The US Food and Drug Administration (FDA) was formed on June 30, 1906 with the passage of the Pure Food and Drugs act, although its origins can be traced back to 1848 and the creation of the Agricultural Division in the US Patent and Trademark Office (USPTO).
The FDA was initially established to regulate food and drug safety and prevent the sale of adulterated or misbranded products. However, when the Federal Food, Drug, and Cosmetic Act was passed in 1938, it set up the modern framework for the regulation of drugs in the US, expanding the agency’s responsibilities.
Now the FDA had the authority to approve or reject new drug products based on their safety and efficacy and to establish requirements for pre-market review and approval of new drugs. This allowed the FDA to enforce standards for the manufacture and distribution of drugs.
The requirement for pre-market evidence of a drug’s safety marked the inception of the New Drug Application (NDA). The firsts applications were submitted in the early 1940s, including applications for drugs that treated bacterial infections, hormone therapies, and mental health conditions.
These early NDAs set the stage for drug development and the FDA’s review and approval process for new drugs. Over the years, the FDA has reviewed and approved thousands of NDAs for new drug products.
What Is an NDA?
New Drug Application: When a company wants to market a new drug in the US, it must submit a marketing application to the FDA for review and approval. There are multiple types of marketing applications, including:
An NDA is a submitted request for permission to market a new drug product, including new molecular entities (NMEs), small molecules, biologics, vaccines, new combinations, new indications, and more.
The NDA must be submitted in a standard format, which is organized using the common technical document (CDT) format, a technical standard for all agency submissions starting from the IND phase. This format provides a standardized way of organizing and submitting regulatory information, and it helps to ensure that the information is consistent and easily accessible.
It’s typical for sponsors to use the Electronic Common Technical Document (eCTD) format, as it is regarded as the fastest delivery method to move the NDA process along between the sponsor and FDA.
Over the years, the application process has evolved to include more stringent requirements and greater scrutiny of the data submitted by drug manufacturers due to advancements in scientific understanding of drugs and their effects as well as increased public attention to drug safety and efficacy.
What Information Does It Need to Include?
An NDA application needs to tell the comprehensive story of the drug and include data the FDA can use to determine whether or not the drug is safe for humans to use as intended. Sponsors must include a wide range of required information, including:
- A cover letter that summarizes the NDA and provides an overview of the information contained in the submission.
- Administrative information about the sponsor of the drug, including the company name, address, and contact information.
- Preclinical study results and laboratory tests, including information about the drug’s safety and efficacy in animal models.
- Clinical studies results, including information about the safety and efficacy of the drug in human subjects, study design, and patient population.
- Statistical analysis results of the clinical trial data, including information about the statistical significance of the results.
- Drug information, including the drug’s composition, manufacturing processes, and proposed labeling. This includes the target product profile, annotated package insert, or the final package insert.
- Manufacturing information, including the facilities and processes used to manufacture the drug. This is used to evaluate the drug’s quality and ensure that it is being produced in accordance with good manufacturing practices.
- Patent information, including the status of patents covering the new drug, the claims made in the patents, licensing agreements, and information on any related litigation. This helps the FDA assess the eligibility of the drug for approval and determine if there are any legal or patent-related issues that need to be addressed.
- Institutional Review Board (IRB) compliance information, including information on clinical trial protocols, ethical approvals, patient safety, and monitoring procedures. This helps the FDA assess the safety and efficacy of the new drug, ensuring that clinical trials were conducted in a manner that protects patient safety and respects patient rights.
- Directions for use, including details on the recommended dose, administration, storage, handling, and labeling of the new drug, which helps the FDA determine if the drug will be safe and effective for its intended use, and if the instructions are clear and easy to understand for healthcare providers and patients.
- Regulatory correspondence between the drug manufacturer and the FDA, including requests for additional information or clarification.
- References cited in the NDA, including articles, reports, and other information sources.
New Drug Application: This information is used together to demonstrate that the product is safe for its intended use and target population, that its benefits outweigh the known risks, and that it can be manufactured in a way that ensures a high-quality product, and can be safely marketed to and used by patients and consumers.
Why Is It An Important Part of Drug Development?
NDAs are essential to drug development because they serve as the primary mechanism for the FDA to evaluate the safety and efficacy of new drugs, providing the federal agency with the information it needs to make an informed decision about whether a new drug should be approved for marketing and what conditions should be attached to its use.
