Founded in 1930, the US Food and Drug Administration (FDA) is a federal agency responsible for protecting public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, and other products subject to regulation.
In 1938, Congress passed the Federal Food, Drug, and Cosmetics (FDC) Act, which requires that drugs be safe before they are allowed on the market. The Kefauver-Harris Drug Amendment of 1962 further ensured that drugs not only be safe but also effective before they receive market authorization.
In 1966, the drug division of the FDA was reorganized into the Office of New Drugs (OND), which began reviewing new drug applications. In 1982, the Bureau of Biologics was merged with the FDA. In 1987, two separate entities were established: the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).
Originally, CDER consisted of six offices, but now it has 13 offices. Today, CDER serves as a consumer watchdog for the thousands of drugs available in the market, supporting innovation and improving patient treatment. The agency accomplishes this by reviewing, approving, and regulating new drugs in the US, including prescription and over-the-counter (OTC) drugs, for safety and effectiveness before a drug company can market its product to the public.
The CDER specifically focuses on evaluating and regulating prescription and over-the-counter (OTC) human drugs, including generic drugs and biologics, in order to ensure their safety and effectiveness for the public. The organization also plays a role in reviewing and approving new drug applications, monitoring the post-approval safety of drugs, and providing scientific and regulatory support for FDA’s drug review process.
The drug approval process often involves rigorous scientific and clinical testing to assess the drug’s potential benefits, risks, and side effects. The FDA also monitors drugs after approval to ensure their ongoing safety and effectiveness and may take action to remove drugs from the market if found unsafe.
The agency’s mission is to promote and protect public health through the regulation of various products and to ensure that these products are safe, effective, and of high quality. The FDA’s drug approval process is a multi-step process that includes preclinical testing, clinical trials, and a review of the drug’s safety and efficacy. The process is designed to ensure that new medicines are safe and effective for the intended use before they are marketed to the public.
The agency’s goal is to ensure that new drugs are safe and effective for their intended use and provide meaningful patient benefits. The approval process is rigorous and thorough, and the FDA can even remove drugs from the market after approval if found unsafe or ineffective.
The FDA's drug approval process is designed to ensure that drugs are safe and effective for their intended use before they are made available to the public, and the journey from demonstrating a molecule's potential as a therapeutic to producing an approved drug today involves several stages, including pre-clinical testing, intricate clinical trials on humans, and post-trial approval by the FDA.
This process can last from 10 to 15 years and can often cost millions or billions of dollars. While one study published in the Journal of Health Economics placed the cost to bring a new medicine to market around $2.8 billion, there has been debate as to the accuracy of this estimate. A more recent study published in JAMA Network about the estimated R&D investment needed to bring a new medicine to market has shown that the median cost hovers around $985 million, while the average cost is around $1.3 billion.
That all said, it is clear that the drug approval process can take a significant amount of time and cost companies hundreds of millions of dollars.
Here's a general step-by-step explanation to how the process goes:
Although this is an adequate explanation of the steps to seeking approval for a new drug, there are different types of FDA drug applications other than IND applications and NDAs that you can submit, based on your situation. We will cover these in more detail below.
The agency’s approval process has undergone significant changes over the course of the 20th and early 21st century, and most notably includes efforts to speed up and streamline the approval process for new drugs, particularly for those that address unmet medical needs.
Its evolution has come about because of a number of factors, including the expansion of federal regulations, the growing complexity of drugs and devices, and the pharmaceutical industry's rise as a major economic power in the United States.
The changes involve embracing new technologies, such as electronic submissions and real-world data, that help increase the efficiency of reviews, establishing a priority review program to expedite the approval process for drugs that offer significant advances over existing treatments, and establishing an accelerated approval process to allow drugs to be approved based on surrogate endpoints (early measures of efficacy) rather than waiting for full clinical proof of efficacy.
Furthermore, the FDA has shifted towards a risk-based approach, where the focus is on balancing the benefits and risks of new drugs, rather than just assessing their safety and efficacy. In addition to these efforts, the agency has also increased its collaboration with international regulators and worked to improve global access to new drugs.
Over the past 20 years, the CDER has consistently introduced new drugs, according to a study in the Journal of Family Medicine and Primary Care. A recent trend in drug development has been the expedited approval of anticancer drugs and biologics. However, the approval of drugs for neurological disorders, such as depression, psychosis, and multiple sclerosis, and lifestyle diseases, like obesity, atherosclerosis, and diabetes, has been relatively slow. The study’s observations highlight the increased focus on research in developing anticancer drugs and biologics.
