Sales Specification

A list of tests, references to analytical procedures, and appropriate criteria for a material as offered for sale. [4]


A portion of a material collected according to a defined sampling procedure. The size of any sample should be sufficient to allow all anticipated test procedures to be carried out, including all repetitions and retention samples. If the quantity of material available is not sufficient for the intended analyses and for the retention samples, the inspector should record that the sampled material is the available sample (see Sampling record) and the evaluation of the results should take account of the limitations that arise from the insufficient sample size. [26]


Person responsible for performing the sampling operations. [26]


Operations designed to obtain a representative portion of a pharmaceutical starting material based on an appropriate statistical procedure, for a defined purpose, e.g. acceptance of consignments, batch release, etc. [3, 17, 18]

Sampling Method

That part of the sampling procedure dealing with the method prescribed for withdrawing samples. [26]

Sampling Plan

Description of the location, number of units and/or quantity of material that should be collected, and associated acceptance criteria. [26]

Sampling Procedure

The complete sampling operations to be performed on a defined material for a specific purpose. A detailed written description of the sampling procedure is provided in the sampling protocol. [26]

Sampling Record

Written record of the sampling operations carried out on a particular material for a defined purpose. The sampling record should contain the batch number, date and place of sampling, reference to the sampling protocol used, a description of the containers and of the materials sampled, notes on possible abnormalities, together with any other relevant observations, and the name and signature of the inspector. [26]

Sampling Unit

Discrete part of a consignment such as an individual package, drum or container. [26]


An increase or decrease in the batch size in batch processing or the throughput capability for continuous processing whether or not different equipment is used. [5]

Secondary Chemical Reference Substance

A secondary chemical reference substance is a substance whose characteristics are assigned and/or calibrated by comparison with a primary chemical reference substance. The extent of characterization and testing of a secondary chemical reference substance may be less than for a primary chemical reference substance. Although this definition may apply inter alia to some substances termed “working standards”, part B of these guidelines is intended to apply to secondary reference substances supplied as “official”, e.g. regional/national standards, and not to manufacturers’ or other laboratories’ working standards. [21]

Secondary Packaging Materials

Packaging materials which do not have direct contact with the excipient.

NOTE 1: Examples of secondary packaging materials are printed or unprinted cartons, labels, over-wraps, and transit containers such as folding boxes, glass, plastics, aluminium films, and foils. They may be combinations of different materials/components.

NOTE 2: Secondary packaging materials may be directly printed or decorated.

NOTE 3: Shipping pallets are not considered secondary packaging materials.

Secondary Reference Standard

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.

Selected Sample

Sample obtained according to a sampling procedure designed to select a fraction of the material that is likely to have special properties. A selected sample that is likely to contain deteriorated, contaminated, adulterated or otherwise unacceptable material is known as an extreme sample. [26]

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. [20]

Semi-permeable Containers

Containers that allow the passage of solvent, usually water, while preventing solute loss. The mechanism for solvent transport occurs by absorption into one container surface, diffusion through the bulk of the container material, and desorption from the other surface. Transport is driven by a partial-pressure gradient. Examples of semi-permeable containers include plastic bags and semirigid, low-density polyethylene (LDPE) pouches for large volume parenterals (LVPs), and LDPE ampoules, bottles, and vials. [13]

Senior Management

Person(s) who direct and control a company or site at the highest levels with the authority and responsibility to mobilise resources within the company or site. (ICH Q10 based in part on ISO 9000:2005) [11]


A measure of the possible consequences of a hazard. [10]

Shelf Life

The length of time during which the excipient meets specification (see also expiration period, re-evaluation interval and retest interval). [4]

Short Duration

in the context of mixed excipients refers to a process that is typically timed in minutes and does not alter the physical or chemical characteristics of the components being processed.

Signed (signature)

The record of the individual who performed a particular action or review. This record can be initials, full handwritten signature, personal seal, or authenticated and secure electronic signature.

Significant Change

Any change that has the potential to alters an excipient?s physical, chemical, or microbiological property from the norm, and/or that may alter the excipient?s performance in the dosage form.

Simple Physical Mixture

refers to the blending of two, or more, different materials in a way that is not intended to change the physical or chemical characteristics of the components. The blending process is generally low shear and of short duration, with limits dependent on the nature of the components being mixed. The process usually involves the use of mechanical agitation which can include paddles within a vessel, or the tumbling of the vessel that contains the different materials.


A defined location of the equipment in which the excipient is manufactured. It may be within a larger facility. A change in site may be to a different part of the existing facility, but in a different operational area, or to a remote facility including a contract manufacturer.

Skip Lot (periodic) Testing

The performance of specified tests at release on pre selected batches and/or at predetermined intervals, rather than on a batch-to-batch basis, with the understanding that those batches not tested must still meet all the acceptance criteria established for that product. This represents a less than full schedule of testing and should therefore be justified, presented to, and approved by, the regulatory authority before implementation. When tested, any failure of the starting material to meet the acceptance criteria established for the periodic (skip lot) test should be handled by proper notification of the appropriate regulatory authority (authorities). If these data demonstrate a need to restore routine testing, then batch-by-batch release testing should be reinstated. [3, 18]

Skip-Lot Testing Program

Periodic or intermittent testing performed for a particular test parameter, which is justified by historical data demonstrating a state of statistical process control. [8]


An inorganic or organic liquid used as a vehicle for the preparation of solutions or suspensions in the manufacture of an excipient. [2]


Standard Operating Procedure

Specific test

A test which is considered to be applicable to particular new drug substances or particular new drug products depending on their specific properties and/or intended use. [12]


A list of tests, references to analytical procedures and appropriate acceptance criteria that are numerical limits, ranges or other criteria for the tests described for a material, that the material is required to meet.


