How to Approve Medicines in the European Union

Because the European Union is composed of several member states, the approval process for medicines should take into account both the unity of European economic integration and the individuality of each member state's independence and autonomy. Therefore, the EU drug approval process both for the entire EU market centralized approval process (centralized Procedure), and member states to do their own non-centralized approval process (Decentralized Procedure), the latter includes member states of the autonomous "Member States Approval Procedure (Independent National Procedure)", the latter includes member states of the autonomous "Member States Approval Procedure (Independent National Procedure)". The latter includes the "Independent National Procedure" of each member state and the "Mutual Recognized Procedure (MRP)" among member states. As such, there are three main routes for applying for marketing authorization for medicines: the Centralized Approval Process, the Member State Approval Process and the Mutual Recognized Process. Botanical drugs also use these routes to apply for marketing authorization of medicines, but only according to the specific circumstances of botanical drugs and adopt one of the application procedures. The EU drug declaration program is divided into categories for the following introduction.

1 Centralized Approval Process for Medicines

The centralized approval process for medicines is one of the most important registration and approval processes for medicines to be approved for marketing in European countries. A marketing authorization for a medicine obtained through the centralized approval process in the EU is valid in any Member State, i.e. the medicine can be sold freely on the market in any Member State. Therefore, the centralized approval procedure is a shortcut for the rapid marketing of medicines throughout Europe. On the other hand, if a medicine is not approved through the centralized approval procedure, it is very difficult to obtain a marketing authorization for the product in a Member State through other approval procedures. A marketing authorization obtained through the centralized approval process is valid for five years, and an application for extension must be submitted to the European Medicines Agency (EMEA) three months before the expiry of the validity period, but the total validity period*** does not exceed 10 years.

The legal basis for the centralized approval process for medicines is Council Regulation (EC) No. 2309/93/Ec, Council Directive 93/4l/Ec and Directive 2001/83/EC. Recently, Council Directive 2004/24/EC and Council Directive 2004/27/Ec amended Directive 2001/83/Ec. Among them, Directive 2001/83/Ec and Directive 2004/24/EC relate to botanical medicinal products.

1.1 Categories of medicinal products subject to centralized approval

Council Decree 2309/93/EC specifies which medicinal products are subject to the centralized approval procedure. According to EEC/2309/93, new compounds and biological products must be applied for under the centralized approval procedure. In addition, there are some medicines that are subject to both centralized and other approval procedures, and EMEA has divided the medicines subject to centralized approval into two main categories.

1.1.1 Biological products include: (1) recombinant DNA technology; (2) prokaryotic and eukaryotic organisms, including transformation of mammalian cells active protein gene coding controlled expression technology; (3) hybridization and monoclonal technology. Products prepared by any of the above biotechnologies must apply to EMEA for marketing authorization for new medicines, i.e., such products can only be approved through a centralized approval process, and no other approval process can be used.

1.1.2 New medicines containing new active substances may, at the will and request of the applicant, be subject to the centralized approval procedure. Such new medicines may be applied for under the centralized approval procedure or under the application procedure of the Member States, but the mutual recognition procedure is generally not used. This category of new medicines involves a new terminology, namely "new active substance". A new active substance is defined as a new chemically, biologically or radiologically active substance for medicinal purposes, which includes: (1) isomers, or mixtures of isomers, compounds, derivatives, or salts of approved medicinal products, which are significantly different in safety and efficacy from the approved "parent" chemical substance. (ii) A biologic substance that has been approved for marketing as a drug A biologic substance that has been approved as a medicinal product by the European Union, but when there is a significant change in the molecular structure, properties of the source substance, or manufacturing process, the changed biologic substance is a new active substance. (iii) A radiopharmaceutical substance of a radionuclide or ligand that has not been approved as a pharmaceutical product by the EU in the past, or where the coupling of the connecting molecule to the radionuclide has not been approved by the EU. Depending on the nature of the constituent substances of the medicines, EMEA also classifies new medicines subject to the centralized approval procedure as follows: ① chemically active substances medicines; ② radiopharmaceuticals; ③ biological products; and ④ botanical products.

In addition, the EU has also made strict definitions in terms of indications for medicines. EU EEC/726/2004 regulation clearly stipulates that after November 20, 2005, the indications for AIDS, cancer, neurodegenerative diseases and diabetes must be applied for in accordance with the centralized approval process; to May 20, 2008, viral diseases, autoimmune diseases and immune-related diseases will be required to apply for in accordance with the centralized approval process. Therefore, applicants for herbal drug submissions should decide whether to use the centralized approval process based on the indication for the herbal drug.

In short, the gradual expansion of the scope of application of the centralized approval process is the trend of the EU's unified management of medicines, and is also a necessity for the integration of the European economy and the unification of the European pharmaceutical market.

1.2 Procedures and institutions of centralized approval

The institution responsible for centralized approval is EMEA, whose main tasks are: (1) to provide the best scientific advice to the member states and the relevant EU institutions on the quality, safety and efficacy of human and veterinary medicines; (2) to set up an expert group consisting of scientists from various countries to provide authoritative pharmacological evaluation of medicines that have passed through the approval procedures of the EU and the member states; (3) to provide a comprehensive and comprehensive assessment of the quality and efficacy of human and veterinary medicines. (ii) establish an expert group of multinational scientists to provide authoritative pharmacological assessment of medicines through the EU approval and Member State approval processes; (iii) establish fast, transparent and effective marketing authorization procedures for medicines within the EU, monitoring procedures and appropriate license revocation procedures; (iv) provide pharmaceutical companies with advice on research on medicines; (v) strengthen the supervision of medicines through coordinated Member State drug surveillance and inspection actions; (vi) establish the necessary databases and electronic contact facilities to promote the rational use of medicines.

