Method for lyophilizing a substance comprising the steps of: placing at least one vial containing the substance in a lyophilization chamber, the at least one vial having an opening in which a stopper is inserted in a closed state in which the stopper does not allow gas exchange between the interior and exterior of the vial ; providing external mechanical means external to the stopper and arranged at the opening for restricting an upward movement of the stopper ; lowering the temperature within the lyophilization chamber to a predefined value below the freezing temperature of the substance ; and reducing the pressure within the lyophilization chamber to a predefined pressure, the predefined pressure being chosen such that the force exerted by it on the stopper lifts the stopper from the closed state to an exchange state in which the stopper is only partly inserted in the opening of the vial allowing gas exchange between the interior and exterior of the vial , wherein the external mechanical means are configured to prevent the stopper from falling off the opening of the at least one vial when the stopper is lifted from the closed state, wherein the movement of the stopper is allowed up to a predefined distance; wherein the lowering of the temperature within the lyophilization chamber to the predefined value is performed before reducing the pressure within the lyophilization chamber to the predefined pressure; and wherein lifting the stopper from the closed state abruptly lowers the pressure within the at least one vial which initiates nucleation in the substance within that vial ; the method being characterized in that providing the mechanical means external to the stopper for restricting the upward movement of the stopper includes positioning of shelves within the lyophilization chamber at a predefined distance from each other. placing at least one vial containing the substance in a lyophilization chamber, the at least one vial having an opening in which a stopper is inserted in a closed state in which the stopper does not allow gas exchange between the interior and exterior of the vial ; providing external mechanical means external to the stopper and arranged at the opening for restricting an upward movement of the stopper ; lowering the temperature within the lyophilization chamber to a predefined value below the freezing temperature of the substance ; and reducing the pressure within the lyophilization chamber to a predefined pressure, the predefined pressure being chosen such that the force exerted by it on the stopper lifts the stopper from the closed state to an exchange state in which the stopper is only partly inserted in the opening of the vial allowing gas exchange between the interior and exterior of the vial , wherein the external mechanical means are configured to prevent the stopper from falling off the opening of the at least one vial when the stopper is lifted from the closed state, wherein the movement of the stopper is allowed up to a predefined distance; wherein the lowering of the temperature within the lyophilization chamber to the predefined value is performed before reducing the pressure within the lyophilization chamber to the predefined pressure; and wherein lifting the stopper from the closed state abruptly lowers the pressure within the at least one vial which initiates nucleation in the substance within that vial ; the method being characterized in that providing the mechanical means external to the stopper for restricting the upward movement of the stopper includes positioning of shelves within the lyophilization chamber at a predefined distance from each other. <EOS>