Following the 2017 salmonellosis outbreak due to the consumption of powdered infant formula (PIF), ANSES updated the report issued in 2008 on the management of the microbial hazards in PIF. The objective of the work was to conduct a hazard analysis of PIF production process and to evaluate the effectiveness of control measures and sampling plans implemented by food operators. Methods: The expertise was carried out by a working group, based on scientific and technical literature and the analysis of four sanitary control plans representative of the diversity of manufacturing processes in France. The manufacturing process of PIF was analyzed to identify potential routes of contamination and key control measures. Contamination and sampling procedures were modeled to estimate the probability of detection of contaminated batches and the related risk. Results: Salmonella spp. and Cronobacter spp. are the main hazards associated with PIF. Contamination may occur after pasteurization originated from contaminated ingredients or the processing environment. Therefore, the safety of PIF is mainly ensured through the strict application of good hygiene practices (prevention of environmental contamination, analysis of ingredients, personal hygiene, cleaning, etc.) and the HACCP principles. The sampling of the finished products cannot be considered as a control measure. Indeed, for statistical reasons, when microbial contamination is low, an unrealistic number of samples need to be tested to detect contaminated batches. Prevention and monitoring of contamination of the processing environment are essential to ensure product safety. The scientific opinion provides general recommendations and proposes tools to identify the sources and routes of contamination, establish an environmental sampling plan and investigate causes in the event of detection of non-conformities. This expertise provides both the competent authorities and food operators with recommendations and operational tools to improve the control of hazards in PIF.