When you put a hole in the center of a blind flange, it is in effect a reducing flange. This is covered by B16.5 2009 in Table 6 on page 70. Depending on the sizes, you may need a hub (i.e. reinforcement) or you may not.
Now, when you put the connection in an off-center position, you no longer have a component which complies with B16.5. If you are dealing with an ASME VIII vessel or piping which allows the use of B16.5 components without calc's, then you are no longer in compliance since you no longer have a B16.5 component.
So... you need to now treat this blind flange as a flat cover per (I'm assuming) VIII Div. 1 UG-34. Calculate the required thickness (a B16.5 flange may fail this calc). Then use UG-39 for area of reinforcement calc's. Note the reduced requirement for area required vs what's required for shells and heads.
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