Numerical limits, ranges, or other suita-ble measures for acceptance of test re-sults.
Active Pharmaceutical Ingredient (API) (or Drug Substance)
Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.
API Starting Material
A raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API Starting Material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API Starting Materials are normally of defined chemical properties and structure.
Batch (or Lot)
A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits. In the case of continu-ous production, a batch may correspond to a defined fraction of the production. The batch size can be defined either by a fixed quantity or by the amount pro-duced in a fixed time interval.
Batch Number (or Lot Number)
A unique combination of numbers, let-ters, and/or symbols that identifies a batch (or lot) and from which the pro-duction and distribution history can be determined.
The level and type (e.g. objectionable or not) of micro-organisms that can be pre-sent in raw materials, API starting mate-rials, intermediates or APIs. Bioburden should not be considered contamination unless the levels have been exceeded or defined objectionable organisms have been detected.
The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements.
A group of hardware components and associated software, designed and as-sembled to perform a specific function or group of functions.
A process or operation integrated with a computer system.
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API during production, sampling, packaging or re-packaging, storage or transport.
A manufacturer performing some aspect of manufacturing on behalf of the original manufacturer.
Describes a process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specifi-cation.
Contamination of a material or product with another material or product.
Departure from an approved instruction or established standard.
Drug (Medicinal) Product
The dosage form in the final immediate packaging intended for marketing. (Reference Q1A)
See Active Pharmaceutical Ingredient
Expiry Date (or Expiration Date)
The date placed on the container/labels of an API designating the time during which the API is expected to remain within established shelf life specifica-tions if stored under defined conditions, and after which it should not be used.
Any component present in the interme-diate or API that is not the desired enti-ty.
A description of the identified and uni-dentified impurities present in an API.
In-Process Control (or Process Control)
Checks performed during production in order to monitor and, if appropriate, to adjust the process and/or to ensure that the intermediate or API conforms to its specifications.
A material produced during steps of the processing of an API that undergoes further molecular change or purification before it becomes an API. Intermediates may or may not be isolated. (Note: this Guide only addresses those intermedi-ates produced after the point that the company has defined as the point at which the production of the API be-gins.)
All operations of receipt of materials, production, packaging, repackaging, labelling, relabelling, quality control, release, storage, and distribution of APIs and related controls.
A general term used to denote raw mate-rials (starting materials, reagents, sol-vents), process aids, intermediates, APIs and packaging and labelling materials.
The residual liquid which remains after the crystallization or isolation processes. A mother liquor may contain unreacted materials, intermediates, levels of the API and/or impurities. It may be used for further processing.
Any material intended to protect an in-termediate or API during storage and transport.
A documented description of the opera-tions to be performed, the precautions to be taken and measures to be applied directly or indirectly related to the man-ufacture of an intermediate or API.
Materials, excluding solvents, used as an aid in the manufacture of an intermedi-ate or API that do not themselves partici-pate in a chemical or biological reaction (e.g. filter aid, activated carbon, etc).
See In-Process Control.
All operations involved in the prepara-tion of an API from receipt of materials through processing and packaging of the API.
Action of proving and documenting that equipment or ancillary systems are properly installed, work correctly, and actually lead to the expected results. Qualification is part of validation, but the individual qualification steps alone do not constitute process validation.
Quality Assurance (QA)
The sum total of the organised arrange-ments made with the object of ensuring that all APIs are of the quality required for their intended use and that quality systems are maintained.
Quality Control (QC)
Checking or testing that specifications are met.
An organizational unit independent of production which fulfills both Quality Assurance and Quality Control responsi-bilities. This can be in the form of sepa-rate QA and QC units or a single individ-ual or group, depending upon the size and structure of the organization.
The status of materials isolated physical-ly or by other effective means pending a decision on their subsequent approval or rejection.
A general term used to denote starting materials, reagents, and solvents intend-ed for use in the production of interme-diates or APIs.
Reference Standard, Primary
A substance that has been shown by an extensive set of analytical tests to be au-thentic material that should be of high purity. This standard can be: (1) obtained from an officially recognised source, or (2) prepared by independent synthesis, or (3) obtained from existing production material of high purity, or (4) prepared by further purification of existing pro-duction material.
Reference Standard, Secondary
A substance of established quality and purity, as shown by comparison to a pri-mary reference standard, used as a refer-ence standard for routine laboratory analysis.
Introducing an intermediate or API, in-cluding one that does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distil-lation, filtration, chromatography, mill-ing) that are part of the established man-ufacturing process. Continuation of a process step after an in-process control test has shown that the step is incom-plete is considered to be part of the nor-mal process, and not reprocessing.
The date when a material should be re-examined to ensure that it is still suitable for use.
Subjecting an intermediate or API that does not conform to standards or specifi-cations to one or more processing steps that are different from the established manufacturing process to obtain ac-ceptable quality intermediate or API (e.g., recrystallizing with a different sol-vent).
See definition for signed
Signed (signature) The record of the individual who performed a particular action or review. This record can be ini-tials, full handwritten signature, person-al seal, or authenticated and secure elec-tronic signature.
An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in the manufacture of an intermediate or API.