Some Important Definitions

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 (see also qualification).

acceptance criteria

Measurable terms under which a test result will be considered acceptable.

action limit

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.

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 and used by either people or goods (PAL, personnel

airlock; MAL, material airlock).

alert limit

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.

as-built

Condition where the installation is complete with all services connected and

functioning but with no production equipment, materials or personnel present.

at-rest

Condition where the installation is complete with equipment installed and

operating in a manner agreed upon by the customer and supplier, but with no

personnel present.

central air-conditioning unit (see air-handling unit)

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 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

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.

containment

A process or device to contain product, dust or contaminants in one zone,

preventing it from escaping to another zone.

contamination

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.

cross-contamination

Contamination of a starting material, intermediate product or finished product

with another starting material or material during production.

design condition

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

regulatory requirements.

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.

facility

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

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.

no-impact system

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

GEP only.

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.

operating limits

The minimum and/or maximum values that will ensure that product and safety

requirements are met.

operating range

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.

point extraction

Air extraction to remove dust with the extraction point located as close as

possible to the source of the dust.

pressure cascade

A process whereby air flows from one area, which is maintained at a higher

pressure, to another area at a lower pressure.

qualification

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.

relative humidity

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

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

induction.

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.)

validation

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).

commingling

The blending of carry-over material from one grade of an excipient with another, usually due to a continuous process.

drug masterfile1

Detailed information concerning a specific facility, process or product submitted to the drug regulatory authority, intended for incorporation into the application for marketing authorization.

model product

A product which simulates a group of similar products.

mother liquor

A concentrated solution from which the product is obtained by evaporation,

freezing, and/or crystallization.

pharmaceutical excipients

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

acceptability;

— 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 United States regulations.