FDA approval terms, in plain language

Our research quotes FDA letters, and FDA letters use the agency's own vocabulary. This page explains those words in plain language. Each entry has three parts:

• In plain words: our explanation, written for someone new to the subject.
• The FDA's words, in a shaded box: quoted from an FDA web page or guidance, with a link so you can read more.
• In our research: where the term appears in a published question page.

The journey in one paragraph#

A company (the sponsor) tests a drug in clinical trials, then asks the FDA to approve it by submitting an NDA or BLA. The FDA reviews it against a deadline set under PDUFA, sometimes asking an advisory committee for outside advice. Then it either approves the drug, or sends a Complete Response Letter saying what must be fixed. After a letter, the company can meet the FDA (often a Type A meeting), fix the problems and resubmit, or appeal. Our research follows companies through exactly this loop.

The application#

New Drug Application NDA

The company's formal request to sell a new drug in the United States. It contains everything learned about the drug in animal and human studies.

“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.”FDA · New Drug Application (NDA)

Aldeyra's reproxalap is NDA 216442; CorMedix's DefenCath is NDA 214520; Verrica's VP-102 is NDA 212905.

Biologics License Application BLA

The same idea as an NDA, for biological products: medicines made from living systems, such as antibodies, gene therapies and engineered viruses.

“A Biologics License Application (BLA) is the formal submission to the U.S. Food and Drug Administration (FDA) through which an applicant requests permission to introduce a biological product into interstate commerce”FDA · Biologics License Applications (BLAs) for CBER-Regulated Products

Replimune's RP1, an engineered virus, is BLA 125827; Outlook's ONS-5010, an antibody, is BLA 761320.

Breakthrough therapy designation

A label the FDA can give a promising drug early, for a serious disease, so that it gets more FDA attention during development. It is not an approval, and it does not promise one.

“Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).”FDA · Breakthrough Therapy

After its second letter, Replimune's 8-K said it “disagrees with the FDA about whether the data set, upon which breakthrough therapy designation was awarded, is sufficient”. Read it →

Special Protocol Assessment SPA

Before running a key trial, a company can ask the FDA to agree on how the trial is designed. An agreement helps, but it does not guarantee approval.

“SPA is a process in which sponsors may ask to meet with FDA to reach agreement on the design and size of certain clinical trials, clinical studies, or animal studies … to determine if they adequately address scientific and regulatory requirements for a study that could support marketing approval.”FDA guidance · Special Protocol Assessment (April 2018)

“… the existence of an SPA agreement does not mean that the application as a whole will meet the statutory standard for approval.”Same guidance, PDF

Outlook had an SPA agreement on its NORSE EIGHT trial; the trial then missed its week-8 endpoint. Aldeyra's filings describe an “SPA - No Agreement letter”. Read it →

Meetings with the FDA#

Type A meeting

An urgent, formal meeting with the FDA, used when a programme is stuck, for example right after a Complete Response Letter.

“Type A meetings are those that are necessary for an otherwise stalled drug or biological product development program to proceed or to address an important safety issue.”FDA guidance · Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products (August 2026)

All five companies with question webs met the FDA in a Type A meeting after a letter. Replimune's, September 2025 →

Type D meeting

A shorter, focused meeting on one or two specific questions.

“Type D meetings are focused on a narrow set of issues at key decision points to provide timely feedback critical to move the program forward (e.g., often one, but typically not more than two issues and associated questions).”Same guidance

Aldeyra held Type A and Type D meetings after its March 2026 letter. Read it →

The review#

PDUFA, goal date and action date

PDUFA is the law under which companies pay the FDA fees to review their applications, and the FDA commits to review deadlines. The deadline for one application is its PDUFA goal date. The date the FDA actually acts (approves, or sends a letter) is the action date.

“The Prescription Drug User Fee Act (PDUFA) was created by Congress in 1992 and authorizes FDA to collect user fees from persons that submit certain human drug applications for review …”FDA · Prescription Drug User Fee Amendments

“The action date tells when an FDA regulatory action, such as an original or supplemental approval, took place.”FDA · Drugs@FDA Glossary of Terms

Replimune's resubmission was given an action date of April 10, 2026: the date of its second letter. Read it →

Advisory committee

A panel of outside experts the FDA can ask for advice on an application. Members often vote, but the vote is advice: the FDA makes the decision.

