we run it each time they change their list. The hope is that the list gets manageable and the client handles the bounces. With a list that large I would say they'll never do that.
I use IMGate/postfix's SAV to clean new big lists before we put one into production. Enormously speeds up list delivery, since undeliverable msgs, esp deliveries that timeout, slow down the outbound MTA and clutter up its mail queue with 10's of 1000's of undeliverable messages that will be deferred and re-tried repeatedly, further boggng down the outbound MTA.
But after initial cleaning, the mailing list manager must do automatic bounce/unsubscribe cleaning.
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