A list of tests, references to analytical procedures and pre-established numerical limits, ranges or other criteria for the tests described, that the material is required to meet.

Specification - Release

The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug product at the time of its release. [13]

Specification - Shelf life

The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of a drug substance throughout its re-test period, or that a drug product should meet throughout its shelf life. [13]


The ability to assess unequivocally the analyte in the presence of components that may be expected to be present. Typically these might include impurities, degradants, matrix, etc.

Specified impurity

An identified or unidentified impurity that is selected for inclusion in the new drug substance or new drug product specification and is individually listed and limited in order to assure the quality of the new drug substance or new drug product. [12]


Statistical Quality Control


Continued conformance of the excipient to its specifications. [1, 3, 7]

Stability Test Method

A stability indicating method that investigates whether or not a particular characteristic of the excipient changes relative to specification over time.

Stable Process

A process is considered stable when the output of the process, regardless of the nature of the processing (batch or continuous), can be demonstrated, by appropriate means, to show a level of variability which consistently meets all aspects of the stated specification, (both pharmacopeia and customer specific) and is thus acceptable for its intended use. [8]


Any individual, group or organization that can affect, be affected by, or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, healthcare professional, regulatory authority, and industry. [10]

Standard Operating Procedure (SOP)

An authorized, written procedure giving instructions for performing operations not necessarily specific to a given product but of a more general nature (e.g. equipment operation, maintenance and cleaning, validation, cleaning of premises and environmental control, sampling and inspection). Certain SOPs may be used to supplement productspecific master and batch production documentation. [17, 20, 23]

Starting Material

A raw material or intermediate defined at the starting point for excipient GMPs and used in the production of an excipient that is incorporated as a significant structural fragment or that is purified to meet the quality requirement for an excipient.

State of Control

A condition in which the set of controls consistently provides assurance of continued process performance and product quality. (ICH Q10) [11]

Statement of Commitment

A declaration by the excipient manufacturer certifying that the DMF is current and that the DMF holder will comply with the statements made there in. [7]

Statistical Control

A process that results in product that exhibits random variation of its property. [4]

Statistical Process Control

A statistical techniques involving ongoing evaluation of measurements to monitor and analyze the variation in processes.

Statistical Quality Control (SQC)

The plotting of sequential test results to show their variation relative to the specification range and their normal variation. [5]


Completely free from microorganisms such that, after inoculation of a suitable nutrient medium under aseptic conditions with the material, and followed by incubation at an appropriate temperature for 14 days, no growth of microorganisms is seen. [4]


The storing of pharmaceutical products up to the point of use. [17, 19]

Storage Condition Tolerances

The acceptable variations in temperature and relative humidity of storage facilities for formal stability studies. The equipment should be capable of controlling the storage condition within the ranges defined in this guideline. The actual temperature and humidity (when controlled) should be monitored during stability storage. Short term spikes due to opening of doors of the storage facility are accepted as unavoidable. The effect of excursions due to equipment failure should be addressed, and reported if judged to affect stability results. Excursions that exceed the defined tolerances for more than 24 hours should be described in the study report and their effect assessed. [13]

Stress Testing (drug product)

Studies undertaken to assess the effect of severe conditions on the drug product. Such studies include photostability testing (see ICH Q1B) and specific testing on certain products, (e.g., metered dose inhalers, creams, emulsions, refrigerated aqueous liquid products). [13]

Stress Testing (drug substance)

Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated testing. [13]

Strongly Suspected Human Carcinogen

A substance for which there is no epidemiological evidence of carcinogenesis but there are positive genotoxicity data and clear evidence of carcinogenesis in rodents. [16]


A third party for outsourced work or services that contribute in whole or in part to the manufacture, testing, distribution and storage of excipients.

Subcutaneous (s.c.)

A route of administration where the drug product is injected beneath the skin. [7]


Demonstration that a process or technique provides expected output.


Person or company providing pharmaceutical starting materials on request. Suppliers may be distributors, manufacturers, traders, etc. (GDP Guide/WHO Good Trade and Distribution Practices) [3, 17, 18]

Supply Chain

Supply chain is defined as all steps in the entire chain of distribution starting from the point at which an excipient is transferred outside the control of the original manufacturer's material a management system downstream to the final user of the excipient. [3]

Supporting Data

Data, other than those from formal stability studies that support the analytical procedures, the proposed re-test period or shelf life, and the label storage statements. Such data include (1) stability data on early synthetic route batches of drug substance, small scale batches of materials, investigational formulations not proposed for marketing, related formulations, and product presented in containers and closures other than those proposed for marketing; (2) information regarding test results on containers; and (3) other scientific rationales. [13]


Products which are not derived from starting materials sourced from plants, animals or minerals and that are not products of fermentation. Note: Also see specific regional or national organic food legislation for additional information on the use of the term synthetic. [6]