Glossary

An Abbreviated New Drug Application is the application for a generic drug. It is abbreviated because it generally need not repeat the preclinical and clinical data in the brand's application. A generic product is comparable to the brand in dosage form, strength, route of administration, quality, performance and intended use.^[1]

An adverse event is anything undesirable that happens to a patient while a product is in use, whether or not the product caused it. In FDA's prescription labeling rules, an adverse reaction is narrower: an undesirable effect reasonably associated with use of the drug. FDA's rule says the term does not cover every adverse event, only those with some basis to believe there is a causal relationship.^[2]

Section 6 of a prescription label in the current format. It describes the drug's overall adverse reaction profile, based on the entire safety database, and lists the reactions seen with the drug.^[2] Older labels use a different layout, so the same fact can sit in a different section.

A panel of scientific experts and consumer representatives recruited by FDA to advise the agency. FDA publishes committee membership and the laws and guidance that govern the committees.^[3]

The Anatomical Therapeutic Chemical classification sorts drugs into groups by the organ or system on which they act and by their therapeutic, pharmacological and chemical properties. Drugs are classified at five levels, from 14 main anatomical or pharmacological groups down to the chemical substance.^[4]

An early trial chosen from a large group of similar cases, usually in an MDL, to test how a jury responds and to inform settlement talks. The outcome binds only the parties to that case.

A Biologics License Application is the application to introduce a biological product into interstate commerce. The framework sits in the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act, with requirements in 21 CFR Parts 600 to 680.^[5]

A warning FDA may require in a box at the top of the label, for certain contraindications or serious warnings, particularly those that may lead to death or serious injury. It ordinarily rests on clinical data and refers the reader to the detailed section.^[6]

Health Canada's Canada Vigilance Adverse Reaction Online Database holds information about suspected adverse reactions to health products. Health Canada's own page says it should not be used on its own to evaluate a health product's safety profile.^[7]

Shorthand for the "Changes Being Effected" supplement: the application holder adds or strengthens a warning, precaution or adverse reaction and may use the changed label on submission, without waiting for FDA's approval. The change must rest on newly acquired information, and the evidence of a causal association must meet the standard for including it in the labeling. The rule is 21 CFR 314.70(c)(6)(iii).^[8] The "0" is informal; a CBE-30 change is distributed no sooner than 30 days after FDA receives it.^[8] The Supreme Court described this mechanism in Wyeth v. Levine.^[9]

A written request to the FDA Commissioner to issue, amend or revoke a regulation or order, or to take or refrain from any other administrative action. FDA's rule sets the form a petition must take.^[10]

The standard from Merck Sharp & Dohme Corp. v. Albrecht for a drug maker arguing that FDA would not have approved the label change a plaintiff says was needed. The Court held that it is evidence showing that the manufacturer fully informed FDA of the justifications for the warning that state law required, and that FDA in turn told the manufacturer it would not approve a change to the label to add that warning. The judge decides it as a question of law.^[11] See Preemption.

The letter FDA sends when it decides it will not approve an application in its present form. It describes the specific deficiencies.^[12]

The National Library of Medicine's site for drug labeling, built on FDA's Structured Product Labeling files. Its "in use" labeling may not match the most recent FDA-approved labeling, and NLM does not review SPL content before publication. For the latest FDA-approved labeling, DailyMed points to Drugs@FDA.^[13]

In Daubert v. Merrell Dow Pharmaceuticals (1993), the Supreme Court held that Rule 702 assigns the trial judge the task of ensuring that an expert's testimony rests on a reliable foundation and is relevant to the task at hand.^[14] Rule 702 now says the proponent must demonstrate to the court that it is more likely than not that the expert's knowledge will help the trier of fact, the testimony rests on sufficient facts or data, it is the product of reliable principles and methods, and the opinion reflects a reliable application of those methods to the facts. A "Daubert motion" asks the court to exclude an expert on these grounds.^[15]

The FDA pathway for a new device with no legally marketed predicate device, for which general controls, or general and special controls, provide reasonable assurance of safety and effectiveness. A device classified through De Novo into class I or class II can serve as a predicate for later 510(k) submissions.^[16]

A doctrine that delays the start of a limitations period until the plaintiff has "discovered" the cause of action. In Merck & Co. v. Reynolds, a securities case against Merck, the Supreme Court discussed the rule and what counts as discovery.^[17]

A statistical screen of spontaneous reports that asks whether a drug and an event are reported together more often than the rest of the database predicts. The standard measures are PRR, ROR, IC and EBGM, the last being the Bayesian shrinkage method FDA uses. A high score flags the pair for review. FDA states that reports cannot establish causation or rates of occurrence.^[18] See Signal.

