1.0 PURPOSE
To lay down the procedure for defining the Glossary of terms.
2.0 SCOPE
2.1 This procedure is applicable in All Departments
3.0 RESPONSIBILITY
3.1 Personnel-Concerned Department
4.0 ACCOUNTABILITY
4.1 Manager-QA
5.0 PROCEDURE
5.1 The Following Glossary terms list commonly used in the plant.
5.1.1 Acceptance criteriaNumerical limits, ranges, or other suitable measures for acceptance of test results.
5.1.2 Active Pharmaceutical Ingredient (API) (or Drug Substance)Any substance or mixture of substances intended to be used in the anufacture 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.
5.1.3 API Starting Material
A material used in the production of an API which is incorporated as a significant structural fragment into the structure of the API. An API Starting Material may be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or it may be produced in-house. API Starting Materials are normally of defined chemical properties and structure.
5.1.4 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 continuous production, a batch may correspond to a defined fraction of the production
batch size may be defined either by a fixed quantity or the amount produced in a fixed time interval.
5.1.5 Batch Number (or Lot Number)
A unique combination of numbers, letters, and/or symbols which identifies a batch (or lot) and from which the production and distribution history can be determined.
5.1.6 Bioburden
The level and type (e.g. objectionable or not) of micro-organisms which may be present in raw materials, API starting materials, intermediates or APIs. Bioburden should not be considered contamination unless the levels have been exceeded or defined objectionable organisms have been detected.
5.1.7 Bulk Product
Any product, which has completed all processing stages up to, but not including, final packaging.
5.1.8 Calibration
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.
or
The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard.
5.1.9 Clean Area
An area with defined environmental control of particulate and microbial contamination, constructed and used in such a way as to reduce the introduction, generation and retention of contaminants within the area.
5.1.10 Change Control
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state.
5.1.11 Computer system
A group of hardware components and associated software designed and assembled to perform a specific function or group of functions.
5.1.12 Computerized System
A process or operation integrated with a computer system.
5.1.13 Contamination
The undesired introduction of impurities of a chemical or Microbiological nature, or of foreign matter, in to or onto a raw material, intermediate, or API during production, sampling, packaging or repackaging, storage or transport.
5.1.14 Cross Contamination
Contamination of a material or of a product with another material or product.
5.1.15 Critical
Describes process step, process condition, test requirement or other relevant parameter or item that must be controlled with in predetermined criteria to ensure that the API meets its specification.
5.1.16 Contract Manufacturer
A company holding an agreement requiring the performance of some aspect of API manufacturing.
5.1.17 Commissioning
An engineering term that covers all aspects of bringing a system or sub-system to a position where it is regarded as being ready for use in pharmaceutical manufacture. Commissioning involves all the basis requirements of Installation Qualification (IQ) and Operational Qualification (OQ).
5.1.18 Concurrent Validation
Validation carried out during routine production of products intended for sale.
5.1.19 Critical Variable Study
A study that serves to measure variables (parameters) critical to the satisfactory operation of a piece of equipment or plant and to assure their operation within monitored and controlled limits. Examples of variables would be pressure, temperature, flow rates, time etc.
5.1.20 Deviation
Departure from an approved instruction or established standard.
5.1.21 Drug (Medicinal) Product
The dosage form in the final immediate packaging intended for marketing.
5.1.22 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 specifications if stored under defined conditions, and after which it should not be used.
5.1.23 Finished Product
A medicinal product, which has undergone all stages of production, including packaging in its final container.
5.1.24 Impurity
Any component present in the intermediate or API that is not the desired entity.
5.1.25 Impurity Profile
A description of the identified and unidentified impurities present in an API.
5.1.26 In-Process Control (or Process Control)
Checks performed during production in order to monitor and, if necessary, to adjust the process and/or to ensure that the intermediate or API conforms to its specifications.
5.1.27 Installation Qualification (IQ)
The performance and documentation of tests to ensure that equipment (such as machines, measuring equipment) used in a manufacturing process, are appropriately selected, correctly installed and work in accordance with established specifications.
