Process of reviewing and assessing the dossier to support a medicinal product in view of its marketing (also called licensing, registration, approval, etc.), obviously finalized by granting of a document also called marketing authorization (equivalent: product license). This process is performed within a legislative framework which defines the requirements necessary for application to the concerned (competent) regulatory authority, details on the assessment procedure (based on quality, efficacy and safety criteria) and the grounds for approval or rejection of the application, and also the circumstances where a marketing authorization already granted may be withdrawn, suspended or revoked.
The application for marketing authorization is called New Drug Application (NDA) in the USA or Marketing Authorization Application (MAA) in the European Union and other countries, or simply registration dossier. Basically, this consists of a dossier with data proving that the drug has quality, efficacy and safety properties suitable for the intended use, additional administrative documents, samples of finished product or related substances and reagents necessary to perform analyzes of finished product as described in that dossier. The content and format of the dossier must follow rules as defined by the competent authorities. For example, since year 2003, the authorities in the United States, the European Union and Japan ask for the Common Technical Document (CTD) format, and more recently, its electronic version – the electronic Common Technical Document (eCTD).
The application is filled with the competent drug regulatory authority in the concerned country, which can be an independent regulatory body or a specialized department in the ministry of health.
In accordance with local legislation, the resulting document allowing to the applicant to market the product may be more detailed (in addition to data identifying the product and its holder it may contain addresses of all manufacturing sites, appended labeling, artwork of packaging components, etc.) until a one-page document called certificate of registration (and containing minimal data identifying the product and its source).
Authorization processes follow either a purely national procedure, with rules and requirements as per national legislation in force, as it occurs in most of countries worldwide, or should follow a centrally approval or a mutual recognition or decentralized procedure within the European Union.
Types of applications
The type of application may vary according to status of the active ingredient.
Thus, if the application concerns a new active ingredient (new active substance, new chemical entity, new molecular entity), one talks about a full application.
Once a new active ingredient authorized, any additional strengths, pharmaceutical forms, administration routes, presentations, as well as any variations (changes to the existing marketing authorization) and extensions shall also be granted an authorization or be included in the initial marketing authorization, being subject of an abridged application.
Special consideration is to be given to application for authorization of biological products and biotechnology products, homeopathic products, herbal drugs, radionuclide generators, kits , radionuclide precursor radiopharmaceuticals and industrially prepared radiopharmaceuticals; in such instances, requirements are specific, in the meaning that they are special, more or less detailed, as per the nature of active ingredient.
In most countries, a marketing authorization is valid for a period of 5 years. After this period, one should apply for renewal of the marketing authorization, usually by providing minimal data proving that quality, efficacy and safety characteristics are maintained and the risk-benefit ratio of the medicinal product is still favourable. However, in the European Union, after one renewal, the marketing authorization shall remain valid for an unlimited period, unless the competent regulatory authority decides otherwise.
If the marketing authorization is not renewed in a due time as requested by the local legislation, in order to maintain the pharmaceutical product on a market, one can apply for re-authorization (re-registration). In such situations, the applicant may be requested to submit the whole items necessary for a full application.
Marketing authorization may be withdrawn, suspended, revoked or varied by regulatory authorities if under normal conditions of use the benefit over risk ratio is no more favorable, the product is harmful, or if it lacks therapeutic efficacy; also, one of the above actions can be taken if the qualitative and quantitative composition or other qualitative aspects (control) are not as currently declared.
Marketing authorization may be also withdrawn, suspended or revoked if the marketing authorization holder or its representative does not fulfill other legal or regulatory obligations necessary to maintaining of product on the market, as per the legislation in force.
Also, the marketing authorization is withdrawn in the EU if the product is not placed on the market within next 3 consecutive years after granting of authorization or if it is no more marketed for 3 consecutive years (so-called “sunset clause”).