The recommendeded way to manage SAFEs is through the GebSAFEManager contract, which allows a single address to open multiple SAFEs.
Pyflex does not fully support GebSAFEManager and so for now you can only use it to interact directly with SAFEEngine. When you interact directly with SAFEEngine, you can only open one 'unmanaged' SAFE per address.
If you're not using pyflex, we recommend you to manage your SAFEs through the app or with geb-js.
The following sections show you how to manage SAFEs without the GebSAFEManager and thus interact with the SAFEEngine contract directly.