5.1.28 Intermediate
A material produced during steps of the processing of an API that must undergo further molecular change or purification before it becomes an API. Intermediates may or may not be isolated.
5.1.29 Liquefiable Gases
Those which, at the normal filling temperature and pressure, remain as a liquid in the cylinder.
5.1.30 Limit of Detection
The lowest amount of analyte in a sample which can be detected but not quantitated as an exact value. The Limit of Detection is mostly a parameter of limit tests.
5.1.31 Limit of Quantitation
The lowest amount of analyte in a sample which can be quantitatively determined with defined precision and accuracy under the stated experimental conditions.
5.1.32 Manifold
Equipment or apparatus designed to enable one or more gas containers to be filled simultaneously from the same source.
5.1.33 Manufacturer
Holder of a Manufacturing Authorisation as described in Article 16 of Directive 75/319/EEC.
5.1.34 Medicinal Plant
Plant the whole or part of which is used for medicinal purpose
5.1.35 Medicinal Product
Any substance or combination of substances presented for treating or preventing disease in human beings or animals. Any substance or combination of substances which may be administered to human beings or animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in human beings or in animals is likewise considered a medicinal product.
5.1.36 Manufacture
All operations of receipt of materials, production, packaging, repackaging, labeling, relabelling, quality control, release, storage, and distribution of APIs and the related controls.
5.1.37 Material
A general term used to denote raw materials (starting materials, reagents, solvents), process aids, intermediates, APIs and packaging and labelling materials.
5.1.38 Mother Liquor
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.
5.1.39 Packaging Material
Any material intended to protect an intermediate or API during storage and transport.
5.1.40 Procedure
A documented description of the operations to be performed, the precautions to be taken and measures to be applied directly or indirectly related to the manufacture of an intermediate or API.
5.1.41 Process Aids
Materials, excluding solvents, used as an aid in the manufacture of an intermediate or API that do not themselves participate in a chemical or biological reaction (e.g. filter aid, activated carbon, etc).
5.1.42 Process Capability Study
A process capability study is a statistical method that compares process information (e.g. X and s) to the upper and lower specification limits.
5.1.43 Prospective Validation
Establishing documented evidence that a process, procedure, system, equipment or mechanism used in manufacture does what it purports to do based on a pre-planned validation protocol.
5.1.44 Production
All operations involved in the preparation of an API, from receipt of materials, through processing and packaging, to its completion as a finished API.
5.1.45 Process Capability Index (CpK)
A process capability index CpK represents the true measure of process capability:
i. CpK = X - LSL
ii. 3s
iii. or USL – X
iv. 3S
v. where
vi. LSL = Lower specification limit
vii. USL = Upper specification limit
viii. X = Mean
ix. s = Standard deviation
5.1.46 Piping & Instrument Diagrams (P&IDs)
Engineering schematic drawings that provide details of the interrelationship of equipment, services, material flows, plant controls and alarms. The P&ID also provide the reference for each tag or label used for identification.
5.1.47 Pre-Determined Acceptance Criteria
The criteria assigned, before undertaking testing, to allow evaluation of test results to demonstrate compliance with a test phase of delivery requirement.
5.1.48 Plant Functional Specifications
Specifications that document functions, standards and permitted tolerances of systems (plant) or system components (equipment) and which define the operating capabilities of the equipment.
5.1.49 Qualification
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.
5.1.50 Quality Assurance (QA)
The sum total of the organised arrangements made with the object of ensuring that all APIs are of the quality required for their intended use and that quality systems are maintained.
5.1.51 Quality Control (QC)
Checking or testing that specifications are met.
5.1.52 Quality Unit(s)
An organizational unit independent of production which fulfills both Quality Assurance and Quality Control responsibilities. This may be in the form of separate QA and QC units or a single individual (or group), depending upon the size and structure of the organization.
5.1.53 Quarantine
The status of materials isolated physically or by other effective means pending a decision on their subsequent approval or rejection.
