[JUSTIFICATION OF USING EQUIVALENCE OF THE INDICES OF QUALITY, SAFETY, AND EFFICACY IN DEVELOPING BIOANALOGS]

We describe general principles of demonstrating biosimilarity, as well as selecting the biosimilarity margins. Any change in the structure of a biological molecule can modify its functional activity. Therefore, therapeutic equivalence between a biosimilar product and the corresponding reference product cannot be demonstrated using a single criterion. To demonstrate biosimilarity between two medicinal products, their various characteristics have to be evaluated which may, directly or indirectly, justify that clinically significant differences are absent. Insufficient understanding of 6ritical quality attributes brings a risk for the biosimilar product developer. This will either increase the number of non-clinical and clinical tests and trials needed or will result in awareness that the manufacturing process needs to be improved at the late stages of development, after investing significant resources in the development process. At the same time, the specification of the biological medicinal product cannot solely ensure safety and efficacy thereof. Properly characterized and controlled manufacturing process, which ensures consistency in its attributes not adequately controlled in specifications but influencing safety and efficacy profiles and showing their relevance in non-clinical tests and clinical trials, is an additional quality assurance factor. Justification of all development strategy details, including biosimilarity margins, has to be provided each time when the development process is initiated or when proceeding to the next steps. All problems encountered by the developer have to be resolved in close communication with the regulatory authority. In order to increase the quality of investigation and developer's adherence to good practices, clinical trial results should be published in detail.