Medicines market authorisation

Committee For Proprietary Medicinal Products, Xotes to Applicants for Marketing Authorisations on the Production and Quality Control of Monoclonal... 

Commission Regulation (EC) No. 1084/2003 of 3 June 2003 concerning the examination of variations to the terms of a marketing authorisation for medicinal products for human use and veterinary medicinal products granted by a competent authority of a Member State... 

An Investigational Medicinal Product Dossier (IMPD) is intended to be more comprehensive than an IB, in that it should contain summaries of available quality data in addition to the safety and efficacy information that constitutes the main part of the IB. In total, it should provide information on the chemistry, manufacture, control and stability ofthe medicinal product, together with the results of non-clinical and clinical studies. In order to avoid repetition, the IB can be cross-referenced for non-clinical and clinical results. Ideally, the IMPD should follow the same structure as that which will be used later for the marketing authorisation application. For products with existing marketing authorisations, the Summary of Product Characteristics may replace the IMPD to varying extents (see Chapter 6). 

It is worthwhile to note that, in the US, where the applicant will just be dealing with a single authority, there is no need to re-submit data that was previously submitted as part of an IN D application to conduct clinical trials. Instead, the applicant can cross-reference the IND file. This does not apply in Europe, because clinical trial applications will have been submitted to individual Competent Authorities, whereas marketing authorisation applications are usually submitted either centrally to the European Medicines Agency (EMEA) or collectively to a number of Competent Authorities. Thus, the files need to be self-supporting. 

The procedures for obtaining a Community marketing authorisation are defined in EC Regulation No. 726/2004. The types of human-use medicinal products for which the procedure may be used are shown in Eigure 6.14. The applicant should notify the EMEA of their intention to submit an application at least 7 months... 

The authorisation of veterinary medicines containing a new chemical entity for use in food-producing animals involves a two-stage application process (i) an application to establish MRLs and (ii) an application for a marketing authorisation. 

Applications to establish MRLs for new pharmacologically active substances must be submitted to the European Medicines Agency (EMEA) at least 6 months in advance of an application for a marketing authorisation. In order to avoid delays, manufacturers are advised to submit an application once all the necessary data are available, as a product authorisation carmot be granted unless established MRLs are in place. The EMEA should be notified of the intent to submit an application 3 to 4 months in advance of the anticipated date, so that a Rapporteur and Co-Rapporteur can be appointed from among the members of the Committee for Veterinary Medicinal Products (CVMP). 

The procedures and timelines for obtaining marketing authorisations for veterinary products are essentially the same as those for human medicines. Extensive guidance can be found in The Rules Governing Medicinal Products in the European Union, Volume 6 - Notice to Applicants, Veterinary Medicinal Products. The products that may follow centralised procedures and receive Community authorisations are shown in Eigure 7.5. All other products must obtain authorisations from national... 

Pharmaceutical products are not sold or supplied before a Qualified Person has certified that each production batch has been produced and controlled in accordance with the requirements of the Marketing Authorisation and any other regulations relevant to the production, control and release of medicinal products. 

Volume 2A Notice to applicants—Medicinal products for human use—Procedures for marketing authorisation Volume 2B Notice to applicants—Medicinal products for human use—Presentation and content of the dossier Volume 2C Notice to applicants—Medicinal products for human use—Regulatory guidelines Commission of the European Communities, Luxembourg, 1998/1998/ 1999 (and amendments)... 

AQ4a The use of ionising radiation in the manufacture of medicinal products (pages 23-30) 3AQ9a Excipients in the dossier for application for marketing authorisation of a medicinal product (pages 67-74)... 

E reflect information in the marketing authorisations of medicinal products... 

The Summary of Product Characteristics (SPC) for a medicinal product reflects the information in the marketing authorisation of the product. It is prepared by the manufacturer and is intended for health professionals. Updates are necessary to reflect any approved changes by the regulatory body in the marketing authorisation. 