While there is debate over whether the changes the FDA has made are beneficial or risky, the changes have helped to speed things up and bring new treatments to patients more quickly, while still ensuring their safety and efficacy.
I know, it's pretty obvious. But let's define the term drug using the FDA's categorization. A drug, as defined by the FDA (and other regulatory authorities) as a substance intended to diagnose, treat, cure, or prevent a disease or condition. Drugs can include prescription medications, over-the-counter remedies, and biological products such as vaccines and blood products. The definition also includes substances used to diagnose, treat, or prevent a disease or condition in animals.
However, the FDA does not consider all substances taken for health purposes as drugs. Herbal products, vitamins, and complementary medical therapies are often defined as "dietary supplements" and are regulated by the CDER. These substances are subject to guidelines set by the Dietary Supplement Health and Education Act of 1994, but are not subject to the same level of testing as substances classified as drugs.
There are some common types of drug applications the FDA reviews that sponsors can submit to receive approval to sell and market a medical product, including the New Drug Application (NDA), Abbreviated New Drug Application (ANDA), Investigational New Drug application, Biologics License Application (BLA), and Over-the-Counter (OTC) Drug Review.
Additionally, there are mechanisms the FDA can use to quickly authorize the use of a medical product or modify an approved drug that include the Emergency Use Authorization (EUA) and Supplement to a Previously Approved Application.
An NDA is a drug application submitted for approval to market a new drug when the sponsor (or applicant)—usually a pharmaceutical company—of a new drug believes that enough evidence on the drug's safety and effectiveness has been obtained to meet FDA's requirements for marketing approval.
It is a comprehensive and rigorous process that helps to ensure that new medicines are safe and effective for their intended use before they are made available to the public, and it may take several years from start to finish. It generally requires significant resources from the sponsor and the FDA.
Nonetheless, NDAs play a crucial role in the drug approval process, as they provide the FDA with the information it needs to evaluate the safety, efficacy, and quality of all new drugs. Each application needs to include specific details about the new drug, including results from preclinical studies, clinical trials, chemistry, manufacturing, and controls information.
The NDA process generally works as follows:
An ANDA is a drug application submitted to the FDA for approval to market generic drugs equivalent to an already approved brand-name drug. The term "abbreviated" is used to describe generic drug applications because they typically do not have to submit preclinical (animal) and clinical (human) data to demonstrate safety and efficacy.
The application process is designed to be more efficient and cost-effective than the traditional New Drug Application (NDA) process and provides a more straightforward pathway for generic drugs to be approved and marketed in the US.
The application must demonstrate the equivalence of the generic drug to the brand-name drug and show that it is safe and effective for its intended use. In some cases, additional clinical trials may be required to further demonstrate the efficacy and safety of the generic drug.
While the ANDA process is typically faster and less expensive than the NDA process, it still requires FDA review and approval before the generic drug can be marketed. Once the applicant receives approval, the product can be marketed, and the brand-name drug it’s modeled on typically loses its market exclusivity, resulting in increased competition and lower drug prices.
The process plays an important role in increasing access to affordable medications by providing a pathway for generic drugs to be approved and marketed in the US. The ANDA process generally works as follows:
An IND is a new drug that is not yet approved for sale or marketing by the FDA, but is undergoing clinical trials to assess its safety and efficacy in humans.
An IND application is a request for permission to administer an experimental drug to humans in a clinical trial. The application is submitted to the FDA by the sponsor seeking approval to begin clinical testing.
Furthermore, according to current federal law, a drug must have an approved marketing application before it can be transported or distributed between states. To meet this requirement, a sponsor may need to seek an exemption if they plan to ship the investigational drug to clinical investigators located in various states.
The IND application needs to contain detailed information about the drug's development, including preclinical laboratory and animal studies, manufacturing processes, and proposed clinical trial plans. It must also include information about the potential benefits and risks of the drug, and how the sponsor plans to minimize these risks during the clinical trial.
Once the IND application is submitted, the FDA reviews it to determine if it is safe for the drug to be tested in humans. The sponsor may proceed with the planned clinical trials if the IND is approved. During clinical trials, the FDA monitors the drug’s safety and its effects on patients. If the results of the clinical trials are promising, the sponsor may submit an NDA to receive approval to market the drug.
