Monday, December 20, 2010
Some Important Definitions
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.
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
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.
Any substance of a defined quality used in the production of a pharmaceutical
product, but excluding packaging materials.
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 (see also qualification).
Measurable terms under which a test result will be considered acceptable.
The action limit is reached when the acceptance criteria of a critical parameter have been exceeded. Results outside these limits will require specified action and investigation.
air-handling unit (AHU)
The air-handling unit serves to condition the air and provide the required air
movement within a facility.
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 and used by either people or goods (PAL, personnel
airlock; MAL, material airlock).
The alert limit is reached when the normal operating range of a critical parameter has been exceeded, indicating that corrective measures may need to be taken to prevent the action limit being reached.
Condition where the installation is complete with all services connected and
functioning but with no production equipment, materials or personnel present.
Condition where the installation is complete with equipment installed and
operating in a manner agreed upon by the customer and supplier, but with no
central air-conditioning unit (see air-handling unit)
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 that the system is maintained in a validated state.
clean area (clean room)1
An area (or room) 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.
Commissioning is the documented process of verifying that the equipment and
systems are installed according to specifications, placing the equipment into
active service and verifying its proper action. Commissioning takes place at the conclusion of project construction but prior to validation.
A process or device to contain product, dust or contaminants in one zone,
preventing it from escaping to another zone.
The undesired introduction of impurities of a chemical or microbial nature, or
of foreign matter, into or on to a starting material or intermediate, during production, sampling, packaging or repackaging, storage or transport.
critical parameter or component
A processing parameter (such as temperature or humidity) that affects the
quality of a product, or a component that may have a direct impact on the
quality of the product.
Contamination of a starting material, intermediate product or finished product
with another starting material or material during production.
Design condition relates to the specified range or accuracy of a controlled variable used by the designer as a basis for determining the performance requirements of an engineered system.
design qualification (DQ)
DQ is the documented check of planning documents and technical specifications
for conformity of the design with the process, manufacturing, GMP and
1 Note: Clean area standards, such as ISO 14644-1 provide details on how to classify air cleanliness by
means of particle concentrations, whereas the GMP standards provide a grading for air cleanliness in
terms of the condition (at-rest or operational), the permissible microbial concentrations, as well as other
factors such as gowning requirements. GMP and clean area standards should be used in conjunction
with each other to define and classify the different manufacturing environments.
direct impact system
A system that is expected to have a direct impact on product quality. These
systems are designed and commissioned in line with good engineering practice
(GEP) and, in addition, are subject to qualification practices.
The built environment within which the clean area installation and associated
controlled environments operate together with their supporting infrastructure.
good engineering practice (GEP)
Established engineering methods and standards that are applied throughout the
project life-cycle to deliver appropriate, cost-effective solutions.
indirect impact system
This is a system that is not expected to have a direct impact on product quality, but typically will support a direct impact system. These systems are designed and commissioned according to GEP only.
Infiltration is the ingress of contaminated air from an external zone into a clean area.
installation qualification (IQ)
IQ is documented verification that the premises, HVAC system, supporting utilities and equipment have been built and installed in compliance with their
approved design specification.
This is a system that will not have any impact, either directly or indirectly, on product quality. These systems are designed and commissioned according to
non-critical parameter or component
A processing parameter or component within a system where the operation,
contact, data control, alarm or failure will have an indirect impact or no impact on the quality of the product.
normal operating range
The range that the manufacturer selects as the acceptable values for a parameter during normal operations. This range must be within the operating range.
The minimum and/or maximum values that will ensure that product and safety
requirements are met.
Operating range is the range of validated critical parameters within which
acceptable products can be manufactured. operational condition
This condition relates to carrying out room classification tests with the normal production process with equipment in operation, and the normal staff present in the room.
operational qualification (OQ)
OQ is the documentary evidence to verify that the equipment operates in accordance with its design specifications in its normal operating range and performs as intended throughout all anticipated operating ranges.
oral solid dosage (OSD)
Usually refers to an OSD plant that manufactures medicinal products such as
tablets, capsules and powders to be taken orally.
performance qualification (PQ)
PQ is the documented verification that the process and/or the total process
related to the system performs as intended throughout all anticipated operating ranges.
Air extraction to remove dust with the extraction point located as close as
possible to the source of the dust.
A process whereby air flows from one area, which is maintained at a higher
pressure, to another area at a lower pressure.
Qualification is the planning, carrying out and recording of tests on equipment and a system, which forms part of the validated process, to demonstrate that it will perform as intended.
The ratio of the actual water vapour pressure of the air to the saturated water vapour pressure of the air at the same temperature expressed as a percentage. More simply put, it is the ratio of the mass of moisture in the air, relative to the mass at 100% moisture saturation, at a given temperature.
standard operating procedure (SOP)
An authorized written procedure, giving instructions for performing operations, not necessarily specific to a given product or material, but of a more general nature (e.g. operation of equipment, 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.
Turbulent flow, or non-unidirectional airflow, is air distribution that is introduced into the controlled space and then mixes with room air by means of
unidirectional airflow (UDAF)
Unidirectional airflow is a rectified airflow over the entire cross-sectional area of a clean zone with a steady velocity and approximately parallel streamlines(see also turbulent flow). (Modern standards no longer refer to laminar flow, but have adopted the term unidirectional airflow.)
The documented act of proving that any procedure, process, equipment, material, activity or system actually leads to the expected results.
validation master plan (VMP)
VMP is a high-level document which establishes an umbrella validation plan for
the entire project, and is used as guidance by the project team for resource and technical planning (also referred to as master qualification plan).
The blending of carry-over material from one grade of an excipient with another, usually due to a continuous process.
Detailed information concerning a specific facility, process or product submitted to the drug regulatory authority, intended for incorporation into the application for marketing authorization.
A product which simulates a group of similar products.
A concentrated solution from which the product is obtained by evaporation,
freezing, and/or crystallization.
Substances, other than the active ingredient, which have been appropriately
evaluated for safety and are included in a drug delivery system to:
— aid in the processing of the drug delivery system during its manufacture;
— protect, support or enhance stability, bioavailability, or patient
— assist in product identification; or
— enhance any other attribute of the overall safety and effectiveness of the drug during storage or use.1 This term appears to be specific to