“Their recommendations are just that--advice--and do not bind the agency to any decision.”FDA · Advisory Committees: Critical to the FDA's Product Review Process

“While committee discussions and final votes are very important to the FDA, the final regulatory decision rests with the agency.”Same page

A committee voted 10 to 3 on RP1 in July 2026, and accelerated approval followed in August. Read it →

Labeling and Prescribing Information

The official instructions that come with an approved drug: what it treats, how to dose it, and its risks. The FDA and the company agree the wording near the end of a review, so draft labels are a sign a review is advanced, but not a promise of approval.

“Human prescription drug labeling: Contains a summary of the essential scientific information needed for the safe and effective use of the drug; and Includes the Prescribing Information, FDA-approved patient labeling (Medication Guides, Patient Package Inserts, and/or Instructions for Use), and/or carton and container labeling.”FDA · Labeling Resources for Human Prescription Drugs

Aldeyra says the FDA sent draft labels in December 2025 and March 2026; the March 2026 letter still refused approval. Read it →

The decision#

Complete Response Letter CRL

The FDA's letter saying it will not approve an application as it stands, and why. It is not a final “no”: it lists the problems (the deficiencies) and often what would fix them. Since July 2025, the FDA has published these letters.

“The FDA issues CRLs for various reasons, most related to safety and efficacy concerns, manufacturing deficiencies, and bioequivalence issues. These deficiencies are detailed in the letter and may also include recommendations for addressing them.”FDA press announcement · July 10, 2025

“This database contains Complete Response Letters (CRLs) associated with approved and unapproved New Drug Applications (NDAs) and Biologics License Applications (BLAs).”openFDA · Complete Response Letters

Every question web starts from one or more of these letters. What did the FDA's second letter to Replimune object to? →

Accelerated approval

A faster route to approval for drugs for serious diseases with few options. Instead of waiting to see whether patients live longer or feel better, the FDA can approve based on an earlier sign (a surrogate endpoint) that is likely to predict that benefit. The company must then prove the benefit in a confirmatory trial.

“The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint.”FDA · Accelerated Approval Program

RP1 received accelerated approval in August 2026, based on response rate and duration of response. Read it →

Traditional approval

The standard kind of approval, based on evidence that the drug actually benefits patients. A drug on accelerated approval can be converted to traditional approval once its benefit is confirmed.

“If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug.”FDA · Accelerated Approval Program

Surrogate endpoint

A measurement that stands in for what patients really care about. Tumour shrinkage on a scan is a surrogate; living longer is the real outcome.

“A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit.”FDA · Accelerated Approval Program

“Clinical outcomes directly measure whether people in a trial feel or function better, or live longer.”FDA · Surrogate Endpoint Resources for Drug and Biologic Development

The FDA's letter on REGENXBIO's RGX-121 questioned whether a biomarker was “reasonably likely to predict clinical benefit”. See the concept preview →

Confirmatory trial and postmarketing requirement

After an accelerated approval, the company must run a further study to confirm the real benefit. This obligation is a postmarketing requirement: it continues after the drug is on sale.

“Drug companies are still required to conduct studies to confirm the anticipated clinical benefit.”FDA · Accelerated Approval Program

Replimune once said RP1 would not be viable without accelerated approval; continued approval may now depend on its Phase 3 trial. Read it →

After a Complete Response Letter#

Resubmission: Class 1 and Class 2

After fixing the problems, the company sends the application back. The FDA sorts resubmissions into two classes. Class 1 is for small items, such as labeling or minor reanalyses, and gets a two-month review goal. Class 2 is everything else, and gets six months.

“Class 1 Resubmission - A resubmission submitted after a CR letter that includes one or more of the following items …” · “Class 2 Resubmission - A resubmission that includes any other item not specified as a Class 1 item …” · “Class 1 within 2 months of the receipt date.” · “Class 2 within 6 months of the receipt date.”FDA (CBER) · SOPP 8405.1, Procedures for Resubmissions to an Application

Replimune and Outlook both filed Class 1 resubmissions in June 2026. Connections across cases →

Formal dispute resolution

An appeal. If a company disagrees with a scientific or medical decision by the FDA review division, it can take the dispute to a higher level of the FDA, such as the Office of New Drugs.

