Glossary

The “quality level that is the worst tolerable” according to ISO 2859-1. It represents the maximum number of defective units, beyond which a batch is rejected. Suppliers can set different AQLs for critical, major and minor defects. The actual AQL set depends on the lot size, the inspection level and the AQL appropriate for the situation.

The acceptable temperature range for storing vaccine is +2°C to +8°C. However, transient excursions outside this range will be tolerated, within the following limits:

no excursion exceeding +20°C for any amount of time (after the appliance is turned on and initially cools)

no excursion below -0.5°C for any amount of time

no excursion below 0°C for longer than 1 hour

following an excursion below 0°C, the appliance must return to safe operating temperature (i.e, consistently between +2°C and +8°C) within 2 hours; this duration will be measured from the moment the temperature drops below 0°C and up until it returns to +2°C

the calculated mean kinetic temperature (MKT) must remain within +2°C to +8°C when the default activation energy is set at 83.144 kJ per mol and when calculated over the duration of any testing that requires maintaining this range.

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

Any cooling or other heat transfer that is powered or driven by anything besides the spontaneous, passive transfer of heat due to temperature differential and related passive effects such as natural convection.

A raw material, intermediate or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement or produced in-house.

A raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house.

The APIMF procedure is one of four ways to provide information on the preparation control and stability of an API intended for use in a prequalified finished pharmaceutical product (FPP). The other three options are: the use of a prequalified API; use of a certificate of suitability (known as a CEP) issued by the European Directorate for the Quality of Medicines; or the submission of complete API information as part of the FPP dossier.

A time-temperature sensitive region on time-temperature indicators whose appearance matches the stability profile of the vaccine that the indicator is monitoring.

A substance or combination of substances used in conjunction with a vaccine antigen to enhance (for example, increase, accelerate, prolong and/or possibly target) or modulate a specific immune response to the vaccine antigen in order to enhance the clinical effectiveness of the vaccine.

An AMC is a legally-binding agreement for an amount of funds to subsidize the purchase, at a given price, of an as yet unavailable vaccine against a specific disease causing high morbidity and mortality in low-income countries.

An electric current that reverses its direction at regularly recurring intervals the value of which varies as a sine wave.

The yearly review which all prequalified immunization devices are required to pass in order to remain on the WHO list of prequalified immunization devices. 

The active ingredient in a vaccine against which the immune response is induced.Antigens may be: (a) live attenuated or inactivated preparations of bacteria, viruses or parasites; (b) crude cellular fractions or purified antigens, including recombinant proteins (that is, those derived from recombinant DNA expressed in a host cell); (c) polysaccharides and conjugates formed by covalent linkage of polysaccharides to components such as mutated or inactivated proteins and/or toxoids; (d) synthetic antigens; (e) polynucleotides (such as plasmid DNA vaccines); or (f) living vectored cells expressing specific heterologous antigens. Also referred to as “immunogen” in other documents. Also used to describe (a) a component that may undergo chemical change or processing before it becomes the antigen or active ingredient used to formulate the final product (also referred to as an “intermediate” in other documents); or (b) an active ingredient present in an unmodified form in the final product (also referred to as “drug substance” or “active substance” in other documents). For example, in this document the term “antigen” applies, in the case of a polysaccharide conjugated vaccine, to the polysaccharide intermediate as well as to the conjugated polysaccharide that will not undergo further modification prior to formulation.

Any powered device intended to provide cooling for vaccine storage or transport.

The person or entity who, by the deadline mentioned in the invitation, submits an expression  of interest (EOI) to participate in this procedure in respect of the product(s) listed in the invitation, together with the required documentation on such product(s).

A person or organization approved by the legal manufacturer or reseller as a competent installer of cold chain equipment or system components and who has been appointed by the employer to carry out the installation of the system.

Time in hours for which a solar-powered appliance, monitoring device or walk-in cold room/freezer room can maintain minimum specified performance under low solar power conditions (rain).

Time in hours that a solar powered refrigerator, or combined refrigerator and water-pack freezer can maintain the vaccine load between +2°C and +8°C under low solar power conditions (rain).

Card to which a time-temperature indicator is permanently attached, containing information to activate (if necessary) and to interpret the appearance of the indicator. The card may be made from any water-resistant material.

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.

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.

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.

The rate and extent to which the active moiety is absorbed from a pharmaceutical dosage form and becomes available at the site(s) of action. Reliable measurements of active pharmaceutical ingredient (API) concentrations at the site(s) of action are usually not possible. The substance in the systemic circulation, however, is considered to be in equilibrium with the substance at the site(s) of action. Bioavailability can therefore be defined as the rate and extent to which the API or active moiety is absorbed from a pharmaceutical dosage form and becomes available in the systemic circulation. Based on pharmacokinetic and clinical considerations it is generally accepted that in the same subject an essentially similar plasma concentration time-course will result in an essentially similar concentration time-course at the site(s) of action.

The batch used to establish bioequivalence or similarity to the comparator product as determined in bioequivalence or biowaiver studies, respectively.

The level and type (objectionable or not) of microorganisms present in raw materials, media, biological substances, intermediates or finished products. Regarded as contamination when the level and/or type exceed specifications.

Two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives, and their bioavailabilities, in terms of rate (Cmax and tmax) and extent of absorption (area under the curve), after administration of the same molar dose under the same conditions, are similar to such a degree that their effects can be expected to be essentially the same.

A test that determines the equivalence between the multisource product and the comparator product using in vivo and/or in vitro approaches.

The BCS is a scientific framework for classifying active pharmaceutical ingredients based upon their aqueous solubility and intestinal permeability. When combined with the dissolution of the pharmaceutical product, the BCS takes into account three major factors that govern the rate and extent of drug absorption (exposure) from immediate-release oral solid dosage forms: dissolution, solubility and intestinal permeability.

An active pharmaceutical ingredient (API) for which the highest dose recommended by WHO (if the API appears on the WHO Model List of essential medicines (EML)) or highest dose strength available on the market as an oral solid dosage form (if the API does not appear on the EML) is soluble in 250 ml or less of aqueous media over the Ph range of 1.2–6.8 at 37 °C (8).

The term biowaiver is applied to a regulatory drug approval process when the efficacy and safety part of the dossier (application) is approved based on evidence of equivalence other than through in vivo equivalence testing.

A multi-dose container consisting of two layers, of which one is shaped to contain the individual doses. Strips are excluded.

Any pharmaceutical product that has completed all processing stages up to, but not including, final packaging.

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.

The documented act of proving that the equipment is performing to predefined tolerances or criteria.

A collection of vials of cells of uniform composition (though not necessarily clonal) derived from a single tissue or cell, and used for the production of a vaccine directly or via a cell bank system. The following terms are used in these Guidelines – master cell bank (MCB): a bank of a cell substrate from which all subsequent cell banks used for vaccine production will be derived. The MCB represents a well characterized collection of cells derived from a single tissue or cell; and working cell bank (WCB): a cell bank derived by propagation of cells from an MCB under defined conditions and used to initiate production of cell cultures on a lot-by-lot basis. Also referred to as “manufacturer’s working cell bank” in other documents.

A document containing the information that is validated and issued for a specific starting material by the competent authority of the exporting country and intended for use by the competent authority in the importing country or in the absence of such an authority by, for example, the manufacturer of the finished product when exporting.

The list of test procedures applied to a particular sample with the results obtained and the acceptance criteria applied. It indicates whether or not the sample complies with the specification.

Refers to a change that includes, but is not limited to, the product composition, manufacturing process, quality controls, equipment, facilities or product labelling information made to an approved MA or licence by the MA holder. Also referred to as “variation” in other documents.

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.

The term chemical reference substance, as used in this text, refers to an authenticated, uniform material that is intended for use in specified chemical and physical tests, in which its properties are compared with those of the product under examination, and which possesses a degree of purity adequate for its intended use.

