Introduction: The development of ATMP biosimilars faces significant challenges due to the complexity of these products, which involve modified cells and genes. Replicating the same efficacy and safety is difficult, and variations in manufacturing can lead to differing clinical outcomes. Additionally, evaluating their safety and efficacy is complicated by biological systems' complexity and immune responses, creating further regulatory hurdles. Key regulatory issues include the absence of clear guidelines and the need for extensive clinical trials. Overcoming these challenges requires a stepwise approach and totality of evidence to ensure biosimilarity, alongside international cooperation and financial support.
Methods: In this article, we conducted a systematic review of the published papers and guidelines in the field of ATMPs, focusing on the challenges in developing biosimilars related to these products.
The development of ATMP biosimilars faces numerous challenges, including the inherent complexity of these products, which involves modified cells and genes. This makes it difficult to create a similar version with the same efficacy and safety. Changes in the manufacturing process can also lead to significant differences in clinical outcomes. Moreover, the evaluation of the safety and efficacy of ATMP biosimilars, due to the complexity of biological systems and various immune responses, poses additional regulatory challenges.
In terms of regulatory challenges, the lack of clear guidelines and the need for extensive clinical trials are among the main issues. Additionally, post-market surveillance is essential to ensure long-term safety and efficacy. Generally, two fundamental concepts are involved in the approval process of biosimilar drugs:
1. Stepwise approach
2. Totality of evidence
The stepwise approach means that at each stage, the focus is on addressing the remaining regulatory questions from the previous stages. In other words, each stage sequentially focuses on the uncertainties left over from the previous stage until these uncertainties are fully resolved.
The totality of evidence refers to the fact that in order to confirm the biosimilarity of a product to the reference drug, a comprehensive assessment of all criteria, including analytical, preclinical, and clinical evaluations, must be conducted. None of these criteria alone is sufficient to prove biosimilarity, and they must be collectively confirmed.
In the areas of quality and safety, ensuring the robustness and reproducibility of the manufacturing process and precise control over cells and genetic materials are key issues.
Economic and legal challenges also include the high costs of development and legal barriers due to patents, which can slow down the entry of biosimilars into the market. Finally, proposed solutions include the development of comprehensive regulatory guidelines, increased international cooperation, and financial support to facilitate the development process and reduce costs.
Results: The development of biosimilars in the ATMP field faces numerous technical, scientific, regulatory, and economic challenges. However, with the increasing demand for these products and their high potential in treating complex diseases, it is essential to develop effective strategies to overcome these challenges.
Conclusion: Regulatory bodies should develop more comprehensive and transparent guidelines for the development of ATMP biosimilars. These guidelines must carefully consider the scientific, technical, and regulatory challenges, providing precise guidance for developers.
Since the development of ATMPs is an emerging and global field, international collaboration between regulatory bodies and manufacturing companies can help establish common standards. Such collaborations can also facilitate evaluation and approval processes across different countries.
Financial support through grants or public and private investments in the development of ATMP biosimilars can help reduce costs and accelerate the development process.
Keywords: ATMP, biosimilar, regulatory challenges, international collaboration, financial support