FDA's public notice of a new safety issue with a drug. When FDA learns of a potential new safety issue, it may require changes to the prescribing information or the Medication Guide, and may release a Drug Safety Communication to alert patients and health professionals.^[19]

FDA's database of approved drug products, with application histories, labeling and review documents. DailyMed points to it for the most current FDA-approved labeling of prescription products.^[13][20]

The same event reported more than once, for example by the patient, the doctor and the company. FDA's page warns that its adverse event data contain duplicate and incomplete reports.^[18] Kelsey counts one report per FAERS case id, finds likely duplicates across case ids by record linkage, and shows how the measures move without them.

The Pharmacovigilance Risk Assessment Committee, the European Medicines Agency's committee for assessing and monitoring the safety of human medicines. It meets monthly, and EMA publishes its agendas, minutes and meeting highlights.^[21]

The FDA Adverse Event Reporting System. It holds adverse event reports, medication error reports and product quality complaints that resulted in adverse events, submitted to FDA for drugs and therapeutic biologics. Events are coded with MedDRA. FDA's pages now carry the name Adverse Event Monitoring System (AEMS), with FAERS shown as the former name.^[22] FDA lists four limits: duplicate and incomplete reports; a report does not establish causation; reports are not verified; and rates of occurrence cannot be established from reports.^[18]

A product liability claim that a manufacturer did not give an adequate warning of a risk. For prescription drugs the question is usually what the label said at the time, and what the manufacturer knew or could have added. Wyeth v. Levine was a failure-to-warn case about the drug Phenergan.^[9]

Whether a product can cause a given injury in the population at all. It is usually decided on epidemiology, trials and mechanism, and it is a common ground for a Rule 702 challenge. See Specific causation.

The Global Unique Device Identification Database. AccessGUDID, its public search, holds device identification information such as the device identifier, device name, company name, MR safety status and premarket submission numbers.^[23]

The Canadian federal health department. Its MedEffect program hosts the adverse reaction database; see Canada Vigilance.^[7]

The Judicial Panel on Multidistrict Litigation decides whether civil actions pending in different federal districts should be transferred to one district for coordinated pretrial proceedings. Its website lists its orders and pending MDLs.^[24] See MDL.

The FDA-approved text that accompanies a prescription drug: indications, dosing, contraindications, warnings, adverse reactions and more. The current format, set by 21 CFR 201.57, puts a Boxed Warning, when there is one, at the top, and then numbered sections, among them 4 Contraindications, 5 Warnings and Precautions and 6 Adverse Reactions.^[6] A label has many versions over time, and the version in force on a given date is often the question.

The doctrine that a prescription product's manufacturer meets its duty to warn by properly warning the prescribing physician, who then advises the patient. In the Fifth Circuit's words, the manufacturer is relieved from warning each patient who receives the product when it properly warns the prescribing physician of the product's dangers.^[25]

The Manufacturer and User Facility Device Experience database, where FDA publishes medical device reports (MDRs). The downloadable files hold voluntary reports since June 1993, user facility reports since 1991, distributor reports since 1993 and manufacturer reports since August 1996. FDA says MDR data are not meant to evaluate event rates or to compare rates across devices, and that a report does not by itself show the device caused the event.^[26]

Multidistrict litigation. Under 28 U.S.C. § 1407, when civil actions involving common questions of fact are pending in different districts, the JPML may transfer them to one district for coordinated or consolidated pretrial proceedings. Each action is remanded to its original court at or before the conclusion of those proceedings, unless it has been terminated before then.^[27]

The Medical Dictionary for Regulatory Activities, a standard medical terminology. FDA codes FAERS adverse events and medication errors in MedDRA terms.^[22] One clinical idea such as "eye damage" can map to many MedDRA terms, so a count depends on the term list behind it.

