The terms listed below are defined specifically for the purposes of this manual. They may be defined differently in other documentation, including annexes in this manual which were, in certain cases, published some years ago.

accountability

Being required to account for one’s conduct and actions, usually to an individual or group but ultimately to the public. Both individuals and organizations may be accountable. There is some overlap between accountability and transparency (see below).

active pharmaceutical ingredient (API)

A substance or compound that is intended to be used in the manufacture of a pharmaceutical product as a therapeutically active compound (ingredient).

advertising

For the purposes of this manual, advertising is considered a part of promotion.

applicant

The person or company who submits an application for marketing authorization of a new pharmaceutical product, an update to an existing marketing authorization, or a variation to an existing marketing authorization.

assessment (report)

See Evaluation Report

authorization holder

The person or company in whose name the marketing authorization has been granted. This party is responsible for all aspects of the product, including quality and compliance with the conditions of marketing authorization. The authorization holder must be subject to legislation in the country that issued the marketing authorization, which normally means being physically located in the country.

authorized person

A person (among key personnel of a manufacturing establishment) responsible for the release of batches of finished products for sale. In some other GMP guides and legal texts, the term qualified person is used to describe analogous functions.

bioequivalence

Two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent and their bioavailabilities (rate and extent of availability), after administration in the same molar dose, are similar to such a degree that their effects can be expected to be essentially the same.

comparator

In this manual, the term comparator is used to mean “the pharmaceutical product with which the new product is intended to be interchangeable in clinical practice”. In any particular market, the comparator should be the first in this list that is available.

X the product for which efficacy, safety and quality have been fully established (often the innovator);

X a market leader that has been authorized for marketing after a process of assessment;

X a market leader that is legally marketed but has not been assessed prior to marketing authorization.

See Annex 7, section 16 for guidance on how to deal with the situation where the comparator proves, on testing, to be of poor quality, e.g. it has poor bioavailability.

container labelling

All information that appears on any part of a container, including that on any outer packaging such as a carton.

dosage form

The form of the completed pharmaceutical product, e.g. tablet, capsule, injection, elixir, suppository.

drug

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.

drug master file

A drug master file (DMF) is a master file that provides a full set of data on an API. In some countries, the term may also comprise data on an excipient or a component of a product such as a container.

drug product

See pharmaceutical product.

drug regulatory authority

A national body that administers the full spectrum of drug regulatory activities, including at least all of the following functions:

X marketing authorization of new products and variation of existing products;

X quality control laboratory testing;

X adverse drug reaction monitoring;

X provision of drug information and promotion of rational drug use;

X good manufacturing practice (GMP) inspections and licensing of manufacturers, wholesalers and distribution channels;

X enforcement operations;

X monitoring of drug utilization.

essential drugs

Essential drugs are those that satisfy the health care needs of the majority of the population. As indicated by the Expert Committee on the Use of Essential Drugs (5), each country may generate its own list of essential drugs.

evaluation report

A critical summary and interpretation of the data, with conclusions, prepared by or on behalf of the drug regulatory authority.

excipient

Any component of a finished dosage form other than the claimed therapeutic ingredient or ingredients.

expert advisory body

A standing advisory board (or committee) of independent experts, including academic experts and practicing health care professionals.

expert report

In European Union usage critical summary and interpretation of the data, with conclusions, prepared by or on behalf of an applicant.

finished product

A product that has undergone all stages of production, including packaging in its final container and labelling.

formulation

The composition of a dosage form, including the characteristics of its raw materials and the operations required to process it.

generic products

The term generic product has somewhat different meanings in different jurisdictions. 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. 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 APIs.

grandfathered

A product that is grandfathered is one that has been granted marketing authorization because it was already being marketed at the time the marketing authorization system was established.

The terms provisional registration or provisional marketing authorization (see below) are preferred, but some countries do not have a separate category of provisional marketing authorization.

immediate release dosage form

A dosage form that is intended to release all the active ingredient on administration with no enhanced, delayed or extended release effect.

innovator pharmaceutical product

The innovator pharmaceutical product is generally that 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.

interchangeability

An interchangeable pharmaceutical product is one that is therapeutically equivalent to a comparator (reference) product.

labelling

The word “labelling” has been avoided in this manual because its meaning is not consistent between Member States. See container labelling and product information.

licence

See marketing authorization.

manufacture (manufacturing)

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

marketing authorization

An official document issued by the competent drug regulatory authority for the purpose of marketing or free distribution of a product after evaluation for safety, efficacy and quality. It must set out, inter alia, the name of the product, the pharmaceutical dosage form, the quantitative formula (including excipients) per unit dose (using INNs or national generic names where they exist), the shelf-life and storage conditions, and packaging characteristics. It specifies the information on which authorization is based (e.g. “The product(s) must conform with all the details provided in your application and as modified in subsequent correspondence”). It also contains the product information approved for health professionals and the public, the sales category, the name and address of the holder of the authorization, and the period of validity of the authorization.

Once a product has been given marketing authorization, it is included on a list of authorized products - the register - and is often said to be “registered” or to “have registration”. Market authorization may occasionally also be referred to as a licence or product licence.

master file

A master file is a data set that is:

X submitted by someone other than a finished product applicant, e.g. the supplier of an active ingredient or the supplier of a packaging component;

X a common feature of more than one product, e.g. sterility test procedures; or

X some other matter that is conveniently dealt with by means of a master file.

