FDA & Biotech Glossary
A comprehensive reference of 50+ key terms used in drug development, FDA regulatory processes, and the biopharmaceutical industry.
Showing all 55 terms
A
Abbreviated New Drug Application (ANDA)
An application submitted to the FDA to request approval of a generic drug product. An ANDA demonstrates that the generic drug is bioequivalent to an already-approved reference listed drug, meaning it delivers the same amount of active ingredient at the same rate. ANDAs do not require the applicant to repeat costly clinical trials already performed for the original drug.
Accelerated Approval
An FDA regulatory pathway that allows drugs for serious conditions to be approved based on a surrogate endpoint rather than a direct measure of clinical benefit. The surrogate endpoint must be reasonably likely to predict clinical benefit. Sponsors receiving accelerated approval are typically required to conduct post-marketing confirmatory trials to verify the anticipated clinical benefit.
Active Pharmaceutical Ingredient (API)
The biologically active component of a drug product that produces the intended therapeutic effect. An API is combined with excipients (inactive ingredients) to create the final dosage form. The quality and purity of the API are critical to drug safety and efficacy, and manufacturing must comply with current Good Manufacturing Practice (cGMP) standards.
Adverse Event
Any undesirable experience associated with the use of a medical product in a patient. Adverse events include side effects, injuries, and any other unintended medical occurrences during treatment, whether or not they are considered related to the drug. Serious adverse events (SAEs) include death, hospitalization, disability, or life-threatening conditions and must be reported to the FDA.
Advisory Committee (AdCom)
An independent panel of outside experts convened by the FDA to provide non-binding recommendations on regulatory decisions, such as whether to approve a drug or require additional data. AdCom meetings are publicly announced and include presentations from both the FDA and the drug sponsor. While the FDA is not obligated to follow AdCom recommendations, it does so in the majority of cases.
B
Biologics License Application (BLA)
A regulatory submission to the FDA requesting permission to introduce a biologic product (such as a vaccine, blood product, gene therapy, or monoclonal antibody) into interstate commerce. A BLA includes data on safety, purity, potency, and manufacturing processes. Unlike NDAs for chemical drugs, BLAs are governed under the Public Health Service Act.
Biosimilar
A biological product that is highly similar to an already-approved reference biologic, with no clinically meaningful differences in safety, purity, or potency. Unlike generic drugs (which are chemically identical copies), biosimilars require analytical, preclinical, and clinical studies to demonstrate similarity because biologics are complex molecules produced by living cells. The FDA approves biosimilars through the 351(k) pathway.
Breakthrough Therapy Designation
An FDA designation granted to drugs intended to treat a serious condition when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies. Breakthrough therapy designation provides all the benefits of fast track designation plus intensive FDA guidance on efficient drug development. This designation was created by the FDA Safety and Innovation Act of 2012.
C
Clinical Hold
An FDA order to delay a proposed clinical investigation or to suspend an ongoing investigation. A clinical hold may be issued for safety concerns, protocol deficiencies, or insufficient information in the IND application. For Phase 1 studies, a clinical hold may be imposed if subjects would be exposed to an unreasonable and significant risk of illness or injury.
Clinical Trial
A research study conducted in human volunteers to evaluate the safety, efficacy, and optimal dosing of a medical intervention. Clinical trials follow a structured protocol and are typically conducted in sequential phases: Phase 1 (safety and dosing), Phase 2 (efficacy and side effects), and Phase 3 (large-scale efficacy confirmation). All clinical trials in the United States must be registered on ClinicalTrials.gov.
Complete Response Letter (CRL)
A letter issued by the FDA to an applicant indicating that the review of an NDA or BLA is complete and the application is not ready for approval in its present form. The CRL describes specific deficiencies that must be addressed before approval can be granted. Common reasons include manufacturing issues, insufficient clinical data, or labeling concerns. Receiving a CRL does not mean the drug will never be approved.