The zones into which the world is divided based on the prevailing annual climatic conditions

Any systematic study on pharmaceutical products in human subjects, whether in patients or other volunteers, in order to discover or verify the effects of, and/or identify any adverse reaction to, investigational products, and/or to study the absorption, distribution, metabolism and excretion of the products with the object of ascertaining their efficacy and safety. Clinical trials are generally divided into Phases I–IV. It is not possible to draw clear distinctions between these phases, and different opinions about details and methodology do exist. However, the individual phases, based on their purposes as related to the clinical development of pharmaceutical products, can be briefly defined as follows:Phase I. These are the first trials of a new active ingredient or new formulations in humans, often carried out in healthy volunteers. Their purpose is to make a preliminary evaluation of safety, and an initial pharmacokinetic/ pharmacodynamic profile of the active ingredient.Phase II. The purpose of these therapeutic pilot studies is to determine activity and to assess the short-term safety of the active ingredient in patients suffering from a disease or condition for which it is intended. The trials are preformed in a limited number of subjects and are often, at a later stage, of a comparative (e.g. placebo-controlled) design. This phase is also concerned with the determination of appropriate dose ranges/regimens and (if possible) the clarification of dose–response relationships in order to provide an optimal background for the design of extensive therapeutic trials.Phase III. This phase involves trials in large (and possibly varied) patient groups for the purpose of determining the short- and long-term safety-efficacy balance of formulation(s) of the active ingredient, and assessing its overall and relative therapeutic value. The pattern and profile of any frequent adverse reactions must be investigated, and special features of the product must be explored (e.g. clinically relevant drug interactions, factors leading to differences in effect, such as age). The trials should preferably be randomized double-blind, but other designs may be acceptable, e.g. long-term safety studies. In general, the conditions under which the trials are conducted should be as close as possible to the normal conditions of use.Phase IV. In this phase studies are performed after the pharmaceutical product has been marketed. They are based on the product characteristics on which the marketing authorization was granted and normally take the form of post-marketing surveillance, and assessment of therapeutic value or treatment strategies. Although methods may differ, the same scientific and ethical standards should apply to Phase IV studies as are applied in premarketing studies. After a product has been placed on the market, clinical trials designed to explore new indications, new methods of administration or new combinations, etc., are normally regarded as trials of new pharmaceutical products.

A product consisting of two or more separate pharmaceutical products in their final dosage form that are packaged together for distribution to patients in the co-packaging.

Any mechanism which prevents the temperature inside a cold room from dropping below +2°C under low ambient temperature conditions, down to the temperature specified by the employer at the time of procurement, subject to a minimum ambient of -15°C.

Any mechanism which prevents the temperature inside a refrigerated vehicle from dropping below +2°C under low ambient temperature conditions, down to the temperature specified by the employer at the time of procurement, subject to a minimum of -10°C.

The cold climate freeze protection life is measured from the moment when the container is closed until the temperature of the coldest point inside the vaccine storage compartment first reaches 0°C at a constant ambient temperature of -20°C.

The empty container is stabilized at +43°C and loaded with coolant-packs that have been prepared in accordance with the manufacturer’s coolant recharging instructions. Cold life is measured from the moment when the container lid is closed until the temperature of the warmest point in the vaccine storage compartment first reaches +10°C (after initially cooling to below +10°C during cool down), at a constant ambient test temperature +43°C.  The vaccine storage compartment must remain above 0°C.

Procedure for collaboration between the World Health Organization (WHO) Prequalification Team (WHO/PQT) and interested national regulatory authorities (NRAs) in the assessment and accelerated national registration of WHO prequalified pharmaceutical products and vaccines.

Head-to-head comparison of a biotherapeutic product with a licensed reference biotherapeutic product (RBP) with the goal of establishing similarity in quality, safety and efficacy. Products should be compared in the same study using the same procedures.

Establishes the tests to be done and acceptable limits to be achieved to demonstrate the lack of a negative effect of specific manufacturing changes on the safety or effectiveness of the product. A comparability protocol is a highly specific, well defined plan for the future implementation of a quality (that is, manufacturing) change. Also referred to as “post-approval change management protocol” in other documents

The activities, including study design, conducting of studies and data evaluation that are designed to investigate whether the pre- and post-change products are comparable. In addition to routine analysis performed during production and control of the antigen or final product, these evaluations typically include a comparison of manufacturing process steps and parameters impacted by the change, characterization studies and an evaluation of product stability following the change. In some cases, nonclinical or clinical data might contribute to the conclusion reached.

The finished pharmaceutical product with which a fixed-dose combination finished pharmaceutical product (FPP) is to be compared. The comparison may be by means of bioequivalence studies or clinical studies of safety and/or effectiveness. A single study may use more than one comparator, for example several single entity FPPs. A comparator may be a placebo.

A comparator for a clinical study for a human insulin product (biotherapeutic product) is an established human insulin product approved by a stringent regulatory authority that has a pharmacological profile similar to that of the product to be assessed for prequalification.

The comparator product is a pharmaceutical product with which the multisource product is intended to be interchangeable in clinical practice. The comparator product will normally be the innovator product for which efficacy, safety and quality have been established. If the innovator product is no longer marketed in the jurisdiction, the selection principle as described in Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products (WHO Technical Report Series, No. 992, Annex 8 (2015)) should be used to identify a suitable alternative comparator product.

A frozen coolant-pack that has been allowed to warm at ambient temperature until some water is present inside the pack. The pack is correctly conditioned as soon as the ice core is able to move inside the pack when it is shaken. The effective temperature of a conditioned icepack in this state is 0°C.

The systematic examination of evidence generated and procedures undertaken by the manufacturer, under requirements established by the regulatory authority, to determine that a medical device is safe and performs as intended by the manufacturer and, therefore, conforms to the Essential Principles of Safety and Performance of Medical Devices.

A body engaged in the performance of procedures for determining whether the relevant requirements in technical regulations or standards are fulfilled. A CAB is authorized to undertake specified conformity assessment activities by a regulatory authority that will ensure that performance of the CAB is monitored and, if necessary, withdraw designation.

Refers to the following components: (a) a primary container closure system is a packaging component (for example, a vial or pre-filled syringe) that is in, or may come into, direct contact with the final Annex 4 183 product dosage form, or components that contribute to the container/closure integrity of the primary packaging material for a sterile product; and (b)  a secondary container closure system is a packaging component (for example, a carton or tray) that is not, and will not be, in direct contact with the dosage form.

A manufacturer performing some aspect of manufacturing on behalf of the original manufacturer.

An organization (commercial, academic or other) to which an applicant may transfer some of its tasks and obligations in relation to the conduct of clinical studies with which the product submitted to WHO for assessment for prequalification. Any such transfer should be defined in writing. Bioequivalence studies are often contracted by the sponsor to a CRO, which will perform some of the tasks of the applicant, but which will also perform the trial. The investigator (clinical part of the study) and the study director (bioanalytical part of the study) are then employees of the CRO.

A CROMF is a document prepared by the CRO containing specific and factual information about the CRO, the conduct of clinical studies as well as the analyses of samples and related operations (including clinical trials, clinical data management, pharmacokinetics and statistical analysis, regulatory affairs, etc.) carried out at the named site. If only part of the operations referred to below is carried out at the site, the site master file needs to be presented only for those operations. 

A coolant-pack cooled to a temperature between + 2°C to +8°C before use.

Any substance that can be transported and repeatedly used to absorb energy in a long-term storage cold box and that is non-hazardous, non-corrosive and non-flammable.

A standard procedure that supports the sustained operation of the long-term storage cold box, for example the freezing of coolant packs. Coolant preparation and the equipment needed for this task may be located away from the site where the long-term storage cold box is used.

A purpose-designed, leak-proof container filled with coolant. 

This is measured from the moment when the appliance lid is closed until the temperature of the warmest point in the vaccine storage compartment first goes below +10°C, at a constant ambient test temperature of +43°C. 

The time in hours required for the appliance to cool, starting from the time the device is switched on and ending when stabilized temperatures are measured at all locations inside the vaccine storage area.

Any action taken to eliminate a nonconformity. However, corrections do not address causes. When applied to pharmaceutical products, corrections can refer to reworking, reprocessing, or regrading of products, or assigning them to a different use, or simply destroying them.

Corrective actions are steps that are taken to eliminate the causes of existing nonconformities in order to prevent recurrence. The corrective action process tries to make sure that existing nonconformities and potentially undesirable situations do not happen again. While corrective actions prevent recurrence, preventive actions prevent occurrence. Both types of actions are intended to prevent nonconformities.

Refers to the actions taken to improve an organization's processes and to eliminate causes of non-conformities or other undesirable situations. CAPA is a concept common across the GXPs (good laboratory practices, good clinical practices and good manufacturing practices), and numerous International Organization for Standardization business standards. The process focuses on the systematic investigation of the root causes of identified problems or identified risks in an attempt to prevent their recurrence (for corrective action) or to prevent occurrence (for preventive action).

A pharmaceutical product which is deliberately and fraudulently mislabelled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products, and counterfeit pharmaceutical products may include products with the correct ingredients, with the wrong ingredients, without active ingredients, with an incorrect quantity of active ingredient or with fake packaging.

A critical observation observed by the WHO inspection group during inspection of a contract research organization, manufacturing site or quality control laboratory indicates that it considers that the product as manufactured risks causing harm to the user.

Data integrity is the degree to which data are complete, consistent, accurate, trustworthy and reliable and that these characteristics of the data are maintained throughout the data life cycle. The data should be collected and maintained in a secure manner, such that they are attributable, legible, contemporaneously recorded, original or a true copy and accurate. Assuring data integrity requires appropriate quality and risk management systems, including adherence to sound scientific principles and good documentation practices.

The period following the deactivation of a temperature recording device using the 'stop’ function, during which it must be possible to recover the data recorded during the recording period.