FDA's medical product safety reporting program for health professionals, patients and consumers. It receives reports from the public and, when appropriate, publishes safety alerts for drugs, biologics and medical devices.^[28]

The Medicines and Healthcare products Regulatory Agency regulates medicines, medical devices and blood components for transfusion in the United Kingdom.^[29]

A New Drug Application is how a sponsor formally proposes that FDA approve a new drug for sale in the United States. Since 1938, every new drug has needed an approved NDA before U.S. commercialization.^[30]

In FDA's rule, data, analyses or other information not previously submitted to the agency, which may include new clinical studies, reports of adverse events or new analyses of previously submitted data such as meta-analyses, if they reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA.^[31] A label change under the CBE process is tied to such information.

FDA's Approved Drug Products with Therapeutic Equivalence Evaluations. It identifies drug products approved on the basis of safety and effectiveness under the Federal Food, Drug, and Cosmetic Act, with related patent and exclusivity information.^[32]

Premarket approval, FDA's review for Class III devices: those that support or sustain human life, are of substantial importance in preventing impairment of human health, or present a potential, unreasonable risk of illness or injury.^[33]

The rule that federal law overrides conflicting state law. In drug cases, the main form is impossibility: state and federal law conflict where it is impossible for a private party to comply with both. In PLIVA v. Mensing, the Court found impossibility for failure-to-warn claims that would have required generic makers to change their labels on their own, because they have a federal duty of "sameness" with the brand label.^[34] A brand maker can raise preemption by showing "clear evidence" that FDA would have rejected the warning.^[11]

A supplement for a major change that must be submitted and approved by FDA before the changed product is distributed. 21 CFR 314.70(b) sets the rule for major changes to the drug substance, product, process, controls, equipment or facilities.^[35] A change that adds or strengthens a warning, precaution or adverse reaction may instead go through CBE when it meets that rule's standard.^[8]

Class I is a situation with a reasonable probability that use of or exposure to a violative product will cause serious adverse health consequences or death. Class II is where it may cause temporary or medically reversible adverse health consequences, or where the probability of serious consequences is remote. Class III is where it is not likely to cause adverse health consequences.^[36]

A Risk Evaluation and Mitigation Strategy is a drug safety program that FDA can require for certain medications with serious safety concerns, to help ensure the benefits outweigh the risks.^[37]

A National Library of Medicine vocabulary of normalized names for clinical drugs, linked to many of the drug vocabularies used in pharmacy management and drug interaction software.^[38]

A type of NDA that contains full reports of investigations of safety and effectiveness but where at least some of the information required for approval comes from studies not conducted by or for the applicant, and for which the applicant has not obtained a right of reference.^[39]

A power under the Food, Drug, and Cosmetic Act. If FDA becomes aware of new safety information that it determines should be in the labeling, it notifies the responsible person, who must within 30 days either submit a supplement proposing the changes or submit a statement of reasons why a change is not warranted.^[40]

A premarket submission to FDA to show that a device is substantially equivalent to a legally marketed device. FDA's order finding substantial equivalence "clears" the device for sale.^[41] The clearance rests on comparison with the predicate device.

A pattern in the data that calls for review. FDA publishes a list of new safety information or potential signals of serious risks identified from its adverse event system.^[22] FDA states that a report does not establish causation.^[18]

Whether a product caused this plaintiff's injury. It is usually decided on the individual's history, timing, dose and alternative explanations. See General causation.

An unsolicited report of an adverse event from a patient, health professional or company, outside a study. MedWatch receives such reports from the public.^[28] FAERS and MAUDE are built largely from them, which is why FDA warns they cannot give rates of occurrence.^[18][26]

Structured Product Labeling, a document markup standard approved by Health Level Seven (HL7) and adopted by FDA as a way to exchange product and facility information. DailyMed publishes labels as SPL.^[42]

A statute that frees a defendant from liability after a legislatively determined time, measured from the date of the defendant's last culpable act, regardless of when the plaintiff was injured or discovered the injury. A statute of limitations runs from when a claim accrues. The Supreme Court drew this line in CTS Corp. v. Waldburger.^[43]

A filing that changes an approved application, for example to change the label. FDA's guidance notes that a supplement to an application is a new drug application.^[39] Label supplements come in the CBE and prior approval forms described above.^[8]

FDA's letter to a company about violations it has found. FDA publishes warning letters in a searchable list, with the posted date, letter issue date, company, issuing office and subject.^[44]

Section 5 of a prescription label in the current format. It describes clinically significant adverse reactions (including any that are potentially fatal, serious even if infrequent, or preventable through appropriate use) and other potential safety hazards.^[45]