The FDA is responsible for ensuring the safety and effectiveness of new drugs and medicines before they are marketed to the public. To achieve this, the FDA reviews various types of data and information submitted by sponsors, including pharmaceutical companies, drug manufacturers, independent investigators, and more.
The data that must be submitted includes preclinical data, results from animal studies, and results from clinical trials. The FDA also inspects the facilities where drugs are manufactured and conducts ongoing monitoring of medicines once they are on the market.
The drug development journey is a complex and multi-step process that includes several phases and can take many years and millions of dollars to complete. The journey typically includes discovery and preclinical research, IND submissions, clinical trials, NDA submissions (marketing application), FDA reviews, and post-market monitoring. In this article, we’ll review INDs and the application process.
An Investigational New Drug (IND) is an experimental drug that has not yet been approved for marketing by a regulatory agency, such as the US Food and Drug Administration (FDA), but is being tested in clinical trials to determine its safety and efficacy. An IND is considered "investigational" because it is still in the process of being investigated, and its safety and effectiveness have not yet been fully established.
The drug’s sponsor must submit an Investigational New Drug application to the FDA to conduct clinical trials on the new drug.
The application must contain data from preclinical studies (pharmacokinetics, dose-response, formulation, toxicology studies), manufacturing information (labeling, production methods, batch records), information regarding the study site (facilities, equipment), and the proposed clinical trial protocol (study design, endpoints, informed consent, adverse event reporting). The FDA reviews the application to ensure that the proposed trials are scientifically sound and ethically conducted and that the drug is safe for use.
In drug development, INDs serve as the starting point for a drug’s journey toward eventual approval and marketing. The submission and subsequent clinical trials are necessary steps in demonstrating the safety and efficacy of the new drug. The process is designed to ensure that new medicines for patients are developed and marketed safely.
If the IND is approved, the sponsor will conduct clinical trials on patients to determine if the drug is effective and safe for use. If the clinical trials are successful, the sponsor may then submit a New Drug Application (NDA), also known as a marketing application, to the FDA for approval to market the drug to the public. NDAs are generally the final step in the drug development process.
The NDA application must include all the data generated from preclinical and clinical studies, information regarding the manufacturing process, quality control data, statistical analysis, labeling for the drug, and more.
The FDA reviews the marketing application to determine whether the drug is safe and effective for its intended use and whether the benefits of the drug outweigh the risks, similar to an IND review. If the agency determines that the drug is safe and effective, it may approve the marketing application and allow it to be marketed in the United States.
In addition to INDs and NDAs, the FDA uses other tools and processes to assess the safety and efficacy of new drugs, including things like adverse event reporting, risk management plans, and Abbreviated New Drug Applications (ANDAs), another type of drug approval application.
Adverse reporting reports any adverse events or side effects associated with drug use, while risk management plans aim to minimize potential risks associated with the new drug.
ANDAs provide information about a generic drug, including quality, safety, and efficacy data of the generic drug and more. The FDA uses this application to determine whether a generic drug is equivalent to a previously approved brand-name drug, or reference listed drug (RLD).
There are two types of INDs: commercial and research. A commercial IND is submitted by a sponsor, such as a drug manufacturer, that intends to market the investigational drug for commercial use once the regulatory agency has approved it.
In contrast, a research IND is submitted by a single investigator or a group of investigators who want to study an investigational drug in a clinical trial. Research INDs are often used for early-phase clinical trials, such as phase 1 trials, when the primary goal is to determine the safety and pharmacokinetics of the drug.
The regulatory agency will review the IND to ensure that the proposed clinical trials being conducted are scientifically sound and ethically run, that the clinical investigator or sponsor-investigator is qualified and experienced and that the drug is reasonably safe for human subjects.
In addition to the commercial and investigator IND categorizations, there are three types of applications:
The IND application process is a critical step in the drug development journey, as it allows drug manufacturers to request permission to conduct clinical trials in humans with an IND. Sponsors can take the following steps to apply for an IND in the US:
Information and reporting requirements for IND applications may vary, making it important to consult with regulatory agencies like the FDA to understand the criteria for IND submissions. A clinical hold may be put in place after an application has been approved, stopping the trial’s initiation or continuation.
This action is taken when the FDA determines a significant safety concern for the study’s participants or the reliability of the data being generated is inaccurate or flawed. Preparation and proper study design are critical.
Working with experienced professionals, such as regulatory affairs specialists, can help ensure a smooth and successful IND application process.
To successfully submit an IND application, you must collect and prepare the following information and materials:
The IND application must be in the format specified by the FDA and include all required information and documentation. The FDA may request additional information or clarification during the review process.
Amendments are changes or additions to an Investigational New Drug application already on file with the FDA. They are a common part of the IND process.
During the IND process, a sponsor may need to make changes to the application for various reasons, including changes in the study design, the addition or removal of clinical investigators, or updates to the manufacturing process.