A date fixed for the individual batch, indicating the completion date of the manufacture. It is normally expressed by a month and a year. The date of the release analysis may be taken as a date of manufacture, provided that the period between the beginning of production and the release of the product is not longer than one-twentieth of the shelf life.

Specific load(s) matched to the energy harvest control (EHC) and supplied by the legal manufacturer/reseller. The defined load(s) would be permanently connected to the EHC or would connect to the EHC with a unique, non-standard electrical connector to restrict the addition of undefined loads with standard electrical connectors.

Departure from an approved instruction or established standard.

An electric current flowing in one direction.

The physical form in which a pharmaceutical product is presented by the manufacturer (form of presentation) and the form in which it is administered (form of administration). Also sometimes referred to as “pharmaceutical form”. Examples include tablet, capsule, elixir, injection, suppository.

Any substance or pharmaceutical product for human or veterinary use that is intended to modify or explore physiological systems or pathological states for the benefit of the recipient. The terms drug, medicine and pharmaceutical product are commonly used interchageably.

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

A pharmaceutical product type that contains a drug substance, generally in association with excipients. This refers to a dosage form in the final immediate packaging intended for marketing.

The active pharmaceutical ingredient and associated molecules that may be subsequently formulated, with excipients, to produce the drug product. Any substance or mixture of substances intended to be used in the manufacture 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.

The EVM initiative provides materials and tools needed to monitor and assess vaccine supply chains and help countries to improve their supply chain performance.

The root mean square value of the maximum input voltage that the device is able to continuously tolerate without any form of electrical or mechanical damage.

The organization that contracts with the legal manufacturer or reseller who will supply the system components and the installation and maintenance advisory services described in specification PQS/E001/CR-FR01.4. The employer will typically contract with an installer who will install and commission the installation under the supervision of a quality assurance (QA) assessor and also with a maintenance contractor who will maintain the installation.

The organization that contracts with the legal manufacturer or reseller who will supply the vehicle and maintenance advisory services described in specification:  WHO/PQS/E002/RV01.1.

The organization that contracts an approved installer to carry out the system installation and commissioning.

The point at which time-temperature exposure has altered the appearance of the active surface so that it exactly matches the reference surface. At this point, and thereafter, the vaccine should no longer be used.

The collection, distribution and use of surplus solar electricity for loads in addition to an immunization appliance.

Accessory control device and/or system to enable the use of surplus solar photovoltaic electricity from a solar-powered immunization appliance for powering additional electricity consuming devices (loads). An EHC may harvest surplus electricity when the active cooling circuit is off and/or when the active cooling circuit is on and sufficient surplus electricity is available.

Measurement and recording device intended to monitor cold chain temperature, performance, events and alarms in walk-in cold rooms and freezer rooms (PQS E001) and refrigeration appliances (PQS E003).

Those pharmaceutical products that satisfy the health care needs of the majority of the population. WHO’s Expert Committee on the Selection and Use of Essential Medicines updates the WHO Model List of Essential Medicines at two-year intervals. Each country may use this model to generate its own list of essential pharmaceutical products.

A multisource product that has been marketed by the applicant or manufacturer associated with the dossier for at least five years and for which at least 10 production batches were produced over the previous year, or, if less than 10 batches were produced in the previous year, not less than 25 batches were produced in the previous three years.

An individual or organization (including a testing laboratory) responsible for evaluating the suitability of the components and services described in a specification for inclusion in the list of WHO-prequalified immunization devices.

an international trade term that describes when a seller makes a product available at a designated location, and the buyer of the product must cover the transport costs. Ex-works is one of the Incoterms (International Commercial Terms, a set of standardized international trade terms) published by the International Chamber of Commerce.

A substance or compound, other than the active pharmaceutical ingredient and packaging materials, that is intended or designated to be used in the manufacture of a pharmaceutical product.

The date after which a compounded preparation should not be stored, transported or used; the date is determined from the date or time the preparation is compounded. It is also known as beyond-use date.

Action taken by the manufacturer to reduce a risk of death or serious deterioration in the state of health associated with the use of a medical device that is already placed on the market.

A communication sent out by the manufacturer or its representative to the device users in relation to a field safety corrective action.

A collection of sealed final containers that is homogeneous with respect to the composition of the product and the risk of contamination during filling. A final lot must therefore have been filled from a formulated bulk in one continuous working session.

A a finished dosage form (for example, suspension or lyophilized cake) that contains an active ingredient, generally but not necessarily in association with inactive ingredients (excipients) or adjuvants. Also sometimes referred to as “finished product” or “drug product”.

A finished dosage form of a pharmaceutical product that has undergone all stages of manufacture, including packaging in its final container and labelling.

A combination of two or more active pharmaceutical ingredients (APIs) in a fixed ratio of doses. This term is used generically to mean a particular combination of APIs irrespective of the formulation or brand. It may be administered as singleentity products given concurrently or as a finished pharmaceutical product.

An intermediate in the drug product manufacturing process, consisting of the final formulation of antigens, adjuvants and excipients at the concentration to be filled into primary containers.

A device to indicate when vaccines have become colder than a specified temperature for a certain period of time. These may be chemical or electronic in operation.

The freeze protection classification is based on the number of user-interventions required to ensure freeze protection:

Grade A, user-independent freeze protection (UIFP): when the appliance is used within its nominated temperature range (+43°C and minimum rated ambient temperature) no intervention is required on the part of the user to ensure that the vaccines will not be exposed to temperatures below 0°C, whatever the position of the vaccine in the vaccine compartment.

Grade B, user-dependent freeze protection (UDFP): even if the appliance is used within its nominated temperature range, the user must comply with a procedure provided by the legal manufacturer and requiring one level of intervention (e.g. the requirement to use baskets or any other single item constitutes one level of intervention by the user) in order to ensure that the vaccines will not be exposed to freezing temperatures outside of the acceptable temperature range.

Grade C, user-dependent freeze protection (UDFP): even if the appliance is used within its nominated temperature range, the user must comply with a procedure provided by the legal manufacturer requiring more than one level of intervention (e.g. the requirement to use baskets and insulation barriers or covers) in order to ensure that the vaccines will not be exposed to freezing temperatures outside of the acceptable temperature range.

A temperature excursion below -0.5°C for longer than 1 hour.

A temperature excursion equal to or below -0.5°C for any amount of time. 

The term generic product has somewhat different meanings in different jurisdictions. The use of this term is therefore avoided as much as possible, and the term multisource pharmaceutical product (see below) is used instead. Generic products may be marketed either under the approved nonproprietary name or under a brand (proprietary) name. They may be marketed in dosage forms and/or strengths different from those of the innovator products (see below). Where the term generic product is used, it means a pharmaceutical product, usually intended to be interchangeable with the innovator product, which is usually manufactured without a licence from the innovator company and marketed after expiry of the patent or other exclusivity rights. The term should not be confused with generic names for active pharmaceutical ingredients.

GHTF was conceived in 1992 in an effort to achieve greater uniformity between national medical device regulatory systems. The aims were to enhance patient safety and increase access to safe, effective and clinically beneficial medical technologies around the world. A partnership between regulatory authorities and regulated industry, it consisted of five Founding Members. These were: Australia, Canada, Japan, United States and the European Union. GHTF no longer exists but its work is continued by the International Medical Device Regulators Forum.

A standard for clinical studies which encompasses the design, conduct, monitoring, termination, audit, analysis, reporting and documentation of the studies and which ensures that the studies are scientifically and ethically sound and that the clinical properties of the pharmaceutical product (diagnostic, therapeutic or prophylactic) under investigation are properly documented.

A quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.

That part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.

Acronym for the group of good practice guides governing the preclinical, clinical, manufacturing, testing, storage, distribution and post-market activities for regulated pharmaceuticals, biologicals and medical devices, such as good laboratory practices, good clinical practices, good manufacturing practices, good pharmacovigilance practices and good distribution practices.

The measured volume of the airspace inside the internal compartment of the appliance with the door or lid shut. For combined appliances the gross freezer volume and the gross refrigerator volume are reported separately.

Direct comparison of the properties of, for example, the similar biotherapeutic product with the reference biotherapeutic product in the same study.

The amount of heat that must be added to convert a unit of mass of a solid into a liquid at its melting-point temperature, or the amount of heat that must be removed to convert a unit of mass of a liquid into a solid at its freezing-point temperature.

A transportable, powered appliance moveable by multiple people for short periods, intended primarily for temporary and/or long-term vaccine storage and transport by powered vehicle. All appliances must be designated by the legal manufacturer as one of three appliance types: lightweight, medium-weight, or heavy-weight.

The time in hours during which all points in the vaccine compartment remain between +2°C and +8°C, at the maximum ambient temperature of the temperature zone for which the appliance is rated, after the appliance has initially cooled and stabilized, the power supply has been subsequently disconnected and no other power sources are actively cooling the device. 