Compassionate Use
Also known as expanded access, this is a regulatory pathway that allows patients with serious or life-threatening conditions to access investigational drugs outside of clinical trials when no comparable or satisfactory alternative therapy options are available. The treating physician must determine that the probable risk from the drug is not greater than the probable risk from the disease. FDA authorization and institutional review board (IRB) approval are required.
D
Drug Master File (DMF)
A confidential submission to the FDA containing detailed information about the facilities, processes, or articles used in the manufacturing, processing, packaging, and storage of drugs. DMFs are not independently reviewed by the FDA but are referenced by other applicants in their regulatory submissions. There are five types of DMFs, with Type II (Drug Substance/API) being the most common.
E
Efficacy
The ability of a drug to produce the desired therapeutic effect under ideal, controlled conditions such as those in a clinical trial. Efficacy is distinguished from effectiveness, which measures how well a drug works in routine clinical practice (real-world settings). A drug must demonstrate both safety and efficacy to receive FDA approval.
Emergency Use Authorization (EUA)
A mechanism that allows the FDA to authorize the use of unapproved medical products or unapproved uses of approved medical products during a public health emergency. An EUA requires that the known and potential benefits of the product outweigh the known and potential risks. EUAs are temporary and may be revised or revoked when the emergency declaration is terminated.
Endpoint
A specific, measurable outcome used in a clinical trial to evaluate whether the drug being studied is effective. Primary endpoints are the main results measured at the end of a trial, while secondary endpoints provide additional information. Surrogate endpoints (such as tumor shrinkage) are used as substitutes for direct measures of clinical benefit (such as survival) when the surrogate is reasonably likely to predict the clinical outcome.
F
Fast Track Designation
An FDA designation designed to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need. Benefits include more frequent meetings with FDA, eligibility for accelerated approval and priority review, and the option for rolling review (submitting completed sections of the application for review before the entire application is complete).
FDA (Food and Drug Administration)
The United States federal agency within the Department of Health and Human Services responsible for protecting public health by regulating the safety and efficacy of drugs, biologics, medical devices, food, cosmetics, and tobacco products. The FDA oversees the drug approval process from preclinical testing through post-marketing surveillance and has the authority to take enforcement actions against products that violate federal law.
First-in-Human
The first clinical trial in which a new investigational drug or biologic is administered to human subjects, typically a small group of healthy volunteers. First-in-human trials (also called Phase 1a or FIH studies) are primarily designed to assess the safety, tolerability, and pharmacokinetics of a drug at various dose levels. The starting dose is determined from preclinical animal studies using established safety factors.
Formulation
The process and composition by which a drug substance (API) is combined with excipients to create the final drug product in a specific dosage form, such as a tablet, capsule, injection, or topical cream. Formulation science considers factors such as drug stability, bioavailability, patient compliance, and route of administration. Changes to formulation can significantly affect a drug's therapeutic performance.
G
Generic Drug
A drug product that contains the same active ingredient, strength, dosage form, and route of administration as an already-approved brand-name drug (reference listed drug). Generic drugs must demonstrate bioequivalence to the reference drug through an Abbreviated New Drug Application (ANDA). They are typically marketed after the expiration of the brand-name drug's patents and exclusivity periods, at significantly lower cost.
Good Manufacturing Practice (GMP)
A set of regulations enforced by the FDA that govern the design, monitoring, and control of pharmaceutical manufacturing processes and facilities. Current Good Manufacturing Practice (cGMP) ensures that drug products are consistently produced and controlled according to quality standards. GMP violations can result in FDA warning letters, import alerts, consent decrees, or product seizures.
I
IND (Investigational New Drug)
An application submitted to the FDA before a new drug can be administered to humans in clinical trials. The IND includes preclinical (animal study) data, manufacturing information, clinical protocols, and investigator qualifications. The FDA has 30 days to review an IND; if no clinical hold is issued within that period, the sponsor may proceed with clinical trials. An IND remains active throughout the entire clinical development program.