The application process has two categories: commercial and research. A commercial IND is for drug sponsors who plan to market the drug after its clinical testing phase, while a research IND is for investigators who conduct studies with the primary aim of obtaining information to support the drug's safety and effectiveness. Additionally, there are three types of applications:
Before a drug is approved, it will undergo a review by a specialized committee or "new drug division," based on the intended use of the drug. The FDA encourages investigators to reach out to the appropriate new drug review division through the Pre-Investigational New Drug Application Consultation Program before formally submitting an IND application.
That all said, the application process typically works as follows:
You can find forms and instructions for the IND application on the FDA’s website.
A BLA is used to approve biological products, complex molecules produced using living cells that can be used to treat various medical conditions. It is also known as a Therapeutic Biologics Application. The primary focus of the BLA process is to demonstrate the safety and efficacy of the biological product for its intended use through preclinical and clinical studies.
The marketing of biological products is authorized according to the regulations of the Public Health Service Act (PHS Act). The legislation mandates that any company producing a biologic for sale across state lines must possess a license for the biologic in question.
To obtain approval, the sponsor of the biological product provides detailed information on the manufacturing process, including the facilities, equipment, and methods used to produce the product. Clinical trials are also conducted to demonstrate the safety and efficacy of the biological product in humans.
Once the necessary information has been gathered, the sponsor submits the BLA to the FDA, including the preclinical and clinical studies results, manufacturing information, and a proposed label for the biological product, just like an NDA, ANDA, and IND application.
The FDA then reviews the BLA and determines whether the biological product is safe, effective, and manufactured according to the highest standards. If the BLA is approved, the biological product can be marketed.
The BLA process typically works as follows:
Over-the-counter drugs are becoming increasingly crucial in the functioning of the American healthcare system. OTC drugs are non-prescription drugs that can be used to treat various common health conditions, such as headaches, colds, and indigestion.
The OTC Drug Review process is a program run by the FDA designed to evaluate the safety and efficacy of over-the-counter drug products. The review aims to ensure that any over-the-counter drug is safe and effective for its intended use and that it is labeled in a way that is easy for consumers to understand and use. This is accomplished by conducting a scientific and regulatory review of each drug product's safety, efficacy, and labeling.
Drugs evaluated under the OTC Drug Review are known as OTC monograph drugs. According to the FDA, an OTC monograph is a set of guidelines for each therapeutic category, including active ingredients, indications, doses, labeling, and testing, which determine whether an OTC drug is considered safe and effective for marketing without the need for an NDA and prior FDA approval.
The review process includes a series of steps, including identifying active ingredients, classifying OTC drugs into different categories, and developing monographs that provide guidelines for the labeling and use of OTC drugs. The monographs are reviewed and updated regularly to reflect the most current scientific and regulatory information.
The drug approval process requires a sponsor of a non-prescription drug to submit either an NDA or an ANDA to the FDA for review. The non-prescription drug's marketing can only occur once the FDA has approved the NDA or ANDA submitted by the sponsor.
However, many non-prescription drugs that have been granted approval through an NDA or ANDA initially received approval as prescription drugs. The switch from prescription to over-the-counter status only occurs after the drug gets FDA approval for marketing as a non-prescription drug.
The application process typically works as follows:
Although we’ve gone over most of this information, it can be helpful to think of application types based on other (similar) categorization methods. This includes name-brand drugs, generic drugs, and over-the-counter drugs.
In addition to drug approval, the FDA oversees medical device approval. The approval process follows a similar path as that for brand-name drugs. Testing usually starts in a laboratory and moves on to animal testing to assess safety. Finally, human testing is performed to verify both safety and effectiveness. If approved, the device will be classified based on risk.
There are additional ways the FDA approves the use of a medical product or device, including EUAs and Supplement to a Previously Approved Application submissions.
EUA is a regulatory mechanism used by the FDA to allow the use of unapproved medical products in emergencies. The EUA process is intended to provide timely access to medical products that may be used to diagnose, treat, or prevent serious or life-threatening diseases or conditions during a public health emergency but does not represent FDA approval.
A EUA is issued when there is a significant potential for a medical emergency, and there are no other adequate, approved, and available options to diagnose, treat, or prevent the disease or condition. It is a temporary authorization, not a guarantee of safety or efficacy.
