# Biosimilar Medicines: From Development Process to Marketing Authorization by the EMA and the FDA
## 3 Biosimilar Medicines Regulatory Framework
The World Health Organization (WHO) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) are crucial entities whose mission is trying to harmonize the regulatory and approval processes of medicines around the world, facilitating global access and acceptance of biosimilars. In 2009, the WHO created its own guidelines on evaluation of similar biotherapeutic products [32; 33]. The ICH works consistently to create a harmonized and efficient regulatory environment between the main global pharmaceutical markets (i.e., EU, US and Japan), aiming to reduce barriers to international trade in medicines, allowing for biosimilars approved in one region to be more easily recognized and accepted in other regions [34; 35]. The ICH created guidelines for development and approval of medicines in general, but some are specific to biological and biosimilar medicines, such as ICH QSE, which helps ensure the consistency of biological products before and after changes to the manufacturing process [23]. At present, the regulatory framework for biosimilar medicines is well-established. Figure 3 presents a timeline of the principal milestones that have shaped this evolution, \begin{table}
\begin{tabular}{l l} \hline \hline
**Year** & **Title** \\ \hline
2014 & Reference Product Exclusivity for Biological Products Filed Under; Draft Guidance for Industry. \\ \hline
2015 & Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; \\  & Guidance for Industry. \\  & Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Guidance for Industry. \\ \hline
2016 & Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product; Guidance for Industry. \\ \hline
2018 & Labelling for Biosimilar Products; Guidance for Industry. \\ \hline
2019 & Considerations in Demonstrating Interchangeability with a Reference Product; Guidance for Industry. \\  & Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related \\  & Considerations; Draft Guidance for Industry. \\ \hline
2020 & Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use for Which the Reference \\  & Product Has Been Licensed; Draft Guidance for Industry. \\  & Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act; Draft \\  & Guidance for Industry. \\ \hline
2021 & New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 3); Draft Guidance for Industry. \\  & Questions and Answers on Biosimilar Development and the BPCI Act; Guidance for Industry. \\ \hline
2022 & Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics; \\  & Guidance for Industry. \\ \hline
2023 & Classification Categories for Certain Supplements Under BsUFA III; Draft Guidance for Industry. \\  & Labeling for Biosimilar and Interchangeable Biosimilar Products; Draft Guidance for Industry. \\  & Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act (Revision 1); \\  & Draft Guidance for Industry. \\ \hline
2024 & Considerations in Demonstrating Interchangeability with a Reference Product: Update; Draft Guidance for Industry. \\  & Postapproval Manufacturing Changes to Biosimilar and Interchangeable Biosimilar Products Questions and Answers; \\  & Draft Guidance for Industry. \\ \hline \hline \end{tabular}
\end{table} 
Table 3: FDA Guidance documents for biosimilar medicines [30]. starting with the implementation of Directive 2001/83/EC and its subsequent amendments, followed by the introduction of the first guideline on biosimilars in 2005 and the subsequent approval of the first biosimilar by the EMA the following year. In 2009, the US initiated the establishment of a regulatory system for biosimilars, coinciding with the publication of the first guideline on these products by the WHO.