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New Drug Application (NDA): Back to the Basics

Jul 23, 2021 | Drug & Biologic Product Submissions, Pharmaceutical and Cosmetics

What is a New Drug Application (NDA)?

Every new drug in the United States needs to come to market through a New Drug Application with the FDA. According to the FDA, “The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. and the data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA.” The idea of the NDA is to tell the entire story of a drug including contents, results of trials and how the drug is manufactured and packaged creating full transparency. The goal of the NDA is to help approvers conclude if the drug is safe and effective in its intended use, if the benefits outweigh the risk, if the labeling is correct, accurate and includes all necessary information and if the methods and controls used in manufacturing will ensure the consistency and efficacy of the drug. The final guidance for NDAs is published in the Code of Regulations (CFR) – 21CFR Part 314.

What Needs To Be Included In A New Drug Application?

According to FDA Guidance Document, Guideline on Formatting, Assembling, and Submitting New Drug and Antibiotic Applications, the application must include an application form which is a cover letter of sorts. This would include information about the applicant and the drug in question and ties the applicant to comply with applicable laws and regulations. A required part of this section is “Contents of Application”. This is a checklist with 15 items that must be included with the application. There is also a requirement to include any Investigational New Drug Applications (INDs) and Drug Master Files (DMFs) that are references within this particular NDA. An index section is required and should be laid out by volume and page number. Next, a summary section the contents of which are outlined in a separate guidance document, Guideline for the Format and Content of the Summary for New Drug and Antibiotic Applications.

The next sections are Review Sections which align with items 4-12 in the Contents of Application Form. According to Cornell Law, “Each technical section is required to contain data and information in sufficient detail to permit the agency to make a knowledgeable judgment about whether to approve the NDA or whether grounds exist under section 505(d) of the Federal Food, Drug, and Cosmetic Act to refuse to approve the NDA.” The contents of each section are detailed in their own separate guidance documents. These sections can include chemistry, manufacturing and controls section, nonclinical pharmacology and toxicology section, human pharmacokinetics and bioavailability section, microbiology section, clinical data section, statistical section and pediatric use section.

There is a samples and labeling section that requires proposed draft labeling or final printed labeling (FPL). Other contents of this section are detailed in the guidance, Guideline for Submitting Samples and Analytical Data for Methods Validation. Case report forms and tabulations are the focus of the next section. This includes patient data in clinical studies, data elements within tables and case reports. The FDA recommends applicants meet with FDA to discuss how much detail is needed for the NDA. They will also recommend best ways to present special supporting information such as x-rays. The last section is Information incorporated by reference. This includes information previously submitted in DMFs or other applications.

Additionally, an applicant can submit presubmission of chemistry, manufacturing and controls 90-120 days prior to submission of the full NDA. The benefit of this presubmission is that it can potentially speed up the application review process.

Three copies of each New Drug Application are required to be submitted to the FDA: an archival copy, a review copy and a field copy.

How Does the FDA Monitor New Drug Applications?

The FDA’s Center for Drug Evaluation and Research (CDER) helps to manage the process of NDA approval. CDER’s evaluation prevents quackery and helps to ensure that both doctors and patients have the information they need to appropriately utilize the drugs once approved. Their main job is to ensure the safety and efficacy of the new drugs whilst ensuring the benefits of the drugs outweigh the risks. The team at CDER does not actually test the drug but review the information provided in the New Drug Application. Before this review, the drug must be tested on animals and then subsequently humans and the results must be included in the NDA. This team is comprised of physicians, statisticians, chemists, pharmacologists and other scientists.

For a drug to receive FDA approval, the drug approval process must follow a very structured framework:
1. Analysis of the target condition and available treatments
2. Assessment of benefits and risks from clinical data
3. Strategies for managing risks

While the data is sometimes subjective, the team does their best to review carefully and determine the risk reward ratio.

To learn more about NDAs, please reach out to the Pharma team at Reed Tech. [email protected]

Sources:, Cornell Law School