Hot zone appliances and units must maintain specified internal storage temperatures while operating at a steady +43°C ambient temperature and over a +43°C/+25°C day/night test cycling temperature range.

Hot zone units must maintain specified internal storage temperatures while operating at a steady +50°C ambient temperature and over a+50°C/+25°C day/night cycling temperature range.

A water-pack frozen to a temperature between -5°C and -25°C before use, to the point where there is no remaining liquid water. Ice-packs can be conditioned by letting them warm to 0°C for use with transport of freeze-sensitive vaccines.

The maximum number of fully frozen water-packs that can remain fully frozen at the end of water-pack storage compartment testing over a multi-day period.

An instrument or apparatus adapted for a specific purpose related to immunization. WHO-prequalified medical devices include temperature monitoring devices, single use injection devices and therapeutic injection devices.

Item of equipment created for use in immunization programmes. WHO-prequalified products include refrigerators and freezers and other vaccine storage products, temperature controlled vaccine transport and delivery products, waste disposal products and cold chain accessories.

The ability of a substance to trigger an immune response or reaction (e.g. development of specific antibodies, T-cell response, allergic or anaphylactic reaction). 

A sudden, non–power frequency change in the steady-state condition of voltage, current or both that is unidirectional in polarity – either primarily positive or negative. Often characterized by extremely high voltages that can cause high levels of current in an electrical circuit for periods ranging from a few millionths to a few thousandths of a second.

Any component present in the drug substance or drug product that is not the desired product, a product-related substance, or excipient including buffer components. It may be either process- or product-related.

A medical device, whether used alone or in combination, intended by the manufacturer for the in vitro examination of specimens derived from the human body solely or principally to provide information for diagnostic, monitoring or compatibility purposesIVDs include reagents, calibrators, control materials, specimen receptacles, software, and related instruments or apparatus or other articles, and are used, for example, for the following test purposes: diagnosis, aid to diagnosis, screening, monitoring, predisposition, prognosis, prediction, determination of physiological status.

Communication by letter, fax or email.

The time in hours during which all points in the vaccine storage compartment remain between +2°C and +8°C, at a constant ambient test temperature of +43°C, after all external power inputs have been disconnected or switched off. This may include both passive as well as active cooling if powered by internal sources integrated into the appliance, e.g. an integrated battery. Independence is distinct from holdover time in that it may include both actively powered and passive cooling, while holdover time includes only passive, thermal cooling capacity.

Generally the pharmaceutical product which was first authorized for marketing (normally as a patented product) on the basis of documentation of efficacy, safety and quality according to requirements at the time of the authorization. When a substance has been available for many years, it may not be possible to identify an innovator pharmaceutical product.

An inspection observation is a finding or a statement of fact made during an inspection and substantiated by objective evidence. Such findings may be positive or negative. Positive observations should take the form of a description of the processes that the firm is carrying out particularly well and that may be considered examples of particularly good practice. Negative observations are findings of non-compliance with requirements.

The complete cold room or freezer installation described in WHO/PQS/E001/CR-FR01.4 and in the companion WHO/PQS/E001/CR-FR01-VP2 and WHO/PQS/E001/CR-FR01-VP.4 documents, together with any other employer’s requirements documentation issued for a specific installation or installations. Including voltage stabilizers and standby generators where these are listed in the employer’s requirements.

The person who installs the solar power system and associated appliance on behalf of the procurement agency.

A person or organization who has been appointed by the employer to carry out the installation of a device or system.

General information card or sheet providing all information necessary for correct use of the device.

The objective intent of the manufacturer regarding the use of a product, process or service as reflected in the specifications, instructions and information provided by the manufacturer. Aspects that are considered in the intended use of an in vitro diagnostic include:

what is detected

its function (e.g. screening, monitoring, diagnosis or aid to diagnosis)

the specific disorder, condition or risk factor of interest that it is intended to detect, define or differentiate

whether it is automated or not

whether it is qualitative or quantitative

the type of specimen(s) required (e.g. serum, plasma, whole blood, tissue biopsy, urine)

testing population

the intended user (e.g. lay person, highly trained laboratory professional, minimally trained health care worker, self-testing)

the intended setting of use (e.g. point of care, reference or diagnostic laboratory setting, primary health care setting).

An interchangeable pharmaceutical product is one which is therapeutically equivalent to a comparator product and can be interchanged with the comparator in clinical practice.

This can be a material produced during steps of the processing of an active pharmaceutical ingredient (API) that undergoes further molecular change or purification before it becomes an API. Intermediates may or may not be isolated, or a material produced during steps in the manufacture of a vaccine that undergoes further processing before it becomes the final product. See also antigen.

Stores that keep and distribute vaccines which are neither at the primary vaccine store nor at the final service delivery level. Such stores are typically located in a regional or district centre.

ICRSs are primary chemical reference substances established on the advice of the WHO Expert Committee on Specifications for Pharmaceutical Preparations. They are supplied primarily for use in physical and chemical tests and assays described in the specifications for quality control of drugs published in The International Pharmacopoeia or proposed in draft monographs. They may be used to calibrate secondary standards.

The shortened scientific name based on the active ingredient. WHO is responsible for assigning INNs to pharmaceutical substances.

Any pharmaceutical product (see definition) or placebo being tested or used as a reference in a clinical trial.

Invitation calling upon interested parties (e.g. manufacturers or other applicants) to submit an expression of interest (EOI) to WHO by a specified deadline for the purpose of participating in the WHO prequalification procedure in respect of the product(s) listed/laboratories defined in the invitation. Such an EOI should be accompanied by the required documentation on the product(s) in question.

Invitation calling upon interested parties (e.g. manufacturers or other applicants) to submit an expression of interest (EOI) to WHO by a specified deadline for the purpose of participating in the WHO prequalification procedure in respect of the product(s) listed in the invitation. Such an EOI should be accompanied by the required documentation on the product(s) in question.

Process of identifying a pharmaceutical product including the following information, as appropriate: name of the product; active ingredient(s), type and amount; batch number; expiry date; special storage conditions or handling precautions; directions for use, warnings and precautions; names and addresses of the manufacturer and/or the supplier.

Information to the user provided on the package label or in the patient information leaflet.

A LIF is a document prepared by the laboratory. It contains specific and factual information about the operations carried out at the named site and any closely integrated operations of the laboratory. If only some of the operations are carried out on the site, the LIF needs to describe only those operations, e.g. sampling, chemical analysis or stability testing.

The natural or legal person with responsibility for the design, manufacture, packaging and labelling of a product or device before it is placed on the market under the person's own name, irrespective of whether these operations are carried out by that person or on their behalf by a third party. A legal manufacturer may commonly contract another company to manufacture products or devices sold under the legal manufacturer’s name. A manufacturer that is contracted in this way is typically known as an original equipment manufacturer (OEM).

An individual or a corporate entity possessing a marketing authorization for a pharmaceutical product.

A commercial entity, licensed to act on behalf of a legal manufacturer, and which carries product liability and warranty responsibilities no less onerous than those carried by the legal manufacturer.

Any end-use device in an electrical circuit (other than the primary appliance and energy harvest control) that can consume power when the electrical circuit is energized. Two categories of electrical loads are considered: defined loads and undefined loads.

Experiments on the physical, chemical, biological, biopharmaceutical and microbiological characteristics of an active pharmaceutical ingredient or finished pharmaceutical product, during and beyond the expected shelf life and storage periods of samples under the storage conditions expected in the intended market. The results are used to establish the re-test period or the shelf life, to confirm the projected re-test period and shelf life, and to recommend storage conditions.

For the purpose of WHO performance evaluation of an in vitro diagnostic, a lot is defined as 'The amount of material that is uniform in its properties and has been produced in one process or series of processes. The material can be either starting material, intermediate material or finished product.” Furthermore, the two lots must be sourced from a representative production run and not produced especially for the purpose of the WHO performance evaluation.

A person or organization contracted by the employer to maintain the installation, devices, and/or appliances.

A major deviation from good manufacturing practice has been observed by the WHO inspection group during inspection of a contract research organization, manufacturing site or quality control laboratory.

All operations of purchase of materials and products, production, quality control, release, storage and distribution of pharmaceutical products, and the related controls.

Manufacturer: any person or legal entity engaged in the manufacture of a product subject to marketing authorization (MA) or licensure. May also refer to any person or legal entity that is an applicant or a holder of a MA or product licence where the applicant assumes responsibility for compliance with the applicable product and establishment standards. See also marketing authorization.

Also referred to as product licence or registration certificate. A legal document issued by the competent medicines regulatory authority that authorizes the marketing or free distribution of a medical product in the respective country after evaluation of safety, efficacy and quality. In terms of quality it establishes inter alia the detailed composition and formulation of the medical product and the quality requirements for the product and its ingredients. It also includes details of the packaging, labelling, storage conditions, shelf life and approved conditions of use. May also be referred to as “product licence” or “licence” in this and other documents.

