Were you trying to drill a socket head cap screw, or a hex head? Should be able to drill socket heads, and then use a washer to get the same surface contact area as a hex head. With all your fab experience I know you know how to drill stainless: slow rpm, lots of pressure, good cutting oil. Don't try carbide drills unless you have a rigid mill, use cobalt or hss. The AN and NAS specs are only for SAE, not metric fasteners. I've never tried a jam nut behind a threaded plate like this but thinking about it I don't know if it will work or not. First, you tighten the bolt into the manifold, which stretches the portion of the bolt between head and the manifold threads and brings the head-side of the threads into friction contact with the manifold threads. Then you put on the rear jam nut and tighten it. That will actually pull the bolt threads and manifold threads apart, stretching the part of the bolt between head and manifold even more, and if you tighten the jam nut to the same torque and use lube everywhere for the same friction, at the same final torque the threads in the manifold would actually be centered between the faces and not in contact at all, so now the only friction contact is between the jam nut threads and the bolt threads which I don't see as any better than no jam nut. You would have to first torque the bolt into the manifold at some lower torque, then tighten the jam nut to a higher torque to allow the bolt threads to shift to the rear in the manifold threads so you get contact in both the manifold and the jam nut. You would have to experiment with a bolt stretch gauge to figure out the two torques to get the clamping force on the flange that you want.
I think you should talk to Remflex to see if they have a compressible graphite gasket that will fit your flange, it should be more blowout resistant. Second, if you are using hex head bolts can you use a lock plate (or whatever the official name is) instead of safety wire? A plate that goes under the bolt head like a washer that hits something to keep it from being able to spin, either a protrusion or make the plate long enough to span two bolt holes. Then you bend up tabs on the plate to make contact with the hex flats so the bolt can't spin.