An applicant for a new marketing authorization or for a variation may make reference to a master file, but must have the permission of the person or company that submitted the master file.

master formula

A document or set of documents specifying the starting materials with their quantities and the packaging materials, together with a description of the procedures and precautions required to produce a specified quantity of a finished product as well as the processing instructions, including in-process controls.

medicine

See drug.

medicinal product

See pharmaceutical product.

multisource (generic) pharmaceutical product

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

new chemical or biological APIs (new APIs)

New chemical or biological APIs are those not previously authorized for marketing for any pharmaceutical use in the country in question. Those provisionally authorized at the time of the initial market inventory are not new pharmaceutical ingredients.

new drug

Any drug that does not match the definition of well established drugs (see below).

new pharmaceutical product

A pharmaceutical product that contains a new API, a new combination of marketed APIs, or a new multisource (generic) product. It may be available either on prescription or without prescription.

newer drug

See new drug.

periodic review

The regular process, usually occurring every five years, by which the validity of a marketing authorization is renewed and information on a product is reviewed (validated), consolidated and sometimes expanded.

pharmaceutical equivalents

Products are pharmaceutical equivalents if they contain the same amount of the same active substance(s) in the same dosage form; if they meet the same or 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 excipients and/or the manufacturing process can lead to differences in product performance.

pharmaceutical product

Any preparation for human or veterinary use that is intended to modify or explore physiological systems or pathological states for the benefit of the recipient.

product information

A document defining information that may be supplied with or about a pharmaceutical product by or on behalf of the marketing authorization holder. The minimum information in the product information is that defined by WHO’s sample product information sheet (see appendix to Annex 8). The content of the product information is agreed between the marketing authorization holder and the DRA at the time the market authorization is issued.

promotion

All informational and persuasive activities by manufacturers and distributors, the effect of which is to induce the prescription, supply, purchase and/or use of medicinal products Ethical criteria for drug promotion, WHO,1988 (see Annex 8). For the purposes of this manual, promotion includes advertising.

provisional marketing authorization

Temporary authorization following the initial market inventory, and pending full approval based on evaluation of quality, safety and efficacy.

provisional registration

See provisional marketing authorization.

quality control

Quality control is concerned with sampling, specifications and testing, and with the organization, documentation and acceptance/rejection procedures which ensure that the necessary and relevant tests are actually carried out and that starting materials, intermediates and finished products are not accepted for use, sale or supply until their quality has been judged to be satisfactory.

register

A list of all the pharmaceutical products authorized for marketing in a particular country. The register is maintained by the drug regulatory authority of the country in question.

registered drug products

Pharmaceutical products that have a marketing authorization.

registration

See marketing authorization.

renewal

The word “renewal” has been avoided in this manual because its meaning is not consistent between Member States. See periodic review and retention fee.

retention fee (for marketing authorization)

A fee paid to maintain marketing authorization, usually annually. Product details are not normally reviewed when retention fees are paid. (See also periodic review)

specification - expiry, check or shelf life

The combination of physical, chemical, biological and microbiological test requirements that an active ingredient must meet up to its retest date or a drug product must meet during its shelf-life.

specification - release

The combination of physical, chemical, biological and microbiological test requirements that determine whether a drug product is suitable for release at the time of its manufacture.

stability

The ability of an active ingredient or a drug product to retain its properties within specified limits throughout its shelf-life. The chemical, physical, microbiological and biopharmaceutical aspects of stability must be considered:

starting material

Any substance of a defined quality used in the production of a pharmaceutical product, but excluding packaging materials.

therapeutic equivalence

Two pharmaceutical products are therapeutically equivalent if they are pharmaceutically equivalent and, after administration in the same molar dose, their effects with respect to both efficacy and safety are essentially the same, as determined from appropriate bioequivalence, pharmacodynamic, clinical or in vitro studies.

tracking

Keeping a record of the progress of an application at all stages.

transparency

The term transparency means (1) defining policies and procedures in writing and publishing the written documentation, and (2) giving reasons for decisions to the affected party. There is some overlap between transparency and accountability (see above).

unregistered drug products

Pharmaceutical products that do not have a marketing authorization.

update

See periodic review.

Validation

The demonstration, with documentary evidence, that any procedure, process, equipment, material, activity, or system actually leads to the expected results.

Variation

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

well-established drugs

APIs (not products) which:

X have been marketed for at least five years in countries that undertake active postmarketing monitoring;

X have been widely used in a sufficiently large number of patients to permit the assumption that safety and efficacy are well known; and

X have the same route of administration and strength, and the same or similar indications as in those countries.

See also well established drug combinations and well established drug products.

Because this definition refers to active pharmaceutical ingredients and not products, it does not take into account possible sensitivities to excipients and other factors that are relevant to therapeutic equivalence.

well-established drug combinations

Combinations of drugs which:

X have been marketed for at least five years in countries which undertake active postmarketing monitoring;

X have been widely used in a sufficiently large number of patients to permit the assumption that safety and efficacy are well known; and

X have the same route of administration and strength, and the same or similar indications as in those countries.

See also well established drugs and well established drug products.

Because this definition refers to active pharmaceutical ingredients and not products, it does not take into account possible sensitivities to excipients and other factors that are relevant to therapeutic equivalence.

well-established drug products

Pharmaceutical products which contain well established drugs, and which:

X have been marketed for at least five years in countries that undertake active post-marketing monitoring;

X have been widely used in a sufficiently large number of patients to permit the assumption that safety and efficacy are well known; and

X have the same route of administration and strength, and the same or similar indications as in those countries.

WHO-type certificate

A certificate of pharmaceutical product of the type defined in the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (see Annex 2).