# Biosimilar Medicines: From Development Process to Marketing Authorization by the EMA and the FDA
## 6 Biosimilar Medicines: Marketing Authorization
### European Medicines Agency and Food and Drug Administration Pathways  
#### 6.2.1 European Medicines Agency  
Directive 2001/83/EC addressed various issues related to the establishment of a legal framework for the regulation of medicines for human use in the EU, such as labelling and packaging, marketing authorization and pharmacovigilance of medicines. Several procedures were established for the approval of medicinal products, as shown in Figure 7[92]. The centralized procedure (CP) is one of the main strategies used for approving medicines in the EU. Regulation (EC) No. 726/2004 outlines the rules governing the marketing authorization application (MAA) through the CP managed by the EMA [94]. This procedure allows for pharmaceutical companies to submit a single MAA, which, if approved, permits the medicine to be marketed in all EU countries, as well as in Iceland, Liechtenstein and Norway [94]. The choice of the CP for the authorization of medicinal products can be mandatory or optional, depending on the type of product and its therapeutic, scientific or technical characteristics [94; 95]. If a medicine does not fall within the mandatory scope of the CP or if the pharmaceutical company does not opt for this route, one of the following procedures must be chosen: A mutual recognition procedure (MRP), in which the applicant with an already authorized medicine in one EU Member State can request its recognition in other EU countries, allowing for Member States to rely on each other's scientific assessments. A decentralized procedure (DP), where the applicant, not yet having a marketing authorization in any EU Member State, can apply for the authorization of a medicine in more than one EU Member State simultaneously. Finally, national authorization is used for medicines that will only be marketed in one Member State [93; 96]. Regarding biosimilars, Directive 2001/83/EC did not initially specify the provisions for them; however, it laid the foundation for their subsequent inclusion and regulation [92]. In 2003, the directive was amended by Directive 2003/63/EC, in which the term \"similar biological medicinal product\" was first introduced into European legislation. The requirements that the CTD of a biosimilar should contain for its approval as well as the need to carry out comparability studies were established [97]. One year later, the directive was revised again, and Directive 2004/27/EC promoted the harmonization of authorization procedures for biosimilars across the EU, simplifying the approval process and ensuring that the same standards were applied in all Member States [98]. Almost all biosimilar medicines available in the EU were approved by the EC through the CP, overseen by the EMA. Eligibility for the approval of a biosimilar medicine under the CP can be granted in various ways, as shown in Table 6. Some biosimilars, including certain low molecular weight heparins obtained through the porcine intestinal mucosa, can receive approval at national level [2]. Figure 7: EU marketing authorization procedures [93]. A request for eligibility must always be submitted, whether the product falls under the mandatory or optional scope. The producer must also provide a justification of eligibility for assessment under the CP [99]. This process requires the involvement of several EMA committees, including the Committee for Medicinal Products for Human Use (CHMP), responsible for the scientific evaluation of the application, which works together with the Biosimilar Medicinal Products Working Party (BMWP), which provides recommendations on non-clinical and clinical issues directly or indirectly relating to biosimilar medicines. In addition, the Pharmacovigilance Risk Assessment Committee (PRAC) for safety-related aspects and risk management also contributes to this process. From the submission of the application to the granting of marketing authorization, it typically takes around 12 to 18 months.