When a sponsor wants to make changes to their application, they must submit an amendment to the FDA. The amendment must include detailed information about the changes being made and why they are necessary. The amendment must also include any updated, relevant information to the application, including revised protocols, manufacturing information, or new safety data.
The FDA reviews amendments to determine if the changes are acceptable and if they impact the safety and efficacy of the investigational drug. If the changes are significant, the FDA may require additional information or request that the sponsor conducts further preclinical or clinical studies before proceeding with the study.
A variety of resources are available for individuals and organizations who want to learn more about INDs, applications, and submissions, including government websites, organizations, conferences, workshops, consultants, and service providers:
It can be helpful to use a combination of these resources to understand INDs and the IND submission process comprehensively. It’s also essential to stay up-to-date on the latest developments and regulatory changes, as these can impact the IND submission process and drug development.
The FDA provides several guidance documents to help individuals and organizations prepare applications, including regulations, clinical trials, preclinical, manufacturing, and application papers, all of which provide information on the requirements and expectations for submissions and help ensure that applications are complete, accurate, and scientifically sound.
These guidance documents are updated periodically to reflect new developments and regulatory changes, and it’s crucial to stay up-to-date on the latest guidance documents to ensure that IND applications are compliant and accurate.
The Center for Drug Evaluation and Research (CDER) is a division of the FDA responsible for reviewing and approving new drugs in the United States.
Because of their role in the drug approval process, the CDER provides various learning courses on topics related to drug development, such as Good Clinical Practice (GCP) training, regulatory submissions, and IND applications.
The guidance and support help companies and individuals seeking to develop and bring new drugs to market better understand the requirements and regulations involved in the IND process, ensuring that applications are complete, well-documented, and meet regulatory requirements.
The IND process and FDA’s approval review are governed by several laws and regulations, including the Federal Food, Drug, and Cosmetic Act (FD&C Act) and its implementing statutes. These regulations provide the framework for developing, testing, and approving new drugs in the United States. The key rules that guide the IND process include the following:
In addition to the laws and regulations mentioned, the application and review process is guided by various policies and procedures, known as the Manual of Policies and Procedures (MaPPs), which is overseen by the CDER. These include instructions like the Guidance for Industry, Draft Guidance, Draft and Final Policy Documents, Standard Operating Procedures (SOPs), and more.
Firstly, the Guidance for Industry provides recommendations on various aspects of drug development and IND submissions, including study design, data quality, patient safety, and more.
The Draft Guidance comprises information on current thinking and evolving regulatory policies and procedures related to drug development and IND submissions. The Draft and Final Policy Documents provide additional guidance on specific topics related to IND applications, such as the format and content of IND submissions, review procedures, and post-approval obligations. You can search for these documents using the FDA’s search page.
Lastly, the FDA’s Standard Operating Procedures (SOPs) offer detailed instructions for reviewing and managing IND applications, including the timeline for review, information requirements, and other key considerations. You can find an updated summary of SOPs required by the FDA in the Federal Register index.
Policies and procedures like these can help ensure the consistent and systematic review of drug approval applications and support the efficient development and approval of new drugs.
The safety and efficacy of marketed drugs are of utmost importance in the United States as they directly impact public health. To ensure that new drugs are safe and effective, the FDA established a comprehensive regulatory framework to oversee the development and approval of new drug products.
An IND application is a critical component of this framework, as it allows the sponsor of a new drug to request permission from the FDA to begin clinical trials. The application must provide extensive information about the proposed drug, including preclinical data, study design, and clinical trial protocols.
Submitting an IND application to the FDA involves:
Once an IND application is received, the FDA reviews it to determine if the proposed clinical trials can proceed safely and effectively. During the review process, the agency may request additional information or clarification from the sponsor or raise concerns about the safety and efficacy of the proposed drug.
If the IND application is approved, clinical trials can proceed. If not, the sponsor may need to revise the application or provide additional information to address the FDA’s concerns.
To receive approval from the FDA for a new drug, laboratories need to produce high-quality data that demonstrate the safety and efficacy of the drug. By leasing new lab equipment, laboratories can ensure that they have access to the latest technology and can produce accurate, reliable data that supports their IND application.
Leasing new lab equipment for preclinical studies and clinical trials can be a good idea for laboratories working to develop a new drug for several reasons, including cost-effectiveness, flexibility, a streamlined procurement process, and access to the latest technology.
By leasing the latest and most advanced equipment, you can conduct preclinical studies and clinical trials using state-of-the-art technology, improving the accuracy and reliability of the data generated.
Leasing equipment can be more cost-effective than purchasing it outright, as it eliminates the need for a significant upfront investment. Additionally, we include maintenance and repairs in our leasing agreements, which helps reduce your chances of paying out-of-pocket for maintenance and unexpected repairs.
You can select equipment specifically suited to their needs and upgrade or switch equipment after the lease has ended, which can be particularly useful for anyone working with a limited budget, as you can prioritize equipment based on the study’s specific needs.
You can also streamline the procurement process when you lease, as you can quickly obtain the necessary equipment for research without going through a more lengthy purchase process.