The assessment and control of potential mutagenic impurities (PMIs) within pharmaceutical products are managed in accordance with the ICH M7 guideline, "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk". This guideline highlights four control options, which can be used to give assurance of control of PMIs to below a level of concern for the intended patient. These controls vary from testing to confirm levels within the active pharmaceutical ingredient or product (ICH M7 Option 1 Control) to a control strategy that relies on process controls and scientific principles in lieu of analytical testing, which can include considerations of fate and purge (measured or predicted) (Option 4). This work provides clarity on when additional data or information can be useful to give greater support to an ICH M7 Option 4 control, illustrated through a series of case studies. These case studies range from examples that have been approved by health authorities for clinical applications and marketing authorizations to those that have not been submitted to regulators at this time. Sound data and scientific rationales are required to support the ICH M7 Option 4 control strategies. These supportive elements can be challenged by regulators, leading to a non-acceptance for the proposed control strategy and a commitment to routine testing (ICH M7 control Options 1, 2, or 3). This study provides an industry perspective of Option 4, approaches with an emphasis on the types of supportive datasets and scientific principles that can be used while remaining aligned with the intention of the ICH M7 guideline, and elaborates on the differences between the different control options.