By requiring rigorous preclinical and clinical testing and a comprehensive evaluation of the data, NDAs help to identify potential safety concerns and ensure that drugs are only approved for marketing if they are safe and effective. This can ultimately lead to better patient outcomes and advances in public health.
The NDA process also requires ongoing monitoring of the drug’s safety and efficacy through periodic reports and updates, providing a mechanism for public health officials and healthcare providers to receive accurate information about the drug.
Which Roles Are Involved in NDA Preparation & Submission?
Planning, preparing, and completing an NDA is a complex and multi-disciplinary effort that involves many different job roles, from nonclinical scientists to chemists to data management teams, physicians, pharmacologists, and more:
- Nonclinical scientists: Nonclinical scientists conduct preclinical tests to see if a new drug is safe and effective before it’s tested on humans. They perform lab and animal studies to see what potential side effects the drug may have, if it’s toxic, and if it’s effective. The results of these tests help the FDA determine if the drug is okay to test on humans.
- Bioanalytical scientists: Bioanalytical scientists design and perform tests to measure the drug and its byproducts in biological samples. This information helps support the drug’s safety and effectiveness and helps determine the correct dosage.
- Chemists: Chemists are responsible for making the drug and ensuring its high quality and consistency. They also help analyze the drug to confirm that it meets the standards outlined in the NDA.
- Clinical operations professionals: Clinical research operations professionals are in charge of planning, carrying out, and managing clinical trials. They pick the study sites, enroll patients, ensure the trials are done correctly, collecting and analyzing data from the trials. The data collected supports the drug’s safety and effectiveness and determines the proper dosage.
- Data standards analysts and managers: Data standards professionals ensure that the data collected during the drug development process is high quality, consistent, and compliant with regulatory requirements. This includes defining and maintaining data standards for collecting, storing, and analyzing data from preclinical and clinical studies.
- Data management professionals: Data management professionals collect, store, and organize the data generated during the drug development process. This includes ensuring the accuracy and completeness of the data and that it is properly stored and backed up. Data management also supports data analysis and the preparation of NDA submissions.
- Physicians: Physicians play a critical role in the NDA process, conducting clinical trials and evaluating the safety and effectiveness of the drug in human subjects. They are responsible for enrolling patients, administering the drug, monitoring the trial, and collecting data on the safety and efficacy of the drug.
- Pharmacovigilance professionals: Pharmacovigilance professionals are responsible for monitoring the drug’s safety once it is on the market. This includes collecting, analyzing, reporting adverse events, and conducting post-marketing surveillance to identify safety concerns. The information gathered by pharmacovigilance is used to update the product label and to inform regulatory agencies and healthcare professionals of any new safety information.
- Pharmacologists: Pharmacologists are responsible for understanding how drugs interact with the human body and how they affect different physiological systems. They conduct preclinical studies to evaluate the safety and efficacy of the drug and provide information on its mechanism of action, pharmacokinetics, and pharmacodynamics. The information generated supports the drug’s safety and effectiveness and determines appropriate dosing.
- Legal professionals: Legal teams are involved in the NDA process to ensure that the drug development process complies with applicable laws and regulations. This includes reviewing the NDA submission to ensure that it complies with legal and regulatory requirements and providing guidance on any potential legal issues.
- Regulatory affairs scientists and specialists: Regulatory affairs professionals ensure that the drug development process complies with regulatory requirements. This includes preparing the NDA submission, communicating with regulatory agencies, and managing the regulatory review process. Regulatory affairs are also responsible for ensuring that the drug is approved for marketing in a timely manner and that it meets the regulatory requirements for commercialization.
- Medical writers: Regulatory medical writers prepare the NDA submission, which includes summarizing the data generated from preclinical and clinical studies and presenting the data in a format that meets regulatory requirements. This includes writing the clinical overview, clinical pharmacology, and statistical analysis sections of the NDA.
New Drug Application: Each of these positions often play a critical role in the NDA process, and their collective efforts are necessary to ensure that a new drug is safe and effective for human use. Submitting an NDA with all the necessary data and information requires a lot of collaboration between all the different individuals and departments to be successful. Assembling a team right away can help streamline the application process.
When Should You Start Planning Your Application?
Beginning the planning process for an NDA should start as early in the drug development process as possible to ensure a successful outcome. Start as soon as you understand the drug’s mechanism of action, safety profile, and efficacy data from preclinical studies.
Doing so can help you stay ahead of regulatory requirements, avoiding potential roadblocks. It also provides you more time to gather your data and perform any additional studies that may be required to support the NDA submission, minimizing delays and ensuring you have…