Indication
A specific disease, condition, or symptom for which a drug is approved or being studied. A single drug may have multiple indications. Each new indication typically requires separate clinical trials and a supplemental NDA (sNDA) or supplemental BLA to obtain FDA approval. The approved indications are described in the drug's prescribing information (label).
Informed Consent
A process by which a potential clinical trial participant voluntarily confirms their willingness to take part in a study after being fully informed about all aspects of the trial, including its purpose, procedures, potential risks and benefits, alternatives, and their right to withdraw at any time. Informed consent is documented through a signed consent form and is required by federal regulations (21 CFR Part 50) for all FDA-regulated clinical research.
L
Label
The FDA-approved prescribing information for a drug product, also known as the package insert or PI. The label contains detailed information about the drug's indications, dosage and administration, contraindications, warnings and precautions, adverse reactions, drug interactions, and use in specific populations. The label is a legally binding document and is distinct from marketing materials. Label updates may be required based on post-marketing safety data.
M
Mechanism of Action (MOA)
The specific biochemical interaction through which a drug produces its pharmacological effect. Understanding a drug's MOA involves identifying the molecular target (such as a receptor, enzyme, or ion channel) and describing how the drug interacts with that target to alter a biological process. The MOA is important for predicting potential drug interactions, side effects, and identifying patient populations most likely to benefit from treatment.
N
New Drug Application (NDA)
A formal application submitted to the FDA requesting approval to market a new drug for sale in the United States. The NDA includes all preclinical and clinical trial data, proposed labeling, manufacturing details, and patent information. The FDA has a standard review period of 10 months (or 6 months for priority review) from the date of filing. An approved NDA permits the manufacturer to market the drug for the specified indication(s).
New Molecular Entity (NME)
An active pharmaceutical ingredient that has never before been approved by the FDA in any form. NMEs represent truly novel drugs as opposed to new formulations, combinations, or indications for previously approved active ingredients. NME approvals are closely tracked by the pharmaceutical industry as a measure of innovation and are reported in the FDA's annual Novel Drug Approvals summary.
Noninferiority Trial
A type of clinical trial designed to demonstrate that a new treatment is not worse than an existing standard treatment by more than a pre-specified margin (the noninferiority margin). Unlike superiority trials, which aim to prove one treatment is better, noninferiority trials show that a new drug provides comparable efficacy while potentially offering advantages such as fewer side effects, more convenient dosing, or lower cost.
O
Off-Label Use
The practice of prescribing an FDA-approved drug for an unapproved indication, age group, dose, or form of administration. Off-label use is legal and common in medical practice, particularly in oncology and pediatrics. However, it is not based on the same level of evidence as approved uses, and pharmaceutical companies are prohibited from promoting their products for off-label purposes.
Orange Book
Officially titled "Approved Drug Products with Therapeutic Equivalence Evaluations," the Orange Book is an FDA publication that lists all approved drug products, their patent and exclusivity information, and therapeutic equivalence evaluations. It is the primary reference used by pharmacists and generic manufacturers to determine whether a generic drug can be substituted for a brand-name product. The Orange Book is updated daily in its electronic version.
Orphan Drug Designation
An FDA designation granted to drugs intended to treat rare diseases or conditions affecting fewer than 200,000 people in the United States. Orphan drug designation provides financial incentives including 7 years of marketing exclusivity upon approval, tax credits for clinical testing costs, and eligibility for FDA grant funding. The Orphan Drug Act of 1983 has been credited with stimulating the development of hundreds of drugs for rare diseases.
P
Patent Cliff
A sharp decline in revenue experienced by a pharmaceutical company when the patent protection on one or more of its key drugs expires, allowing generic competitors to enter the market. Generic entry typically reduces the brand-name drug's market share significantly within months. Patent cliffs are a major consideration in pharmaceutical business strategy and often drive mergers, acquisitions, and pipeline investment decisions.