“This guidance describes the formal dispute resolution (FDR) procedures for sponsors that wish to appeal a scientific and/or medical issue to the office or center level and provides a structured process for resolving disputes.”FDA guidance · Formal Dispute Resolution: Sponsor Appeals Above the Division Level (November 2017)

Outlook says its appeal was granted in May 2026; Aldeyra announced its intent to file one in September 2026. Read it →

The evidence standard#

Substantial evidence of effectiveness

The legal bar a drug must clear: enough good-quality evidence that experts could fairly conclude the drug works. When a letter says the data are “insufficient to conclude substantial evidence of effectiveness”, it means this bar was not met.

“… substantial evidence is defined as: evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have …”FDA draft guidance · Demonstrating Substantial Evidence of Effectiveness (2026), quoting section 505(d) of the FD&C Act

The FDA's second letter to Replimune: “unanimously determined data presented are insufficient to conclude substantial evidence of effectiveness”. Read it →

Adequate and well-controlled study

A study designed so its results can be trusted: usually comparing the drug against a control group, with methods fixed in advance. When the FDA asks for “an additional adequate and well-controlled study”, it is asking for another trial of that quality.

FDA's draft guidance explains how a sponsor “can rely on one scientifically rigorous adequate and well-controlled clinical investigation with confirmatory evidence to satisfy the statutory substantial evidence of effectiveness standard”.FDA draft guidance · Demonstrating Substantial Evidence of Effectiveness (2026)

Aldeyra's 2023 and 2025 letters both asked for “at least one additional adequate and well controlled study”. Read it →

Confirmatory evidence

Supporting evidence that, together with one strong trial, can be enough for approval: for example a second, smaller study, or data showing how the drug works in the body. Not the same as a confirmatory trial after accelerated approval.

“FDA will consider many factors in assessing whether one adequate and well-controlled trial plus confirmatory evidence is sufficient for demonstrating substantial evidence of effectiveness.”Same draft guidance

Outlook reports that the FDA's Office of New Drugs found its NORSE TWO trial, with confirmatory evidence including NORSE EIGHT, established substantial evidence. Read it →

Manufacturing and inspections#

Chemistry, manufacturing and controls CMC

Everything about making the drug consistently and safely: the ingredients, the factory, the process, the tests. A drug can work in trials and still be refused because of CMC problems. (CMC is an industry term; the FDA's press announcement lists “manufacturing deficiencies” as one of the main reasons for letters.)

CorMedix's two letters on DefenCath turned on its manufacturer and a heparin supplier, not on whether the drug worked. Read it →

Inspection and Form 483

Before approving a drug, the FDA may inspect the factories that will make it. If inspectors see problems, they hand the company a Form 483 listing their observations at the end of the visit.

“An FDA Form 483 is issued to firm management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts.”FDA · Form 483 Frequently Asked Questions

NAI, VAI and OAI

The FDA's grade for an inspection, from best to worst: NAI (no action), VAI (problems the company can fix voluntarily), OAI (serious problems; the FDA may act).

“No Action Indicated (NAI) classification indicates a facility is in an acceptable state of compliance.” · “Voluntary Action Indicated (VAI) classification indicates the inspection found objectionable conditions or practices but the agency has determined the facility can voluntarily correct its deficiencies and will not recommend any action.” · “Official Action Indicated (OAI) classification indicates a facility is in an unacceptable state of compliance.”FDA · Inspection Classification Database

Verrica's contract manufacturer was classified VAI in November 2021, then OAI after a reinspection in May 2022, days before Verrica's third letter. Read it →

Warning letter

A public FDA letter telling a company it has found significant violations. A warning letter to a supplier can hold up another company's application if that supplier makes an ingredient for it.

“When FDA identifies what it believes are significant violation(s) of federal requirement(s), FDA notifies the appropriate party.”FDA · About Warning and Close-Out Letters

A heparin supplier's warning letter, about a different product, became a condition in CorMedix's second letter. Read it →

Drug master file DMF

A confidential file a supplier gives the FDA about how it makes an ingredient or material, so that drug companies can rely on it without seeing the supplier's secrets.

“Drug master files (DMFs) are submissions to FDA used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products.”FDA · Drug Master Files (DMFs)

Human factors

Whether real people (nurses, doctors, patients) can use a product safely as designed: open it, measure it, apply it, without mistakes. For a drug that comes with a device or applicator, the FDA reviews this too. (Our explanation; the term comes from the FDA's device and combination-product guidance.)

Verrica's 2020 letter turned on a glass ampule that users struggled to break. Read it →

Sources#

All quotations on this page were checked against the FDA pages and documents linked beside them on October 7, 2026. FDA pages change; if a link has moved, search the title on fda.gov.

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