The Technical Education Committee Symposium, Management of DNA reactive (mutagenic) impurities in drug development, sponsored by the Parenteral Drug Association (PDA) Japan Chapter, was held online on November 5, 2020. The symposium focused on the control of mutagenic impurities per ICH M7, and the speakers presented calculation methods and operational challenges regarding the use of purge factor calculations during the application of Option 4. In this symposium, risk assessment of nitrosamine impurities, which have recently become a significant issue in pharmaceutical quality control, was also a key topic. This article summarizes the presentation of each speaker at the symposium.

Continuous manufacturing is a manufacturing method in which raw materials are entered continuously in the manufacturing process throughout the duration of the process, and products are produced continuously through the manufacturing. Continuous manufacturing is applicable in various ways: Where all the stages of manufacturing process are continuous, from charging raw materials to discharging final products; and where only certain stages of the manufacturing process are continuous. With its continuous process operation, continuous manufacturing will be expected to maintain production efficiency irrespective of the equipment scale. By adjusting such as the continuous operating time in the process, continuous manufacturing can cater for a wide range of batch size. Therefore the same manufacturing equipment can be used from the developmental phase to the commercial phase. Continuous manufacturing is considered an efficient manufacturing technology, and considered to be one of major manufacturing technology in pharmaceutical production. Number of guidelines, however, published by regulatory agencies regarding continuous manufacturing is limited. There is no guideline by regulatory agencies specific to continuous manufacturing of biotechnological products. In this paper, we described points to consider when designing control strategy of continuous manufacturing of biotechnological products.