PDUFA (Prescription Drug User Fee Act)
A United States federal law first enacted in 1992 that authorizes the FDA to collect fees from drug manufacturers to fund the drug review process. Under PDUFA, the FDA sets target action dates (PDUFA dates) by which it aims to complete its review of new drug applications. PDUFA dates are closely watched by the pharmaceutical industry and investors as they indicate when an FDA approval decision is expected.
Phase 1 Clinical Trial
The first stage of clinical testing in humans, typically involving 20 to 100 healthy volunteers or patients. Phase 1 trials are primarily designed to evaluate the safety, tolerability, pharmacokinetics (how the body processes the drug), and pharmacodynamics (how the drug affects the body) of an investigational drug. Dose-escalation studies help determine the maximum tolerated dose and identify dose-limiting toxicities.
Phase 2 Clinical Trial
The second stage of clinical testing, typically involving several hundred patients with the target disease or condition. Phase 2 trials are designed to evaluate the drug's efficacy (whether it works), determine the optimal dosage, and further assess safety. Phase 2 trials are often divided into Phase 2a (dose-finding) and Phase 2b (efficacy). Approximately 33% of drugs that enter Phase 2 testing proceed to Phase 3.
Phase 3 Clinical Trial
The third and typically largest stage of clinical testing, involving several hundred to several thousand patients across multiple sites. Phase 3 trials (also called pivotal trials) are designed to confirm the drug's efficacy, monitor side effects, compare the drug to commonly used treatments, and collect information for the drug label. Successful Phase 3 results are generally required to support an NDA or BLA submission.
Phase 4 Clinical Trial
Clinical studies conducted after a drug has received FDA approval and is on the market. Phase 4 trials (also called post-marketing studies) are designed to gather additional information about a drug's long-term risks, benefits, and optimal use in broader patient populations. Some Phase 4 studies are required by the FDA as a condition of approval, particularly for drugs that received accelerated approval.
Pivotal Trial
A clinical trial (usually Phase 3) that provides the primary evidence of efficacy and safety used to support a regulatory submission for marketing approval. Pivotal trials are typically randomized, controlled, and adequately powered to detect a clinically meaningful treatment effect. The FDA generally requires at least one (and often two) adequate and well-controlled pivotal studies to approve a new drug.
Placebo
An inactive substance or treatment that looks identical to the active drug being studied but contains no therapeutic ingredient. Placebos are used as comparators in clinical trials to help distinguish actual drug effects from the psychological effects of receiving treatment (the placebo effect). Placebo-controlled trials are considered the gold standard for establishing drug efficacy, though ethical considerations sometimes require the use of active comparators instead.
Post-Marketing Surveillance
The ongoing monitoring of a drug's safety after it has been approved and is available for widespread clinical use. Post-marketing surveillance relies on voluntary adverse event reporting through the FDA's MedWatch system, mandatory reporting by manufacturers, and active surveillance databases. This phase can identify rare or long-term adverse effects not detected during clinical trials due to limited sample sizes and study durations.
Priority Review
An FDA review designation that shortens the target review time for an NDA or BLA from the standard 10 months to 6 months. Priority review is granted to applications for drugs that, if approved, would represent a significant improvement in safety or effectiveness compared to available therapies. Priority review affects only the review timeline and does not change the scientific or evidentiary standards required for approval.
Purple Book
The FDA's database of licensed biological products, including biosimilars and interchangeable biosimilars. Similar in purpose to the Orange Book for drugs, the Purple Book provides information about FDA-licensed biological products regulated under the Public Health Service Act. It indicates whether a biosimilar has been determined to be interchangeable with its reference product, meaning it can be substituted by a pharmacist without the prescriber's intervention.
R
Randomized Controlled Trial (RCT)
A type of clinical study in which participants are randomly assigned to receive either the experimental treatment or a control (placebo or active comparator). Randomization minimizes selection bias and ensures that known and unknown confounding factors are distributed evenly between treatment groups. Double-blind RCTs, where neither participants nor investigators know the treatment assignments, are considered the highest level of evidence for determining drug efficacy.
