New drug application requirements and the FDA review process
A new drug application seeks FDA approval to market a drug in the US. Learn what an NDA contains, how review works and how it differs from an ANDA.
A new drug application (NDA) asks the FDA to approve a new drug for marketing in the United States. It supplies the evidence FDA needs on safety and effectiveness, manufacturing and controls, and proposed labeling, as described in FDA's NDA overview.
The term covers more than a new chemical entity. 21 CFR 314.3 includes both stand-alone 505(b)(1) applications and 505(b)(2) applications, plus amendments and supplements. A 505(b)(2) application remains an NDA. It relies at least partly on investigations not conducted by or for the applicant, and the applicant has not obtained a right of reference or use.
A pharma NDA prepared in the UK still follows 21 CFR Part 314. UK marketing authorisation is a separate system.
NDA versus ANDA and BLA
A 505(b)(2) application stays inside the NDA category. Reliance on other investigations does not mean the application can skip new studies. The test is who conducted the investigations the applicant relies on, and whether the applicant has a right of reference or use, under §314.3.
An abbreviated new drug application, or ANDA, is the generic-drug route. It references a listed drug and supplies the required sameness information and bioequivalence evidence. An approved petition can allow certain differences. FDA says ANDAs generally do not repeat the preclinical and clinical investigations establishing safety and effectiveness. Sameness and bioequivalence evidence is still required. See §314.94 and FDA's ANDA overview.
A biologics license application, or BLA, seeks a license under section 351 of the Public Health Service Act. The application needs evidence of safety, purity and potency, plus manufacturing and stability information. A BLA is its own route, not an NDA subtype and not an ANDA for a biologic. The application requirements sit in 21 CFR 601.2.
Wrong-route NDA filings can stop before review. FDA may refuse to file a 505(b)(2) application for a duplicate that is eligible for the ANDA route. It will refuse to file an NDA for a product that must be licensed under the Public Health Service Act, under §314.101.
What an NDA contains under 21 CFR 314.50
21 CFR 314.50 sets the content and format of an NDA submission. The application must include every investigation the applicant sponsored, plus other pertinent information the applicant has received or obtained from any source.
The list changes with the submission type. A 505(b)(2) application, an amendment or a supplement may need only the relevant portions, not every item in the same form. Use the table as a content map, not as an electronic-submission checklist. Every row is §314.50.
| Dossier content | What it covers | Provision |
|---|---|---|
| Administration and index | Signed form, applicant and product details, proposed indications, referenced applications, submission type, enclosure checklist and full index | (a)-(b) |
| Application summary | Annotated proposed labeling, scientific rationale, marketing history, technical summaries and benefit-risk discussion | (c) |
| Chemistry, manufacturing and controls | Composition, manufacturing methods and controls, manufacturers, specifications, analytical procedures, stability and expiration dating; environmental assessment or exclusion claim | (d)(1) |
| Nonclinical evidence | Relevant pharmacology, toxicology, reproductive and developmental evidence, animal ADME information, and GLP statements or explanations | (d)(2) |
| Human pharmacokinetics and bioavailability | Study descriptions, analytical and statistical methods, compliance statements, or support for an applicable waiver | (d)(3) |
| Microbiology | Required information for anti-infective drugs | (d)(4) |
| Clinical and statistical evidence | Relevant studies, integrated safety and effectiveness information, benefit-risk summaries and supporting statistical evaluations | (d)(5)-(6) |
| Pediatric use | Integrated pediatric-use information and information required by §314.55 | (d)(7) |
| Labeling, analytical information and samples | Required labeling and analytical information; physical samples on FDA request | (e) |
| Patient-level records | Specified tabulations and case-report forms, with further records on request | (f) |
| Other applicable documents | References and authorizations, translations, patent information, applicable certifications, claimed exclusivity information and financial certification or disclosure | (g)-(k) |
Microbiology is for anti-infective drugs, not for every NDA. Pediatric use has its own row. Physical samples go in only when FDA asks for them, so don't ship a sample set with every filing. Case-report forms are required for deaths and for discontinuations caused by an adverse event, unless FDA waives that requirement. The application summary is not required for supplements under §314.70. Those limits are in §314.50(c), (e) and (f).
§314.50 also sets copy format, including electronic format. But the paper-copy counts are still printed in the regulation, which is a poor guide to a current electronic filing. Check the electronic-submission requirements that apply to the NDA in front of you.
NDA filing is different from approval
Within 60 days of receipt, FDA decides whether an NDA may be filed. Filing means the submission is complete enough to permit substantive review. FDA can refuse filing for specified completeness, format and compliance deficiencies, under §314.101.
Filing is not approval.
Once the application is in substantive review, FDA asks whether it meets the standards for safety and effectiveness, manufacturing and controls, and labeling. Approval also requires that no applicable refusal ground blocks it, under §314.105.
How long does FDA NDA review take?
FDA's goal is to take action within six months on a priority review and within ten months on a standard review. Those are action goals, not approval dates. Priority review does not change the scientific or medical standard for approval, or the evidence required, according to FDA's priority-review explanation.
Check the timing that applies to the particular application.
Approval letters and complete response letters
An approval letter approves the application on the conditions in §314.105. The product cannot be marketed before the approval date. Tentative approval leaves the product unapproved.
A complete response letter, or CRL, means FDA will not approve the application in its present form. It describes the deficiencies FDA has identified and, when possible, recommends corrective actions. FDA can issue a CRL for inadequate supporting data before it finishes the required inspections or the labeling review. A CRL does not always mean every review activity is done. See §314.110.
After a CRL, the applicant can resubmit and address every deficiency, withdraw the application, or request an opportunity for a hearing. A Class 1 resubmission of an NDA or efficacy supplement starts a two-month review cycle on the date FDA receives it. A Class 2 resubmission starts a six-month review cycle on that receipt date. A CRL is different from a refusal to file, and the applicant can continue, under §314.110.
Where to find an approved NDA in the FDA database
FDA's Drugs@FDA explanation is the public route to approved human brand-name and generic prescription drugs, OTC drugs and many therapeutic biologics. Drugs@FDA includes most drug products approved since 1939. For products approved since 1998, FDA has posted most patient information, labels, approval letters and reviews. It does not hold every historical application dossier.
RegAffairs AI's answer on new drug applications gives a source-linked account of 21 CFR Part 314. For a named product, the approval letter and review are in Drugs@FDA when FDA has posted them.