This is the name of what we used to know simply as the data sheet, or colloquially as the package insert. The SPC is the document that must be submitted in draft by companies to the MHRA/Reference Member State/European Medicines Evaluation Agency upon application for a marketing authorisation and, once approved, must then be provided to prescribers or suppliers of medicines, either with the product or at the time of promotion or within the previous 15 months of promotion of the product, written or verbal. The SPC includes the prescribing information for the product and represents the product licence approval for the medicine (see Section 12.2.1.1). It is the definitive statement between the competent authority and the company and, more importantly, is becoming the common basis of communication between the... 

The use by the medical profession of medicines with no current marketing authorisation and of authorised medicines outside the terms of their marketing authorisation raises various regulatory issues. Leaving aside use in a clinical trial, such products are also used to treat the particular clinical needs of individual patients. This is known variously as named patient, particular patient or compassionate use supply. The first of these terms is misleading, because there has never been any requirement to identify a particular patient and for the purposes of this chapter the term particular patient supply is used instead. 

There is only limited EC legislation dealing with the supply of medicinal products for particular patient use and there were no relevant provisions prior to 1989. Article 6.1 of Directive 2001/83/EC (previously article 3 of Directive 65/65/EEC) sets out the general rule that a medicinal product must have a marketing authorisation before being placed on the market. However, article 5, which repeats wording introduced by Directive 89/341/EEC, provides an exception from this general rule ... 

Significant changes to the legal basis for the exemptions, rather than to their scope, were introduced by the Medicines for Human Use (Marketing Authorisations Etc.) Regulations... 

Regulation 3(1) of the 1994 Regulations states that no medicinal product may be placed on the market or distributed by way of wholesale dealing, unless it has a marketing authorisation. This replaces the product licence requirement in section 7 of the act. The exemptions to this requirement are provided for by regulation 3(2) and Schedule 1 to the regulations. They permit supply for individual patients and also enable practitioners to hold limited supplies of stocks of imauthorised medicines. The provisions apply equally to doctors and dentists. 

The schedule only provides exemptions from the requirement to hold a marketing authorisation. Other activities involved in the supply of medicines on a particular patient basis need to be carried out under the appropriate authorisations. 

Section 8(2) of the Medicines Act 1968 requires those involved in the manufacture or assembly of a medicinal product to hold a manufacturer s licence. In fact. Schedule 1 to 1994 Regulations requires the manufacturer/assembler in the United Kingdom of an unlicensed product for particular patient supply to hold a particular type of manufacturer s licence (a manufacturer s special licence). It should also be noted that Section 23 of the act prohibits the manufacture of a medicinal product unless that product has a marketing authorisation, or is exempt from the marketing authorisation requirement. 

Patent protection under general law usually lasts for up to around 20 years. This creates a difficulty in relation to medicinal products, as it can take some 12 years for the products to undergo research, development, the extensive clinical trials that are required in order to obtain a marketing authorisation and the authorisation process itself. These steps are also extremely expensive. The amount of time that remains during which the patent holder can exploit his patent and recoup his massive investment can be severely curtailed in relation to medicinal products. For this reason, the European Community has provided a form of additional patent-related protection for medicinal products authorised within the European Community, by means of a Supplementary Protection Certificate. A patent holder may apply for a certificate that takes effect at the end of the term of the basic patent, for a period equal to the period that elapsed between the date on which the application for the basic patent was lodged and the date of the first authorisation to place a product derived from the patent on the market in the Community, reduced by a period of 5 years. The maximum duration of the certificate is 5 years. The certificate applies to all medicinal products derived from the basic patent, but the additional time that can be obtained under the SPC is calculated in relation to the first product derived from the patent, authorised in the EU. 

The UK MEIRA has recently drawn special attention to several areas of interest and have highlighted adverse reactions in children and the elderly. Children pose a particular problem because they are seldom studied in clinical trials that form the basis of marketing authorisation submissions. The consequence of this is that children are prescribed medicines which are not licensed for that age group and little experience of possible adverse effects is available. The elderly are also under-represented in pre-marketing clinical trials and are also subject to diminished metabolic activity in respect of numerous commonly used drugs. 

In the European Union, a medicinal product may only be placed on the market when the competent authority of a Member State for its own territory (national authorisation) has issued a marketing authorisation or when the European Commission (EC) has granted an authorisation for the entire Community (Commimity authorisation). 

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