5.1.54 Raw Material
A general term used to denote starting materials, reagents, and solvents intended for use in the production of intermediates or APIs.
5.1.55 Reconciliation
A comparison, making due allowance for normal variation, between the amount of product or materials theoretically and actually produced or used.
5.1.56 Recovery
The introduction of all or part of previous batches of the required quality into another batch at a defined stage of manufacture.
5.1.57 Reprocessing
The reworking of all or part of a batch of product of an unacceptable quality from a defined stage of production so that its quality may be rendered acceptable by one or more additional operations.
5.1.58 Return
Sending back to the manufacturer or distributor of a medicinal product which may or may not present a quality defect.
5.1.59 Reference Standard, Primary
A substance that has been shown by an extensive set of analytical tests to be authentic material that should be of high purity. This standard may be obtained from an officially recognized source or may be prepared by independent synthesis or by further purification of existing production material.
5.1.60 Reference Standard, Secondary
A substance of established quality and purity, as shown by comparison to a primary reference standard, used as a reference standard for routine laboratory analysis
5.1.61 Reprocessing
Introducing an intermediate or API, including 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., distillation, filtration, chromatography, milling) that are part of the established manufacturing process. Continuation of a chemical reaction after an in-process control test shows the reaction to be incomplete is considered to be part of the normal process, and not reprocessing.
5.1.62 Retest Date
The date when a material should be re-examined to ensure that it is still suitable for use.
5.1.63 Retrospective Validation
Validation of a process for a product which has been marketed based upon accumulated manufacturing, testing and control batch data.
5.1.64 Re-Validation
A repeat of the process validation to provide an assurance that changes in the process/equipment introduced in accordance with change control procedures do not adversely affect process characteristics and product quality.
5.1.65 Reworking
Subjecting an intermediate or API that does not conform to standards or specifications to one or more processing steps that are different from the established manufacturing process so that its quality may be made acceptable (e.g., recrystallizing with a different solvent).
5.1.66 Starting material
Any substance used in the production of a medicinal product, but excluding packaging materials.
5.1.67 Sensitivity
Capacity of the test procedure to record small variations in concentration of a component, with a defined degree of precision.
5.1.68 Simulated Product
A material that closely approximates the physical and, where practical, the chemical characteristics (e.g. viscosity, particle size, pH etc.) of the product under validation. In many cases, these characteristics may be satisfied by a placebo product batch.
5.1.69 Sterility
Sterility is the absence of living organisms. the conditions of the sterility test are given in the European pharmacopoeia.
5.1.70 System
Is used in the sense of a regulated pattern of interacting activities and techniques which are united to form an organised whole.
5.1.71 Signed (signature)
The record of the individual who performed a particular action or review. This record may be initials, full handwritten signature, personal seal, or authenticated and secure electronic signature.
5.1.72 Solvent
An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in the manufacture of an intermediate or API.
5.1.73 Specification
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. “Conformance to specification” means that the material, when tested according to the listed analytical procedures, will meet the listed acceptance criteria.
5.1.74 Validation
A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria.
5.1.75 Validation Protocol
A written plan stating how validation will be conducted and defining acceptance criteria. For example, the protocol for a manufacturing process identifies processing equipment, critical process parameters/operating ranges, product. characteristics, sampling, test data to be collected, number of validation runs, and acceptable test results.
5.1.76 Validation Master Plan
A document providing information on the company’s validation work programme. It should define details of and timescales for the validation work to be performed. Responsibilities relating to the plan should be stated.
5.1.77 Validation Report
Document reporting the validation activities, the validation data and the conclusions drawn.
5.1.78 Yield, Expected
The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production based on previous laboratory, pilot scale, or manufacturing data.
5.1.79 Yield, Theoretical
The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production.
5.1.80 Worst Case
A condition or set of conditions encompassing upper and lower processing limits and circumstances, within standard operating procedures, which pose the greatest chance of product or process failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure.
END OF DOCUMENT
Glossary of terms, quality assurance, mixture of substances
