Study On Inherent Safety And Risk Control Technology For API CDMO Enterprise

Contract Development and Manufacture Organization(CDMO)industry for Active Pharmaceutical Ingredients(API)is growing fast with high-efficiency and low-cost because of the implementation of innovative drug R&D system.Fire and explosion accidents of the API CDMO industry occur frequently due to inherent risk.The overall requirements and expectations are getting higher and higher on EHS performance from public,regulatory authorities,and multinational customers.It becomes more and more important and urgent that how to improve inherent safety performance of API CDMO.This paper aims at presenting the technique of risk control for entire process based on inherent safety which can be accepted by API CDMO industry and convenient for engineering designs.This paper study how to reduce the EHS risk from the source of engineering design via screening the critical and acceptable technique of risk control for entire process during the design stage refer to the Best Acceptable Technique(BAT)and the inherent safety concept of"EHS by Design" through evaluating the level of risk with Comprehensive Inherent Safety Index(CISI)method focuses on the production which produce the different products using two modular equipment chain with same multi-functional reactor as main body installed in a multi-purpose workshop of API CDMO.The overall inherent safety index of modular equipment chain depended on five aspects according to CISI calculation process:chemical flow,chemical severity,chemical reactivity,equipment operation process parameters and process connection between equipment.This paper evaluated the risk factors focuses on the production which produce the different products using two modular equipment chain with same multi-functional reactor as main body only underlining from four aspects including the severity of chemicals,chemical reactivity,process operation of equipment operation and equipment facilities except for the flow of chemicals because the flow of chemicals was affected by the specific process route,material balance and raw material ratio.The results of the evaluation showed that there was no significant difference in numerical value,which indicated that under the similar process and chemical conditions,the overall inherent safety index(ITISI)of the two modular equipment chain was approximate.Therefore,the CISI method was suitable for the analysis of different process routes of the same product,especially the comparative analysis between continuous process with batch process.The application limitation of the CISI method focused on the two products with similar batch process comparation,such as the enlargement of calculation results,the larger range of parameters,and the risk of missing judgment.The paper screened and put into use the critical and acceptable technique of risk control for entire process during the design stage refer to the BAT and the inherent safety concept of "EHS by Design" in view of the above risks,including equipment layout design of multi-purpose workshop;design of raw material storage,transportation and feeding(warehouse and tank farm);design of reactor and container;design of process control system;design of solid-liquid separation;design of discharge system and collection tank;design of utility(such as cooling,vacuum)and facilities.The main purpose of above is to solve how to continuously,stably,safety and reliably operate and dispose many flammables,explosive,toxic and harmful chemicals in the production plant,and at the last to reduce the EHS risk to the tolerance level from the source of engineering design.At present,the project successfully passed the completion acceptance and complete continuous and stable operation.Study result in this paper is to help to systematically understand the technique of risk control for entire process based on inherent safety which can be accepted by API CDMO industry and convenient for engineering designs,and to help to the new project to reduce the EHS risk to the tolerance level from the source of engineering design,so as to meet the EHS requirements from the government and customers,enhance the sustainable development ability and competitiveness of enterprise.