EMEA has four review committees: Committee for Human Medicinal Products (CilMP), Committee for Veterinary Medicinal Products (CVMP), Committee for Orphan Medicinal Products (CVMP), and Committee for Orphan Medicinal Products (CVMP). The Committee for Human Medicinal Products (CilMP), the Committee for Veterinary Medicinal Products (CVMP), the Committee for Orphan Medicinal Products (COMP), and the Committee for Herbal Medicinal Products (HMPC). They are responsible for the approval and management of chemical and biological products, veterinary medicines, orphan drugs (drugs for rare diseases) and herbal medicines (botanical medicines including Chinese medicines) in that order. Once approved by EMEA, medicines can be freely marketed and sold throughout the EU. The Committee for Herbal Medicines, which was only established in September 2004, is responsible for the approval of herbal medicines at EU level, such as centralized approval and adjudication review (see below).

2 Member State approval procedures for medicines

Member State approval procedures are a type of decentralized approval procedure. The Member State approval process for medicines is the process by which medicines are approved by the respective Medicines Review Authorities (MRAs) of the Member States of the European Union (EU) for medicines other than those that are subject to a centralized approval process. Each member state of the EU has its own pharmaceutical regulations, and the regulations and technical requirements for the approval of medicines in member states are not the same. Therefore, the Member State approval process for medicines actually requires the submission of declarations in accordance with the national regulations and their latest technical requirements. Specifically, in which member country to apply for marketing authorization of pharmaceutical products, according to which member country's pharmaceutical regulations and technical requirements to provide the corresponding information. If the centralized approval process emphasizes the coordination and unity of the EU's drug approval standards, while the member state approval process highlights the independence and differences of the member states' drug approval standards. It can be seen that the European drug approval is actually a combination of the above unity and independence.

The web pages of the competent authorities for the approval of medicines in the EU member states can be found on the Internet (http://heads.medagencies.org/). These web pages provide information on the regulations, filing procedures and technical requirements for the approval of medicines in their respective member states. Through these sites, information on the approval and registration of medicines in the European countries can be accessed by clicking on the map.

3 Mutual Approval Process for Medicines

The mutual approval process is also a decentralized process. The mutual recognition process does not have its own independent approval body, procedures and technical requirements like the centralized approval process. It is based on the approval process of member states. The approval process of the mutual authorization procedure takes place in the respective medicines approval authorities of the Member States. As a result, the mutual authorization procedure is often categorized under the Member State procedure in the relevant EU medicines regulatory documents, rather than being listed as a separate application category. Unlike the Member State procedure, once a medicinal product is approved through the mutual recognition procedure and has been approved in the first Member State, the other Member States involved in the mutual recognition procedure usually have to recognize the decision of the first Member State to approve the product and grant marketing authorization accordingly. According to the relevant documents of the European Union, the basic principle of the mutual recognition procedure is that if a member state of the European Union approves the marketing of a pharmaceutical product, other member states should also approve the marketing of the pharmaceutical product in their own countries unless there are sufficient grounds to reject it. A good reason is a suspicion that there are serious problems with the safety, efficacy or quality control of the product, which may pose a health risk to patients. In the event of disagreement between Member States, EMEA's Committee for Medicinal Products for Human Use (CPMP) has the power to carry out a scientific evaluation of a traditional medicinal product, after which the CPMP will issue a specialized decision on the medicinal product that is binding on all Member States, which must comply with the CPMP's resolution. The legal basis for the mutual recognition procedure in the Member States is EU Council Directives 65/65/EEC and 75/319/EC. Council Directive 93/39/EC in turn regulates how the mutual recognition procedure is to be carried out.

In the application of the mutual recognition procedure, there are the following two cases: (1) when a pharmaceutical product has been approved for marketing in a member state, you can use the mutual recognition procedure for pharmaceutical products to apply for marketing in other member states. ② pharmaceutical products have never been in the EU countries to obtain marketing authorization, the first application for marketing, the applicant in addition to a member state application, at the same time to other one or more member states to apply for mutual recognition. Mutual recognition of the basic requirements of the procedure is: to the member states must be submitted to the declaration of information and documents must be identical. The mutual recognition procedure is in principle completed within 90 days, and the maximum time required is about 300 days. 90 days refers to the first case of the mutual recognition procedure mentioned above; 300 days refers to the second case of the mutual recognition procedure mentioned above. This procedure applies mainly to commonly used medicines. This procedure enables medicines to move quickly from the market of one Member State to the markets of other Member States. The Mutual Recognition procedure has a large scope of application and can also be used for simplified applications for traditional herbal medicines. This application procedure is the main way for Chinese medicines to enter the EU market. The advantage is that it is not like the "centralized approval process": if it is rejected, the drug's European **** body marketing door is closed.

4 The EEA adjudication process

When a medicinal product may pose a risk to public health if approved through the Mutual Approval process, i.e. when Member States are not able to reach a unified conclusion on whether to grant a marketing authorization for a certain medicinal product, the disputed case can be entrusted to the EEA to adjudicate, i.e. to resolve the differences between the Member States at the level of the EEA. In other words, the differences between member states are resolved at the level of the EEA. This is the EEA adjudication review procedure. The review process starts with a scientific re-examination of the applied-for medicinal product by the CPMP organization of the EEA, followed by a EEA resolution that is binding on the Member State concerned. The E*** body adjudicative review procedure is usually used when there is either a divergence of opinion between the Member States or when it is necessary to consider it from the E*** body's point of view. This review procedure is a special form of the centralized procedure.