Active pharmaceutical ingredient (API)
Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical dosage form and that, when so used, becomes an active ingredient of that pharmaceutical dosage form. 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.
Airlock
An enclosed space with two or more doors, which is interposed between two or more rooms, e.g. of differing classes of cleanliness, for the purpose of controlling the airflow between those rooms when they need to be entered. An airlock is designed for use either by people or for goods and/or equipment.
Authorized person
The person recognized by the national regulatory authority as having the responsibility for ensuring that each batch of finished product has been manufactured, tested and approved for release in compliance with the laws and regulations in force in that country.
Batch (or lot)
A defined quantity of starting material, packaging material, or product processed in a single process or series of processes so that it is expected to be homogeneous. It may sometimes be necessary to divide a batch into a number of sub-batches, which are later brought together to form a final homogeneous batch. In the case of terminal sterilization, the batch size is determined by the capacity of the autoclave. In continuous manufacture, the batch must correspond to a defined fraction of the production, characterized by its intended
homogeneity. The batch size can be defined either as a fixed quantity or as the amount produced in a fixed time interval.
Batch number (or lot number)
A distinctive combination of numbers and/or letters which uniquely identifies a batch on the labels, its batch records and corresponding certificates of analysis, etc.
Batch records
All documents associated with the manufacture of a batch of bulk product or finished product. They provide a history of each batch of product and of all circumstances pertinent to the quality of the final product.
Bulk product
Any product that has completed all processing stages up to, but not including, final packaging.
Calibration
The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established.
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.
Consignment (or delivery)
The quantity of a pharmaceutical(s), made by one manufacturer and supplied at one time in response to a particular request or order. A consignment may comprise one or more packages or containers and may include material belonging to more than one batch.
Contamination
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or on to a starting material or intermediate during production, sampling, packaging or repackaging, storage or transport.
Critical operation
An operation in the manufacturing process that may cause variation in the quality of the pharmaceutical product.
Cross-contamination
Contamination of a starting material, intermediate product or finished product with another starting material or product during production.
Finished product
A finished dosage form that has undergone all stages of manufacture, including packaging in its final container and labelling.
In-process control
Checks performed during production in order to monitor and, if necessary, to adjust the process to ensure that the product conforms to its specifications. The control of the environment or equipment may also be regarded as a part of inprocess control.
Intermediate product
Partly processed product that must undergo further manufacturing steps before it becomes a bulk product.
Large-volume parenteral
Sterile solutions intended for parenteral application with a volume of 100 ml or more in one container of the finished dosage form.
Manufacture
All operations of purchase of materials and products, production, quality control, release, storage and distribution of pharmaceutical products, and the related controls.
Manufacturer
A company that carries out operations such as production, packaging, repackaging, labelling and re-labelling of pharmaceuticals.
Marketing authorization (product licence, registration certificate)
A legal document issued by the competent drug regulatory authority that establishes the detailed composition and formulation of the product and the pharmacopoeial or other recognized specifications of its ingredients and of the final product itself, and includes details of packaging, labelling and shelf-life.
Master formula
A document or set of documents specifying the starting materials with their
quantities and the packaging materials, together with a description of the procedures and precautions required to produce a specified quantity of a finished
product as well as the processing instructions, including the in-process controls.
Master record
A document or set of documents that serve as a basis for the batch documentation (blank batch record).
Packaging
All operations, including filling and labelling, that a bulk product has to undergo in order to become a finished product. Filling of a sterile product under aseptic conditions or a product intended to be terminally sterilized, would not normally be regarded as part of packaging.
Packaging material
Any material, including printed material, employed in the packaging of a pharmaceutical, but excluding any outer packaging used for transportation or shipment. Packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product.
Pharmaceutical product
Any material or product intended for human or veterinary use presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in the exporting state and/or the importing state.
Production
All operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing, packaging and repackaging, labelling and relabelling, to completion of the finished product.
Qualification
Action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results. The meaning of the word “validation” is sometimes extended to incorporate the concept of qualification.
Quality assurance
“Quality assurance” is a wide-ranging concept covering all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. Quality assurance therefore incorporates GMP and other factors, including those outside the scope of this guide such as product design and development.
Quarantine
The status of starting or packaging materials, intermediates, or bulk or finished products isolated physically or by other effective means while a decision is awaited on their release, rejection or reprocessing.
Reconciliation
A comparison between the theoretical quantity and the actual quantity.
Recovery
The introduction of all or part of previous batches (or of redistilled solvents and similar products) of the required quality into another batch at a defined stage of manufacture. It includes the removal of impurities from waste to obtain a pure substance or the recovery of used materials for a separate use.
Reprocessing
Subjecting all or part of a batch or lot of an in-process drug, bulk process intermediate (final biological bulk intermediate) or bulk product of a single batch/ lot to a previous step in the validated manufacturing process due to failure to meet predetermined specifications. Reprocessing procedures are foreseen as occasionally necessary for biological drugs and, in such cases, are validated and pre-approved as part of the marketing authorization.
Reworking
Subjecting an in-process or bulk process intermediate (final biological bulk intermediate) or final product of a single batch to an alternate manufacturing process due to a failure to meet predetermined specifications. Reworking is an unexpected occurrence and is not pre-approved as part of the marketing authorization.
Self-contained area
Premises which provide complete and total separation of all aspects of an operation, including personnel and equipment movement, with well established procedures, controls and monitoring. This includes physical barriers as well as separate air-handling systems, but does not necessarily imply two distinct and separate buildings.
Specification
A list of detailed requirements with which the products or materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation.
Standard operating procedure (SOP)
An authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material (e.g. equipment operation, maintenance and cleaning; validation; cleaning of premises and environmental control; sampling and inspection). Certain SOPs may be used to supplement product-specific master and batch production documentation.
Starting material
Any substance of a defined quality used in the production of a pharmaceutical product, but excluding packaging materials.
Validation
Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system actually leads to the expected results