New Drug Application

For decades, the regulation and control of new drugs in the United States has been based on the New Drug Application (NDA). Since 1938, every new drug has been the subject of an approved NDA before U.S. commercialization. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA.

The NDA has evolved considerably during its history. When the Food, Drug, and Cosmetic Act (FD&C Act) was passed in 1938, NDAs were only required to contain information pertaining to the investigational drug's safety. In 1962, the Kefauver-Harris Amendments to the FD&C Act required NDAs to contain evidence that a new drug was effective for its intended use as well, and that the established benefits of the drug outweighed its known risks.

The NDA was again the subject of change in 1985, when the FDA completed a comprehensive revision of the regulations pertaining to NDAs. While this revision, commonly called the NDA Rewrite, modified content requirements, it was mainly intended to restructure the ways in which information and data are organized and presented in the NDA to expedite FDA reviews.

Fundamentals of NDA Submissions

Although the quantity of information and data submitted in NDAs can vary significantly, the components of NDAs are more uniform. The components of any NDA are, in part, a function of the nature of the subject drug and the information available to the applicant at the time of submission. As outlined in Form FDA-356h, Application to Market a New Drug for Human Use Or As An Antibiotic Drug For Human Use, NDAs can consist of as many as 15 different sections:

• Index;
• Summary;
• Chemistry, Manufacturing, and Control;
• Samples, Methods Validation Package, and Labeling;
• Nonclinical Pharmacology and Toxicology
• Human Pharmacokinetics and Bioavailability;
• Microbiology (for anti-microbial drugs only);
• Clinical Data;
• Safety Update Report (typically submitted 120 days after the NDA's submission);
• Statistical;
• Case Report Tabulations;
• Case Report Forms;
• Patent Information;
• Patent Certification; and
• Other Information.

NDA Content and Format Requirements

Although the exact requirements are a function of the nature of a specific drug, the NDA must provide all relevant data and information that a sponsor has collected during the product's research and development.

The FDA has numerous guidelines that relate to NDA content and format issues. These guidelines can be obtained from CDER's Drug Information Branch (DIB). Below is a partial list of some newer Guidances of interest. See DIB's Guidance Documents for a complete list of available guidelines online and instructions on how to obtain them.

Subject-Related CDER Guidances of Interest (examples)

• Drug Master Files (09/89)

NDA Classifications

CDER classifies new drug applications with a code that reflects both the type of drug being submitted and its intended uses. The numbers 1 through 7 are used to describe the type of drug:

1- New Molecular Entity
2- New Salt of Previously Approved Drug (not a new molecular entity)
3- New Formulation of Previously Approved Drug (not a new salt OR a new molecular entity)
4- New Combination of Two or More Drugs
5- Already Marketed Drug Product - Duplication (i.e., new manufacturer)
6- New Indication (claim) for Already Marketed Drug (includes switch in marketing status from prescription to OTC)
7- Already Marketed Drug Product - No Previously Approved NDA

The following letter codes describe the review priority of the drug:

S- Standard review for drugs similar to currently available drugs.
P- Priority review for drugs that represent significant advances over existing treatments.

For a list of addresses to send applications to, go to the Address page.

Click here for a list of general drug categories for drug products.

Source: U.S. Food and Drug Administration Center for Drug Evaluation and Research Handbook.