A formal application to the national regulatory authority for approval to market a new medicine. The purpose of the MA application is to determine whether the medicine meets the statutory standards for safety, effectiveness, product labelling information and manufacturing. Also referred to as “licence application” in other documents.

For the purposes of this website, the term marketing authorization holder refers to any person or entity that holds the legal responsibility for the product on the market by submission of the required documentation on a product that has been listed after evaluation as registered or approved. It also refers to a person or legal entity allowed to apply for a change to the MA or licence. Also referred to as the “manufacturer” or “applicant” in this and other documents.

A general term used to denote raw materials (starting materials, reagents, solvents), process aids, intermediates, active pharmaceutical ingredients and packaging and labelling materials.

The mass of an appliance when fully loaded with vaccines at a density of 0.8 kg per litre of vaccine net storage capacity and with any components necessary to operate within the acceptable temperature range fully prepared and in place.

The weight of a container when fully loaded with coolant-packs and vaccines with a density of 0.8 kg per litre of vaccine storage capacity.

A type of photovoltaic (PV) to battery charge control that optimizes solar array output by operating as a direct current (DC)-to-DC converter. It uses the DC input from the PV array and converts it back to a different DC voltage and current so that the PV module is correctly matched to the battery. This allows a solar array to be wired at optimal voltage to overcome long cable distances that otherwise would result in excessive voltage drop or unacceptably large cable diameter. 

Any substance or pharmaceutical product for human or veterinary use that is intended to modify or explore physiological systems or pathological states for the benefit of the recipient. On ths website, the terms medicine and pharmaceutical product (see below) are used interchangeably.

A national body that administers the full spectrum of medicine regulatory activities, including at least all of the following functions in conformity with national medicine legislation:

marketing authorization of new products and variations of existing products

quality control laboratory testing

monitoring of adverse drug reactions

provision of information on medicines and promotion of rational use of medicines

good manufacturing practice inspections and licensing of manufacturers, wholesalers and distribution channels

enforcement operations

monitoring of drug use.

A transportable, powered appliance moveable by a single person or multiple people for short periods, intended primarily for longer-range transportation by a vehicle (e.g. truck, motorbike, camel). All appliances must be designated by the legal manufacturer as one of three appliance types: lightweight, medium-weight, or heavy-weight.

A branch of science that refers to microbes of all of types, including bacteria, viruses, rickettsia, protozoa, fungi and prions. Derived words (such as microbiological) have a similar meaning.

Cold life with a full coolant load at the minimum rated ambient temperature.

The lowest constant ambient temperature at which the vaccine storage compartment remains above 0°C. The test is carried out at +15°C unless the manufacturer specifies a lower figure.

The lowest constant ambient temperature at which the acceptable temperature range can be maintained with a full vaccine load. All models must be able to operate at a continuous minimum ambient temperature of +10.0°C or lower while maintaining the acceptable temperature range.

Moderate zone units must maintain an acceptable temperature range while operating at a steady +27°C ambient temperature and over a+27°C/+10°C day/night cycling temperature range.

The Montreal Protocol, finalized in 1987, is a global agreement to protect the stratospheric ozone layer by phasing out the production and consumption of ozone-depleting substances. 

Multisource pharmaceutical products are pharmaceutically equivalent products that may or may not be therapeutically equivalent. Multisource pharmaceutical products that are therapeutically equivalent are interchangeable.

The net storage capacity is the space where it is suitable (both thermally and ergonomically) to store vaccines with any components necessary to operate within the acceptable temperature range fully prepared and in place. If a legal manufacturer would declare more than one vaccine storage capacity for the same internal and external dimensions, they must prequalify with different branding, one model for each different storage volume. The capacity will be published as volume in litres.

Actives that have not previously been authorized for marketing as a drug for use in humans in the country in question.

Nonconformity refers to a failure to comply with requirements. A requirement is a need, expectation or obligation. It can be stated or implied by an organization, its customers or other interested parties. There are many types of requirements. These include quality requirements, customer requirements, management requirements, product requirements, process requirements and legal requirements. Whenever an organization fails to meet one of these requirements, a nonconformity occurs.

Storage in dry, well-ventilated premises at temperature of 15–25 °C or,depending on climatic conditions, up to 30 °C. Extraneous odours, other indications of contamination, and intense light have to be excluded.

Verifiable information or records pertaining to the quality of an item or service or to the existence and implementation of a quality system element, which is based on visual observation, measurement or test.

Use of a medicine outside the scope of regulatory authorization.

Those pharmacopoeias recognized by the national regulatory agencies (e.g. national pharmacopoeia (if applicable), the British Pharmacopoeia, the European Pharmacopoeia, The International Pharmacopoeia, the Japanese Pharmacopoeia and the United States Pharmacopeia).

The study carried out by the manufacturer on production batches according to a predetermined schedule in order to monitor, confirm and extend the projected re-test period (or shelf life) of the active pharmaeutical ingredient, or confirm or extend the shelf life of the finished pharmaceutical product.

The component or components being referred to function as normally expected. More explicitly with respect to the appliance, the cooling circuit functions as required by the thermostat.

In relation to replaceable batteries operating life the period following initial activation of the device until the battery is expected to fail. In the case of devices with non-replaceable batteries the period is measured from the date of delivery to the purchaser, rirrespective of whether the device is activated on that date.

Usually refers to an OSD plant that manufactures medicinal products such as tablets, capsules and powders to be taken orally.

Product licensed and approved by a stringent regulatory authority on the basis of a full dossier with comprehensive data on non-clinical and clinical studies.

An “other observation” observed by the WHO inspection group during inspection of a manufacturing site, quality control laboratory or contract research organization indicates that a minor lapse or minor deviation from good manufacturing practice has been observed in the case of a manufacturing site, and from good clinical practice in the case of a contract research organization.

A situation where an electrical device is subjected to a greater electrical load than that for which it was designed. Results in larger than design electric current passing through conductors, leading to excessive generation of heat, and the risk of fire or damage to equipment.

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.

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.

Cooling or heat transfer driven exclusively by temperature differential that occurs spontaneously through and between the components of the appliance, its content and the ambient temperature.

Products are pharmaceutical alternative(s) if they contain the same active pharmaceutical moiety or moieties but differ in dosage form (e.g. tablets versus capsules), strength, and/or chemical form (e.g. different salts or different esters). Pharmaceutical alternatives deliver the same active moiety by the same route of administration but are otherwise not pharmaceutically equivalent. They may or may not be bioequivalent or therapeutically equivalent to the comparator product.

The physical form in which a medicine is presented; the name of a dosage form combines its physical form and the intended route of administration, e.g. a tablet (to be swallowed), oral suspension (liquid suspension of solid particles intended for oral intake and swallowing).

Products are pharmaceutical equivalents if they contain the same molar amount of the same active pharmaceutical ingredients (APIs) in the same dosage form, if they meet comparable standards and if they are intended to be administered by the same route. Pharmaceutical equivalence does not necessarily imply therapeutic equivalence, as differences in the API solid state properties, the excipients and/or the manufacturing process and other variables can lead to differences in product performance.

A substance, other than the active pharmaceutical ingredient, which has been appropriately evaluated for safety and is included in a medicines delivery system to:

aid in the processing of the medicines delivery system during its manufacture

protect, support or enhance stability, bioavailability or patient acceptability

assist in pharmaceutical product identification

enhance any other attribute of the overall safety and effectiveness of the medicine during its storage or use.

Any substance or combination of substances marketed or manufactured to be marketed for treating or preventing disease in human beings, or with a view to making a medical diagnosis in human beings, or to restoring, correcting or modifying physiological functions in human beings.

Any substance of a defined quality used in the production of a pharmaceutical product, but excluding packaging materials. This includes active pharmaceutical ingredients and pharmaceutical excipients.

The specificity of pharmacopoeial reference substances has been addressed in the introduction of ISO Guide: General requirements for the competence of reference material producers. “Pharmacopoeial standards and substances are established and distributed by pharmacopoeial authorities following the general principles of this Guide. It should be noted, however, that a different approach is used by the pharmacopoeial authorities to give the user the information provided by certificate of analysis and expiration dates” (*).*International Organization for Standardization. General requirements for the competence of reference material producers. 2006, ISO Guide 34.

A material, other than water, which changes state between solid and liquid or changes between two different solid crystallization states over a defined temperature range, absorbing or releasing heat during the phase change. This process is reversible and can be useful for thermal control in cold chain devices and products. PCM-based buffers must comply with PQS/E005/PCMC0.1– PCM specification for phase-change material containers.

A loss of power on one phase of a three-phase system.  Typically caused by a failed fuse, thermal overload, severed conductors, worn contacts or other types of mechanical failure.