Real-World Evidence (RWE)
Clinical evidence regarding the usage, potential benefits, and risks of a medical product derived from analysis of real-world data, which includes electronic health records, claims databases, patient registries, and other sources outside of traditional clinical trials. The 21st Century Cures Act (2016) requires the FDA to evaluate the use of RWE to support new indications for approved drugs and to satisfy post-marketing study requirements.
Recall (Class I/II/III)
An action taken by a firm to remove a product from the market when there is reason to believe it may be in violation of FDA regulations. Class I recalls involve situations where the use of or exposure to the product carries a reasonable probability of serious adverse health consequences or death. Class II recalls involve situations where the product may cause temporary or medically reversible adverse health consequences. Class III recalls involve products that are unlikely to cause adverse health consequences.
Reference Listed Drug (RLD)
The FDA-approved brand-name drug product to which a generic drug applicant must demonstrate bioequivalence. The RLD is identified in the FDA's Orange Book and serves as the standard against which the safety and efficacy of a generic drug are compared. Selection of the appropriate RLD is one of the first steps in developing a generic drug product through the ANDA pathway.
REMS (Risk Evaluation and Mitigation Strategy)
A required risk management plan that uses strategies beyond professional labeling to ensure that the benefits of certain prescription drugs outweigh their risks. REMS may include medication guides, communication plans for healthcare providers, and elements to assure safe use (ETASU) such as restricted distribution programs. The FDA can require a REMS at the time of approval or post-approval if new safety information emerges.
S
Safety Signal
Information arising from one or multiple sources (including observations, experiments, and post-marketing surveillance) that suggests a new, potentially causal association or a new aspect of a known association between a drug and an adverse event. Detection of a safety signal does not necessarily mean that the drug caused the event; it indicates the need for further investigation. The FDA uses various data mining tools and surveillance systems to detect safety signals.
Section 505(b)(2)
A regulatory pathway under the Federal Food, Drug, and Cosmetic Act that allows an NDA applicant to rely in part on FDA's findings of safety and efficacy for a previously approved drug (or on published scientific literature) rather than conducting all required studies independently. This pathway is commonly used for new formulations, new dosage forms, new combinations, or new indications of previously approved drugs, and is sometimes described as a hybrid between a full NDA and an ANDA.
SIC Code
Standard Industrial Classification code, a four-digit numerical code assigned by the U.S. government to classify the primary business activity of a company. In the pharmaceutical and biotech industry, relevant SIC codes include 2833 (Pharmaceutical Preparations), 2834 (In Vitro Diagnostic Substances), 2835 (Diagnostic Substances), 2836 (Biological Products), and 3841 (Surgical and Medical Instruments). SIC codes are used by the SEC in EDGAR filings and by researchers to identify and compare companies within the same industry.
Supplemental NDA (sNDA)
An application submitted to the FDA requesting approval to change the labeling, formulation, manufacturing process, or approved indications for a drug that has already received NDA approval. An sNDA for a new indication requires clinical data demonstrating the drug's safety and efficacy for the proposed new use. Supplemental BLAs serve the same function for biological products. sNDAs allow companies to expand the uses of existing drugs without filing an entirely new NDA.
T
Therapeutic Equivalence
A determination by the FDA that two drug products are pharmaceutical equivalents (same active ingredient, dosage form, strength, and route of administration) and are bioequivalent, meaning they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling. Therapeutic equivalence codes (such as AB-rated) are published in the Orange Book and indicate whether generic substitution is appropriate.
W
Warning Letter
An official FDA communication sent to a company or individual when the FDA has identified significant regulatory violations that may lead to enforcement action if not promptly corrected. Warning letters are issued for violations such as GMP failures, unapproved marketing claims, data integrity issues, or failure to report adverse events. Companies typically have 15 business days to respond with a corrective action plan. Warning letters are made publicly available on the FDA website.