# Biosimilar Medicines: From Development Process to Marketing Authorization by the EMA and the FDA
## 6 Biosimilar Medicines: Marketing Authorization  
### Data Requirements  
The introduction of a biosimilar into the pharmaceutical market implies obtaining a marketing authorization from the competent regulatory authorities. This process demands that manufacturers submit an application containing relevant evidence about the product that is grouped and organized in a single document, called a Common Technical Document (CTD). The CTD is an internationally recognized standard format created by the ICH for the presentation of regulatory information on medicines, aiming to promote the harmonization and standardization of regulatory requirements in different regions of the world [84]. For many years, the CTD was exclusively a paper document, but at the moment, the use of the electronic version of the Common Technical Document (eCTD) is mandatory when applying to the EMA and strongly recommended by the FDA [85; 86]. Figure 6: Example of a clinical switching study design of an interchangeable biosimilar candidate [81]. The CTD for biosimilar medicines contains some differences compared to a new biological product. Although they have the same structure, the content and focus of a biosimilar CTD heavily emphasizes the comparability between the biosimilar and the reference product across all modules [87]. Module 1 should provide a summary of the evidence used to prove that the product for which the application is submitted is a biosimilar. Details of the biosimilar such as its active substance, raw materials and manufacturing process should be included together with differences from the relevant attributes of the reference medicine. Changes during the development process that could affect the comparability exercise should be mentioned. The comparability exercise with the reference medicine in terms of quality, safety and efficacy must be described, as well as the reference medicine used throughout the entire development program. With regard to module 2, it should contain the normal mandatory requirements for all medicines, namely, a quality overall summary and a non-clinical and clinical overview [87; 88]. The major differences are in modules 3, 4 and 5. In the third module, in addition to detailed information on the manufacturing process, including cell line characterization, culture conditions, purification methods and scale-up procedures, it also contains data focused on demonstrating comparability to the reference biological product, including studies conducted to establish similarity between the CQAs of both products. In addition, the analytical techniques and quality control procedures used during this evaluation should also be included in this module. Regarding modules 4 and 5, which include information on non-clinical and clinical studies, respectively, the extent to which these studies should be carried out is less for biosimilar medicines than for the biological reference medicine, since there are previous data on the original medicine. However, in addition it is necessary to carry out a comparative exercise to assess the similarity between the two products in terms of pharmacokinetic/pharmacodynamic and immunogenicity profile to guarantee the safety, efficacy and quality of the new biosimilar [87; 88; 89]. Table 5 compares in detail the general data requirements for the reference product and the biosimilar medicine in relation to modules 3, 4 and 5 of the CTD, which include information on quality, non-clinical and clinical studies, respectively.