A voltage variation in a three-phase system in which the voltage magnitudes and/or the phase angle differences between the different phases are not equal.  Expressed as the percentage calculated by dividing the maximum voltage deviation from the phase voltage average, by the three-phase voltage average.

A batch of an active pharmaceutical ingredient or finished pharmaceutical product manufactured by a procedure fully representative of and simulating that to be applied to a full production-scale batch. For example, for solid oral dosage forms, a pilot scale is generally, at a minimum, one-tenth that of a full production scale or 100 000 tablets or capsules, whichever is the larger; unless otherwise adequately justified.

These describe the various activities and courses of action adopted by WHO in fulfilling its responsibilities vis-à-vis prequalification of immunization devices. They are fully described in the standard operating procedures.

Standardized prequalification procedure of WHO to assess, in principle, whether candidate products:

meet WHO technical guidance on quality, safety and efficacy, including compliance with WHO's recommended standards for good clinical practice, good manufacturing practices, good laboratory practices and good distribution practices

adhere to the principles laid out in the WHO guidelines on the international packaging and shipping of vaccines

meet relevant operational packaging and presentation specifications, for the purpose of providing guidance to interested United Nations agencies and WHO Member States in their procurement decisions.

United Nations agencies and WHO Member States using information resulting from WHO prequalification should perform additional steps of qualification prior to purchasing such products, including ensuring financial stability and standing of the supplier, ability to supply the required quantities, security of the supply chain, pre-shipment quality control and other related aspects, including the registration status of the products to be procured.

Preventive actions are steps taken to eliminate the causes of undesirable nonconformities or situations that could occur, but have not yet done so. While corrective actions prevent recurrence, preventive actions prevent occurrence. See also corrective action. Both types of actions are intended to prevent nonconformities.

Activities associated with the upkeep of equipment to protect against normal wear and tear. This type of maintenance requires minimal skills and training and is usually scheduled for regular intervals (daily, weekly or monthly). On-site workers who have received appropriate training are responsible for preventive maintenance.

A batch of an active pharmaceutical ingredient or finished pharmaceutical product used in a stability study, from which stability data are submitted in a registration application for the purpose of establishing a retest peropd or shelf life.

Vial, ampoule, pre-filled device, plastic dispenser or tube containing vaccine or diluent.

Store which receives vaccine directly from the vaccine manufacturer.

The process of purchasing or otherwise acquiring any pharmaceutical product, vaccine, or nutraceuticals for human use. For the purpose of this website, procurement means the preselection of products and manufacturers through a procedure of qualification, including prequalification (see above) and continuous monitoring thereafter, purchase of the prequalified products from prequalified manufacturers (linked to the specific product) through defined purchasing mechanisms, storage and distribution.

A procurement agency in the context of this website is defined as any organization purchasing pharmaceutical products, vaccines, or other health sector goods or is otherwise involved in their prequalification (see above), purchasing, storage and distribution. With respect to immunization devices, a procurement agency is an organization that purchases the equipment covered in a WHO specification and provides the qualified supplier with details of the installation site(s).

Information on pharmaceutical products submitted by manufacturers or suppliers in any of the formats specified in the procurement agency’s guidelines (including product dossiers, product questionnaires or other formats) to obtain prequalification for the products.

Printed materials that accompany a prescription medicine and all labelling items, namely: (a) prescribing information (an instruction circular that provides product information on indication, dosage and administration, safety and efficacy, contraindications and warnings, along with a description of the product for health care providers (also referred to as “summary of product characteristics” or “package insert” in various countries); (b) patient labelling or consumer information; (c) inner label or container label; and (d) outer label or carton.

A process for withdrawing or removing a pharmaceutical product from the pharmaceutical distribution chain because of defects in the product, complaints of serious adverse reactions to the product and/or concerns that the product is or may be counterfeit. The recall might be initiated by the manufacturer, importer, wholesaler, distributor or a responsible agency.

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.

A batch of an active pharmaceutical ingredient or finished pharmaceutical product manufactured at production scale by using production equipment in a production facility as specified in the application.

A document which states the background, rationale and objectives of the trial and describes its design, methodology and organization, including statistical considerations, and the conditions under which it is to be performed and managed. The protocol should be dated and signed by the investigator, the institution involved and the sponsor. It can also function as a contract.

Action of proving and documenting that any premises, systems and equipment are properly installed and/or work correctly and lead to the expected results.Qualification is often a part (the initial stage) of validation, but the individual qualification steps alone do not constitute process validation. It is the work done to prove that the supply system will deliver products of the quality required and specified on a routine basis, meeting all the applicable quality requirements.

The suitability of either an active pharmaceutical ingredient or a pharmaceutical product for its intended use. This term includes such attributes as the identity, strength and purity.

“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 good manufacturing practice and other factors, including those outside the scope of this guide such as product design and development.

The person or entity appointed by the employer to assess the quality and suitability of manufacturing sites and/or candidate-approved installers.

Systems and quality control procedures that are established to ensure that the trial is performed and the data are generated in compliance with good clinical practices and good laboratory practices. These include procedures to be followed which apply to ethical and professional conduct, standard operating procedures, reporting, and professional qualifications or skills of personnel.

A physical, chemical, biological or microbiological property or characteristic. A critical quality attribute refers to a characteristic or property that should be within an appropriate limit, range or distribution to ensure the desired product quality.

In the context of this website, quality change refers to a change in the manufacturing process, product composition, quality control testing, equipment or facility. May also be referred to as “chemistry manufacturing and control (CMC) change”.

All measures taken, including the setting of specifications, sampling, testing and analytical clearance, to ensure that raw materials, intermediates, packaging materials and finished pharmaceutical products conform with established specifications for identity, strength, purity and other characteristics.

An appropriate infrastructure, encompassing the organizational structure, procedures, processes and resources, and systematic actions necessary to ensure adequate confidence that a product or service will satisfy given requirements for quality.

A member of staff who has a defined responsibility and authority for ensuring that the management system related to quality is implemented and followed at all times.

A handbook that describes the various elements of the quality management system for assuring the quality of the test results generated by a laboratory.

A systematic process for the assessment, control, communication, and review of risks to the quality of the pharmaceutical product across the product life-cycle.

Explicit written test procedures and requirements that must be met.

An appropriate infrastructure, encompassing the organizational structure, procedures, processes and resources, and systematic actions necessary to ensure adequate confidence that a product (or services) will satisfy given requirements for quality.

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.

Sample in which the different fractions of the material have an equal probability of being represented.

All records or certified copies of original observations, clinical findings or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Such material includes laboratory notes, memoranda, calculations and documents, as well as all records of data from automated instruments or exact, verified copies, e.g. in the form of photocopies or microfiches. Raw data can also include photographic negatives, microfilm or magnetic media (e.g. computer diskettes) and optical media (CD-ROMs).

A general term used to denote starting materials, reagents and solvents intended for use in the production of starting materials, intermediates, active pharmaceutical ingredients or final products.

The rate at which the active surface responds to time-temperature exposure.

Experiments on the physical, chemical, biological, biopharmaceutical and microbiological characteristics of a drug, during and beyond the expected shelf life and storage periods of samples under the storage conditions expected in the intended market. The results are used to establish the shelf life, to confirm the projected shelf life, and to recommend storage conditions.

A rebranded product is identical in every respect to the product manufactured by the original manufacturer, except that the product is labelled with the 'rebranded' product name and product code, and bears the rebrander's name.

A process for withdrawing or removing a pharmaceutical material from the distribution chain because of defects in the materials or complaints of a serious nature. The recall might be initiated by the manufacturer/importer/distributor or a responsible agency.

The person or organization responsible for receiving something that has sent to them by a sender.

The period between the activation of the device using the ‘start’ button or switch and the de-activation of the device either automatically or by using the ‘stop’ button or switch.

A biotherapeutic product that:

has been licensed and approved by a stringent regulatory authority on the basis of a full dossier with comprehensive data on non-clinical and clinical studies

is used as the comparator for head-to-head comparability studies with the similar biotherapeutic product in order to show similarity in terms of quality, safety and efficacy.

This definition does not refer to measurement standards such as international, pharmacopoeial, or national standards or reference standards.

A reference product is a pharmaceutical product with which the new product is intended to be interchangeable in clinical practice. The reference product will normally be the innovator product for which efficacy, safety and quality have been established. Where the innovator product is not available, the product which is the market leader may be used as a reference product, provided that it has been authorized for marketing and its efficacy, safety and quality have been established and documented.

A sample of a batch of starting material, packaging material, intermediate or finished product which is stored for the purpose of being analysed should the need arise during the shelf life of the batch concerned.

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 can be:

obtained from an officially recognized source

prepared by independent synthesis

obtained from existing production material of high purity

prepared by further purification of existing production material.

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.

Microorganisms defined at least to the genus and species level, catalogued and described according to its characteristics and preferably stating its origin. Normally obtained from a recognized national or international collection.

