Your overall anti-spam system should have manual emergency blocks
We mostly rely on a commercial anti-spam system for our incoming spam filtering (as described here), and many other people rely on a variety of open source options for their spam filtering. This generally works very well, with us (and you) getting to offload the work of maintaining a high quality anti-spam system to other people (and it's certainly a lot of work). But not always (and not just because it malfunctions). The realities of life are that sooner or later you will be hit by a spam run that your anti-spam system doesn't recognize, either because the spam run is really new or because it's pretty specific to you.
Much of the time, you can shrug your shoulders and let this go. No anti-spam system is perfect and one of the tradeoffs you make when relying on a third-party system is that it's broadly out of your hands (sometimes this is an advantage). But some of the time this isn't going to be good enough; either the volume or the threat to your users will be so high that you can't just sit on your hands.
(Modern ransomware is making this clear by creating a potentially very high cost of allowing some things through.)
When this day comes to pass, you'll want to have the ability to step in and block the traffic even though your automated anti-spam system is happy with it. This can take many forms, depending on how you want to handle it; you could figure out how to write custom rules for your anti-spam system (so you can outright block certain sorts of files or certain URLs or whatever), or you can build blocking features into your mailer configuration itself, or any number of other options.
Having been through having to do this on the fly during an emergency, my strong suggestion is that you build the infrastructure for these manual blocks now, before you need them. It's some additional up front work and if you're lucky you may never need it, but doing it now when you have time to plan and test and figure out the best way to do things beats having to do it on the fly, under pressure.
Sidebar: What I think you should have manual blocks for
On the one hand attacker ingenuity is very deep, but on the other hand certain patterns repeat over and over again. So my view is that you can probably cover most ground with the ability to put in place manual blocks against sending IPs, sending domains, file extensions (including inside file containers like ZIP files), and whole and partial URLs (for phishing campaigns). You might also want a general message header and body regular expression matching system, but that's starting to feel like scope creep to me.
(Of course real scope creep would be to start by creating a general, generic framework for writing relatively arbitrary manual blocks on message attributes.)
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