medical devices to the public faster than the traditional review process could deliver them. However, the need for speed during a national public health crisis does not mean that safety or efficacy are compromised. The EUA process ensures the careful evaluation of core requirements for safety and efficacy to protect consumers, while balancing the benefits and risks of making a drug, vaccine, or device available to the public in the middle of a crisis.
- US Food and Drug Administration. Development & Approval Process | Drugs. Available at https://www.fda.gov/drugs/development-approval-process-drugs. Accessed 8/27/21.
- US Food and Drug Administration. How Drugs are Developed and Approved. Available at https://www.fda.gov/drugs/development-approval-process-drugs/how-drugs-are-developed-and-approved. Accessed 8/27/21.
- com. FDA Drug Approval Process. Available at https://www.drugs.com/fda-approval-process.html. Accessed 8/27/21.
- US Food and Drug Administration. Vaccine Development 101. Available at https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-development-101. Accessed 8/27/21.
- US Food and Drug Administration. What are Medical Countermeasures? Available at https://www.fda.gov/emergency-preparedness-and-response/about-mcmi/what-are-medical-countermeasures. Accessed 8/27/21.
- US Food and Drug Administration. Emergency Use Authorization. Available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization. Accessed 8/27/21
- US Food and Drug Administration. MCM Emergency Use Authorities. Available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/mcm-emergency-use-authorities. Accessed 8/27/21.
- US Food and Drug Administration. Emergency Use Authorization of Medical Products and Related Authorities. Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities. Accessed 8/27/21.
- US Food and Drug Administration. Emergency Use Authorization—Archived Information. Available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization-archived-information. Accessed 8/27/21.
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