A colour patch against which the colour of the active surface can be directly compared.

A contiguous geographical area within with the legal manufacturer or reseller is able to provide the full range of services described in specification WHO/PQS/E001/CR_FR01.

A contiguous geographical area within which the legal manufacturer or supplier has previously supplied vehicles in low- and middle-income countries.

Any statutory system of approval required at national level as a precondition for introducing a pharmaceutical product on to the market.

The process whereby regulatory requirements, approaches and systems become more similar or aligned over time as a result of the adoption of internationally recognized technical guidance, standards and best practices.

Relates to the information associated with a submission for approval by a regulatory authority. The submitted version is defined by all of the documentation related to development, manufacture and intended use, labelling and post-market surveillance of the product and all the documented evidence supporting the safety and performance claims associated with that submission. If any aspect of this documentation differs in any way between the submissions to different regulatory authorities or assessment bodies (United States Food and Drug Administration, Health Canada, a Notified Body for CE marking, etc.) it is considered to be a different regulatory version.

The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of an API or FPP at the time of its release.

A system including programmable temperature and event monitor and peripheral devices in compliance with WHO PQS E006/TR03.

A commercial entity, licensed to act on behalf of a legal manufacturer and which carries product liability and warranty responsibilities no less onerous than those carried by the legal manufacturer.

A sample of a fully packaged unit from a batch of finished product. It is stored for identification purposes (for example, of presentation, packaging, labelling, patient information leaflet, batch number and expiry date) should the need arise during the shelf life of the batch concerned.

Combination of the probability of occurrence of harm and severity of the harm.

The estimation of the risk associated with the identified hazards.

A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the evaluation of risk associated with exposure to those hazards.

The sharing of information about risk and risk management between the decisionmaker and other stakeholders.

The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk.

The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description.

A detailed description of the activities that continuously ensure patients' safety and their benefit from a medicinal ingredient. A risk management plan includes:

safety specifications, which summarize the known and potential safety issues and missing information about the rDNA-derived biotherapeutic

a pharmacovigilance plan to further evaluate important known or potential safety concerns and to provide post-marketing data where relevant information is missing

a risk minimization plan, which provides proposals on how to minimize any identified or potential safety risk.

Review or monitoring of output or results of the risk management process considering (if appropriate) new knowledge and experience about the risk.

The ability of the procedure to provide analytical results of acceptable accuracy and precision under a variety of conditions.

The load applied to a cold room or freezer room floor arising from the routine use of metal-wheeled manual pallet trucks and/or powered or manually operated rubber-wheeled pallet lifting equipment.

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.

A product in a given presentation (identified by its name, content of active pharmaceutical ingredient(s) (API(s)), dosage form, strength, batch number, production date (if known), expiration date, collection date and name of manufacturer or labelled registration holder) collected at the specific sample collection site. It means that the same product characterized by the same name, content of APIs, dosage form, strength, batch, and from the same manufacturer collected in two different sites represents two samples. Each sample should consist of the number of dosage units (e.g. tablets, capsules, ampoules, vials or bottles) required by the sampling plan.

Operations designed to obtain a representative portion of a pharmaceutical product, based on an appropriate statistical procedure, for a defined purpose, e.g. acceptance of consignments or batch release.

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

A plan that contains detailed identification of sites where samples will be collected, medicines to be sampled, minimum number of dosage units to be collected per sample, number of samples to be collected per medicine and total number of samples to be collected in the area for which the sampling plan is prepared. It also contains detailed instructions for sample collectors.

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.

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.

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

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.

A carton which contains a number of individual primary containers. Most countries have traditionally stored and distributed vaccines in these cartons.

A substance whose characteristics are assigned and/or calibrated by comparison with a primary reference substance. The extent of characterization and testing of a secondary reference substance may be less than for a primary reference substance.Note: Often referred to as an “in-house” working standard.

A preparation of live cells (prokaryotic or eukaryotic) or viruses constituting the starting material for the vaccine antigen. A seed lot is of uniform composition (although not necessarily clonal), is derived from a single culture process and is aliquoted into appropriate storage containers, from which all future vaccine production will be derived either directly or via a seed lot system. A master seed lot (MSL) is a lot or bank of cells or viruses from which all future vaccine production will be derived. The MSL represents a well-characterized collection of cells or viruses of uniform composition. May also referred to as “master virus seed” for virus seeds, “master seed bank” or “master seed antigen”. A working seed lot (WSL) is a cell or viral seed lot derived by propagation from the MSL under defined conditions and used to initiate production of vaccines on a lot-by-lot basis. May also be referred to as “working virus seed” for virus seeds, “working seed bank” or “working seed antigen”.

The person or organization responsible for sending something to a receiver. 

An event that is associated with death, admission to hospital, prolongation of a hospital stay, persistent or significant disability or incapacity, or is otherwise life threatening in connection with a clinical trial.

The period of time during which a pharmaceutical product, if stored as indicated on the label, is expected to comply with the specification as determined by stability studies on a number of batches of the product. The shelf life is used to establish the expiry date of each batch.

Insulated packaging used for shipping vaccines, as described in the WHO document: Guidelines on the international packaging and shipping of vaccines (WHO/IVB/05.23).

An accidental electrical circuit in a device with no or low resistance when compared to that of the normal circuit, especially one resulting from the unintended contact of components and consequent accidental diversion of current.

A biotherapeutic product that is similar in terms of quality, safety and efficacy to a reference biotherapeutic product.

Absence of a relevant difference in the parameter of interest. A difference that is expected to induce a difference in clinical effect, such as better impurity profile, could be accepted. No differences exist that are expected to induce impact on clinical activities based on a comparability or similarity exercise.

A site master file is a document prepared by the manufacturer containing information with respect to the production and/or control of pharmaceutical manufacturing operations carried out at a named site, and to any closely integrated operations at adjacent and/or nearby buildings. If only part of a pharmaceutical operation is carried out.

A supply of power intended to simulate solar array output at specific instantaneous solar radiation values.

An assembly of solar module(s), electrical cabling, support structure, control and energy storage (e.g. battery, water/ice or PCM) complying with specification WHO/PQS/E003/PV 01.

The minimum average daily solar radiation on the plane of the solar array that is required to properly power the solar refrigerator, or combined refrigerator and water-pack freezer, expressed in kWh/m²/day.

the quality standard (that is, tests, analytical procedures and acceptance criteria) provided in an approved application to confirm the quality of antigens (drug substances), final products (drug products), intermediates, raw materials, reagents, components, in-process materials, container closure systems and other materials used in the production of the antigen (drug substance) or final product (drug product). For the purpose of this definition, acceptance criteria mean numerical limits, ranges or qualitative criteria for the applied tests. It serves as a basis for quality evaluation.

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.

Instrument for measuring time‒temperature indicator optical density (OD) values.

The ability of a drug to retain its properties within specified limits throughout its shelf life. The following aspects of stability are to be considered: chemical, physical, microbiological and biopharmaceutical.

Long-term and accelerated (and intermediate) studies undertaken on primary and/or commitment batches according to a prescribed stability protocol to establish or confirm the retest period (or shelf life) of an active pharmaceutical ingredient or the shelf life of a finished pharmaceutical product.

A series of tests designed to obtain information on the stability of a pharmaceutical product in order to define its shelf life and utilization period under specified packaging and storage conditions.

Solar power system capable of independently powering 100% of all electrical management system electrical needs.

Common electrical connectors including all USB receptacles, 12 volts of direct current (VDC) receptacles as used in vehicles and 120/230 VAC (volts of alternating current) receptacles as used in buildings and electrical generators.

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.

Normative references about the product manufacturing process and product performance, quality and safety. In evaluating immunizations devices for prequalification, WHO applies standards defined by the International Organization for Standarizationm (ISO) wherever possible. In addition to ISO standards, WHO draws on the standards of other relevant international or national bodies in different parts of the world.

The appearance of the active surface of the indicator at the time when the indicator is activated.

Any material used at the beginning of the manufacturing process, as described in a marketing authorization or product licence. Generally, the term refers to a substance of defined chemical properties and structure that contributes an important and/or significant structural element (or elements) to the active substance (for example in the case of vaccines, synthetic peptides, synthetic glycans and starting materials for adjuvants). The starting material for an antigen (drug substance) obtained from a biological source is considered to consist of: (a)  cells; (b) microorganisms; (c) plants, plant parts, macroscopic fungi or algae; or (d) animal tissues, organs or body fluid from which the antigen (drug substance) is derived.

In relation to non-replaceable batteries, the period measured from the date of delivery of the device to the sender to the time at which the ‘start’ function may be activated and a sufficient operating life would remain.

