# 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
#### 6.2.2 Food and Drug Administration  
To be able to market their products on the US market, manufacturers must submit an application to the FDA to ensure that their product complies with the statutory requirements for approval, including meeting standards for safety, efficacy and quality. The FDA has several well-established approval pathways, depending on the characteristics of the product, as shown in Figure 8.  
Biological products are regulated under section 351(a) of the Public Health Service Act (PHSA) by submitting a Biologics License Application (BLA) that contains all information and data necessary to prove that the product is safe, pure and potent. Regarding biosimilar medicines, the Biologics Price Competition and Innovation Act (BPCIA) of 2009, enacted as part of the Patient Protection and Affordable Care Act (PPACA) in 2010, amended the PHSA and introduced section 351(k). This section established an abbreviated licensure pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed biological reference product. This section delineates the requirements for the demonstration of biosimilarity or interchangeability with the reference product and the procedures for the submission and review of these products' applications [102; 103; 104]. There are some general requirements that the application must include to be approved by the 351(k) pathway, such as a demonstration that the product is biosimilar to a reference product already approved through analytical, non-clinical and clinical studies, unless the FDA decides that, in its discretion, certain studies are not necessary. Moreover, the product must use the same mechanism(s) of action for the intended condition(s) of use known for their reference. The condition(s) of use proposed in the labelling should be the ones that have been previously approved for the reference product and it must contain the same route of administration, dosage form and strength. Lastly, all details regarding the manufacturing and packaging of the product must comply with the established requirements to guarantee the safety, purity and potency of the product [105]. After ensuring that their product meets all the requirements mentioned above, the manufacturer submits a BLA to the FDA. The evaluation of biosimilar and interchangeable products involves the collaboration of several teams, namely, the Center for Drug Evaluation and Research (CDER), which regulates biological products mostly produced by biotechnology methods, with the help of the Office of Therapeutic Biologics and Biosimilars (OTBB), which coordinates and supports all biosimilar and interchangeable product-related activities. In addition, the Center for Biologics Evaluation and Research (CBER) regulates a variety of biological products, such as blood and blood components, gene therapy products and human tissue [9; 106]. The contribution of all these teams in the process of reviewing the application is crucial to determine whether the product meets the regulatory requirements for approval, including demonstrating biosimilarity to the reference product and meeting standards for safety, efficacy and quality. Figure 8: Approval pathways for originator biologics and biosimilar/interchangeable products [21]. The review process includes a total of six major steps, namely, pre-submission activities, process submission, planning and conducting a scientific/regulatory review of the application, taking official action and finally post-action feedback to the applicent. The time from application submission until the official action is decided is usually up to 10 months. This procedure is relatively quick, as the agency is interested in speeding up the review process for biosimilars to increase access to quality biological medicines and promote competition. However, it is necessary to ensure that the product has the desired safety and efficacy, so this timeline can vary considerably depending on the complexity of the product and the availability of data for the FDA to proceed with the review process.