Mass spectrometry based multi-attribute method (MAM) has been commonly proposed to be implemented as a quality control (QC) method for monitoring product critical quality attributes (CQA) of biotherapeutics. Different from characterization methods, regulatory requirements should be followed for developing a QC method for release and stability testing. However, there are some method specific issues for MAM as an advanced technology, for example the additional considerations for method validation and new peak detection feature based on the intended use. Because the ultimate implementation goal of MAM is to replace and consolidate several conventional methods, such as Cation Exchange Chromatography (CEX) for the control of charge variants and Hydrophilic Interaction Chromatography (HILIC) for the control of glycan variants, additional regulatory considerations should also be addressed before its final implementation, for example the comparison between MAM and conventional methods and product specific risk assessment. In this presentation, major regulatory points-to-consider and relevant data expectation to support MAM implementation will be discussed with several case studies along with strategies of rolling in MAM at an appropriate stage during product development.