A regulatory authority which is:

a. a member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), being the European Commission, the US Food and Drug Administration and the Ministry of Health, Labour and Welfare of Japan also represented by the Pharmaceuticals and Medical Devices Agency

or an ICH observer, being the European Free Trade Association, as represented by Swissmedic, and Health Canada (as before 23 October 2015)

or a regulatory authority associated with an ICH member through a legally-binding, mutual recognition agreement, including Australia, Iceland, Liechtenstein and Norway (as before 23 October 2015).

Note: This interim definition is currently being revised.

A multi-dose container consisting of two layers, usually provided with perforations, suitable for containing single doses of solid or semi-solid preparations. Blisters are excluded.

Commonly used term for employee of a manufacturing company that is undergoing inspection who is presented as possessing expertise in a particular area or subject and who can therefore answer related questions and requests for futher information made by the inspection team.

Substandard medicines are pharmaceutical products that fail to meet either their quality standards or their specifications, or both. Each pharmaceutical product that a manufacturer produces has to comply with quality assurance standards and specifications, at release and throughout its shelf life, according to the requirements of the territory of use. Normally, these standards and specifi cations are reviewed, assessed and approved by the applicable national or regional medicines regulatory authority before the product is authorized for marketing.

Summary of product characteristics approved by the competent authority. The information may alternatively be presented in the container or package label.

Written request submitted to the national regulatory authority (NRA) to approve a change in the original application for a marketing authorization (MA) (or product licence) or any other notification to add to (that is, supplement) the information in the original MA or product licence file. A prior approval supplement is a supplement requiring approval from the NRA prior to implementation of the change. May also be referred to as “change application dossier”.

A person providing pharmaceutical products and materials on request. Suppliers may be agents, brokers, distributors, manufacturers or traders. Where possible, suppliers should be authorized by a competent authority.

Any electricity a solar direct device appliance cannot use because:

the appliance does not require electricity at that instant

electricity being generated is insufficient to power the appliance at that instant

electricity is powering the appliance and there is surplus electricity that the appliance cannot use at that instant.

Continuous, systematic collection, analysis and interpretation of health-related data needed forthe planning, implementation, and evaluation of public health practice.

The local or remote programmable electronic temperature and event logging system specified in WHO/PQS/E006 performance specifications.

A key strategic document that contains a detailed description of desirable future product design characteristics, features or functions. It explains the reason for each desirable characteristic and states the date by which the feature must be included in products seeking to achieve or to maintain prequalified status. A TPP captures user needs via inputs and product feedback from the operating environment, guiding product development so that it responds to needs that have arisen in that operating environment. TPPs are intended to stimulate further feedback and dialogue with product manufacturers. They are not intended to be proscriptive about how product user needs should be met, but rather to stimulate new ideas and solutions. They do not impose any implicit or explicit obligation on manufacturers to achieve all of the desirable product characteristics. For example, during the dialogue process it may emerge that some of these characteristics are technically difficult to achieve or may drive up costs. In such circumstances, these characteristics may appear as optional performance requirements in the final specification. Manufacturers that are able to satisfy these optional requirements may be at a competitive advantage and serve to incentivize to other manufacturers to reach that same level of performance.

Temperate zone units must operate within the proper storage temperatures at a steady +32°C ambient temperature and over a +32°C/+15°C day/night cycling temperature range.

The time it takes for temperatures within an appliance to reach the acceptable temperature range and attain full holdover or autonomy.

A corrugated cardboard or fibreboard box which contains a number of individual secondary packs. Cartons of this type are increasingly being used to store and to distribute vaccine.

Commercially prepared reagent sets, with accessory devices, containing all of the major componentsand literature necessary to perform one or more designated diagnostic tests or procedures.

Therapeutic activity refers to the successful prevention, diagnosis and treatment of physical and mental illnesses; improvement of symptoms of illnesses; as well as beneficial alteration or regulation of the physical and mental status of the body and development of a sense of general well-being.

Two pharmaceutical products are considered to be therapeutically equivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and, after administration in the same molar dose, their effects, with respect to both efficacy and safety, are essentially the same when administered to patients by the same route under the conditions specified in the labelling. This can be demonstrated by appropriate equivalence studies, such as pharmacokinetic, pharmacodynamic, clinical or in vitro studies.

A device that indicates when vaccines have exceeded a specified threshold temperature. These may be chemical or electronic in operation.

Traceability aims at ensuring that the results of laboratory measurements using procedures of lower metrological order are reproducible and scientifically acceptable by referring to an internationally agreed denominator by means of a reference procedure of highest metrological order and/or a primary reference material.

Defining policies and procedures in writing and publishing the written documentation, and giving reasons for decisions to the public.

User-selected load devices that are not supplied by the legal manufacturer/reseller as a defined load with the appliance and energy harvest control system.

An abnormal decrease in the root mean square value of the input voltage from the nominal value for a period longer than half a cycle of the nominal input waveform.

With respect to an electronic component or device, to operate continually, without pause.

The person responsible for the day-to-day operation and monitoring of the room, vehicle, appliance or installation.

Refrigeration technology that requires appliance users (e.g. healthcare workers) to perform specific actions (user-interventions) in order to ensure vaccine protection against freezing temperatures (e.g. store vaccines in baskets, away from compartment wall surfaces).

Refrigeration technology that does not require appliance users (e.g. healthcare workers) to perform any specific actions (user-interventions) in order to ensure vaccine protection against freezing temperatures.

Any activity that is required to be executed by appliance users (e.g. healthcare workers) in order to ensure safe operation of the appliance (e.g. vaccine protection against freezing temperatures, condensation removal from compartment, etc.). Activities could include, but are not limited to, basket storage, storage compartment covers, thermostat/fuel adjustment, placement of removable compartment covers, liners or barriers, draining of condensation, charging a battery, or thermally conditioning the appliance or components thereof.

Any activity that is required to be executed by equipment users in order to ensure vaccine protection against freezing. Activities could include the addition of a removable liner to the vaccine carrier or the conditioning of icepacks before placement in the carrier.

A preparation containing antigens capable of inducing an active  immune response for the prevention, amelioration or treatment of infectious diseases.

The relative reduction in disease incidence or severity in vaccinated individuals compared to unvaccinated individuals measured in a randomized, placebo-controlled clinical trial. In the context of these Guidelines, vaccine efficacy has a broad meaning and relates to all clinical data obtained to ensure vaccine efficacy, immunogenicity or field effectiveness.

The volume of the vaccine storage compartment measured with the full number of coolant-packs in place. Capacity will be published as length, width and height in centimetres and volume in litres. If the volume is not rectangular in horizontal cross-section, the capacity may be published as area in square centimetres, height in centimetres and volume in litres.

The compartment within an appliance which is designated by the legal manufacturer as suitable for storing vaccine.

A label containing time-temperature sensitive material which is placed on a vaccine vial to register cumulative heat exposure over time. Vaccines produced by different manufacturers may have different heat stability characteristics and may therefore be assigned different VVMs based on a vaccine’s thermostability profile as determined by laboratory testing.

Action of proving, in accordance with the principles of good manufacturing practice/good clinical practices/good laboratory practices, that any procedure, process, equipment, material, activity or system actually and consistently leads to the expected results (see also qualification).

A laboratory test device to simulate a variety of secondary loads operating on an adjustable range of direct current (DC) electricity input.

A change to any aspect of a pharmaceutical product, including but not limited to, the change of use of a starting material, a change to formulation, method and site of manufacture, specifications for the finished product and ingredients, container and container labelling and product information.

Describes in detail how the performance of a product or device will be tested or otherwise evaluated as part of the PQS???? product prequalification procedure. Each performance specification is accompanied by at least one corresponding verification protocol.

A small container for parenteral medicinal products, with a stopper and overseal; the contents are removed after piercing the stopper. Both single-dose and multi-dose types exist.

The empty container is stabilized at +18°C and loaded with warm-packs that have been stabilized at the same temperature for a minimum of 24 hours. Warm life is measured from the moment when the container is closed, until the temperature of the coldest point inside the vaccine storage compartment first reaches 0°C at a constant ambient temperature of -20°C.

A coolant-pack typically stabilized at room temperature, up to a recommended maximum of +24°C. Warm water-packs are used for the transport of freeze-sensitive vaccines during exposure to sub-zero ambient temperatures.

A flat, leak proof, plastic container, filled with tap water, complying generally with specification PQS/E005/IP01.

The maximum weight and number of water-packs that can be fully frozen, in one batch, during a 24-hour freezing cycle.

The maximum weight and number of fully frozen water-packs that can remain fully frozen at the end of freezing capacity testing.WHO Collaborating CentreWHO Collaborating Centres are institutions designated by the WHO Director-General to form part of an international collaborative network carrying out activities in support of WHO’s programmes at all levels. 

The worst-case temperature in refrigerators is to be the lowest temperature measured during testing and the worst-case temperature in freezers is to be the highest temperature measured during testing. The reading must refer to a point lying within the zone allocated for the storage of vaccines.