if ( is_admin() ) {
    require_once WPF_DIR_PATH . 'includes/admin/class-updater.php'; // this file contains the class WPF_Plugin_Updater(); it only loads in the admin.
}

if ( ! is_admin() ) {
    return; // if we're not in the admin, quit
}

$edd_updater = new WPF_Plugin_Updater(); // Fatal error, class not found, because the file wasn't included. Somehow WPMU is running this line of code outside of the admin, despite the line above.