The formulation of the concept of internal transfer as a stage for assessing the process scalability on the example of the scheme for obtaining substance 6-methyluracil

Abstract

Aim. To introduce the concept of internal (laboratory) transfer, in which the transferring party is a pharmaceutical development specialist, and the receiving party is a technology transfer specialist. The study involved determining the main directions of laboratory scaling, searching for visual approaches to its implementation, as well as performing calculations for increased raw material loads using conversion factors.

Materials and methods. The study object when determining the transfer algorithm was substance 6-methyluracil, which synthesis was in the conditions of the pharmaceutical enterprise JSC “Farmak”. During the internal transfer of the active pharmaceutical ingredient (API), the approved laboratory method for obtaining API 6-methyluracil was tested (scaled). The methodological approach was applied to evaluate the effectiveness of technology transfer processes at various stages, including development, transfer, and adaptation of technologies to production conditions. The reporting documentation of production sites was analyzed.

Results. To ensure proper scaling and testing of the technology, key research areas for the technology transfer were identified, including the adaptation of laboratory process parameters to scaling conditions, reproduction of the laboratory methods for obtaining the substance under laboratory scaling conditions, and evaluation of the process efficiency, including cost-effectiveness. As a result of laboratory scaling with the integrated use of these approaches, the finished product was obtained. This product met the qualitative and quantitative requirements established during the pharmaceutical development and matched the quality of the laboratory sample of the finished product. Based on the data obtained, the efficiency of the scaling process was assessed by comparing (before and after) with the data from the laboratory method. It was determined that during laboratory scaling, the consumption rates per kilogram of the product decreased compared to the laboratory development data, resulting in a reduced cost of the final product.

Conclusions. The technological process for obtaining 6-methyluracil is suitable for scaling under laboratory transfer conditions. All technological parameters identified at the pharmaceutical development stage and adapted for the scalable process were successfully confirmed during the laboratory transfer. The laboratory equipment that maximally simulated production conditions was selected for the transfer process. Additionally, the quantitative yield of the product with reduced consumption rates was confirmed. The target product obtained fully complies with the target quality profile defined during the pharmaceutical development.