21 CFR Part 11 - Terms and Acronyms
AIQ (Analytical Instrument Qualification)
Process of ensuring that an instrument is suitable for its intended application.
Acronym covering the FDA’s definition of data integrity of electronics records. Complete, consistent and accurate record include data that is “Attributable, Legible, Contemporaneously recorded, Original (or a true copy) and Accurate. Contemporaneous recording of test data in important as manual transcription at a late time introduces the potential for human error.
In terms of electronic records, computer generated time stamped audit trail provides credence and providence to digital produced signatures and retained records. Upon request, operators must be ready to provide a copy of the audit trail associated with a specific electronic record to the FDA Inspector either on paper or via electronic means.
System(s) where a company can verify the identity of all users prior to granting access to an ER/ES system where only electronic signatures are required (username & password combination). This is different from an Open System where a company cannot identify all users prior to granting access to an ERES system. In open systems, digital signatures are required in addition to electronic signatures (e.g., HTTPS, digital certificate, etc.)
An electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified.
A compilation of any symbol(s) executed to be the legally binding equivalent of an individual’s handwritten signature.
Any combination of text, graphics, data, audio, or pictorial information represented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer.
Acronym for Electronic Record/Electronic Signature.
International Organization for Standardization (founded 1947). ISO is an independent, non-governmental international organization with a membership of 165 national standards bodies. In 2015 ISO made 1,505 standards, had 162 members and 3,535 technical committees, worked on 1,827 new projects and was involved with 702 international organizations.
Japanese Pharmacopeia, Official pharmacopoeia of Japan.
United States Pharmacopoeia (founded 1820). USA is a scientific non-profit organization that sets standards for the identity, strength, quality and purity of medicines, food ingredients and dietary supplements manufactured, distributed and consumed worldwide. USP’s drug standards are enforceable in the United States by the Food and Drug Administration, and these standards are used in more than 140 countries.
Preferred Terms for Measuring Detection Capability of a Measurement System
Limit of Blank (LoB)
LoB is the highest measured test result likely to be observed (typically at 95% certainty) for a sample containing no analyte. It is the highest test response expected to be observed when a blank sample containing no analyte is repeatedly sampled – values above LoB are not consistent with the absence of analyte. LoB replaces what had become familiar as the analytical sensitivity of a method, and defines the upper limit when measuring a blank sample. If a blank sample yields a test result that is greater than the LoB, this is a Type I error, the risk is designated α, and usually assigned a risk of 0.05
Limit of Detection (LoD)
LoD is the lowest concentration where analyte can be detected 95% of the time (a 5% likelihood of a false negative). Alternatively stated, LoD is the true value where the likelihood of a false negative measurement is 5%. LoD is determined by first determining LoB and then conducting a study using replicate results of a test sample with a very low concentration of the analyte. Mathematically, LoD can be calculated as LoD = LoB + (1.645 × the SD of a low concentration sample). If a sample with low concentration of the analyte is measured below the LoD, this is termed a Type II error and the risk of this false negative is designated β. The LoD is set at a concentration where the risk of such an error is 0.05
Limit of Quantification (LoQ)
Where LoB and LoD are statistical constructs, establishing LoQ depends on pre-defined acceptance criteria. LoQ is the lowest amount of analyte that can be reliably measured (i.e., with a given imprecision). Unfortunately, these performance requirements are not universally established and must be decided and stated by the assay developer. Practically, LoQ is the lowest concentration at which the analyte can be reliably detected when some predefined goals for accuracy and precision are satisfied. This accuracy requirement should be determined by considering the clinical utility of the analyte.