The application and authorization process is intended to provide timely access to medical products during public health emergencies. It differs from the drug approval process, which typically requires more extensive data and a demonstration of long-term safety and efficacy. It generally works as follows:
A Supplement to a Previously Approved Application is a type of regulatory submission to the FDA and is used to modify an approved drug product or the information in its approved application while ensuring that the changes do not harm the safety and efficacy of the drug.
The sponsor of an approved drug can apply to modify the product, its labeling, or the approved information to address new information or make other changes. Typical changes that may be made through the application include product labeling updates, manufacturing processes changes, or new indications for use.
The application process typically involves submitting data and information demonstrating that the proposed changes do not negatively impact the drug’s safety and efficacy. The FDA then reviews this information and decides whether to approve the proposed changes.
If the change is approved, it can be implemented, and the drug can continue to be marketed. The Supplement to a Previously Approved Application process involves several steps:
The FDA provides several resources for drug approval applications, including guidance documents, regulations, forms, and additional information on the drug review process. The agency also provides information on the requirements for preclinical studies, clinical trials, and the submission of NDAs, BLAs, and more.
Furthermore, the agency provides information on its review criteria, post-approval requirements, and regulatory pathways, such as the 505(b)(2) and accelerated approval processes.
Guidance documents reflect the FDA’s current position on specific subjects and offer guidance to both FDA review staff and product applicants/sponsors on processing, content evaluation/approval of applications, and the design, production, manufacturing, and testing of regulated products. They aim to promote consistency in the agency’s regulatory approach and outline inspection and enforcement procedures.
It’s important to note that the guidelines are not legally binding, and you may take alternative approaches as long as they comply with applicable laws and regulations. For specific guidance inquiries, we recommend reaching out to the originating office.
Furthermore, you can access guidance documents for various drug application preparations and submissions by visiting the FDA website. For example, to learn more about IND preparation, visit the Guidances (Drugs) page and search using the keyword “investigational.”
If you’d like to view the entire collection of CDER guidelines, you can refer to the Guidance Index. For inquiries on a particular guideline, we recommend reaching out to the originating office.
Based on what’s available on the FDA’s website, it’s clear that the FDA’s objective is to enforce laws passed by the US Congress and regulations set by the agency. Doing so allows the agency to safeguard consumers’ health, safety, and financial well-being.
The way it meets this objective is by following the law according to the Federal Food, Drug, and Cosmetic Act, which serves as the primary food and drug law in the US. It aims to give consumers peace of mind by ensuring that food is pure, safe, and produced in sanitary conditions; that drugs, devices, and cosmetics are safe and effective; and that labeling and packaging accurately reflect the contents and is not misleading.
The CFR is a compilation of final regulations issued by Federal agencies, including the Food and Drug Administration (FDA). It contains final regulations set forth in the Federal Register, a daily publication of proposed and final rules, meeting notices, and more. The FDA’s portion is responsible for interpreting the Federal Food, Drug, and Cosmetic Act and other related laws. The majority of regulations related to food and drugs can be found in Section 21 of the CFR, which documents all actions required by Federal law for drug sponsors.
The CFR is organized into 50 broad subject areas, or titles, each representing an area regulated by the Federal government. The CFR documents and codifies all regulations issued by Federal agencies and provides a unified and organized representation of Federal regulations, making it easier for the public to understand and access information on Federal regulations. The CFR serves as an official and permanent record of these regulations, and is updated annually.
The FDA evaluates a drug application based on several factors to determine whether it should be approved, delayed, or denied, including the drug's safety, efficacy, and more.
If the drug is safe and effective in clinical trials, it is more likely to be approved by the FDA. The agency will consider the design and conduct of the trials, as well as the results. The drug must demonstrate that it is effective for its intended use and does not pose an unreasonable risk of harm to patients. If the results of the trials are not compelling or there are concerns about the drug’s safety, the FDA may delay or deny approval.
Another factor that may impact the approval of a drug application is the manufacturing process. The FDA must be confident that the drug can be manufactured consistently and with high quality. If there are concerns about the manufacturing process, the FDA may delay or deny approval until these issues are resolved.
In some cases, the FDA may also consider other factors, such as the unmet medical need for the drug and the potential benefit to patients. If a drug offers a significant advantage over existing treatments and is considered a priority for patients, it may be approved even if there are some associated uncertainties or risks.
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